The company did not use an adjuvant in the failed study.
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For people over 65, it offers Fluad, which includes adjuvant, for $74.99.
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GSK also used adjuvant technology to develop vaccines against pandemic influenza in 2009.
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A new component was also introduced to stimulate stronger immunity, known as an adjuvant.
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"That's the reason for the boost and the reason for the adjuvant," he said.
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The shot also contains an adjuvant, or booster, made by the U.S. biotech company Agenus.
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The lower lobe of my left lung was removed, followed by four rounds of adjuvant chemotherapy.
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All of the women were cancer-free when they completed five years of adjuvant hormone-based therapy.
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Watch them demo here: Antibiotic Adjuvant: Delivering AI-powered decision support software designed to monitor and reduce antibiotic resistance.
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Vaccines also often contain a substance called an adjuvant, which is designed to spur the immune system into action.
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The company's new investment round was led by Adjuvant Capital, with additional participation from Euclidean Capital and Topspin Partners .
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But one of the vaccines was packaged with an experimental type of adjuvant developed by the researchers, called CAF01.
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The goal of such so-called adjuvant therapy is to destroy any lingering cancer cells not killed by initial treatment.
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The data suggest that women with ER-positive breast cancer should at least consider continuing adjuvant therapy beyond five years, the authors conclude.
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"Our adjuvant technology has previously been used successfully in the pandemic flu setting," Thomas Breuer, the chief medical officer of GSK Vaccines, said.
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The adjuvant has been shown to boost the response rate of other types of vaccines, and it proved very effective here too, Carter says.
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What makes Shingrix so much better is the inclusion of a substance called an adjuvant that boosts the body's immune response to the vaccine.
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The analyst added that Bristol-Myers is testing Opdivo in nine late-stage adjuvant trials and as maintenance therapy in small-cell lung cancer.
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By using an adjuvant, companies are able to reduce the amount of antigens required, thereby creating more vaccine doses — a critical opportunity in a pandemic.
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William Blair analyst Matt Phipps in a client note said the new approval may help the drug expand into the "maintenance and adjuvant therapy settings".
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And the shot with adjuvant (FLUAD) has an immune-boosting supplement; it's meant for people with weaker immune systems who need a little help making antibodies.
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As a result Kepler Cheuvreux analyst David Evans last month cut his forecasts for peak adjuvant sales of Perjeta to $1.5 billion, from $3.5 billion previously.
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"We now have good evidence that extending adjuvant (hormone-based) therapy beyond five years continues to suppress and reduce recurrence and mortality," Hayes said by email.
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"One way that adjuvant breast cancer treatment works is to kill and/or stop the undetectable cancer cells from growing and dividing," Farias said by email.
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The researchers analyzed dietary information for 1,018 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored trial of adjuvant chemotherapy.
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The partnership will bring together GSK's strength in developing adjuvant — a substance to enhance the body's immune response to antigens — with CEPI-funded entities interested in testing their vaccine.
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"They're doing various gradations of RV144—an extra booster, a different adjuvant," says Jay Levy, a virologist at UC San Francisco and one of the people who discovered HIV.
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"The data are important, they show there is a very significant clinical benefit, and they give us hope for the adjuvant study we have been running," Mr Soriot said.
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That approach relies on using an agent known as an adjuvant, which helps create stronger and longer-lasting immunity against infections than a vaccine can provide on its own.
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"With Kadcyla, the approximately 60 percent share of sales generated by Herceptin as an adjuvant would be secured for several years," wrote Michael Nawrath, of Zuercher Kantonalbank, in a note.
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They added an immune booster to the vaccine, called an adjuvant, which was deemed safe in their 100 person trial — making it the first one deemed safe for intradermal use.
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Commins, who is at the University of North Carolina, at Chapel Hill, has identified a candidate, an enzyme in the tick's saliva called dipeptidyl-peptidase that works as an adjuvant.
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Five percent of patients who wore the cap had no hair loss, and 33 percent lost 25 percent or less of their hair by the end of their adjuvant chemotherapy.
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In 1967, he became chairman of the National Surgical Adjuvant Breast and Bowel Project, a consortium of academic medical centers organized by the National Cancer Institute to run large clinical trials.
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The pharmacy also supplied them with what's known as an adjuvant, in this case a cream that when applied to the injection site would hopefully help boost the efficacy of the vaccine.
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Read more: A coalition backed by Bill Gates is funding biotechs that are scrambling to develop vaccines for the deadly Wuhan coronavirusIn particular, GSK will offer up its pandemic vaccine adjuvant platform.
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"It shows that what was done 120 years ago with Coley's Toxins deserves to be revisited again today, using bacteria as an adjuvant to stimulate the immune system to fight cancer," Saha says.
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Those who are not can expect to pay $40.99 for a quadrivalent shot, while both options for those 65 and older — the high-dose shot and the one with adjuvant — each cost $69.99.
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The primary objective of AIM2CERV is to compare the disease free survival of AXAL to placebo administered in the adjuvant setting following concurrent chemotherapy and radiotherapy (CCRT) administered with curative intent to patients with HRLACC.
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"We know that adjuvant (hormone-based) therapy for 5 years substantially reduces the risk of recurrence and mortality," said senior study author Dr. Daniel Hayes of the University of Michigan Comprehensive Cancer Center in Ann Arbor.
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"What has changed is we have these scientific advances in early detection and treatment, we have mammography, we have adjuvant chemotherapy for breast cancer, we have hormone therapy, we have now even targeted therapy," Jemal said.
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Based on a survey of oncologists, Jefferies expects U.S. cancer doctors to use Perjeta in 44 percent of post-surgery, or adjuvant, patients currently treated with Herceptin, which translates into a revenue opportunity of around $4.3 billion.
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His team is now working on isolating the protein from a few different strains of N. gonorrhoeae and creating a proper adjuvant, the chemical in a vaccine that indicates to the immune system that something is hazardous.
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The company is presently running a large trial to determine whether the medicine can improve outcomes in so-called adjuvant therapy — which is given to earlier stage patients after they have undergone surgery — with results due in 2019.
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The results, published earlier this week in the journal The Lancet Infectious Diseases, pertained to a pool of 430 infants and toddlers who were given the oral vaccine, given either on its own or with an additional adjuvant.
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"Taking oral magnesium supplements regularly can help lower blood pressure and can be considered as an inexpensive, safe, and adjuvant antihypertensive therapy," said Song, of the Richard M. Fairbanks School of Public Health at Indiana University in Indianapolis.
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"In the maternal setting, the use of an adjuvant has really given us a profound response, and so we want to change that piece of the formulation" for the trial in older adults, Chief Executive Stanley Erck told Reuters.
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Some people are using a high-dose regimen of CBD-rich oils (also called cannabidiol, the pain-relieving ingredient in marijuana) as an adjuvant when battling cancer (as an agent that helps to make their primary treatment work better).
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"In our study, we found that breast cancer patients in adjuvant chemotherapy, were indeed capable of performing the required exercise, so it is feasible for cancer patients to do the exercise training we are proposing," Hojman noted in an email interview.
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He also weathered allegations of scientific fraud before being fully vindicated and restored to his previous post as chair of the cancer cooperative group, the National Surgical Adjuvant Breast and Bowel Project at the University of Pittsburgh School of Medicine.
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Older people often have weaker immune responses to the vaccine, so experts suggest those 65 and older get either a high-dose shot, which has four times the regular dosage, or a shot with adjuvant, an ingredient that boosts immune response.
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So far Yervoy is the only drug approved in the post-surgery or adjuvant setting for this deadliest form of skin cancer, but the high doses of the medicine needed mean it can cause severe side effects and, as a result, use is limited.
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Undeterred, Dr Bekker has run a small trial to prove the safety of a new version of the Thai vaccine, adapted to combat the strain of HIV most common in South Africa and also given a better adjuvant—a booster chemical that promotes a vaccine's efficacy.
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There is currently no evidence to suggest a benefit to delaying chemo in light of Covid-19 risks, the group says, although there may be cases in which adjuvant chemotherapy, meaning chemotherapy that's given in combination with another type of treatment, such as surgery or radiation, may be appropriate to delay.
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Instead of the classical spadework Dorman advocates, scientists would use genetic and protein engineering techniques to build a vaccine from scratch, taking pieces of the HIV virus, bits of other viruses that the immune system kind of knows what to do with, "adjuvant" agents that boost an immune response…bits and pieces chained together into an exquisite corpse of immune-goosing biotechnology.
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An adjuvant agent modifies the effect of another agent, so adjuvant therapy modifies other therapy.
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Carboplatin has also been used for adjuvant therapy of stage 1 seminomatous testicular cancer. Research has indicated that it is not less effective than adjuvant radiotherapy for this treatment, while having fewer side effects. This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.
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MF59 is an immunologic adjuvant that uses squalene. It is Novartis' proprietary adjuvant that is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells. MF59 is the first oil-in-water influenza vaccine adjuvant to be commercialized in combination with a seasonal influenza virus vaccine. MF59 is used as an adjuvant in Canada, Europe and the United States.
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Adjuvant chemotherapy and/or radiotherapy in malignant SFT remains controversial.
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Adjuvant therapy, also known as adjunct therapy, add-on therapy, and adjuvant care, is therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
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The mechanism of action of the adjuvant is not entirely understood.
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The addition of another modality of treatment is referred to as adjuvant (literally helping) therapy, compared to its use as the initial (primary) therapy, also referred to as radical therapy. Consequently, many of these patients have been treated with adjuvant radiation, with or without chemotherapy. In the above series of reports of minimally invasive surgery, many (30–80%) patients received adjuvant radiation.
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Adjuvant use generally is accompanied by undesirable side effects of varying severity and duration. Research on new adjuvants focuses on substances which have minimal toxicity while retaining maximum immunostimulation. Investigators should always be aware of potential pain and distress associated with adjuvant use in laboratory animals. The most frequently used adjuvants for antibody production are Freund's, Alum, the Ribi Adjuvant System and Titermax.
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For example, radiotherapy or systemic therapy is commonly given as adjuvant treatment after surgery for breast cancer. Systemic therapy consists of chemotherapy, immunotherapy or biological response modifiers or hormone therapy. Oncologists use statistical evidence to assess the risk of disease relapse before deciding on the specific adjuvant therapy. The aim of adjuvant treatment is to improve disease-specific symptoms and overall survival.
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Aluminum salts, known as "alum", were the first adjuvant used for licensed vaccines, and are the adjuvant of choice in some 80% of adjuvanted vaccines. The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines. A potential drawback of adjuvanted vaccines is that the virus evolves in a way to avoid the induced vaccine response, making the adjuvant-vaccine technology misdesigned against a changed virus. Such a change would require revised manufacturing and increased costs that discourage the routine use of adjuvants.
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For seminoma, the three standard options are: active surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. For non-seminoma, the options include: active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection. As is the case for all reproductive cancers, a degree of caution is taken when deciding to use adjuvant therapy to treat early stage testicular cancer. Though the 5-year survival rates for stage I testicular cancers is approximately 99%, there still exists controversy over whether to overtreat stage I patients to prevent relapse or to wait until patients experience relapse.
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Recent meta-analyses have proposed two adjuvant therapies which may help in the eradication of H. pylori. Periodontal therapy or what is known as scaling and root planing and probiotics both need further studies to confirm their adjuvant role.
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Virosomes therefore represent an innovative, broadly applicable adjuvant and carrier system with prospective applications in areas beyond conventional vaccines. They are one of only three adjuvant systems widely approved by regulatory authorities and the only one that has carrier capabilities.
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In early stage cervical cancers, research suggests that adjuvant platinum-based chemotherapy after chemo-radiation may improve survival. For advanced cervical cancers, further research is needed to determine the efficacy, toxicity and effect on the quality of life of adjuvant chemotherapy.
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If the tumor can be removed surgically, people may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally excised), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007.
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Radiotherapy may be used in the adjuvant setting or for palliative treatment of cholangiocarcinoma.
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In glioblastoma multiforme, adjuvant chemoradiotherapy is critical in the case of a completely removed tumor, as with no other therapy, recurrence occurs in 1–3 months. In early stage one small cell lung carcinoma, adjuvant chemotherapy with gemcitabine, cisplatin, paclitaxel, docetaxel, and other chemotherapeutic agents, and adjuvant radiotherapy is administered to either the lung, to prevent a local recurrence, or the brain to prevent metastases. In testicular cancer, adjuvant either radiotherapy or chemotherapy may be used following orchidectomy. Previously, mainly radiotherapy was used, as a full course of cytotoxic chemotherapy produced far more side effects then a course of external beam radiotherapy (EBRT).
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5-fluorouracil, which inhibits thymidylate synthase, was later shown to improve survival when used as an adjuvant to surgery in treating patients with colon cancer. Similarly, the landmark trials of Bernard Fisher, chair of the National Surgical Adjuvant Breast and Bowel Project, and of Gianni Bonadonna, working in the Istituto Nazionale Tumori di Milano, Italy, proved that adjuvant chemotherapy after complete surgical resection of breast tumours significantly extended survival — particularly in more advanced cancer.
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Titermax is a mixture of compounds used in antibody generation and vaccination to stimulate the immune system to recognise an antigen given together with the mixture. Titermax is a recently developed immune adjuvant. It is a water-in- oil emulsion and consists of squalene, an emulsifier (sorbitan monooleate 80), a patented block copolymer and microparticulate silica (Stills 2005). Toxicity seems to be lower than other water in oil adjuvant such as Freund's adjuvant.
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Patients that have tumors small enough to take out with surgery will receive endocrine therapy after their surgery, which is part of adjuvant therapy. Large tumors may receive neo-adjuvant therapy via chemotherapy or radiation to shrink the tumor small enough to operate on.
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This suggests that adjuvant stem cell transplantation can increase the efficacy of PVE without increasing risk.
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Introduction of neo-adjuvant chemotherapy also changes the standard of care for a more advanced stage, but localized breast cancers as 80% of women had a response to chemotherapy. The studies helped establish the length of neo-adjuvant chemotherapy needed and the increase in survival and disease-free survival when compared to women who did not receive neo-adjuvant chemotherapy. Disease-free survival improved three to four-fold and neo- adjuvant became the standard of care for a patient with larger tumors and nodal disease but no distant metastases. In collaboration with Carl Mansfield, she reported on ten-year experience with interstitial implants in the breast to deliver the boost dose.
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Specol (trade name Stimune) is a water in oil adjuvant composed of defined and purified light mineral oil (Stills. 2005). It has been suggested as an alternative to Freund's adjuvant for hyperactivation of the immune response in rabbits (Leenaars et al. 1994). Specol can be used for antigens of low immunogenicity and can be administered equally effectively by the subcutaneous or intraperitoneal routes. The histological lesions produced are fewer than those produced by using Complete Freund's adjuvant.
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Similarly, several common adjuvant therapies are noted for having the potential of causing cardiovascular disease. In such cases, physicians must weigh the cost of future recurrence against more immediate consequences and consider factors, like age and relative cardiovascular health of a patient, before prescribing certain types of adjuvant therapy. One of the most notable side effects of adjuvant therapy is the loss of fertility. For pre-pubescent males, testicular tissue cryopreservation is an option for preserving future fertility.
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However, since most micrometastatic tumor cells are in the nonproliferative G0 phase, standard cytotoxic chemotherapies may not be as useful. Therefore, adjuvant chemotherapy and adjuvant radiation therapy are more effective to eliminate micrometastases, since they are aimed to target dividing and quiescent cells. Adjuvant therapies are administered after the removal of the lymph nodes. The significance of these therapies is to serve as a “clean up” method for those cells that have migrated elsewhere from the primary tumor.
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Adjuvant chemotherapy is effective in preventing the outgrowth of micrometastatic disease from colorectal cancer that has been removed surgically. Studies have shown that fluorouracil is an effective adjuvant chemotherapy among patients with microsatellite stability or low-frequency microsatellite instability, but not in patients with high-frequency microsatellite instability.
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In pharmacology, adjuvants are drugs that have few or no pharmacological effects by themselves, but may increase the efficacy or potency of other drugs when given at the same time. For instance, caffeine has minimal analgesic effect on its own, but may have an adjuvant effect when given with paracetamol (acetaminophen).Zhang, WY, A benefit-risk assessment of caffeine as an analgesic adjuvant, Drug Safety (2001), 24(15): 1127-42. Caffeine as an analgesic adjuvant for acute pain in adults. (2012).
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There are two basic types of Freund's adjuvants: Freund's Complete Adjuvant (FCA) and Freund's Incomplete Adjuvant (FIA). FCA is a water-in-oil emulsion that localizes antigen for release periods up to 6 months. It is formulated with mineral oil, the surfactant mannide monoleate and heat killed Mycobacterium tuberculosis, Mycobacterium butyricum or their extracts (for aggregation of macrophages at the inoculation site). This potent adjuvant stimulates both cell mediated and humoral immunity with preferential induction of antibody against epitopes of denatured proteins.
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The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery has been controversial since the 1980s. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is a continuing tendency for clinicians in the US to be more ready to use adjuvant radiotherapy than those in Europe. Many clinical trials have tested a variety of treatment combinations since the 1980s, but have failed to settle the matter conclusively.
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Tariquidar (INN/USAN) is a P-glycoprotein inhibitor undergoing research as an adjuvant against multidrug resistance in cancer.
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Among commonly used adjuvants are Complete and Incomplete Freund's adjuvant and solutions of aluminum hydroxide or aluminum phosphate.
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Freund's complete adjuvant is a solution of inactivated Mycobacterium tuberculosis in mineral oil developed in 1930. It is not safe enough for human use. A version without the bacteria, that is only oil in water, is known as Freund's incomplete adjuvant. It helps vaccines release antigens for a longer time.
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It is also used as an agricultural spray adjuvant for water-soluble insecticides, herbicides, and fungicides. There, it functions to bind iron and calcium cations that are present in both well water and plant cells. It is particularly effective as an adjuvant for 2,4-D (amine), glyphosate, and glufosinate herbicides.
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Diabetes in BB rats can be prevented by a single injection of mycobacterial adjuvants such as complete Freund's adjuvant (FCA).Sadelain MW, Qin HY, Sumoski W, Parfrey N, Singh B, Rabinovitch A. Prevention of diabetes in the BB rat by early immunotherapy using Freund's adjuvant. J Autoimmun; 1990 ; 3:671-80.
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Because the treatment is essentially for a risk, rather than for provable disease, it is accepted that a proportion of patients who receive adjuvant therapy will already have been cured by their primary surgery. Adjuvant systemic therapy and radiotherapy are often given following surgery for many types of cancer, including colon cancer, lung cancer, pancreatic cancer, breast cancer, prostate cancer, and some gynaecological cancers. Some forms of cancer fail to benefit from adjuvant therapy, however. Such cancers include renal cell carcinoma, and certain forms of brain cancer.
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Those claims have not been validated by scientific research. Adjuvant chemotherapy has been used in malignant melanoma, but there is little hard evidence to use chemotherapy in the adjuvant setting. However, melanoma is not a chemotherapy- resistant malignancy. Dacarbazine, temozolomide, and cisplatin all have a reproducible 10–20% response rate in metastatic melanoma.
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Vincristine, Adriamycin, and bleomycin are used for adjuvant chemotherapy, but their effects are not good enough according to published series.
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In immunology, an adjuvant is a substance that potentiates and/or modulates the immune responses to an antigen to improve them. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens." In the early days of vaccine manufacture, significant variations in the efficacy of different batches of the same vaccine were correctly assumed to be caused by contamination of the reaction vessels.
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Though options for fertility preservation exist (e.g., embryo preservation, oocyte cryopreservation, ovarian suppression, etc.), they are more often than not time-consuming and costly. As a result of complications that can stem from liberal use of adjuvant therapy, the philosophy surrounding the use of adjuvant therapy in the clinical setting has shifted towards the goal of doing as little harm as possible to patients. The standards for dose intensity of adjuvant treatments and treatment duration are regularly updated to optimize regimen efficiency while minimizing toxic side effects that patients must shoulder.
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Radiation therapy (also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.
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Medications used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer when used with other treatments. There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.
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MIS416 is a vaccine adjuvant and "immunogen co-delivery system". In 2011, in an NIH publication MIS416 was described as a "non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity". In 2015, Innate Immunotherapeutics described it as an "immunomodulator" for "patients with chronic progressive multiple sclerosis".
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Rhabdomyosarcomas are highly chemosensitive, with approximately 80% of cases responding to chemotherapy. In fact, multi-agent chemotherapy is indicated for all patients with rhabdomyosarcoma. Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%. Modern survival rates with adjuvant therapy are approximately 60–70%.
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In this case, the adjuvant is called a tank mix adjuvant. When delivered in-can, adjuvants may be quite effective. However, because of the limited space or limited compatibility in a pesticide formulation, not all necessary adjuvants may be included in-can. Thus, the addition of tank mix adjuvants may be necessary to optimize performance of the pesticide.
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AS04 (Aka. "Adjuvant System 04") is a trade name for combination of adjuvants used in various vaccine product by GlaxoSmithKline (GSK), in particular the Fendrix Hepatitis B vaccine. It consists of aluminum hydroxide and monophosphoryl lipid A (MPL). Furthermore, it is the successor of AS03 which is a Squalene based adjuvant approved for pandemic vaccine by the EMA.
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IOMAI was acquired by Intercell in 2008 and the technology was the subject of a development license to GSK in 2009. Dr. Glenn pioneered needle free delivery to the skin and spawned general interest in skin-targeting vaccine technologies, including intradermal delivery and the use of the heat labile toxin as an adjuvant and the adjuvant patch.
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In Europe and Japan, polysaccharide-K (brand name Krestin), a chemical derived from Trametes versicolor, is an approved adjuvant for cancer therapy.
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224-240Kushner, Rose (1984), Is Aggressive Adjuvant Chemotherapy the Halsted Radical of the '80s?, CA Cancer J Clin 1984; 34:345-351.
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The Council of Producers & Distributors of Agrotechnology offers participating companies the ability to self-certify their spray adjuvant products in the USA.
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It has been reported to induce immune response comparable to Freund's adjuvant in rabbit and other research animal while producing fewer histological lesions.
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Anti-inflammatory effect and low ulcerogenic activity of etodolac, a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug, on adjuvant-induced arthritis in rats.
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However, it has been found a single dose of carboplatin is as effective as EBRT in stage II testicular cancer, with only mild side effects (transient myelosuppressive action vs severe and prolonged myelosuppressive neutropenic illness in normal chemotherapy, and much less vomiting, diarrhea, mucositis, and no alopecia in 90% of cases. Adjuvant therapy is particularly effective in certain types of cancer, including colorectal carcinoma, lung cancer, and medulloblastoma. In completely resected medulloblastoma, 5-year survival rate is 85% if adjuvant chemotherapy and/or craniospinal irradiation is performed, and just 10% if no adjuvant chemotherapy or craniospinal irradiation is used. Prophylactic cranial irradiation for acute lymphoblastic leukemia (ALL) is technically adjuvant, and most experts agree that cranial irradiation decreases risk of central nervous system (CNS) relapse in ALL and possibly acute myeloid leukemia (AML), but it can cause severe side effects, and adjuvant intrathecal methotrexate and hydrocortisone may be just as effective as cranial irradiation, without severe late effects, such as developmental disability, dementia, and increased risk for second malignancy.
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Neratinib was discovered and initially developed by Wyeth; Pfizer continued development up to Phase III in breast cancer, and licensed it to Puma Biotechnology in 2011. In September 2016, Puma submitted a new drug application to the U.S. Food and Drug Administration (FDA) for neratinib as a treatment for some people with HER-2 positive breast cancer. In July 2017, it was approved in the United States for adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, (after adjuvant trastuzumab-based therapy).FDA approves neratinib for extended adjuvant treatment of early stage HER2-positive breast cancer.
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Since most early-stage endometrial cancer cases are diagnosed early and are typically very curable with surgery, adjuvant therapy is only given after surveillance and histological factors determine that a patient is at high risk for recurrence. Adjuvant pelvic radiation therapy has received scrutiny for its use in women under 60, as studies have indicated decreased survival and increased risk of second malignancies following treatment. In advanced-stage endometrial cancer, adjuvant therapy is typically radiation, chemotherapy, or a combination of the two. While advanced-stage cancer makes up only about 15% of diagnoses, it accounts for 50% of deaths from endometrial cancer.
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Freund's adjuvant is a solution of antigen emulsified in mineral oil and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant (FCA or CFA) is composed of inactivated and dried mycobacteria (usually M. tuberculosis), whereas the incomplete form (FIA or IFA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T. Freund.
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Adjuvant chemotherapy appears to be ineffective in people with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data. . Retrieved 13 March 2007.
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In 2015, a comprehensive meta-analysis of 47 trials and 11,107 patients revealed that NSCLC patients benefit from adjuvant therapy in the form of chemotherapy and/or radiotherapy. The results found that patients given chemotherapy after the initial surgery lived 4% longer than those who did not receive chemotherapy. The toxicity resulting from adjuvant chemotherapy was believed to be manageable.
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In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.
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Alum was the first aluminium salt used as an adjuvant, but has been almost completely replaced by aluminium hydroxide and aluminium phosphate for commercial vaccines.
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Chevallier, A., The Encyclopedia of Medicinal Plants, 1996 The saponins of this tree are also considered to have adjuvant properties for vaccine solutions.Singh, Manmohan, 2007.
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In Paget's disease, the most common type of adjuvant therapy is radiation following breast-conservative surgery. Adjuvant therapy may also consist of anticancer drugs or hormone therapies. Hormonal therapy reduces the production of hormones within the body, or prevents the hormones from stimulating the cancer cells to grow, and it is commonly used in cases of invasive cancer by means of drugs such as tamoxifen and anastrozole.
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A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant which is an oil-in-water emulsion of squalene oil.
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Though it has not been shown to increase survival, it can reduce the risk of complications after surgery. If a unilateral salpingo-oophorectomy or other surgery is performed, additional chemotherapy, called "adjuvant chemotherapy", can be given. Adjuvant chemotherapy is used in stage 1 cancer typically if the tumor is of a high histologic grade (grade 3) or the highest substage (stage 1c), provided the cancer has been optimally staged during surgery. Bevacizumab may be used as an adjuvant chemotherapy if the tumor is not completely removed during surgery or if the cancer is stage IV; it can extend progression-free survival but has not been shown to extend overall survival.
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Concomitant or concurrent systemic cancer therapy refers to administering medical treatments at the same time as other therapies, such as radiation. Adjuvant hormonal therapy is given after prostate removal in prostate cancer, but there are concerns that the side effects, in particular the cardiovascular ones, may outweigh the risk of recurrence. In breast cancer, adjuvant therapy may consist of chemotherapy (doxorubicin, trastuzumab, paclitaxel, docetaxel, cyclophosphamide, fluorouracil, and methotrexate) and radiotherapy, especially after lumpectomy, and hormonal therapy (tamoxifen, letrozole). Adjuvant therapy in breast cancer is used in stage one and two breast cancer following lumpectomy, and in stage three breast cancer due to lymph node involvement.
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The first-line treatment is surgical resection with wide margins. Chemotherapy (e.g. high-dose doxorubicin) and often radiotherapy are done as adjuvant and/or neoadjuvant treatment.
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Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.
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However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.
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The term "adjuvant therapy," derived from the Latin term adjuvāre, meaning "to help," was first coined by Paul Carbone and his team at the National Cancer Institute in 1963. In 1968, the National Surgical Adjuvant Breast and Bowel Project (NSABP) published its B-01 trial results for the first randomized trial that evaluated the effect of an adjuvant alkylating agent in breast cancer. The results indicated that the adjuvant therapy given after the initial radical mastectomy "significantly decreased recurrence rate in pre-menopausal women with four or more positive axillary lymph nodes." The budding theory of using additional therapies to supplement primary surgery was put into practice by Gianni Bonadonna and his colleagues from the Instituto Tumori in Italy in 1973, where they conducted a randomized trial that demonstrated more favorable survival outcomes that accompanied use of Cyclophosphamide Methotrexate Fluorouracil (CMF) after the initial mastectomy.
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Successful validation was seen with Canadian and Dutch cohorts. Adjuvant! seemed less applicable to a British cohort and accordingly PREDICT is being developed in the United Kingdom.
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Physical activity interventions may also have beneficial effects on health related quality of life, anxiety, fitness and physical activity in women with breast cancer following adjuvant therapy.
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The mainstay of treatment is surgical excision. Two adjuvant therapeutic strategies are Stereotactic surgery (SRS) and fractionated convention radiotherapy (FCRT). Both are highly effective means of treatment.
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If stage II or III disease is confirmed, adjuvant chemotherapy (including or not including postoperative radiotherapy) improves survival by 4% at five years. The combination of vinorelbine and cisplatin is more effective than older regimens. Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Chemotherapy before surgery in NSCLC that can be removed surgically may improve outcomes.
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Adjuvant chemotherapy is also typically reserved for anaplastic ganglioglioma, but has been used anecdotally in partially resected low grade spinal cord gangliogliomas which show evidence of disease progression.
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In 2005, encouraging but mixed results of vaccination were reported with the BCR/ABL1 p210 fusion protein in patients with stable disease, with GM-CSF as an adjuvant.
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As such, identified CYP27A1 inhibitors, including the marketed drugs anastrozole, fadrozole, bicalutamide, dexmedetomidine, ravuconazole, and posaconazole, have been proposed as potential adjuvant therapies in ER-positive breast cancer.
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Amifostine (ethiofos) is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by Clinigen Group under the trade name Ethyol.
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Since seminoma can recur decades after the primary tumor is removed, patients receiving adjuvant chemotherapy should remain vigilant and not assume they are cured 5 years after treatment.
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However, when Quillaia saponins, cholesterol and phospholipids are mixed under the specific stoichiometry that forms ISCOMs, this haemolytic activity is practically eliminated, while the adjuvant activity is retained.
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Unlike classical seminoma, spermatocytic tumors rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.
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The Ii molecule—fused with a viral vector to a conserved region of the Hepatitis C virus (HCV) genome—has been tested as an adjuvant for a HCV vaccine in a cohort of 17 healthy human volunteers. This experimental vaccine was well- tolerated, and those who received the adjuvanted vaccine had stronger anti-HCV immune responses (enhanced magnitude, breadth and proliferative capacity of anti-HCV-specific T-cells) compared with volunteers who received the vaccine that lacked the Ii adjuvant. The Ii molecule might also prove to be useful as an adjuvant for a future vaccine for the SARS-CoV-2 virus, if this enhancing effect can be demonstrated to apply to the appropriate antigen(s).
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In 1976, shortly after Bonadonna's landmark trial, Bernard Fisher at the University of Pittsburgh initiated a similar randomized trial that compared the survival of breast cancer patients treated with radiation after the initial mastectomy to those who only received the surgery. His results, published in 1985, indicated increased disease-free survival for the former group. Despite the initial pushback from the breast cancer surgeons who believed that their radical mastectomies were sufficient in removing all traces of cancer, the success of Bonadonna's and Fisher's trials brought adjuvant therapy to the mainstream in oncology. Since then, the field of adjuvant therapy has greatly expanded to include a wide range of adjuvant therapies to include chemotherapy, immunotherapy, hormone therapy, and radiation.
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Merck KGaA currently relies on third-party manufacturers to supply the product candidate: On Baxter International Inc. (Baxter), for the manufacture of tecemotide, and on GlaxoSmithKline plc (GSK) for the manufacture of the adjuvant in tecemotide called monophosphoryl lipid A (MPL). If tecemotide is not approved until 2015, GSK may terminate its obligation to supply the adjuvant MPL. In this case, Oncothyreon would retain the necessary licenses from GSK required to have the adjuvant MPL manufactured, but the transfer of the process to a third party would delay the development and commercialization of tecemotide.Oncothyreon’s Annual Report 2013 (Form 10-K) GSK is developing the MAGE A3 vaccine in Phase 3, a direct competitor to tecemotide (see section below).
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A breast-conserving surgery consists in the removal of the nipple, areola and the part of the breast that is affected by cancer. In most cases, adjuvant treatment is part of the treatment schema. This type of treatment is normally given to patients with cancer to prevent a potential recurrence of the disease. Whether adjuvant therapy is needed depends upon the type of cancer and whether the cancer cells have spread to the lymph nodes.
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Computer models consider several traditional factors concurrently to derive individual survival predictions and calculations of potential treatment benefits. The validated algorithms can present visually appealing graphics that assist in treatment decisions. In addition, other classifications of breast cancers do exist and no uniform system has been consistently adopted worldwide. Adjuvant! is based on US cohorts and presents colored bar charts that display information that may assist in decisions regarding systemic adjuvant therapies.
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Oncotype DX is a genetic recurrence-scoring tool that measures expression of certain genes associated with breast cancer. A higher score indicates a higher chance of recurring cancer. One project, the TAILORx study, uses the Oncotype DX score to gauge the need for adjuvant therapy and to predict the response to such adjuvant chemotherapy treatments. Pritchard was able to confirm Oncotype DX as a useful tool in deciding upon treatment for low scoring patients.
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The standard initial treatment is to remove as much of the tumor as possible without worsening neurologic deficits. Radiation therapy has been shown to prolong survival and is a standard component of treatment. There is no proven benefit to adjuvant chemotherapy or supplementing other treatments for this kind of tumor. Although temozolomide is effective for treating recurrent anaplastic astrocytoma, its role as an adjuvant to radiation therapy has not been fully tested.
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DNA has been shown to be a potent adjuvant to boost the immune response to antigens encoded by vaccines. cGAMP, through IRF3 activation of STING, stimulates transcription of interferon. This makes cGAMP a potential vaccine adjuvant capable of boosting inflammatory responses. Studies have shown that vaccines encoded with the chicken antigen, ovalbumin (OVA), in conjunction with cGAMP, were able to activate antigen-specific T and B cells in a STING-dependent manner in vivo.
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In Non-small cell lung carcinoma (NSCLC), surgically removed tumors that receive no further therapy have a better survival if ERCC1-positive than if ERCC1-negative. Thus ERCC1 positivity is a favorable prognostic marker, referring to how the disease will proceed if not further treated. ERCC1-positive NSCLC tumors do not benefit from adjuvant platinum chemotherapy. However, ERCC1-negative NSCLC tumors, prognostically worse without treatment, derive substantial benefit from adjuvant cisplatin-based chemotherapy.
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Immunohistologically assessed levels of cyclin B could determine if women with stage 1, node negative, hormone receptor positive breast cancer were likely to benefit from adjuvant therapy. In general women with this cancer have a very good prognosis, with mortality in 10 years of only 5%. Therefore, it is rare for oncologists to recommend adjuvant chemotherapy in these cases. However, in a small subset of patient this type of cancer is unexpectedly aggressive.
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Aluminium is an adjuvant ingredient in some vaccines. An adjuvant is a certain type of ingredient that is used to help the body's immune system create a stronger immune response after receiving the vaccination. Aluminium is in a salt form and is used in the following compounds: aluminium hydroxide, aluminium phosphate, and aluminium potassium sulfate. In chemistry, a salt is the ionic version of an element; another example is table salt: (sodium) and (chloride).
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Surfactants, solvents, and preservatives are inert ingredients, or adjuvants, that are commonly added to glyphosate-based herbicide formulations. Some products contain all the necessary adjuvants, including surfactant; some contain no adjuvant system, while other products contain only a limited amount of adjuvant. Some formulations require the addition of surfactants to the spray tank before application. The names of inert ingredients used in glyphosate formulations are usually not listed on the product labels.
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Tomatine has been used as a reagent in analytical chemistry for precipitating cholesterol from solution. Also, tomatine is known to be an immune adjuvant in connection with certain protein antigens.
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If the pelvis is irradiated, prostatitis, proctitis, dysuria, metritis, diarrhea, and abdominal pain can occur. Adjuvant hormonal therapy for prostate cancer may cause cardiovascular disease, and other, possibly severe, side effects.
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As an adjuvant treatment, use of chemotherapy as an alternative to radiation therapy in the treatment of seminoma is increasing, because radiation therapy appears to have more significant long-term side effects (for example, internal scarring, increased risks of secondary malignancies, etc.). Two doses, or occasionally a single dose of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy. The concept of carboplatin as a single-dose therapy was developed by Tim Oliver, Professor of Medical Oncology at Barts and The London School of Medicine and Dentistry. However, very long- term data on the efficacy of adjuvant carboplatin in this setting do not exist.
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Selection of antigen quantity for immunization varies with the properties of the antigen and the adjuvant selected. In general, microgram to milligram quantities of protein in adjuvant are necessary to elicit high titer antibodies. Antigen dosage is generally species, rather than body weight, associated. The so-called “window” of immunogenicity in each species is broad but too much or too little antigen can induce tolerance, suppression or immune deviation towards cellular immunity rather than a satisfactory humoral response.
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Titermax represents a newer generation of adjuvants that are less toxic and contain no biologically derived materials. It is based upon mixtures of surfactant acting, linear, blocks or chains of nonionic copolymers polyoxypropylene (POP) and polyoxyethylene (POE). These copolymers are less toxic than many other surfactant materials and have potent adjuvant properties which favor chemotaxis, complement activation and antibody production. Titermax adjuvant forms a microparticulate water-in-oil emulsion with a copolymer and metabolizable squalene oil.
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If the cancer is not particularly advanced, patients may be offered careful surveillance by periodic CT scans and blood tests, in place of adjuvant treatment. Before 1970, survival rates from testicular cancer were low. Since the introduction of adjuvant chemotherapy, chiefly platinum-based drugs like cisplatin and carboplatin, the outlook has improved substantially. Although 7000 to 8000 new cases of testicular cancer occur in the United States yearly, only 400 men are expected to die of the disease.
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Exemestane is indicated for the adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to it for completion of a total of five consecutive years of adjuvant hormonal therapy. US FDA approval was in October 2005. Exemestane is also indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.Aromasin For Advanced Breast Cancer on Aromasin.
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There are a number of possible additional therapies. Surgery can be followed by radiation therapy and/or chemotherapy in cases of high-risk or high-grade cancers. This is called adjuvant therapy.
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Quil A is still a mixture of more than 25 different saponin molecules. One of them, the saponin QS21, is being investigated for possible beneficial adjuvant effects on the human immune system.
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"Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer". Invest New Drugs. and Wilson's disease,Roberts EA, Schilsky L, 2008.
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Psychiatric problems in general practice: an Egyptian perspective. A. Okasha Read at the Egyptian French Medical Conference, October 1986. 103\. Anticonvulsant as an adjuvant in the treatment of bipolar and schizophrenic disorders.
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Debridement is done in necrotic ulcers. In gangrenous digits, amputation is frequently required. Above-knee and below- knee amputation is rarely required. Streptokinase has been proposed as adjuvant therapy in some cases.
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Adjuvants can often alter the nativity of the protein. Generally, absorbed protein antigens in a preformed oil-in-water emulsion adjuvant, retain greater native protein structure than those in water-in-oil emulsions.
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In another study published in 2011, pleuran reduced the incidence of upper respiratory tract infections and increased the number of circulating NK cells. Pleuran is also being studied as a potential immunologic adjuvant.
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Adjuvant chemotherapy is a recent innovation, consisting of some combination of paclitaxel (or other taxanes like docetaxel), doxorubicin (and other anthracyclines), and platins (particularly cisplatin and carboplatin). Adjuvant chemotherapy has been found to increase survival in stage III and IV cancer more than added radiotherapy. Mutations in mismatch repair genes, like those found in Lynch syndrome, can lead to resistance against platins, meaning that chemotherapy with platins is ineffective in people with these mutations. Side effects of chemotherapy are common.
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Chemotherapy is curative in approximately 20% of advanced ovarian cancers; it is more often curative with malignant germ cell tumors than epithelial tumors. Adjuvant chemotherapy has been found to improve survival and reduce the risk of ovarian cancer recurring compared to no adjuvant therapy in women with early stage epithelial ovarian cancer. Chemotherapy in ovarian cancer typically consists of platins, a group of platinum-based drugs, combined with non-platins. Common therapies can include paclitaxel, cisplatin, topotecan, doxorubicin, epirubicin, and gemcitabine.
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The copolymer is coated with emulsion stabilizing silica particles which allows for incorporation of large amounts of a wide variety of antigenic materials. The adjuvant active copolymer forms hydrophilic surfaces, which activate complement, immune cells and increased expression of class II major histocompatibility molecules on macrophages. Titermax presents antigen in a highly concentrated form to the immune system, which often results in antibody titers comparable to or higher than FCA. Specol: Specol is a water in oil adjuvant made of purified mineral oil.
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However, three medications have been identified for clinical benefit in GIST: imatinib, sunitinib, and regorafenib. Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl inhibition, also inhibits both c-kit tyrosine kinase mutations and PDGFRA mutations other than D842V, is useful in treating GISTs in several situations. Imatinib has been used in selected neoadjuvant settings. In the adjuvant treatment setting, the majority of GIST tumors are cured by surgery, and do not need adjuvant therapy.
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Agenus has advanced two of its own CPM candidates into early drug development and the company is planning to advance several more antibodies in clinical trials. Today, Agenus is focused on developing a range of immuno-oncology products, including the Prophage vaccines, multiple checkpoint modulators (also known as checkpoint inhibitors or checkpoint antibodies) and its QS21-Stimulon adjuvant. The company's personalized, heat shock protein-based vaccines are in Phase 2 studies. The QS-21 Stimulon adjuvant platform is partnered with GlaxoSmithKline and Janssen.
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Nventa originally advanced HspE7 as a single-agent therapy into multiple Phase 2 clinical trials with positive results, including trials in cervical dysplasia and recurrent respiratory papillomatosis (RRP). These trials were initiated prior to the discovery that potency could be greatly enhanced by addition of a vaccine adjuvant,International HPV Conference Poster: “NVENTA PRESENTS HSPE7 DATA AT INTERNATIONAL HPV CONFERENCE” / Nventa Press Release, November 5, 2007 and, as a result, Nventa is currently developing HspE7 combined with the adjuvant Poly-ICLC. A Phase 1b study has been completed assessing the safety and tolerability of HspE7 with Poly-ICLC in four cohorts totaling 17 patients with CIN. All patients were administered 500 mcg of HspE7 with each of the four cohorts receiving escalating doses of adjuvant – 50, 500, 1,000 and 2,000 mcg.
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Biovest International, Inc (OTCQB: BVTI) is a Minneapolis-based biotechnology company. Their active immunotherapy, BiovaxID, is a cancer vaccine whose first indication is intended to be consolidation/adjuvant therapy of follicular Non- Hodgkin's Lymphoma.
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In more severe cases, tympanostomy tubes can be inserted, possibly with adjuvant adenoidectomy as it shows a significant benefit as far as the resolution of middle ear effusion in children with OME is concerned.
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The B subunits of toxins in this family is relatively harmless on its own. CtxB is routinely used as a neuronal tracer. Elt-IB has been looked into as an adjuvant in trandermal vaccines.
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Edible algae based vaccination is a vaccination strategy under preliminary research to combine a genetically engineered sub-unit vaccine and an immunologic adjuvant into Chlamydomonas reinhardtii microalgae. Microalgae can be freeze-dried and administered orally.
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In the future, reversible PVE may also play a role in treating patients with chronic hepatic insufficiency to increase functional liver tissue, as opposed to just being used as an adjuvant therapy for liver resection.
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Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. A 2013 Cochrane review in cystic fibrosis found no evidence of benefit. Acetylcysteine is used in the treatment of obstructive lung disease as an adjuvant treatment.
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A number of studies are currently underway to determine whether immunomodulatory agents which have proven effective in the metastatic setting are of benefit as adjuvant therapy for patients with resected stage 3 or 4 disease.
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Although FCA has historically been the most widely used adjuvant, it is one of the more toxic agents due to non-metabolizable mineral oil and it induces granulomatous reactions. Its use is limited to laboratory animals and it should be used only with weak antigens. It should not be used more than once in a single animal since multiple FCA inoculations can cause severe systemic reactions and decreased immune responses. Freund's Incomplete Adjuvant has the same formulation as FCA but does not contain mycobacterium or its components.
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The major histocompatibility complex class II-associated invariant chain (CD74)—fused with a viral vector to a conserved region of the HCV genome—has been tested as an adjuvant for an HCV vaccine in a cohort of 17 healthy human volunteers. This experimental vaccine was well-tolerated, and those who received the adjuvanted vaccine had stronger anti-HCV immune responses (enhanced magnitude, breadth and proliferative capacity of anti-HCV-specific T helper cells) compared with volunteers who received the vaccine that lacked this adjuvant.
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Since testicular cancers can spread, patients are usually offered adjuvant treatment - in the form of chemotherapy or radiotherapy - to kill any cancerous cells that may exist outside of the affected testicle. The type of adjuvant therapy depends largely on the histology of the tumor (i.e. the size and shape of its cells under the microscope) and the stage of progression at the time of surgery (i.e. how far cells have 'escaped' from the testicle, invaded the surrounding tissue, or spread to the rest of the body).
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Supporting the activities of ASTM is the Council of Producers & Distributors of Agrotechnology (CPDA), an organization of inert (or other) ingredient and adjuvant manufacturers. CPDA certifies adjuvants by creating certain minimum standards that must be met in order to receive the CPDA stamp of certification. In Canada, adjuvants are regulated by the Pest Management Regulatory Agency (PMRA) section of Health Canada. Each adjuvant must be tested and be proven to be safe and effective with every active ingredient with which it will be used.
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Bacillus Calmette-Guérin (BCG) was approved by the FDA in 1990 as a vaccine for early-stage bladder cancer. BCG can be administered intravesically (directly into the bladder) or as an adjuvant in other cancer vaccines.
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Immunogenic cell death types are divided according to molecular mechanisms leading up to, during and following the death event. The immunogenicity of a specific cell death is determined by antigens and adjuvant released during the process.
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Oral exemestane 25 mg/day for 2–3 years of adjuvant therapy was generally more effective than 5 years of continuous adjuvant tamoxifen in the treatment of postmenopausal women with early-stage estrogen receptor-positive/unknown receptor status breast in a large well-designed trial. Preliminary data from the open-label TEAM trial comparing exemestane with tamoxifen indicated in 2009 that exemestane 25 mg/day is also effective in the primary adjuvant treatment of early-stage breast cancer in postmenopausal women. Interim phase III trial results in 2011 showed that adding everolimus to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone. A Phase III trial was reported in 2011, concluding that the use of exemestane in postmenopausal women at an increased risk for breast cancer reduced the incidence of invasive breast cancer.
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FOLFIRI is used for colorectal cancer and gastric cancer. FOLFIRI is effective in the treatment of metastatic colorectal cancer, but it has not been shown to be effective in the adjuvant therapy of colon and rectal cancer.
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Histologic grade and fertility desires of the patient are key considerations in determining treatment options. In adult women postoperative adjuvant chemotherapy is standard except for stage I /grade 1 disease. In pediatric patients, surgery alone is standard.
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IDRI is collaborating with the United States Agency for International Development to develop a malaria vaccine with the Walter Reed Army Institute of Research using Walter Reed's CelTOS malaria antigen in conjunction with IDRI's GLA-SE adjuvant.
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These rumours generally make unfounded claims that the vaccine is dangerous and they may also promote conspiracy theories. For example, Newsweek states that some chain e-mails make false claims about squalene (shark liver oil) in vaccines. The New York Times also notes that anti-vaccine groups have spread "dire warnings" about formulations of the vaccine that contain squalene as an adjuvant. An adjuvant is a substance that boosts the body's immune response, thereby stretching the supply of the vaccine and helping immunize elderly people with a weak immune system.
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The general procedure to produce polyclonal antibodies is as follows: # Antigen preparation # Adjuvant selection and preparation # Animal selection # Injection process # Blood serum extraction An antigen/adjuvant conjugate is injected into an animal of choice to initiate an amplified immune response. After a series of injections over a specific length of time, the animal is expected to have created antibodies against the conjugate. Blood is then extracted from the animal and then purified to obtain the antibody of interest. Inoculation is performed on a suitable mammal, such as a mouse, rabbit or goat.
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But the strong toxicity of the adjuvant and inability to obtain sufficient count of parasites from human blood stopped further efforts in this way. In 1967 irradiated malaria sporozoites (extracted from salivary glands of infected mosquitos) induced immune response in mice without the need of the adjuvant and similar evidence obtained in human volunteer trials. The mice were exposed to irradiated mosquitos infected by malaria parasites. Mice and volunteers did not acquire malaria because mosquitos and the sporozoites were irradiated and their immune cells triggered response that could protect them from following infection.
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For post-pubescent males, this side effect can be assuaged through semen cryopreservation. For pre-menopausal females, options to preserve fertility are oftentimes much more complex. For example, breast cancer patients of fertile age oftentimes have to weigh the risks and benefits associated with starting an adjuvant therapy regimen after primary treatment. In the some low-risk, low-benefit situations, forgoing adjuvant treatment altogether can be a reasonable decision, but in cases where the risk of metastasis is high, patients may be forced to make a difficult decision.
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Khammari A., Knol A.C., Nguyen J.M., Bossard C., Denis M.G., Pandolfino M.C., Quéreux G., Bercegeay S., Dréno B. 2014. " Adoptive TIL transfer in the adjuvant setting for melanoma: long- term patient survival ". Journal of Immunology Research. 2014: 186212.
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Cervarix also contains AS04, a proprietary adjuvant that has been found to boost the immune system response for a longer period of time. Cervarix is manufactured by GlaxoSmithKline. An alternative product, from Merck & Co., is known as Gardasil.
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In 2007, tests in mice of the same aluminum hydroxide adjuvant as used in AVA were reported as resulting in adverse neuropathy symptoms. This led the investigators to suggest a possible role for the vaccine in Gulf War syndrome.
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Observations of severe side effects in the above 40 phase II and phase III studies were also recorded. Many more side effects have been reported for conjunctive and adjuvant treatment with docetaxel as well as rare post-marketing events.
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Inhaled ciclosporin has also shown promise in several other lung conditions. Early stage studies in mice have shown some benefit of ciclosporin as an adjuvant therapy in lung cancer when administered as a liposome aerosol in conjunction with paclitaxel.
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Other medications will often be given to aid pain management and other symptoms. The treatment of breast cancer with doxorubicin and cyclophosphamide is enhanced by adjuvant treatment with docetaxel. Docetaxel is also used in combination with capecitabine, a DNA synthesis inhibitor.
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This is related to the induction of Th17 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). Pancreatic islets express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.
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Mitochondrial membrane potential is hyperpolarized to prevent voltage-sensitive permeability transition pores (PTP) from triggering of apoptosis. The ketogenic diet is being investigated as an adjuvant therapy for some cancers, including glioma, because of cancer's inefficiency in metabolizing ketone bodies.
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This is related to the induction of Th17 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). Pancreatic islets express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration.
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High-risk melanomas may require adjuvant treatment, although attitudes to this vary in different countries. In the United States, most patients in otherwise good health will begin up to a year of high-dose interferon treatment, which has severe side effects, but may improve the patient's prognosis slightly. However, the British Association of Dermatologists guidelines on melanoma state that interferon is not recommended as a standard adjuvant treatment for melanoma. A 2013 meta-analysis suggested that the addition of interferon alpha increased disease-free and overall survival for people with AJCC TNM stage II-III cutaneous melanoma.
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They are thought to be able to potentiate the link between the innate and adaptive immune responses. Due to the diverse nature of substances that can potentially have this effect on the immune system, it is difficult to classify adjuvants into specific groups. In most circumstances they consist of easily identifiable components of micro- organisms that are recognised by the innate immune system cells. The role of delivery systems is primarily to direct the chosen adjuvant and antigen into target cells to attempt to increase the efficacy of the vaccine further, therefore acting synergistically with the adjuvant.
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Ribi adjuvants are oil-in-water emulsions where antigens are mixed with small volumes of a metabolizable oil (squalene) which are then emulsified with saline containing the surfactant Polysorbate 80. This system also contains refined mycobacterial products (cord factor, cell wall skeleton) as immunostimulants and bacterial monophosphoryl lipid A. Three different species oriented formulations of the adjuvant system are available. These adjuvants interact with membranes of immune cells resulting in cytokine induction, which enhances antigen uptake, processing and presentation. This adjuvant system is much less toxic and less potent than FCA but generally induces satisfactory amounts of high avidity antibodies against protein antigens.
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In September 2020, eleven of the vaccine candidates in clinical development used adjuvants to enhance immunogenicity. An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID-19 virus or influenza virus. Specifically, an adjuvant may be used in formulating a COVID-19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID-19 infection in vaccinated individuals. Adjuvants used in COVID-19 vaccine formulation may be particularly effective for technologies using the inactivated COVID-19 virus and recombinant protein-based or vector-based vaccines.
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Shingrix is a suspension for intramuscular injection consisting of a lyophilized recombinant varicella zoster virus (VZV) glycoprotein E (gE) antigen that is reconstituted at the time of use with AS01B suspension as an immunological adjuvant. The antigen is a purified truncated form of the glycoprotein, expressed in Chinese hamster ovary cells. The AS01B adjuvant suspension is composed of 3-O-desacyl-4'- monophosphoryl lipid A (MPL) from Salmonella (Minnesota strain) and a saponin molecule (QS-21) purified from Quillaja saponaria (soap bark tree) extract, combined in a liposomal formulation consisting of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution.
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The selection criteria underpinning the decision for possible use of imatinib in these settings include a risk assessment based on pathological factors such as tumor size, mitotic rate, and location can be used to predict the risk of recurrence in GIST patients. Tumors <2 cm with a mitotic rate of <5/50 HPF have been shown to have lower risk of recurrence than larger or more aggressive tumors. Following surgical resection of GISTs, adjuvant treatment with imatinib reduces the risk of disease recurrence in higher risk groups. In selected higher risk adjuvant situations, imatinib is recommended for 3 years.
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A motif found throughout the history of cancer therapy is the tendency for overtreatment. From the time of its inception, the use of adjuvant therapy has received scrutiny for its adverse effects on the quality of life of cancer patients. For example, because side effects of adjuvant chemotherapy can range from nausea to loss of fertility, physicians regularly practice caution when prescribing chemotherapy. In the context of melanoma, certain treatments, such as Ipilimumab, result in high grade adverse events, or immune-related adverse events, in 10-15% of patients that parallel the effects of metastatic melanoma itself.
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The role of adjuvant therapy in malignant melanoma is and has been hotly debated by oncologists. In 1995 a multicenter study reported improved long-term and disease-free survival in melanoma patients using interferon alpha 2b as an adjuvant therapy. Thus, later that year the U.S. Food and Drug Administration (FDA) approved interferon alpha 2b for melanoma patients who are currently free of disease, to reduce the risk of recurrence. Since then, however, some doctors have argued that interferon treatment does not prolong survival or decrease the rate of relapse, but only causes harmful side effects.
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The Morisco study authors concluded that their results demonstrated that adjuvant treatment with CoQ10 in addition to conventional therapy significantly reduced the number of hospitalizations for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure.
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A bacterial alpha-galactosidase that efficiently removes linear alpha-gal ends from molecules has been identified. It could be useful for xenotransplantation in the future. Human reaction to alpha-gal has beneficial uses as a vaccine adjuvant and for enhancing wound healing.
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This study of more than 800 women, which was the first project to emerge from the NIH meeting, concluded that while chemotherapy involving the drug thiotepa positively affected the survival rates of premenopausal women, physicians were hesitant to begin using systemic adjuvant therapy.
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In the preparation for the 1990 Persian Gulf campaign, whole cell pertussis vaccine was used as an adjuvant for anthrax vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent.
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The presence of three factors for the prognosis has been suggested, whether there is a palpable mass of the disease, whether lymph nodes are positive and whether there is an underlying malignant cancer. If there is none of these, the five- and 10-year survival is 85% and 80% respectively, with adjuvant chemotherapy even 95% and 90%. If there is a palpable mass, it is 32% and 31% respectively, with adjuvant chemotherapy (40% and 35%). Positive lymph-nodes have been positively associated with a palpable mass and affect the prognosis to be now just 28% survival after 10 years (vs 79% without palpable mass and without affected lymph-nodes).
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Although some results were seen in FDCS patients treated with CHOP, they were far from consistent. Using a chemotherapy regimen designed for another cancer is an archaic “guess-and-check” way of treating a disease. In 2008 the largest review of FDCS was published as a retrospective analysis on 98 patients and the authors recommended that surgery with no adjuvant treatment be the standard for FDCS treatment. Patients treated with surgery alone had a recurrence rate of 40% and those treated with adjuvant therapy after surgery did not have a significantly different recurrence rate. Radiation and/or chemotherapy had no significant effect in improving patients’ disease-free survival.
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By contrast, monoclonal antibodies are derived from a single cell line Many methodologies exist for polyclonal antibody production in laboratory animals. Institutional guidelines governing animal use and procedures relating to these methodologies are generally oriented around humane considerations and appropriate conduct for adjuvant (agents which modify the effect of other agents while having few if any direct effects when given by themselves) use. This includes adjuvant selection, routes and sites of administration, injection volumes per site and number of sites per animal. Institutional policies generally include allowable volumes of blood per collection and safety precautions including appropriate restraint and sedation or anesthesia of animals for injury prevention to animals or personnel.
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There are many adjuvants, some of which are inorganic (such as alum), that also carry the potential to augment immunogenicity. Two common salts include aluminium phosphate and aluminium hydroxide. Aluminium salts are the most commonly-used adjuvants in human vaccines. Their adjuvant activity was described in 1926.
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Patients treated with standard chemotherapy regimens can experience "second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems." As such to minimize overtreatment and avoid potential long-term toxicity caused by adjuvant therapy, most patients today are treated with active surveillance.
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Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. European Journal of Cancer, 39(1), pp.70-77. Using a cloning approach, one patient was shown to have a CD4+ T cell response to HLA-DR1-restricted peptide 267-282.
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In the event of positive margins or locally advanced disease found on pathology, adjuvant radiation therapy may offer improved survival. Surgery may also be offered when a cancer is not responding to radiation therapy. However, because radiation therapy causes tissue changes, prostatectomy after radiation has higher risks of complications.
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Vet Med (Praha) 47: 234–240. Hemorrhagic septicemia is the most important bacterial disease of cattle and buffaloes in Pakistan.Munir R, Akhtar S and Afzal MM (1994) Evaluation of three oil–adjuvant vaccines against Pasteurella multocida in buffalo calves. Revue Scientifique Technique Office International des Epizooties 13: 837-843.
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NOD mice are also susceptible to developing other autoimmune syndromes, including autoimmunine sialitis, autoimmune thyroiditis, autoimmune peripheral polyneuropathy etc. Diabetes in these mice can be prevented by a single injection of mycobacterial adjuvants such as complete Freund's adjuvant (FCA) or Bacille de Calmette et Guérin or BCG vaccine.
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Patients injected with expanded TILs directed against gp100 showed tumor regression but also significant adverse side effects such as uveitis. Adoptive transfer of TILs can increase the survival of melanoma patients when it is used as an adjuvant therapy, i.e. after a surgery and before the appearance of metastases.
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There are several non-pharmacological interventions which are recommended for prevention and treatment of post- stroke hemiplegic shoulder pain. These include proper positioning, range of motion exercises, motor retraining, and adjuvant therapies like neuromuscular electric stimulation (NMES) (e.g. functional electric stimulation (FES)). The use of slings remains controversial.
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St. Vincent's actively participates in a number of ongoing prevention and treatment trials including: the STAR study, the Prostate Cancer Prevention Trial, The National Surgical Adjuvant Breast and Bowel Project (a national cooperative study with the University of Kentucky), the Gynecologic Oncology Group and various pharmaceutical sponsored studies.
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Guanidinium thiocyanate is also used for its denaturing effect on various biological samples. Guanidinium chloride is used as an adjuvant in treatment of botulism, introduced in 1968, but now its role is considered controversial – because in some patients there was no improvement after the administration of this drug.
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In animal studies, cetyl myristoleate was first reported to block inflammation and prevent adjuvant-induced arthritis at very high doses in rats. Other studies using identical and similar methods have failed to replicate this effect. In follow- up studies in mice, a modest anti-inflammatory effect was observed.
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Routine PET or ultrasound scanning, chest X-rays, complete blood count or liver function tests are not recommended. For people who have undergone curative surgery or adjuvant therapy (or both) to treat non-metastatic colorectal cancer, intense surveillance and close follow-up have not been shown to provide additional survival benefits.
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As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions.
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MRI scans may provide evidence for this occurrence. Chemotherapy patients may require greater volume of neural circuitry to complete neuropsychological tasks compared to others. Positron Emission Tomography (PET) is also used to study post-chemotherapy cognitive impairment. In one study in 2007, scans were taken of patients exposed to adjuvant chemotherapy.
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Skin sensitisation: This is a method that determines if a chemical causes an allergic reaction. The chemical adjuvant is injected to boost the immune system. In the past it was performed on guinea pigs, and applied on a shaved patch of skin. Substances are assessed based on appearance of skin.
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It is a non-adjuvant test. In the test, Guinea pigs are exposed to a high dose of the substance. They are then given a challenge dose, which is the highest dose that does not cause irritation. The test has been largely superseded by the murine local lymph node assay.
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After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed.
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It has therefore been proposed as a potential treatment for sleep disorders such as narcolepsy and to improve vigilance in old age, particularly in the treatment of conditions such as Alzheimer's disease. It also potentiated the effects of antipsychotic drugs, and has been suggested as an adjuvant treatment for schizophrenia.
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On 12 July 2005, the European pharmaceuticals giant GlaxoSmithKline completed the acquisition of Corixa. GSK had formerly made use of the Corixa's MPL (Monophosphoryl lipid A, a derivative of the lipid A molecule), an adjuvant in some of their vaccines. On 31 March 2006, Corixa's doors closed after over 11 years in business.
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Alexander von Gabain and Max L. Birnstiel. Fritz's graduate work primarily focused on the development of a novel vaccine adjuvant IC31 and defended his thesis on "The effects of antimicrobial peptides on the immune system". He received his Master of Science degree in December 2000 and Doctor of Philosophy degree in September 2004.
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The closely related Schweizer's reagent is used for the production of cuprammonium rayon. Most pesticides contain ammonium sulfate. Ammonium sulfate is used as an agricultural spray adjuvant for water-soluble insecticides, herbicides, and fungicides. There, it functions to bind iron and calcium cations that are present in both well water and plant cells.
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Kerr is Professor of Cancer Medicine and former Fellow of Corpus Christi College, Oxford. He is also President-Elect for European Society for Medical Oncology (2009). Kerr’s clinical research into adjuvant therapy of early stage colorectal cancer has contributed to saving thousands of lives over the past two decades.Lancet, 370(9604):2020-9.
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There are many medical techniques to remove splinters safely. Common medical techniques include the Elliptical Technique and the String Technique.Blankstein A, Cohen I, Heiman Z, Salai M, Diamant L, Heim M, et al. Ultrasonography as a diagnostic modality and therapeutic adjuvant in the management of soft tissue foreign bodies in the lower extremities.
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AIs inhibit the enzyme aromatase that converts testosterone to estrogen and that is used clinically in treatments of breast cancer in postmenopausal women. Currently, two types of NSAIs are used for breast cancer, anastrozole and letrozole. They are used as first-line therapy in metastatic breast cancer and also in adjuvant treatment .
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CD4+ T cells has already been successfully induced in non-small-cell lung carcinoma patients vaccinated with MAGE-3 recombinant protein. Two cohorts were analyzed: one receiving MAGE-3 protein alone, and one receiving MAGE-3 protein with adjuvant AS028. Of nine patients in the first cohort, three developed marginal antibody titers and another one had a CD8+ T cell response to HLA-A2-restricted peptide MAGE-3 271-279. In contrast, of eight patients from the second cohort vaccinated with MAGE-3 protein and adjuvant, seven developed high-titered antibodies to MAGE-3, and four had a strong concomitant CD4+ T cell response to HLA- DP4-restricted peptide 243-258. One patient simultaneously developed CD8+ T cells to HLA-A1-restricted peptide 168-176.
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Overall survival data were not mature at the time of the IDFS analysis. The U.S. Food and Drug Administration (FDA) granted the application for ado-trastuzumab emtansine priority review designation and breakthrough therapy designation for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual disease after pre-operative systemic treatment.
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Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor and occurs mainly in men ages 38 to 83. However, one such patient treated with a radical cystectomy followed by combined S-1 and Cisplatin adjuvant chemotherapy did demonstrate promising long-term survival of 90 months.
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MF59 is an oil- in-water emulsion of squalene adjuvant used in some human vaccines. Over 22 million doses of a vaccine with squalene have been administered with no safety concerns. The plant extract QS21 is a liposome made up of plant saponins. It is a part of the Shingrix vaccine approved in 2017.
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In particular, the saponins from Quillaja saponaria are used in veterinary vaccines as adjuvant (e.g., foot-and-mouth disease vaccines, helping to enhance the immune response). Initially the crude fraction was used. Later on, a purified mixture called Quil A was developed by Dalsgaard, which was more effective and caused fewer local side reactions.
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The use of Diosmectite as an adjuvant to rehydration therapy for acute infectious functional diarrhea in children may reduce the duration of diarrhea by starting its use from day one; it increases cure rate by third day; and may reduce stool output but has no effect on hospitalization rates or need for intravenous therapy.
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The binding and disintegration properties of isolated Nelumbo starch have been compared with maize and potato starch; Nelumbo starch is shown to be superior as an adjuvant in the preparation of tablets.Mukherjee PK. et al. Pharmaceutical application of starch isolated from Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae). Ind J Pharm Sci 1996; 58: 59–66.
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Chitosan and derivatives have been explored in the development of nanomaterials, bioadhesives, wound dressing materials, improved drug delivery systems, enteric coatings, and in medical devices. Chitosan nanofiber membranes have a high degree of biocompatibility and may support new bone formation. Chitosan is under research as an adjuvant for a potential intranasal vaccine delivery method.
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In (6th ed.) Abnormal Psychology p. 196. New York: McGraw-Hill. . Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms in people who have tried multiple courses of medication. Limited evidence suggests stimulants, such as amphetamine and modafinil, may be effective in the short term, or as adjuvant therapy.
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Other benign tumors of minor salivary glands are treated similarly. Malignant salivary tumors usually require wide local resection of the primary tumor. However, if complete resection cannot be achieved, adjuvant radiotherapy should be added to improve local control. This surgical treatment has many sequellae such as cranial nerve damage, Frey's syndrome, cosmetic problems, etc.
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The apiogalacturonan in Lemna has been researched for several nutritional and biotechnology applications in animal models. In brief, it has been shown to have gastric-protection and immune-adjuvant properties. It is also cyroprotective and this application has been patented. The apiogalacturonan from Zostera Marina currently is used in a variety of cosmetic functions.
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While many alternatives are available, there is no particular well-established protocol to guide adjuvant therapy. Among the available options there is: surgery, alternative corticosteroid delivery, radiation therapy, non-steroidal anti-inflammatory drugs, cytotoxic agents (chlorambucil, cyclophosphamide), corticosteroid sparing immunosuppressants (methotrexate, cyclosporine, azathioprine), IV immune-globin, plasmapheresis, and biologic treatments (such as TNF-α inhibitors).
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Surgery can be attempted in case of inefficient result with medications for ovulation induction. Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling" (puncture of 4-10 small follicles with electrocautery), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH.
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P27 may also allow clinicians to better select an appropriate treatment for a patient. For example, patients with non-small cell lung cancer who were treated with platinum based chemotherapy showed reduced survival if they had low levels of p27. Similarly low levels of p27 correlated with poor results from adjuvant chemotherapy in breast cancer patients.
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Antobodies against adenylate cyclase toxin are also present in the serum of humans infected with B. pertussis. Adenylate cyclase toxin based constructs have been proven to elicit the production of neutralizing antibodies, but lack the cytotoxicity associated with the complete toxin. Genetically detoxified adenylate cyclase toxin also serves in promoting the Th1/Th17 response, acting as an adjuvant.
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Apiose- and the Xylose-substituted variants of above molecule. QS-21 is a purified plant extract used as a vaccine adjuvant. It is derived from the soap bark tree (Quillaja saponaria), which is native to the country of Chile. The extract contains water-soluble triterpene glycosides, which are members of a family of plant-based compounds called saponins.
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The aneurysmal bone cyst can be treated with a variety of different methods. These methods include open curettage and bone grafting with or without adjuvant therapy, cryotheraphy, sclerotherapy, ethibloc injections, radionuclide ablation, and selective arterial embolization. En-block resection and reconstruction with strut grafting are the most common treatments and procedures that prevent recurrences of this type of cyst.
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Bonnie Dunbar ended relations with the company and sued them. Zonagen would not develop any commercial product from research relating to the zona pellucida—despite naming itself after it. Its next project was to create an adjuvant. These products modify the effects of the active ingredient in a drug without having any direct effects of their own.
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When stimulated with OVA peptide, the T cells from mice vaccinated with OVA + cGAMP were shown to have elevated IFN-g and IL-2 when compared to animals receiving only OVA. Furthermore, the enhanced stability of cGAMP, due to the unique 2’-5’ phosphodiester bond, may make it a preferred adjuvant to DNA for in vivo applications.
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This positions HMGB1 at the intersection of sterile and infectious inflammatory responses. ADP-ribosylation of HMGB1 by PARP1 inhibits removal of apoptotic cells, thereby sustaining inflammation. TLR4 binding by HMGB1 or LPS (lipopolysaccharide) sustains ADP-ribosylation of HMGB1 by PARP1 thereby serving as an amplification loop for inflammation. HMGB1 has been proposed as a DNA vaccine adjuvant.
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Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for nonseminoma.
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Immune stimulating complexes (ISCOMs) are spherical open cage-like structures (typically 40 nm in diameter) that are spontaneously formed when mixing together cholesterol, phospholipids and Quillaja saponins under a specific stoichiometry. The complex displays immune stimulating properties and is thus mainly used as a vaccine adjuvant in order to induce a stronger immune response and longer protection.
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Trials of AIs in the adjuvant setting, when given to prevent relapse after surgery for breast cancer, show that they are associated with a better disease-free survival than tamoxifen, but few conventionally-analyzed clinicals trials have shown that AIs have an overall survival advantage compared with tamoxifen, and there is no good evidence they are better tolerated.
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On February 2012, IDRI launched the world’s first clinical trial of the visceral leishmaniasis vaccine. The vaccine is a recombinant form of two fused Leishmania parasite proteins with an adjuvant. Two phase 1 clinical trials with healthy volunteers are to be conducted. The first one takes place in Washington and is followed by a trial in India.
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Depending on what form of treatment is used, adjuvant therapy can have side effects, like all therapy for neoplasms. Chemotherapy frequently causes vomiting, nausea, alopecia, mucositis, myelosuppression particularly neutropenia, sometimes resulting in septicaemia. Some chemotherapeutic agents can cause acute myeloid leukaemia, in particular the alkylating agents. Rarely, this risk may outweigh the risk of recurrence of the primary tumor.
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A 2018 study published details of a new potential preclinical drug candidate for the treatment for visceral leishmaniasis with an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. There is no good vaccine candidate which prevents kala azar. A 2019 paper described designing an immunologic adjuvant which would make a VL vaccine more effective.
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Pharma Recht 2010 ; 32 : 581-5Hampel M, Dally I, Walles T, Steger V, Veit S, Kyriss T, Friedel G. Impact of neo-adjuvant radiochemotherapy on bronchial tissue viability. Eur J Cardiothorac Surg. 2010; 37: 461-6 As a specialist in lung cancer treatment Walles could also demonstrate that lung cancer can be detected in the patients' breath.
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Over the years, BIG has developed and successfully run numerous large, phase 3 clinical trials involving thousands of international investigators and institutions. These clinical trials include HERA (HERceptin Adjuvant), MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy), and ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation). Many BIG studies have been practice-changing, for example, putting aromatase inhibitors on the map (BIG 1-98), changing how we treat young women with breast cancer (SOFT), leading to a major breakthrough in treating HER2-positive breast cancer (HERA), or helping physicians evaluate which women with early breast cancer could be spared chemotherapy after surgery (MINDACT). Most BIG trials incorporate a substantial translational research component and emphasise the collection and banking of biological specimens for future research.
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For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead. The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative “adjuvant” treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.
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While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon cancer is not routine due to the sensitivity of the bowels to radiation. Just as for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages of rectal cancer. For locally advanced rectal cancer, neoadjuvant chemoradiotherapy has become the standard treatment.
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Calcium dobesilate is indicated in states of fragility and altered capillary permeability, e.g. diabetic retinopathy, chronic venous disease and hemorrhoidal disease. In combination with lidocaine or with lidocaine and dexamethasone, the drug enters the composition of preparations for the therapy of hemorrhoidal disease. In association with potassium hydrodex-sulfate enters the composition of adjuvant gels in the treatment of varicose veins.
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As well as the active antigen derived from A/California/7/2009 (H1N1), the vaccine contains an immunologic adjuvant AS03 which consists of DL-α-tocopherol (vitamin E), squalene and polysorbate 80. Thiomersal (thimerosal) is added as a preservative. Being manufactured in chicken eggs, it contains trace amounts of egg proteins. Additional important non-medicinal ingredients are formaldehyde, sodium deoxycholate, and sucrose.
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Radiosurgery refers to the radiotherapy technique of giving a precise high-dose of radiotherapy that is guided by a computer. Postoperative (adjuvant) thoracic radiotherapy generally should not be used after curative- intent surgery for NSCLC. Some people with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy. For potentially curable SCLC cases, chest radiotherapy is often recommended in addition to chemotherapy.
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The most common cancer among women in the United States is breast cancer (123.7 per 100,000), followed by lung cancer (51.5 per 100,000) and colorectal cancer (33.6 per 100,000), but lung cancer surpasses breast cancer as the leading cause of cancer death among women. Researchers attribute the reduction in breast cancer mortality to improved treatment, including the increased use in adjuvant chemotherapy.
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For example, 99mTc-EC20 was reported to concentrate in the livers, spleens and arthritic extremities of adjuvant-induced arthritic rats via a folate-dependent mechanism. Development of folate-drug conjugates for inflammation therapy is underway. It is expected that ailments which harbor activated macrophages (such as arthritis, psoriasis and inflammatory bowel disease) may someday be treatable with folate-targeted medicines.
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Cancer vaccines seek to target a tumor-specific antigen as distinct from self-proteins. Selection of the appropriate adjuvant to activate antigen-presenting cells to stimulate immune responses, is required. Bacillus Calmette-Guérin, an aluminum-based salt, and a squalene- oil-water emulsion are approved for clinical use. An effective vaccine should also stimulate long term immune memory to prevent tumor recurrence.
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It is the first adjuvanted seasonal flu vaccine marketed in the United States. It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant. Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older.
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VBT is used to treat any remaining cancer solely in the vagina, whereas EBRT can be used to treat remaining cancer elsewhere in the pelvis following surgery. However, the benefits of adjuvant radiotherapy are controversial. Though EBRT significantly reduces the rate of relapse in the pelvis, overall survival and metastasis rates are not improved. VBT provides a better quality of life than EBRT.
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It is listed as an ingredient in root beer and cream soda. The extract of quillaia is used in the manufacture of food additives (E number 999). It is used as a humectant in baked goods, frozen dairy products, and puddings and as a foaming agent in soft drinks. It is also applied in some "natural" spray adjuvant formulations for agriculture.
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Alfaxolone/alfadolone is short-duration, intravenous anaesthetic made from a combination of two steroidal compounds, alfaxalone and alfadolone of which the former is the primary anaesthetic agent. Alfadolone acts to increase the solubility of the mixture in which it is dissolved, a polyethylated castor oil adjuvant. Anaesthetic efficacy is achieved by allosteric potentiation of the GABAA chloride channel to produce 'fast' synaptic inhibition.
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Surgical removal of the tumor, neoadjuvant chemotherapy prior to tumor removal, and liver transplantation have been used to treat these cancers. Primary liver transplantation provides high, long term, disease-free survival rate in the range of 80%, in cases of complete tumor removal and adjuvant chemotherapy survival rates approach 100%. The presence of metastases is the strongest predictor of a poor prognosis.
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Swainsonine has a potential for treating cancers such as glioma and gastric carcinoma. However, a phase II clinical trial of GD0039 (a hydrochloride salt of swainsonine) in 17 patients with renal carcinoma was discouraging. Swainsonine's activity against tumors is attributed to its stimulation of macrophages. Swainsonine also has potential uses as an adjuvant for anti-cancer drugs and other therapies in use.
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Debate about treatment duration has become a relevant issue for many public health policy makers because administering trastuzumab for a year is very expensive. Consequently, some countries with a taxpayer-funded public health system, such as New Zealand, chose to fund limited adjuvant therapy. However, subsequently New Zealand has revised its policy and now funds trastuzumab treatment for up to 12 months.
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GABOB is used medically as a racemic mixture. Relative to GABA, GABOB has more potent inhibitory effects on the central nervous system, perhaps due to its greater capacity to cross the blood–brain barrier. However, GABOB is of relatively low potency as an anticonvulsant when used by itself, and is more useful as an adjuvant treatment used alongside another anticonvulsant.
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For malignant tumours, the surgery may be radical and usually is followed by adjuvant chemotherapy, sometimes by radiation therapy. In all cases, initial treatment is followed by surveillance. Because in many cases Leydig cell tumour does not produce elevated tumour markers, the focus of surveillance is on repeated physical examination and imaging. In males, a radical inguinal orchiectomy is typically performed.
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Filippino Lippi was born in Prato, Tuscany, the illegitimate son of the painter Fra Filippo Lippi and Lucrezia Buti. Filippino first trained under his father. They moved to Spoleto, where Filippino served as workshop adjuvant in the construction of the Cathedral. When his father died in 1469, he completed the frescoes with Storie della Vergine (Histories of the Virgin) in the cathedral.
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Methoxyamine is an orally bioavailable small molecule inhibitor with potential adjuvant activity.NCI Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER), which may result in an increase in DNA strand breaks and apoptosis. This agent may potentiate the anti-tumor activity of alkylating agents. Examples of drugs incorporating the methoxyamine unit are brasofensine and gemifloxacin.
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Corticosteroids remain the main treatment modality for IOI. There is usually a dramatic response to this treatment and is often viewed as pathognomonic for this disease. Although response is usually quick, many agree that corticosteroids should be continued on a tapering basis to avoid breakthrough inflammation. Although many respond to corticosteroid treatment alone, there are several cases in which adjuvant therapy is needed.
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It is still in question by researchers whether this treatment method to rid the body of this small cluster of cells that may or may not progress is worth the side effects that it may cause. Side effects include fatigue, hair loss, nausea, or vomiting. In addition, adjuvant therapies do not always result in a cure and they do not benefit all patients.
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Radiation therapy is commonly used in prostate cancer treatment. It may be used instead of surgery or after surgery in early stage prostate cancer (adjuvant radiotherapy). Radiation treatments also can be combined with hormonal therapy for intermediate risk disease, when surgery or radiation therapy alone is less likely to cure the cancer. Some radiation oncologists combine external beam radiation and brachytherapy for intermediate to high-risk situations.
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Pristane is known to induce autoimmune diseases in rodents. It is used in research to understand the pathogenesis of rheumatoid arthritis and lupus. It is used as a lubricant, a transformer oil, an immunologic adjuvant, and an anti-corrosion agent, biological marker, plasmocytomas inducer and in production of monoclonal antibodies. Biosynthetically, pristane is derived from phytol and is used as a biomarker in petroleum studies.
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If not treated, pemphigus can be fatal, usually from overwhelming opportunistic infection of lesions. The most common treatment is the administration of oral steroids, especially prednisone, often in high doses. The side effects of corticosteroids may require the use of so-called steroid-sparing or adjuvant drugs. One of the most dangerous side effects of high-dosage steroid treatments is intestinal perforations, which may lead to sepsis.
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This same positive and negative selection mechanism, but in peripheral tissues, is known as clonal anergy. The mechanism of clonal anergy is important to maintain tolerance to many autologous antigens. Active suppression is the other known mechanism of T cell tolerance. Active suppression involves the injection of large amounts of foreign antigen in the absence of an adjuvant which leads to a state of unresponsiveness.
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Its risk of recurrence has not yet been quantified. Research on hyperbaric oxygen therapy to reduce side effects is also ongoing. The results of the PORTEC 3 trial assessing combining adjuvant radiotherapy with chemotherapy were awaited in late 2014. There is not enough evidence to determine if people with endometrial cancer benefit from additional behavioural and life style interventions that are aimed at losing excess weight.
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Merial produces a recombinant vaccine consisting of canarypox virus carrying FeLV gag and env genes (sold as PUREVAX FeLV in the US and Eurifel FeLV in Europe). This is thought to be safer than the old vaccine as it does not require an adjuvant to be effective. Although this is a live virus, it originates from a bird host and so does not replicate in mammals.
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Chinese literature denotes four different roles to drugs (which in this case are different herbs used in tonics) – the emperor, minister, assistant and envoy. This translates respectively to the principle drug, the associate drug, the adjuvant drug and the messenger drug. Not all herbal tonics include all four of these components. Having a mix of these balance out toxic qualities of some sole herbs.
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Subsequently, Bt cotton has added other delta endotoxins. Products such as Bt cotton, Bt brinjal and genetically modified maize have received attention due to a number of issues, including genetically modified food controversies, and the Séralini affair. Cry1Ac is also a mucosal adjuvant (an immune-response enhancer) for humans. It has been used in research to develop a vaccine against the amoeba Naegleria fowleri.
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Parathyroidectomy is now a part of the standard management of cases of primary hyperparathyroidism. The management of burns, including fluid replacement, surface management and respiratory management, is based on the work carried out by Cope and his colleagues at Massachusetts General. Cancer treatment now is focused on limited surgery and adjuvant chemoradiotherapy rather than radical surgery, and medical education now takes psychosocial considerations into account.
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Potential contaminated water should also be chlorinated. Vaccination: An inactivated vaccine with oil adjuvant can be administered and has proven to be reasonably successful to prevent the clinical signs of the disease. This vaccine is given before hens start to lay eggs, usually between 14 and 20 weeks of age. Several vaccine are available: Izovac EDS, Nobilis EDS, AVIVAC-EDS-76 and other EDS '76 available vaccines.
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Image showing Gastrointestinal Stromal Tumor after surgical removal Localized, resectable adult GISTs, if anatomically and physiologically feasible, surgery is the primary treatment of choice. Surgery can be potentially curative, but watchful waiting may be considered in small tumors in carefully selected situations. Post-surgical adjuvant treatment may be recommended. Lymph node metastases are rare, and routine removal of lymph nodes is typically not necessary.
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Bushey, R. Gains FDA Approval for Common Bladder Cancer. Drug Discovery & Development, Fri, 02/03/2017. Nivolumab, and other PD-1 inhibitors, appear to be effective in people with brain metastases and for cancer in people with autoimmune diseases. Nivolumab is indicated for the adjuvant treatment of people with melanoma with involvement of lymph nodes or in people with metastatic disease who have undergone complete resection.
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DCs link the innate immune system with the adaptive immune system through phagocytosis and MHC presentation of foreign antigen. The type 1 IFN response initiated by DCs, perhaps through recognition of phagocytosed DNA, has an important co- stimulatory effect. This has recently led to speculation that 2’-3’ cGAMP could be used as a more efficient and direct adjuvant than DNA to induce immune responses.
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All these factors related to the antibiotics use, the chronicity of the disease, and the emergence of resistant bacteria demand more exploration for different strategies such as antibiotic adjuvant therapy. Currently, no reliable clinical trial evidence shows the effectiveness of antibiotics for pulmonary exacerbations in people with cystic fibrosis and Burkholderia cepacia complex or for the use of antibiotics to treat nontuberculous mycobacteria in people with CF.
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Often multiple therapies may be tried simultaneously (combination therapy or polytherapy). Thus combination chemotherapy is also called polychemotherapy, whereas chemotherapy with one agent at a time is called single-agent therapy or monotherapy. Adjuvant therapy is therapy given in addition to the primary, main, or initial treatment, but simultaneously (as opposed to second-line therapy). Neoadjuvant therapy is therapy that is begun before the main therapy.
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Ketorolac package from Russia Ketorolac is used for short-term management of moderate to severe pain. It is usually not prescribed for longer than five days, due to its potential to cause kidney damage. Ketorolac is effective when administered with paracetamol to control pain in newborns because it does not depress respiration as do opioids. Ketorolac is also an adjuvant to opioid medications and improves pain relief.
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When externally administered, GLP-2 produces a number of effects in humans and rodents, including intestinal growth, enhancement of intestinal function, reduction in bone breakdown and neuroprotection. GLP-2 may act in an endocrine fashion to link intestinal growth and metabolism with nutrient intake. GLP-2 and related analogs may be treatments for short bowel syndrome, Crohn's disease, osteoporosis and as adjuvant therapy during cancer chemotherapy.
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He was cremated at Feuerhalle Simmering, where also his ashes are buried. Holzknecht joined the Vienna Psychoanalytic Society in 1910. He later also treated Sigmund Freud, making an unsuccessful adjuvant irradiation attempt for Freud's oral cavity squamous cell carcinoma (to which Freud eventually succumbed). His name is included on the Monument to the X-ray and Radium Martyrs of All Nations erected in Hamburg, Germany in 1936.
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Nventa is also developing two additional therapeutic vaccine programs based on its CoVal technology—a Hsp – HBV (hepatitis B) fusion, and prototypes of Hsp fusion proteins with influenza antigens. In June 2008, Nventa announced the development of a proprietary vaccine adjuvant, Poly IC – Poly Arginine (Poly-ICR), for use with both therapeutic and prophylactic vaccines. Poly-ICR is a TLR3 agonist that, when combined with a disease-specific antigen, can induce both cytotoxic (T cell) and antibody (B cell) immune responses against that antigen. As yet unpublished pre-clinical data indicate that Poly-ICR, in combination with a tumor-associated antigen, increases antigen-specific CD8 T-cell levels, while both inducing regression of tumors and preventing tumor growth in mouse models.Company Press Release, “NVENTA DEVELOPS PROPRIETARY VACCINE ADJUVANT” / June 18, 2008 The company developed Poly-ICR for both internal use and for external licensing opportunities.
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Costs are difficult to estimate but one US study, based on estimates of 25% of all OPC patients receiving surgery alone and 75% surgery followed by adjuvant therapy, using the criteria of the NCCN, found that this approach was less expensive than primary chemoradiation. Early stage disease is associated with a relatively favourable outcome, for which single modality therapy is recommended, the choice depending on tumour location and accessibility. For instance unilateral tonsil or tongue base tumours will generally be treated with transoral resection and selective ipsilateral neck dissection. On the other hand, a large midline tongue lesion would require bilateral neck dissection, but in the absence of what are considered adverse pathology (positive margins, extracapsular extension) will likely be treated by surgery alone or radiation including ipsilateral or bilateral neck radiation fields, with surgery for those instances where the likelihood of adjuvant therapy is low.
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Further hydrogenation of furfuryl alcohol leads to tetrahydrofurfuryl alcohol (THFA), which is used as a solvent in agricultural formulations and as an adjuvant to help herbicides penetrate the leaf structure. Another important solvent made from furfural is methyltetrahydrofuran. Furfural is used to make other furan derivatives, such as furoic acid, via oxidation, and furan itself via palladium catalyzed vapor phase decarbonylation. Furfural is also a specialized chemical solvent.
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Plasmid DNA itself appears to have an adjuvant effect on the immune system. Bacterially derived DNA can trigger innate immune defence mechanisms, the activation of dendritic cells and the production of TH1 cytokines. This is due to recognition of certain CpG dinucleotide sequences that are immunostimulatory. CpG stimulatory (CpG-S) sequences occur twenty times more frequently in bacterially-derived DNA than in eukaryotes. This is because eukaryotes exhibit “CpG suppression” – i.e.
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Development of subunit vaccines requires the identification of protective antigens and their formulation in a suitable adjuvant. Trichuris muris is an antigenically similar laboratory model for T. trichiura. Subcutaneous vaccination with adult excretory–secretory products (ES) protects susceptible mouse strains from T. muris. Larval stages may contain novel and more relevant antigens which when incorporated in a vaccine induce worm expulsion earlier in infection than the adult worm products.
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Similarly, with node-positive tumors, males increase survival using the same adjuvants as affected females, namely both chemotherapy plus tamoxifen and other hormonal therapy. There are no controlled studies in males comparing adjuvant options. In the vast majority of males with breast cancer hormone receptor studies are positive, and those situations are typically treated with hormonal therapy. Locally recurrent disease is treated with surgical excision or radiation therapy combined with chemotherapy.
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Over-the-counter veterinarian- use mineral oil is intended as a mild laxative for pets and livestock. Certain mineral oils are used in livestock vaccines, as an adjuvant to stimulate a cell-mediated immune response to the vaccinating agent. In the poultry industry, plain mineral oil can also be swabbed onto the feet of chickens infected with scaly mites on the shank, toes, and webs. Mineral oil suffocates these tiny parasites.
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An adjuvant can also act as an irritant, which engages and amplifies the body's immune response. A tetanus, diphtheria, and pertussis (DPT) vaccine, for example, contains small quantities of inactivated toxins produced by each of the target bacteria, but also contains some aluminium hydroxide. Such aluminium salts are common adjuvants in vaccines sold in the United States and have been used in vaccines for more than 70 years.
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The monoclonal antibody farletuzumab is being researched as an adjuvant to traditional chemotherapy. Another type of immunotherapy involves vaccines, including TroVax. An alternative to BEP chemotherapy, a regimen of 3 cycles of carboplatin and etoposide, is a current topic of research for germ cell malignancies. Intraperitoneal chemotherapy has also been under investigation during the 2000s and 2010s for its potential to deliver higher doses of cytotoxic agent to tumors.
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Malignant giant cells are commonly found — and vary in relative proportion to a greater or lesser degree — in both primary tumors and metastatases of many different variants of lung carcinomas. A number of authors have noted that bizarre malignant giant cells occur more commonly in primary and secondary tumors — including any remaining tumor "deposits" — that have previously been treated with chemotherapy and/or radiation therapy in adjuvant or neoadjuvant protocols.
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In the first half of the 20th century there were first attempts to protect people from malaria. At the beginning Pasteur's approach of developing bacterial vaccines was used as a big hope in eradication of this fatal disease. But inactivated malaria sporozoites (by formalin) were ineffective in inducing the protection. In 1948 inactivated merozoites with an adjuvant were used for preventing lethal malaria to kill a group of monkeys.
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Epidemiologic and preclinical lab studies indicate that metformin has anti- tumor effects, via at least two mechanisms, both involving activation of the AMP-activated protein kinase (AMPK). A large-scale phase III trial of metformin in the adjuvant breast cancer setting is being planned in 2009. Triple-negative breast cancer cells rely on glutathione-S-transferase Pi1, and an inhibitor (LAS17) shows encouraging results in a pre-clinical study.
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Cancer prehabilitation refers to the assessments and interventions that are conducted just after diagnosis but before cancer treatment begins. A panel of experts has highlighted the importance of establishing rehabilitation services prior to the oncological treatment to optimize tolerance to surgery or adjuvant treatments, minimize toxicity and improve outcomes. Recent clinical studies have shown that cancer prehabilitation and rehabilitation can increase function and may improve outcomes and disability rates.
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In combination with a peptide antigen, α-GalCer is able to stimulate a strong immune response against the epitope. The CD1d:glycolipid:TCR interaction activates the iNKT cell which can then activate the dendritic cell. This causes the release of a range of cytokines and licenses the dendritic cell to activate a peptide- specific T cell response. This adjuvant acts through this cellular interaction, rather than through classic pattern recognition receptor pathways.
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Tiratricol is not approved for sale in Canada or the United States. It was once an approved drug in Brazil, but its marketing authorization was suspended in 2003, effectively prohibiting its sale. Tiratricol is still available in France for therapy of thyroid hormone resistance and adjuvant therapy of thyroid cancer.Laboratoires DB PHARMA: Teatrois information It is available as an orphan drug to be prescribed by registered specialists in Europe.
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Zhao, Y., Zhan, Y., Burke, K.A., Anderson, W. F.: Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells. Exp. Hemat., 33: 428-434, 2005. Purification from the serum demonstrated that the factor was Interleukin 12. During the 12 years that Anderson has been in prison, IL-12 has been shown to potentially be a very important adjuvant drug in cancer treatment.
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Ganoderma lingzhi Some mushrooms are used or studied as possible treatments for diseases, particularly their extracts, including polysaccharides, glycoproteins and proteoglycans. In some countries, extracts of polysaccharide-K, schizophyllan, polysaccharide peptide, or lentinan are government-registered adjuvant cancer therapies, even though clinical evidence of efficacy in humans has not been confirmed. Historically in traditional Chinese medicine, mushrooms are believed to have medicinal value, although there is no evidence for such uses.
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Topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy. Oral potassium iodide or colchicine may induce rapid resolution.Patients who have a potential systemic infection or in whom corticosteroids are contraindicated can use these agents as a first-line therapy. In one study, indomethacin, 150 mg per day, was given for the first week, and 100 mg per day was given for 2 additional weeks.
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Roquinimex (Linomide) is a quinoline derivative immunostimulant which increases NK cell activity and macrophage cytotoxicity. It also inhibits angiogenesis and reduces the secretion of TNF alpha. Roquinimex has been investigated as a treatment for some cancers (including as adjuvant therapy after bone marrow transplantation in acute leukemia) and autoimmune diseases, such as multiple sclerosis and recent-onset type I diabetes. Several trials have been terminated due to serious cardiovascular toxicity.
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Viola canescens, a species from India, exhibited in vitro activity against Trypanosoma cruzi. Viola has been evaluated in different clinical indications in human studies. A double blind clinical trial showed that the adjuvant use of Viola odorata syrup with short-acting β-agonists can improve the cough suppression in children with asthma. In another study intranasal administration of Viola odorata extract oil showed to be effective in patients with insomnia.
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Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
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Dose-dense chemotherapy (DDC) has recently emerged as an effective method of adjuvant chemotherapy administration. DDC uses the Gompertz curve to explain tumor cell growth after initial surgery removes most of the tumor mass. Cancer cells that are left over after a surgery are typically rapidly dividing cells, leaving them the most vulnerable to chemotherapy. Standard chemotherapy regimens are usually administered every 3 weeks to allow normal cells time to recover.
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These include such products as Gonacon, an adjuvant vaccine which delivers a high dosage of a competitor ligand of the hormone GnRH to female mammals (e.g. whitetail deer). The complex formed of GnRH and the Gonacon molecule promotes production of antibodies against the animal's own GnRH, which themselves complex with GnRH. This encourages an extended duration of the drug's effects (namely, reduction of active/unbound GnRH in the animal's system).
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Resection is an option in cholangiocarcinoma, but fewer than 30% of cases of cholangiocarcinoma are resectable at diagnosis. After surgery, recurrence rates are up to 60%. Liver transplant may be used where partial resection is not an option, and adjuvant chemoradiation may benefit some cases. 60% of cholangiocarcinomas form in the perihilar region and photodynamic therapy can be used to improve quality of life and survival time in these unresectable cases.
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The WHO states that no severe side effects have been associated with these vaccines, although they can produce mild inflammation at the site of injection. The safety of squalene-containing influenza vaccines have also been tested in two separate clinical trials, one with healthy non- elderly people, and one with elderly people, in both trials the vaccine was safe and well tolerated, with only weak side-effects, such as mild pain at the injection site. A 2009 meta-analysis brought together data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvanted vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the normal rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines".
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The venom is also administered with an adjuvant, like aluminium hydroxide or sodium alginate, to stimulate the immunological response. When the venom is injected, the body will produce antibodies. These will bind components – the variability of peptides – of the venom, which prevent further activity of the molecule and are ultimately removed by the immune system of the body. These antibodies are collected and purified from the blood and then packaged in mostly a liquid form.
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AVA contains aluminium hydroxide (alhydrogel) to adsorb PA as well as to serve as an adjuvant (immune enhancer). As such it is believed to stimulate humoral, but not cell-mediated, immunity. Each dose of the vaccine contains no more than 0.83 mg aluminum per 0.5 mL dose. (This is near the allowed upper limit of 0.85 mg/dose.) It also contains 0.0025% benzethonium chloride as a preservative and 0.0037% formaldehyde as a stabilizer.
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The vaccine is supplied in separate vials, one containing the adjuvant, and the other the inactivated virus, which require mixing before intramuscular injection. Originally it was thought that two doses given 21 days apart would be required for full efficacy. Subsequent testing has allowed the UK programme to consist of just a single dose for most people, with a two-dose schedule for children under the age of 10 years and immunocompromised adults.
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Treatment largely follows patterns that have been set for the management of postmenopausal breast cancer. The initial treatment is surgical and consists of a modified radical mastectomy with axillary dissection or lumpectomy and radiation therapy with similar treatment results as in females. Also, mastectomy with sentinel lymph node biopsy is a treatment option. In males with node-negative tumors, adjuvant therapy is applied under the same considerations as in females with node-negative breast cancer.
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Chemotherapy is used in a multimodality treatment plan generally for more advanced, unresectable or reoccurring tumors. Cyclophosphamide, vincristine and doxorubicin have been used as neoadjuvant chemotherapy drugs for grade C esthesioneuroblastoma before surgical resection, producing fair outcomes. Cisplatin and etoposide are often used to treat esthesioneuroblastoma as neoadjuvants or adjuvants with radiotherapy or surgery.Porter A.B., Bernold D.M., Giannini C., et al: Retrospective review of adjuvant chemotherapy for esthesioneuroblastoma. J Neurooncol 2008; 90: pp.
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This, in turn, reduces the amount of antibioitcs and fly repellent needed during high-risk seasons. The vaccine is marketed in multidose vials and has an adjuvant to create a long-term subcutaneous depot. This means no booster shot is necessary, but severe local reaction can be seen in people who accidentally inoculate themselves. Calves as young as one week old can be treated and no meat, milk, or export slaughter withdrawal is needed.
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The first trial of epirubicin in humans was published in 1980. Upjohn applied for approval by the U.S. Food and Drug Administration (FDA) in node-positive breast cancer in 1984, but was turned down because of lack of data. In 1999 Pharmacia (who had by then merged with Upjohn) received FDA approval for the use of epirubicin as a component of adjuvant therapy in node-positive patients. Patent protection for epirubicin expired in August 2007.
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As of 2019, an oral flu vaccine was in clinical research. The oral vaccine candidate is based on an adenovirus type 5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant. In 2020, a phase II human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine.
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To avoid its toxic adverse effects Xanthium sibiricum must be processed. Hepatotoxicity has been reported with products containing Reynoutria multiflora (synonym Polygonum multiflorum), glycyrrhizin, Senecio and Symphytum. The evidence suggests that hepatotoxic herbs also include Dictamnus dasycarpus, Astragalus membranaceous, and Paeonia lactiflora; although there is no evidence that they cause liver damage. Contrary to popular belief, Ganoderma lucidum mushroom extract, as an adjuvant for cancer immunotherapy, appears to have the potential for toxicity.
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Significant inhibitory activity, caused by hot water extract of black tea of Sikkim variety, has been observed against carrageenin, histamine, serotonin, and prostaglandin-induced pedal inflammation. The extract also inhibited exudative inflammation, cotton pellet-induced granuloma formation and adjuvant-induced polyarthritis. The extract has also shown significant inhibition against glucose oxidase-mediated inflammation. The observations have established the efficacy of this particular variety of black tea in the chronic phase of inflammation.
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There are many commercially available immunologic adjuvants. Selection of specific adjuvants or types varies depending upon whether they are to be used for research and antibody production or in vaccine development. Adjuvants for vaccine use only need to produce protective antibodies and good systemic memory while those for antiserum production need to rapidly induce high titer, high avidity antibodies. No single adjuvant is ideal for all purposes and all have advantages and disadvantages.
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Regional chemotherapy is when chemotherapy is administered directly into the cerebrospinal fluid, an organ, or a body cavity, for example, the abdomen. In this way, the drugs will mainly affect cancer cells in that area. However, the type of chemotherapy that is administered to the patient depends on the type and stage of the cancer. Additionally, chemotherapy can be used as an adjuvant therapy after radiation to lower the risk of recurrence in the patient.
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Polyclonal antibodies are generated in 1 sheep, 1 goat, and 3 New Zealand white rabbits with each immunogen. The initial subcutaneous injections are given to the 10 animals including 3 rabbits, 1 sheep, and 1 goat on multiple sites with the defatted powdered immunogen and Freunds Complete Adjuvant. Titer values of collected antisera are evaluated by a noncompetitive ELISA method with walnut protein from abstracts of the proper raw or roasted immunogen.
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The lead COVID-19 vaccine candidate by Medicago is a coronavirus VLP grown in the Australian weed, Nicotiana benthamiana. Medicago is developing the COVID-19 vaccine candidate in collaboration with the governments of Canada and Quebec, and by using an adjuvant manufactured by GlaxoSmithKline. As of August 2020, the Medicago vaccine candidate is being evaluated for safety, toxicity, and immune response in a Phase I clinical trial at two locations in Quebec.
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NeuVax has been tested as adjuvant treatment in nearly 200 breast cancer patients over a total of 5 years, and has shown to be safe and effective in Phase 2 trials. As a result, two additional NeuVax trials registered or underway are: (1) a 700 patient Phase 3 trial for FDA approval - not yet recruiting and (2) a 300 patient Phase 2 trial studying the combination of NeuVax and Herceptin® (trastuzumab).
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However, the industry itself has several efforts underway in order to self regulate the products. The ASTM International (ASTM) E35.22 committee is the committee that defines agricultural tank mix claims for the industry. The standard E1519 defines the various claims that an adjuvant may make and reference the methods by which the claim may be proven. The methods are tests, which when applied to a given sample, prove that the material meets the claimed standard.
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DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center. There is no standard protocol for the disease;Talarico F, Iusco D, Negri L, Belinelli D: Combined resection and multi-agent adjuvant chemotherapy for intra- abdominal desmoplastic small round cell tumour: case report and review of the literature.
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Physiotherapy (physical therapy) is sometimes used as an adjuvant to other methods of treatment in TMD. There are many different approaches described, but exercises aiming to increase the range of mandibular movements are commonly involved. Jaw exercises aim to directly oppose the negative effects of disuse that may occur in TMD, due to pain discouraging people from moving their jaw. After initial instruction, people are able to perform a physical therapy regimen at home.
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Inflammation in the subcutis following vaccination is considered to be a risk factor in the development of VAS, and vaccines containing aluminum were found to produce more inflammation. Furthermore, particles of aluminum adjuvant have been discovered in tumor macrophages. In addition, individual genetic characteristics can also contribute to these injection-site sarcomas. The incidence of VAS is between 1 in 1,000 to 1 in 10,000 vaccinated cats and has been found to be dose- dependent.
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Schwartz's principles of surgery: self assessment and board review, 8th edition, chapter 11, patient safety, errors, and complications in surgery In case of lumpectomy, the formation of a seroma at the lumpectomy site has been cited in medical literature as being beneficial, with claims that it can contribute to preserve the contour of the breast. In some cases a seroma may need to be drained prior to a course of radiotherapy adjuvant to surgery.
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Specific delta-endotoxins that has been used for genetic engineering include Cry3Bb1 found in MON 863 and Cry1Ab found in MON 810, both of which are corn species. Cry3Bb1 is particularly useful because it kills the coleopteran insects such as the corn rootworm, an activity not seen in other Cry proteins. Other common toxins include Cry2Ab and Cry1F in cotton and corn. In addition, Cry1Ac is effective as a vaccine adjuvant in humans.
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Mastectomy rates vary tremendously worldwide, as was documented by the 2004 'Intergroup Exemestane Study', an analysis of surgical techniques used in an international trial of adjuvant treatment among 4,700 females with early breast cancer in 37 countries. The mastectomy rate was highest in central and eastern Europe at 77%. The USA had the second highest rate of mastectomy with 56%, western and northern Europe averaged 46%, southern Europe 42% and Australia and New Zealand 34%.
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The primary treatment of TEN is discontinuation of the causative factor(s), usually an offending drug, early referral and management in burn units or intensive care units, supportive management, and nutritional support. Current literature does not convincingly support use of any adjuvant systemic therapy. Initial interest in Intravenous immunoglobulin (IVIG) came from research showing that IVIG could inhibit Fas-FasL mediated keratinocyte apoptosis in vitro. Unfortunately, research studies reveal conflicting support for use of IVIG in treatment of TEN.
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Vaccine delivery is a very common application of bacterial surface display. There are two types of live bacterial vaccines that can be made: # Normally pathogenic bacteria are weakened so they are no longer pathogenic. # Commensal or food-grade bacteria which are not pathogenic. Using bacterial surface display of antigens is a valuable alternative to conventional vaccine design for various reasons, one of them being that the proteins expressed on the bacterial cell surface can act favourably as an adjuvant.
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TCT has been classified as an adjuvant molecule because of the stimulating effects it has on the immune system. Cellular damage associated with TCT is thought to be a result of increased levels of nitric oxide (NO) secretion by mucosal cells as part of an innate defense response to extracellular lipopolysaccharide (LPS) and TCT. In humans, peptidoglycan recognition proteins, e.g. PGRPIαC, appear to bind with TCT and consequently induce the Tumor Necrosis Factor Receptor (TNFR) pathway.
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For advanced (stage IV) and unresectable lung tumors, the first-line therapy is platinum-based doublet chemotherapy, combining cisplatin or carboplatin with another cytotoxic agent. Regimens strongly depend on each patient performance status and response, and when the risk of adverse events could worsen quality of life significantly, basic supportive care is more recommended. Chemotherapy is also used as an adjuvant therapy following surgery to kill remaining cancer cells in patients with stage IIA, IIB and IIIA NSCLC.
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Adenocarcinoma is a non-small cell lung carcinoma, and it is not as responsive to radiation therapy compared to small cell lung carcinoma. However, radiotherapy may be used as an adjuvant therapy for patients who have undergone a resection surgery to reduce the risk of lung cancer relapse. It may also benefit inoperable tumors that are localized to the chest and be part of palliative care to improve quality of life in patients not responding to surgery or chemotherapy.
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Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumor's tendency to show a perineural discontinuous growth, meaning that it follows nerves and different "nests" of the tumor can exist without a connection to the original tumor. Therefore, MRI-images should be analysed following nerve tracts up to the brainstem. Adjuvant or palliative radiotherapy is commonly given following surgery.
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While acute pain responses are normal in AC1 knockout mice, behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant as well as nerve injury were reduced or abolished. Considering AC1 is highly expressed in neurons including the ACC, Zhuo proposed that AC1 acts as a key drug target for inhibiting chronic pain related plasticity in the brains.Zhuo, M (2012) AC1 as a target for treating chronic pain. Drug Discovery Today, 17:573-582.
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The adequacy of surgical resection is a major factor in determining the role of postoperative adjuvant therapy. In the presence of a positive margin on pathological examination, most radiation oncologists recommend radiation to the primary site, and concurrent chemotherapy. A negative margin is more likely to be treted with lower doses and a smaller treatment volume. Also the removal of a bulky tumour may allow reduced dosage to adjacent uninvolved pharyngeal structures and hence less effect on normal swallowing.
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Bernard Fisher (August 23, 1918 – October 16, 2019) was an American surgeon and a pioneer in the biology and treatment of breast cancer. He was a native of Pittsburgh. He was Chairman of the National Surgical Adjuvant Breast Project at the University of Pittsburgh School of Medicine. His work established definitively that early-stage breast cancer could be more effectively treated by lumpectomy, in combination with radiation therapy, chemotherapy, and/or hormonal therapy, than by radical mastectomy.
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Lymphadenoectomy is often performed for infiltrative cases. In lieu of surgery, radiotherapy is also an option and is especially preferred for elderly patients or for inoperable cases where the tumour size if too large. This form of treatment is also considered as possible adjuvant therapy following excision to combat the high recurrence rate. However, there are side effects of radiotherapy, including but not limited to: vulvitis, post-radiation atrophy of mucus membranes, vaginal stenosis and sexual dysfunction.
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Because of its significant adverse effects, traditional chemotherapy has been saved for late-stage highly metastasized cases of MCC. While some chemotherapeutic regiments have been shown to have transient effects, studies have not found any significant long-term effect on recurrence rate or life expectancy. As of 2015, there were no FDA-approved standard chemotherapy regimens for MCC treatment. The most recent American guidelines do not recommend adjuvant chemotherapy, citing a lack of evidence to suggest improved outcomes.
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Mature teratomas, or dermoid cysts, are rare tumors consisting of mostly benign tissue that develop after menopause. The tumors consist of disorganized tissue with nodules of malignant tissue, which can be of various types. The most common malignancy is squamous cell carcinoma, but adenocarcinoma, basal-cell carcinoma, carcinoid tumor, neuroectodermal tumor, malignant melanoma, sarcoma, sebaceous tumor, and struma ovarii can also be part of the dermoid cyst. They are treated with surgery and adjuvant platinum chemotherapy or radiation.
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Adjuvant therapy, which refers to therapy given after a primary surgery, has not been found to be beneficial in renal cell cancer. Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed. This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.
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These antibodies are combined with an adjuvant and given as a vaccine. The murine immune system essentially "amplifies" a small mass of TAA antibodies into a much larger mass used to vaccinate humans. Because the antibody produced using the "anti-idiotypic" process closely resembles the original epitope of the antigen, these antibodies can be used to induce immune responses from cellular to antibody-antigen for a given antigen, e. g., TAA, when administered as a vaccine to a human.
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It has not been demonstrated that adjuvant treatment (chemotherapy or radiation therapy) improves the survival rate for patients with BOTs. Response to the usual cytotoxic agents is low, probably related to the slow proliferation of these tumours. Neither do they seem to respond to oestrogen inhibitors in spite of being positive oestrogen receptors in 90% of cases. For this reason, there are no current indications for the use of chemotherapy or hormone therapy even in advanced cases.
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Research suggests no difference in overall survival time between sequential single agent chemotherapy and combination chemotherapy. Sequential single agent chemotherapy may have a more positive effect on progression-free survival. Taxanes are very active in metastatic breast cancer, and abraxane is approved for patients with metastatic breast cancer who either relapsed within six months of adjuvant chemotherapy or failed to respond to combination chemotherapy. This has a higher response rate than solvent-based paclitaxel (15% vs 8%).
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A Phase I advanced solid tumor study is currently ongoing at Roswell Park Cancer Institute. The Principal Investigator for this trial is Alex Adjei, M.D., Ph.D., FACP, Chair of the Department of Medicine and Senior Vice President of Clinical Research at Roswell Park Cancer Institute. Additionally, entolimod may also be developed as an adjuvant to standard radiation and chemotherapy, which will allow using of more aggressive measures to attack malignant cells and increase the effectiveness of cancer treatment.
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Elesclomol (INN, codenamed STA-4783) is a drug that triggers apoptosis (programmed cell death) in cancer cells. It is being developed by Synta Pharmaceuticals and GlaxoSmithKline as a chemotherapy adjuvant, and has received both fast track and orphan drug status from the U.S. Food and Drug Administration for the treatment of metastatic melanoma. Retrieved November 30, 2008. Synta Pharmaceuticals announced on February 26, 2009 the suspension of all clinical trials involving Elesclomol due to safety concerns.
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Problems posed by the differences in the human and rodent immune systems have been overcome using a few strategies, so as to enable researchers to study autoimmune disorders using humanized models. NSG mice engrafted with PBMCs and administered with myelin antigens in Freund’s adjuvant, and antigen-pulsed autologous dendritic cells have been used to study multiple sclerosis. Similarly, NSG mice engrafted with hematopoietic stem cells and administered with pristane have been used for studying lupus erythematosus.
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However, trials were recently discontinued due to lack of efficacy seen in patients suffering from severe sepsis. On the other hand, modified versions of lipid A can be used as components of vaccines (adjuvants) to improve their effect. Monophosphorylated lipid A (MPL) is an FDA approved adjuvant that consists of a heterogeneous mixture of lipid A from Salmonella minnesota R595. The major lipid A species present in MPL lacks one of the two phosphate groups and five acyl chains.
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Overall, the mainstay of the treatment for salivary gland tumor is surgical resection. Needle biopsy is highly recommended prior to surgery to confirm the diagnosis. More detailed surgical technique and the support for additional adjuvant radiotherapy depends on whether the tumor is malignant or benign. Surgical treatment of parotid gland tumors is sometimes difficult, partly because of the anatomical relationship of the facial nerve and the parotid lodge, but also through the increased potential for postoperative relapse.
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Other drugs are often used to help pain medications combat various types of pain, and parts of the overall pain experience. Hence they are called analgesic adjuvant medications. Gabapentin--an anti-epileptic --not only exerts effects alone on neuropathic pain, but can potentiate opiates. While perhaps not prescribed as such, other drugs such as Tagamet (cimetidine) and even simple grapefruit juice may also potentiate opiates, by inhibiting CYP450 enzymes in the liver, thereby slowing metabolism of the drug .
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Long grew up in a family of six children, with parents working in academia and medicine, and her early life involved living in Europe and the United States. Long has conducted research on many clinical trials in melanoma, including adjuvant and metastatic melanoma. Long has also researched immuno-oncology, which she says is the ‘penicillin moment’ which will be able to turn cancer into ‘treatable conditions’. She has focussed on immuno-oncology in melanoma and targeted therapies.
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Trabectome surgery has also proven to be a valuable adjuvant at the point of both valved and non-valved tube shunt implantation. When comparing patients undergoing Baerveldt tube implantation alone with those undergoing the same procedure combined with trabectome surgery, both groups showed similar intraocular pressure and visual acuities after the procedures. The combined patients required fewer pressure-lowering drops. These results show that trabectome surgery could improve post-operative quality of life by reducing necessary medication [16].
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Product marketing for carmofur started in 1981. Carmofur has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients in China, Japan, and Finland for many years. Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival. Carmofur has been shown to inhibit the SARS-CoV-2 main protease, and is therefore a promising lead compound to develop new antiviral treatment for COVID-19.
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It has been known that centromere misregulation contributes to mis-segregation of chromosomes, which is strongly related to cancer and abortion. Notably, overexpression of many centromere genes have been linked to cancer malignant phenotypes. Overexpression of these centromere genes can increase genomic instability in cancers. Elevated genomic instability on one hand relates to malignant phenotypes; on the other hand, it makes the tumor cells more vulnerable to specific adjuvant therapies such as certain chemotherapies and radiotherapy.
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Amyris joined partnership with IDRI (Infectious Disease Research Institute) in July, 2020 for a planned COVID-19 RNA (ribonucleic acid) vaccine technology program. The program combines IDRI's expertise in combating infectious diseases with Amyris' fermentation platform technology, with the goal to create semi- synthetic squalene-based adjuvants at scale. IDRI's RNA vaccine platform is expected to offer significant differentiated advantages over other RNA vaccines currently in development and will be further enhanced by a scalable Amyris adjuvant.
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The vancomycin regimen has replaced the traditional use of metronidazole due to its greater efficacy, safety profile, and lower recurrence rates. In patients who cannot tolerate vancomycin, fidaxomicin is an acceptable option with similar efficacy and even lower recurrence rates than vancomycin. In cases of fulminant CDI, adjuvant therapy with parenteral metronizadole plus oral vancomycin or fidaxomicin is suggested. About 20% of patients who successfully complete therapy of primary infection with metronidazole or vancomycin will experience a relapse.
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Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin was better than other comparable regimens in advanced nonresectable cancer. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used.
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For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient. In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.
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His research group focuses on improving care through the development of new treatment approaches. He also recognizes the importance of de-escalating therapy in patients who can do just as well with less treatment. In collaboration with the Department of Defense and the National Cancer Institute, Winer is also the principal investigator on a study sponsored by the Alliance for Clinical Trials in Oncology, assessing the use of aspirin as adjuvant therapy for node-positive breast cancer patients.
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There is not enough evidence to determine which chemotherapy approach is associated with the highest quality of life. There is also insufficient evidence to determine if treating people with NSCLC a second time when the first round of chemotherapy was not successful (second-line chemotherapy) causes more benefit or harm. Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging.
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Gas vesicle gene gvpC from Halobacterium sp. is used as delivery system for vaccine studies. Several characteristics of the protein encoded by the gas vesicle gene gvpC allow it to be used as carrier and adjuvant for antigens: it is stable, resistant to biological degradation, tolerates relatively high temperatures (up to 50 °C), and non-pathogenic to humans. Several antigens from various human pathogens have been recombined into the gvpC gene to create subunit vaccines with long-lasting immunologic responses.
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TRPA1 knockout mice showed near complete attenuation of nocifensive behaviors to formalin, tear-gas and other reactive chemicals . TRPA1 antagonists are effective in blocking pain behaviors induced by inflammation (complete Freund's adjuvant and formalin). Although it is not firmly confirmed whether noxious cold sensation is mediated by TRPA1 in vivo, several recent studies clearly demonstrated cold activation of TRPA1 channels in vitro. In the heat-sensitive loreal pit organs of many snakes TRPA1 is responsible for the detection of infrared radiation.
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Nematode vaccines marketed to date have been of the irradiated larval type and used exclusively for the treatment of animals. These vaccines are not stable and require annual production, involving the yearly production and sacrifice of donor animals for passage. There has been much interest in the production of subunit vaccines against human and agricultural parasites since the early 1980s. Development of subunit vaccines requires the identification of protective antigens and their formulation with a suitable adjuvant to stimulate the immune response appropriately.
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Treatment of lung squamous-cell carcinoma depends on many factors including stage, resectability, performance status and genomic alterations acquired by the individual tumor. Therapy of early-stage SCC mimics that of other histologic types of NSCLC. Early stage (I, II and IIIA) lung SCC are typically resected surgically, and cytotoxic chemotherapy and/or radiation may be used as an adjuvant therapy following surgery. On the other hand, advanced, metastatic or recurrent lung SCC are given first-line systemic therapy with a palliative (i.e.
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As with other forms of refractive surgery, keratoconjunctivitis sicca, colloquially referred to as 'dry eye,' is the most common complication of PRK, and can be permanent. In more advanced cases, recurrent erosions occur during sleeping from adherence of the corneal epithelium to the upper eyelid with rapid eye movement. Adjuvant polyunsaturated fatty acids (PUFAs) with high Omega-3 content before and after surgery improves sicca, possibly due to their anti-inflammatory effects. Foods containing PUFAs include flax and fish oil.
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The cancer outcomes (local control, regional control, and survival) for transoral resection followed by adjuvant therapy are comparable to primary chemoradiation, so that treatment decisions depend more on treatment-related morbidity, functional outcome, and quality of life. Patient factors also need to be taken into account, including general baseline functionality, smoking history, anesthesia risk, oropharyngeal function, swallowing and airway protection and potential for rehabilitation. Patient preference is equally important. Many clinical trials are under way focussing on deintensification, often with risk stratification, e.g.
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In developing countries, moringa has the potential to improve nutrition, boost food security, foster rural development, and support sustainable landcare. It may be used as forage for livestock, a micronutrient liquid, a natural anthelmintic, and possible adjuvant. Moringa oleifera leaf powder was as effective as soap for hand washing when wetted in advance to enable anti-septic and detergent properties from phytochemicals in the leaves. Moringa oleifera seeds and press cake have been implemented as wastewater conditioners for dewatering and drying fecal sludge.
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Adjuvant radiotherapy is commonly used in early-stage (stage I or II) endometrial cancer. It can be delivered through vaginal brachytherapy (VBT), which is becoming the preferred route due to its reduced toxicity, or external beam radiotherapy (EBRT). Brachytherapy involves placing a radiation source in the organ affected; in the case of endometrial cancer a radiation source is placed directly in the vagina. External beam radiotherapy involves a beam of radiation aimed at the affected area from outside the body.
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HER2 is an established therapeutic target within breast cancer, and the activation of HER2 is observed in approximately 20% of breast cancers as a result of overexpression. Trastuzumab, the first HER2-targeted drug developed in 1990, interferes with HER2 signalling. In 2001, a study showed that adding trastuzumab to chemotherapy improved overall survival in women with HER2-positive metastatic breast cancer. Then, in 2005, it was shown that trastuzumab is effective as an adjuvant treatment in women with early-stage breast cancer.
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The drug also prevented metastasis of the cancer to other regions of the body. Results from this clinical study were published in The New England Journal of Medicine in 2003, and two years later the therapy was approved by Health Canada. Later studies suggested that extending treatment with an aromatase inhibitor like Letrozole to ten years further increases disease-free survival rates. Another study looked at the effects of adjuvant therapies like Letrozole in women of different ages, both premenopausal and postmenopausal.
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One clinical trial used high intravenous doses of vitamin C (66 mg/kg/hour for 24 hours, for a total dose of around 110 grams) after severe burn injury, but despite being described as promising, it has not been replicated by independent institutions and thus is not a widely accepted treatment. Based on that study, the American Burn Association (ABA) considers high-dose ascorbic acid an option to be considered for adjuvant therapy in addition to the more accepted standard treatments.
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Triazolam is usually used for short-term treatment of acute insomnia and circadian rhythm sleep disorders, including jet lag. It is an ideal benzodiazepine for this use because of its fast onset of action and short half-life. It puts a person to sleep for about 1.5 hours, allowing its user to avoid morning drowsiness. Triazolam is also sometimes used as an adjuvant in medical procedures requiring anesthesia or to reduce anxiety during brief events, such as MRI scans and nonsurgical dental procedures.
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When patients have MDR-TB, they require longer periods of treatment—about two years of multidrug regimen. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure.
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Much of Eisenberg's work in the early-2000s involved the clinical use of chemotherapy in the adjuvant and metastatic settings. During this period Eisenberg published studies on Colorectal cancer,Marshall JL, Eisenberg SG, Johnson MD, Hanfelt J, et al. "A Phase II Trial of ISIS 3521 (CGP 64128A) in Patients with Metastatic Colorectal Carcinoma", Clinical Colorectal Cancer, November 2004 (4):268-74. and the use of a new chemotherapy technique for colon cancer patients using Irinotecan, 5-Fluorouracil, and Leucovorin.
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Craniopharyngiomas are usually successfully managed with a combination of adjuvant chemotherapy and neurosurgery. Recent research describes the rare occurrence of malignant transformations of these normally benign tumors. Malignant craniopharyngiomas can occur at any age, are slightly more common in females, and are usually of the adamantinomatous type. The malignant transformations can take years to occur (although one in five of the diagnosed cases were de novo transformations), hence the need for lengthier follow-up in patients diagnosed with the more common benign forms.
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Exocrine pancreatic cancer has one of the lowest 5-year survival rates out of all cancers. Because of the poor outcomes associated with surgery alone, the role of adjuvant therapy has been extensively evaluated. A series of studies has established that 6 months of chemotherapy with either gemcitabine or fluorouracil, as compared with observation, improves overall survival. Newer trials incorporating immune checkpoint inhibitors such as the inhibitors to programmed death 1 (PD-1) and the PD-1 ligand PD-L1 are under way.
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There is a limited amount of information on the effectiveness of chemotherapy or chemoradiation, and is not indicated for local tumors. Chemotherapy may be used in advanced tumors, to allow for local resection and in order to avoid exenteration [total removal of the eyeball and contents of the eye socket]. These treatments typically use 5-fluorouracil or cisplatin, also used in head and neck cancers. Few studies have shown that topical adjuvant chemotherapy is also effective in treating periocular SGC.
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Vannoni has never produced scientific evidence concerning the efficacy of the method, but has always advocated its validity. These alleged benefits are highlighted by multiple videos, often self-produced, some of which were broadcast on television, most of the time showing children. From the investigations of the Prosecutor of Turin, the benefits shown in the videos were not measured scientifically and objectively and were the result of exaggeration or adjuvant therapies to which the children were subjected, or normal physical growth that continued despite the disease.
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Herpevac) have failed to protect humans from acquiring genital herpes in several clinical trials. In contrast, the success of the live- attenuated chickenpox vaccine demonstrates that an appropriately live- attenuated α-herpesvirus may be used to safely control human disease. The challenge of achieving vaccines that are both safe and effective has led to two opposing approaches in HSV vaccine development: increasing the efficacy of subunit vaccines (primarily by improving adjuvant formulations), and increasing the safety of live-attenuated vaccines (including the development of "non-invasive" vaccines).
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Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. This discovery was championed by Julius Wagner-Jauregg, who won the 1927 Nobel Prize for Medicine for his discovery of the therapeutic value of malaria inoculation in the treatment of neurosyphilis. Later, hyperthermal cabinets (sweat-boxes) were used for the same purpose.Spink, W.W. "Infectious diseases: prevention and treatment in the nineteenth and twentieth centuries" U of Minnesota Press, 1978, p. 316.
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Hamatsa shaman after having spent several days in the woods as part of an initiation ritual. Influenced by her early collaboration with Simonton, Achterberg subsequently researched the similarities and differences between the potential use of imagery as an intervention adjuvant to contemporary medicine, and its use in ancient indigenous healing rituals, particularly those she identified as part of a shamanic tradition, which she described in her book Imagery in Healing.Moss, D., Mind-Body Medicine - In Memorium: Jeanne Achterberg, The Saybrook Forum, 3 August 2012. Mind-Body Medicine.
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When administered to diabetes prone NOD mice, Freund's complete adjuvant (FCA) prevented juvenile-onset diabetes. When combined with spleen cells, FCA was said to have reversed diabetes. In 2006, these claims were confirmed that even without spleen cells FCA can restore insulin producing beta cells in pancreas of NOD mice. Although newspapers have described the 2006 findings as confirming the earlier experiments, a report from NIH was released on November 23, 2006 in Science confirming the participation of spleen cells in reversing end-stage diabetes.
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In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an adjuvant is also added, this contains squalene, vitamin E and an emulsifier called polysorbate 80.Pandemic H1N1 (pH1N1) Influenza Vaccine Quick Reference Guide. Winnipeg Regional Health Authority. 2009. To make the live vaccine, the virus is first adapted to grow at and then grown at this temperature until it loses the ability to cause illness in humans, which requires the virus to grow at normal human body temperature of .
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Later, > Hilleman recalled, "I think that [Blumberg] deserves a lot of credit, but he > doesn't want to give credit to the other guy." Robert Purcell, a virologist, has emphasized the importance of the hepatitis B vaccine; in figuring out the hepatitis viruses, generally. In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S. Food and Drug Administration (FDA) approval. It uses recombinant HB surface antigen, similar to previous vaccines, but includes a novel CpG 1018 adjuvant, a 22-mer phosphorothioate- linked oligodeoxynucleotide.
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For about 20% of people, surgery is not sufficient to control their laryngeal papillomatosis, and additional nonsurgical and/or medical treatments are necessary. , these treatments alone are not sufficient to cure laryngeal papillomatosis, and can only be considered supplemental to surgery. Some varieties of nonsurgical treatments include interferon, antiviral drugs (especially cidofovir, but also ribavirin and acyclovir), and photodynamic therapy. The monoclonal antibody against Vascular Endothelial Growth Factor (VEGF), Bevacizumab has shown promising result as an adjuvant therapy in the management of recurrent respiratory papillomatosis.
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No high quality evidence has evaluated the use of bleomycin in this condition. Proton therapy affords a reduction in dose to critical structures compared to conventional photon radiation, including IMRT, for patients with craniopharyngioma. The most effective treatment 'package' for the malignant craniopharyngiomas described in literature is a combination 'gross total resective' surgery with adjuvant chemoradiotherapy. The chemotherapy drugs paclitaxel and carboplatin have shown a clinical (but not statistical) significance in increasing the survival rate in patients who have had gross total resections of their malignant tumours.
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Because each cancer is unique, the vaccine is derived from the patient's own tumor sample. To process these samples, Agenus has established a multi-product Good Manufacturing Practices (GMP) facility, which has already helped process over 1,000 tumor samples from across the globe. The company's QS-21 Stimulon® adjuvant platform strengthens and broadens immune responses to antigens on cancers or foreign invaders’ surfaces. Agenus has multiple partnerships around this product to study its effects with vaccines for diseases including Alzheimer's, melanoma, and malaria.
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These patients, unlike many patients with similarly appearing neoplasms, respond well to the tyrosine kinase inhibitor, imatinib. The drug often causes long-term complete hematological and cytogenic remissions as doses well below those used to treat chronic myelogenous leukemia. Primary or acquired drug resistance to this drug is very rare. Additional adjuvant chemotherapy may be necessary if a patients disease is unresponsive to tyrosine kinase inhibitor therapy and/or progresses to more aggressive disease phase similar to that seen in the blast crisis of chronic myelogenous leukemia.
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As a result of this research, on January 8, 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma. On May 1, 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.
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Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling" (puncture of 4–10 small follicles with electrocautery, laser, or biopsy needles), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH. (Ovarian wedge resection is no longer used as much due to complications such as adhesions and the presence of frequently effective medications.) There are, however, concerns about the long-term effects of ovarian drilling on ovarian function.
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High doses of temozolomide in high-grade gliomas yield low toxicity, but the results are comparable to the standard doses. Antiangiogenic therapy with medications such as bevacizumab control symptoms, but do not appear to affect overall survival in those with glioblastoma. The overall benefit of anti-angiogenic therapies as of 2019 is unclear. In elderly people with newly diagnosed glioblastoma who are reasonably fit, concurrent and adjuvant chemoradiotherapy gives the best overall survival but is associated with a greater risk of haematological adverse events than radiotherapy alone.
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The name "alum" is also used, more generally, for salts with the same formula and structure, except that aluminium is replaced by another trivalent metal ion like chromium(III), and/or sulfur is replaced by another chalcogen like selenium. The most common of these analogs is chrome alum . In most industries, the name "alum" (or "papermaker's alum") is used to refer to aluminium sulfate ·n, which is used for most industrial flocculation. In medicine, "alum" may also refer to aluminium hydroxide gel used as a vaccine adjuvant.
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The heightened gonadotropin levels also upregulate the aromatase promoter, increasing aromatase production in the setting of increased androgen substrate. This would counteract the effect of the aromatase inhibitor in premenopausal women, as total estrogen would increase. Ongoing areas of clinical research include optimizing adjuvant hormonal therapy in postmenopausal women with breast cancer. Although tamoxifen (a SERM) traditionally was the drug treatment of choice, but the ATAC trial showed that AI gives superior clinical results in postmenopausal women with localized estrogen receptor positive breast cancer.
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In the U.S. and the rest of the developed world, surgery is the treatment standard for all stages of ovarian cancer. For later stages, adjuvant chemotherapy has been shown to improve patient survival. Lymphadenectomy and lymph node chemotherapy have also been demonstrated to improve survival for ovarian cancer patients of all stages.R. Angioli, F. Plotti, I. Palaia, M. Calcagno, R. Montera, E.V. Cafà, et al. Update on lymphadenectomy in early and advanced ovarian cancer, Curr Opin Obstet Gynecol, 20 (1) (2008), pp. 34–39.
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Radiation therapy is an adjuvant treatment for most women who have undergone lumpectomy and for some women who have mastectomy surgery. In these cases the purpose of radiation is to reduce the chance that the cancer will recur locally (within the breast or axilla). Radiation therapy involves using high-energy X-rays or gamma rays that target a tumor or post surgery tumor site. This radiation is very effective in killing cancer cells that may remain after surgery or recur where the tumor was removed.
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Adjuvant System 04 (AS04) is a mixture of 4 agonist monophosphoryl lipid A (MPL) and aluminum hydroxide. It is one of the ingredients of the human papillomavirus vaccine (HPV). Sientists studied AS04-adjuvanted HPV vaccine and it shows high and justified immune response against to HPV antigens. Not only that but the patients who took HPV-16/18 AS04-adjuvanted vaccine previously showed that on the second or subsequent doses immune responded stronger and rapidly, which tells that it builds immune memory in the body.
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Hyperthermia therapy or heat therapy is also a kind of adjuvant therapy that is given along with radiation or chemotherapy to boost the effects of these conventional treatments. Heating the tumor by Radio Frequency (RF) or Microwave energy increases oxygen content in the tumor site, which results in increased response during radiation or chemotherapy. For example, Hyperthermia is added twice a week to radiation therapy for the full course of the treatment in many cancer centers, and the challenge is to increase its use around the world.
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However, about one third of patients do not respond to this therapy, and increased AGR2 may be one reason. There is a positive correlation for a higher level of AGR2 expression with poor therapeutic results in ERα-positive breast cancer patients. Agr2 mRNA expression is elevated in in vitro and in vivo studies responding to tamoxifen adjuvant therapy, so AGR2 is likely provides an agonistic effect on tamoxifen. Therefore, AGR2 is a possible predictive biomarker when selecting patients with ER-positive breast cancer to participate this therapy.
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The Dyson Center for Cancer Care is a full- service cancer treatment and support center, the only of its kind in the Mid- Hudson Valley. The Dyson Center at VBMC is affiliated with the National Surgical Adjuvant Breast and Bowel Project and conducts clinical research with assistance from the National Cancer Institute and the Community Clinical Oncology Program (CCOP). The radiotherapy suite on-site offers three types of radiation therapy: image-guided radiation therapy (IGRT), stereotactic body radiotherapy (SBRT), and intensity-modulated radiation therapy (IMRT).
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Patients expected to receive radiation therapy as part of their adjuvant treatment are also commonly considered for delayed autologous reconstruction due to significantly higher complication rates with tissue expander-implant techniques in those patients. While waiting to begin breast reconstruction until several months after radiation therapy may decrease the risk of complications, this risk will always be higher in patients who have received radiation therapy. As with many other surgeries, patients with significant medical comorbidities (e.g., high blood pressure, obesity, diabetes) and smokers are higher-risk candidates.
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MIS416 is a microparticle derived from the cytoskeleton of P. acnes, a species of bacteria present on the skin of most adults that causes acne. MIS416 was originally developed as a vaccine adjuvant, a component of vaccines that helps to activate an immune response against the vaccine target. Bacteria-derived microparticles have several advantages over traditional adjuvants related both to their size and biological properties. Because MIS416 is engulfed by immune cells, it is being investigated as an immunotherapy-based treatment for solid tumors.
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Ability to draw more generalized conclusions from research to date has been limited by lack of controlled trials, and inconsistency in study design in terms of disease severity, IVIG dose, and timing of IVIG administration. Larger, high quality trials are needed to assess the actual benefit of IVIG in TEN. Numerous other adjuvant therapies have been tried in TEN including, corticosteroids, ciclosporin, cyclophosphamide, plasmapheresis, pentoxifylline, acetylcysteine, ulinastatin, infliximab, and granulocyte colony-stimulating factors (if TEN associated- leukopenia exists). There is mixed evidence for use of corticosteroids and scant evidence for the other therapies.
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As predicted by studies in animal models, drugs were most effective when used in patients with tumours of smaller volume. Another important strategy developed from this — if the tumour burden could be reduced first by surgery, then chemotherapy may be able to clear away any remaining malignant cells, even if it would not have been potent enough to destroy the tumor in its entirety. This approach was termed "adjuvant therapy". Emil Frei first demonstrated this effect — high doses of methotrexate prevented recurrence of osteosarcoma following surgical removal of the primary tumour.
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The discovery that certain toxic chemicals administered in combination can cure certain cancers ranks as one of the greatest in modern medicine. Childhood ALL, testicular cancer, and Hodgkins disease, previously universally fatal, are now generally curable diseases. Conventional cytotoxic chemotherapy has shown the ability to cure some cancers, including testicular cancer, Hodgkin disease, non-Hodgkin lymphoma, and some leukemias. It has also proved effective in the adjuvant setting, in reducing the risk of recurrence after surgery for high-risk breast cancer, colon cancer, and lung cancer, among others.
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This can make it a useful adjuvant treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as cancer, where opioid analgesics may be required for long periods and development of tolerance reduces clinical efficacy of these drugs. Proglumide has also been shown to act as a δ-opioid agonist, which may contribute to its analgesic effects. Proglumide also works as a placebo effect amplifier for pain conditions. When injected visibly to a subject, its analgesic effect is bigger than a similarly administered placebo.
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Examples of antigenic targets of hookworm vaccines currently in clinical trials include Na-ASP-2 from N. americanus, Ac-APR-1 from Ancylostoma caninum, Ac'-APR-1 and Na- GST-1/Alhydroge. In a clinical trial a vaccine containing recombinant Na-ASP-2 with Alhydrogel as an adjuvant was found to increase Th2 helper cells and IgE. Both the Th2 helper cells and IgE antibody are important players in recognition and immunoregulation against parasites. The vaccine containing recombinant Na-ASP-2 resulted in significantly decreased risk of a hookworm infection.
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Nventa originally advanced HspE7 as a single-agent therapy into multiple Phase 2 clinical trials with positive results, including trials in cervical dysplasia and recurrent respiratory papillomatosis (RRP). These trials were initiated prior to the discovery that potency could be greatly enhanced by addition of a vaccine adjuvant.International HPV Conference Poster: “NVENTA PRESENTS HSPE7 DATA AT INTERNATIONAL HPV CONFERENCE” / Nventa Press Release, November 5, 2007 Nventa is currently developing HspE7 combined with the TH1-directed adjuvant Poly- ICLC. A Phase 1b study is complete, assessing safety and tolerability in 17 patients with CIN.
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Colorectal carcinomas that lacked p27 were shown to have increased p27-specific proteolysis and a median survival of only 69 months compared to 151 months for patients with high or normal levels of p27. The authors proposed clinicians could use patient specific levels of p27 to determine who would benefit from adjuvant therapy. Similar correlations were observed in patients with non-small cell lung cancer, those with colon, and prostate cancer. So far studies have only evaluated the prognostic value of p27 retrospectively and a standardized scoring system has not been established.
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NAGly has been hypothesized to have a neurophysiological function of pain suppression, supported by evidence that it suppresses formalin-induced pain behavior in rats. In particular, peripherally administered NAGly inhibited phase 2 pain behavior, suggesting either a direct suppression of nociceptive afferents on the nerve or an indirect modulation of the afferents' interstitial environment. In either case, these findings hold promise for NAGly as a means of mitigating postoperative or chronic pain. NAGly is also effective in acute pain models, reducing mechanical allodynia and thermal hyperalgesia induced by intraplantar injection of Fruend's complete adjuvant.
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The dosage of LY-2140023 given to patients has varied by clinical trial, though dosages have typically ranged between 10 mg and 40 mg twice daily (BID). In an early phase II monotherapy trial, the dosage shown to be efficacious was 40 mg BID. Later trials investigating the use of LY-2140023 as an adjuvant to the antipsychotic medications already used by patients participating in the study utilized a lower dose of 20 mg BID. If treatment was well tolerated after a week at this target dose, the dose was increased to 40 mg BID.
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In a more recent paper published in the Journal of Urology, he reported that the recurrence rate was only 20% in his patient cohort with a positive surgical margin and therefore, the routine adjuvant radiation therapy would over treat 80% of the patients.Wieder JA, Soloway MS. Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer. J Urol, 160(2):299-315, 1998.Simon MA, Kim S, Soloway MS. Prostate specific antigen recurrence rates are low after radical retropubic prostatectomy and positive margins.
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Principles for adoptive T cell therapy of human viral diseases. Annual review of immunology, 13(1), pp.545-586. furthermore, recent reports suggest that immunization (using either adjuvant or dendritic cells with pure tumor peptides) can result in productive anti-tumor immunity that is restricted by MHC class I.Feltkamp, M.C., Smits, H.L., Vierboom, M.P., Minnaar, R.P., De Jongh, B.M., Drijfhout, J.W., Schegget, J.T., Melief, C.J. and Kast, W.M., 1993. Vaccination with cytotoxic T lymphocyte epitope‐containing peptide protects against a tumor induced by human papillomavirus type 16‐transformed cells.
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An adjuvant is typically thought of as a substance used in combination with the antigen to produce a more substantial and robust immune response than that elicited by the antigen alone. This is achieved through three mechanisms: by affecting the antigen delivery and presentation, by inducing the production of immunomodulatory cytokines, and by affecting the antigen presenting cells (APC). Adjuvants can consist of many different materials, from cell microparticles to other particulated delivery systems (e.g. liposomes). Adjuvants are crucial in affecting the specificity and isotype of the necessary antibodies.
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There is increasing concern that the use of very potent adjuvants could precipitate autoimmune responses, making it imperative that the vaccine is focused on the target cells only. Specific delivery systems can reduce this risk by limiting the potential toxicity and systemic distribution of newly developed adjuvants. Studies into the efficacy of malaria vaccines developed to date have illustrated that the presence of an adjuvant is key in determining any protection gained against malaria. A large number of natural and synthetic adjuvants have been identified throughout the history of vaccine development.
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It is currently being tested as an adjuvant in various vaccines in attempts to improve their efficacy. It is believed to enhance both humoral and cell-mediated immunity. Isolation of QS-21 destroys the soap bark tree, which has resulted in regulation of the tree by the governments where it is grown. A semi-synthesis strategy relies on purifying the prosapogenin (triterpene and branched trisaccharide) part of the molecule and adding the rest of QS-21 synthetically; this is reported to increase the yield by 2 orders of magnitude.
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Additionally, proponents of this theory allege that the disorder can manifest anywhere from 2 days to 23 years after exposure. Shoenfeld has also named Sjögren's syndrome as potentially being another facet of ASIA. In 2013, the authors of a textbook on autoimmune diseases concluded that "there exists persuasive evidence for ASIA," but noted that several academic and governmental agencies had dismissed the possibility of a link between silicone and autoimmune disease. However, apart from the theoretical concept of ASIA, there is a lack of reproducible evidence for any causal relationship between adjuvant and autoimmune condition.
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Preferred drugs (and other treatments) are also referred to a "first line" or "primary" while others are called "second line", "third line" etc. A drug may be indicated as an "adjunct" or "adjuvant", added to a first line drug. Off-label: Off-label indications are drugs that are used for medical indications that have not been approved by the FDA. Off label indications often have some clinical significance to back the use, but they have not gone through the extensive testing required by the FDA to have an official labeled indication.
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Although chemoradiation became a treatment standard based on clinical trials and in particular, meta-analyses, a subsequent population based study of patients with OPC, indicated no advantage to the addition of chemotherapy to radiation in either HPV+OPC or HPV-OPC, and significant concerns about added toxicity. Chemotherapy also has a role, combined with radiation, in the postoperative setting (adjuvant therapy). Generally it is used where the pathology of the resected specimen indicates features associated with high risk of locoregional recurrence (e.g. extracapsular extension through involved lymph nodes or very close margins).
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Defined tumor antigens decrease the risk of autoimmunity, but because the immune response is directed to a single epitope, tumors can evade destruction through antigen loss variance. A process called "epitope spreading" or "provoked immunity" may mitigate this weakness, as sometimes an immune response to a single antigen can lead to immunity against other antigens on the same tumor. For example, since Hsp70 plays an important role in the presentation of antigens of destroyed cells including cancer cells, this protein may be used as an effective adjuvant in the development of antitumor vaccines.
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Recurrence of early stage endometrial cancer ranges from 3 to 17%, depending on primary and adjuvant treatment. Most recurrences (75–80%) occur outside of the pelvis, and most occur two to three years after treatment, 64% after two years and 87% after three years. Higher- staged cancers are more likely to recur, as are those that have invaded the myometrium or cervix, or that have metastasized into the lymphatic system. Papillary serous carcinoma, clear cell carcinoma, and endometrioid carcinoma are the subtypes at the highest risk of recurrence.
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Optimal and usual protein antigen levels for immunizing specific species have been reported in the following ranges: # rabbit, 50–1000 µg; # mouse, 10–50 µg; # guinea pig, 50–500 µg; and # goat, 250–5000 µg. Optimal “priming” doses are reported to be at the low end of each range. The affinity of serum antibodies increases with time (months) after injection of antigen-adjuvant mixtures and as antigen in the system decreases. Widely used antigen dosages for “booster” or secondary immunizations are usually one half to equal the priming dosages.
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Pritchard demonstrated that women with high levels of Her-2 expression have a better response to the anthracycline containing drugs in a clinical trial. Pritchard's research suggests that the Her-2 gene could be useful as a possible predictor of the adjuvant therapy that is most effective in certain patients. Her study demonstrated ways in which chemotherapy can be tailored to the specific patient. The goal of such tailored therapy is that patients can be spared the toxicity and side effects of drugs that they do not actually need.
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It is used for the treatment of wet macular degeneration and is administered as an intravitreal injection, that is, into the eye. For cancer treatment, is given intravenously in combination with the other cancer drugs 5-fluorouracil and irinotecan and the adjuvant folinic acid. On 27 August 2014, Eylea was also indicated for the treatment of people with visual impairment due to diabetic macular oedema, according to the updated summary of product characteristics. In May 2019 FDA expanded the indication for aflibercept to include all stages of diabetic retinopathy.
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In some settings, an extraction catheter may be used to attempt to aspirate (remove) the thrombus prior to balloon angioplasty. While the use of intracoronary stents do not improve the short term outcomes in primary PCI, the use of stents is widespread because of the decreased rates of procedures to treat restenosis compared to balloon angioplasty. Adjuvant therapy during an angioplasty includes intravenous heparin, aspirin, and clopidogrel. Glycoprotein IIb/IIIa inhibitors are often used in the setting of primary angioplasty to reduce the risk of ischemic complications during the procedure.
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The delivery system helps adjuvant the vaccine, increasing the size of the immune response. Thirdly, polyclonal antibodies do not appear to have the cardiotoxicity that has been observed in >10% of patients on Herceptin. The potential for immune memory may mean that the treatment effect is long-lasting (by contrast antibodies have a short half-life – that of Herceptin is only 12 days – meaning that the patient has to have infusions every 1–3 weeks). The vaccine would be available intra-muscularly, where Herceptin and Perjeta have to be given by regular infusions.
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An exception to this is where the anatomical position of the tumour means that surgery is technically difficult or complex. For example, rectal GIST often requires radical surgery to achieve complete resection, involving abdominoperineal resection and permanent stoma. In these situations, the use of neoadjuvant imatinib can significantly decrease both tumour size and mitotic activity, and permit less radical sphincter-preserving surgery. A substantial proportion of GIST tumors have a high risk of recurrence as estimated by a number of validated risk stratification schemes, and can be considered for adjuvant therapy.
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Axillary sentinel lymph node biopsy, as a method of screening for metastatic disease in otherwise non-invasive DCIS, is falling out of favor because the risks of procedure outweigh any effect on outcomes. For DCIS, chemotherapy is not recommended, but tamoxifen may be recommended for tumors which contain an abundance of estrogen receptors. For patients with invasive ductal carcinoma who have lumpectomies, lymph node biopsy and radiation therapy are usually recommended. Adjuvant chemotherapy is often recommended, but it may not be recommended if the tumor is small and there are no lymph node metastases.
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The disease is aggressive and therefore has been treated aggressively with chemotherapy followed by bone marrow transplantation. However, of 6 patients treated with a tyrosine kinase inhibitor, ruxolitinib, 5 experienced complete remissions and have survived for at least 30 months. One patient relapsed after 18 months ruxolitinib therapy and required Hematopoietic stem cell transplantation (HSCT). The efficacy of ruxolitinib therapy in this therapy requires a larger study; ultimately, the drug may find use as initial single therapy or as an adjuvant to reduce tumor load prior to combination with HCST.
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Several proved to function successfully in mice, however, these proteins alone did not effectively interact with the human immune system due to not inducing a good immune response in order for the protection to be achieved. Later, by addition of outer membrane vesicles that contain lipopolysaccharides from the purification of blebs on gram negative cultures. The addition of this adjuvant (previously identified by using conventional vaccinology approaches) enhanced immune response to the level that was required. Later, the vaccine was proven to be safe and effective in adult humans.
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It is particularly effective as an adjuvant for 2, 4-D (amine), glyphosate, and glufosinate herbicides.American Elements – The material science company; tetraammine copper(II) sulfate monohydrate; CAS 10380-29-7 The brilliant dark blue-violet color and a good solubility make tetraammine copper (II) sulfate an excellent chemical to dye fabrics. Some of the recent research and development for copper include various studies of tetraaminecopper (II) sulfate. One such research is "Chemical reduction method for preparing copper nano-powder with high purity using sodium hypophosphite as reductant", which uses tetraaminecopper (II) sulfate.
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Transcranial direct-current stimulation is a modification of the traditionally available direct current applied with 2 saline soaked electrodes (active and reference: 5-35 cm2) with active placed at the area to be stimulated and reference electrode placed at the contralateral supraorbital region in the forehead. Focality of the current passes depends upon the position of the electrode, its dimensions and the current density. The duration of the stimulation varies from 5-20 mins with intensities of 0.5-2.0 mA. It has been successfully introduced as a promising therapeutic adjuvant in various rehabilitation procedures.
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Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.
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After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.
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Ludwig Cancer Research: 4-Antibody had been working on the checkpoint targets for several years in collaboration with Ludwig Cancer Research, one of the world's most renowned institutions for research into cancer and the immune system. The leader of the Ludwig collaborative laboratory at Memorial Sloan Kettering Cancer Center, Jedd Wolchok, is recognized as one of immuno-oncology's leading pioneers. GlaxoSmithKline (GSK): March 2012, GSK paid Agenus $9 million to include additional rights to the two firms’ agreement around Agenus’ QS-21 Stimulon® adjuvant. The deal amended license and manufacturing terms.
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This much more stringent requirement prevents both the widespread use and questionable content present in the United States. In the UK, the Chemical Regulations Directorate (CRD), part of the Health and Safety Executive, oversees the use of adjuvants. CRD defines an adjuvant as a substance other than water which is not in itself a pesticide but which enhances or is intended to enhance the effectiveness of the pesticide with which it is used. Adjuvants for use with agricultural pesticides have been categorised as extenders, wetting agents, sticking agents and fogging agents.
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The adjuvant enhances the immune response of the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials. Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved. The final stage in vaccine manufacture before distribution is fill and finish, which is the process of filling vials with vaccines and packaging them for distribution. Although this is a conceptually simple part of the vaccine manufacture process, it is often a bottleneck in the process of distributing and administering vaccines.
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DAHANCA 19 (2007 –2012, 619 pts) - Randomized study of Zalutumumab (anti-EGFr) as adjuvant to radiotherapy. ClinicalTrials.gov Identifier: NCT00496652 DAHANCA 20 (2006 – 30 pts) – Phase II study of palliative radiotherapy. ClinicalTrials.gov Identifier: NCT00400426 DAHANCA 21 (2007 – 97 patients) – Behandling af mandibulær osteoradionekrose med hyperbar oxygen (HBO). Et klinisk randomiseret studie. ClinicalTrials.gov Identifier: NCT00760682 DAHANCA 22 (2007 – 30 pts) – Registration study study of sentinel lymphnode (with EORTC 24021) DAHANCA 23 (2009 – never activated) Estimation of tumor hypoxia using 18F -FAZA Positron Emissions Tomografi in operable head and neck squamous cell carcinoma.
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There is generally a lack of evidence comparing the effectiveness of all treatment options. High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management. Nodal spread: # Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven. # Radiotherapy # Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis.
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The treatment of cases with disease spreading beyond regional lymph nodes has been variable, ranging from simple excision to radical resections accompanied by adjuvant radiotherapy and/or chemotherapy, depending on the location of disease. Mean disease-free survival for MASCSG patients has been reported to be 92 months in one study. The tyrosine kinase activity of NTRK3 as well as the ETV6-NTRK3 protein is inhibited by certain tyrosine kinase inhibitory drugs such as Entrectinib and LOXO-101; this offers a potential medical intervention method using these drugs to treat aggressive MASCSG disease.
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Trimethylglycine can act as an adjuvant of the polymerase chain reaction (PCR) process, and other DNA polymerase-based assays such as DNA sequencing. By an unknown mechanism, it aids in the prevention of secondary structures in the DNA molecules, and prevents problems associated with the amplification and sequencing of GC-rich regions. Trimethylglycine makes guanosine and cytidine (strong binders) behave with thermodynamics similar to those of thymidine and adenosine (weak binders). It has been determined under experiment that it is best used at a final concentration of 1 M.
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Cytoreductive “debulking” surgery may be performed prior to chemotherapy treatment in order to decrease the physical mass of the tumour and thus reduce the number of chemotherapy cycles needed. The typical advanced presentation as well as extra-ovarian spread seen in HGSC can require aggressive debulking procedures. In some cases total abdominal hysterectomy will be performed, in other cases where the patient intends to bear children a salpingo-oophorectomy is performed instead. Typical chemotherapy is six cycles of intraperitoneally-delivered platinum-base adjuvant chemotherapy with agents such as carboplatin.
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AHCC has been proposed as a treatment for cancer, but research into its effectiveness has produced only uncertain and inconclusive evidence. Detailed research is needed into the pharmacology of AHCC before any recommendation of its use as an adjuvant therapy can be made. Studies have suggested that AHCC supplementation may affect immune outcomes and immune cell populations, suggesting that it has anti-inflammatory effects. Moreover, available data have demonstrated that AHCC may possibly reduce symptoms, improve survival, and shorten recovery time in animal models infected with viruses, bacteria, and fungal infections.
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In 1972, ICI Pharmaceuticals Division abandoned development of tamoxifen for financial reasons. The drug was subsequently reinvented from a failed contraceptive, to become tamoxifen, the gold standard for the adjuvant treatment of breast cancer and the pioneering medicine for chemprevention for high risk women. Two books, Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health (Imperial College Press 2013) and Tamoxifen Pioneering Medicine in Breast Cancer (Springer 2013) tell this story. 1980 saw the publication of the first trial to show that tamoxifen given in addition to chemotherapy improved survival for patients with early breast cancer.
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KLH is purified from the hemolymph of Megathura crenulata by a series of steps that typically includes ammonium sulfate precipitation and dialysis, and may involve chromatographic purification to obtain the highest purity. KLH purification may also include endotoxin removal, but this step is often unnecessary because the endotoxin serves as an adjuvant when injected for antibody production. If the protein becomes denatured or if the copper ions are lost in the purification process, the opalescent blue color disappears and the solution becomes a dull grayish color. Denaturation of KLH also results in a tendency of the protein to aggregate and precipitate from solution.
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Mortensen et al. hypothesize that the dosage (100 mg three times daily) and the formulation of the Q10 used in the Q-SYMBIO clinical trial may have resulted in the patients reaching a required "therapeutic threshold in serum and tissue of CoQ10" needed to reduce the number of major adverse cardiovascular events. The formulation used in the trial has been demonstrated to have good bio-availability in controlled studies. In 2019, AL Mortensen, FL Rosenfeldt, and KJ Filipiak evaluated the treatment effect of Coenzyme Q10 adjuvant treatment in the European sub- population of the Q-SYMBIO clinical trial.
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This cytokine serves to induce maturation of plasmacytoid dendritic cells (PDCs) so that they can display their antigens to T helper cells. The mechanism in which eukaryotic DNA activates these cells is still as yet unclear; however, immunogenic CpG sequences have been found to either activate PDCs or act as adjuvant in the response to eukaryotic DNA. CpG motif DNA acts via the pattern recognition receptor, toll-like receptor 9, found highly expressed in PDCs and B cells. The T helper cells then activate B cells, which are also in the presence of these antigens, causing the production of autoantibodies.
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Further testing results are to show if the vaccine is a viable candidate against genital herpes. There has not been any recent announcement by Agenus regarding the vaccine HerpV, which seems to have been taken off from the company's research product pipeline. Genocea Biosciences has developed GEN-003, a first-in-class protein subunit T cell-enabled therapeutic vaccine, or immunotherapy, designed to reduce the duration and severity of clinical symptoms associated with moderate-to-severe HSV-2, and to control transmission of the infection. GEN-003 includes the antigens ICP4 and gD2, as well as the proprietary adjuvant Matrix-M.
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Ketoprofen is generally prescribed for arthritis-related inflammatory pains or severe toothaches that result in the inflammation of the gums. Ketoprofen topical patches are being used for treatment of musculoskeletal pain. Ketoprofen can also be used for treatment of some pain, especially nerve pain such as sciatica, postherpetic neuralgia and referred pain for radiculopathy, in the form of a cream, ointment, liquid, spray, or gel, which may also contain ketamine and lidocaine, along with other agents which may be useful, such as cyclobenzaprine, amitriptyline, acyclovir, gabapentin, orphenadrine and other drugs used as NSAIDs or adjuvant, atypical or potentiators for pain treatment.
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Ipilimumab was approved by the U.S. Food and Drug Administration (FDA) in March 2011, to treat people with late-stage melanoma that has spread or cannot be removed by surgery. It was later approved by the US FDA on October 28, 2015, for stage 3 patients as adjuvant therapy. On February 1, 2012, Health Canada approved ipilimumab for "treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease." Ipilimumab was approved in the European Union (EU), for second line treatment of metastatic melanoma in November 2012.
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Since 1975, breast cancer rates have declined in the U.S., largely due to mammograms and the use of adjuvant treatments such as radiotherapy. Local recurrence rates are greatly reduced by postoperative radiotherapy, which translates into improved survival: Preventing four local recurrences can prevent one breast cancer death. In one of the largest published studies so far called (ELIOT),Veronesi U, Orecchia R, Patrick Maisonneuve p, et al. “Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial”.]“Lancet Oncol. “ 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(13)70497-2. Epub 2013 Nov 11.
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The production of CCL18 is induced by T-helper 2 type cytokines, namely IL-4 and IL-13. Coupled with the fact that CCL18 is highly expressed in patients with allergic asthma and other hypersensitivity diseases, CCL18 seems to play an important role for generating and maintaining a T-helper 2 (Th2) type response. Furthermore, the addition of CCL18 as an adjuvant for a malaria vaccine have shown efficacy, perhaps by recruiting immune cells to the site of vaccination. Finally, CCL18 is expressed by dendritic cells in the germinal center of inflamed lymph nodes, and recruits naïve B-cells for antigen presentation.
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The president is directly subordinated to the Chief of Staff and is assisted by a Directive Council he presides over, formed by IASD military and civilian Adjuvant Directors, the ISSMI Director, the CeMiSS Director acting as secretary, the CeFLI Direction and the Chief of Defence. The Directive Council examines and expresses its opinions on study programs of the two formation institutes, on activities of sessions and courses, on the evaluation system of Attending Officers and on all the organizational and functional aspects of CASD, aimed at increasing the maximum level of synergy in the use of the available human, material and financial resources.
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A schematic diagram showing the operation of alt= With a recurrence up to 15-25% for early-stage patients, adjuvant chemotherapy needs to couple with surgical resection of tumor to ensure full salvage. For systemic chemotherapy (issued orally or intravenously), the regimen is standardised in every FIGO staging to comprise bleomycin, etoposide, and cisplatin, also known as the BEP treatment. Patients should be issued with 3-4 cycles of BEP to ensure full salvage. Depending on the personalised conditions, some patients who are non-responders to BEP therapy will be prescribed with salvage therapy, which consists of cisplatin, ifosfamide and paclitaxel.
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A test for HPV called the Digene HPV test is highly accurate and serves as both a direct diagnosis and adjuvant to the all-important Pap smear, which is a screening device that allows for an examination of cells but not tissue structure, needed for diagnosis. A colposcopy with directed biopsy is the standard for disease detection. Endocervical brush sampling at the time of Pap smear to detect adenocarcinoma and its precursors is necessary along with doctor/patient vigilance on abdominal symptoms associated with uterine and ovarian carcinoma. The diagnosis of CIN or cervical carcinoma requires a biopsy for histological analysis.
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Seung-Yong Seong (born c. 1965) is a South Korean immunologist and microbiologist known for his study of innate immune system response and his development of the damage-associated molecular pattern (DAMP) model of immune response initiation in collaboration with Polly Matzinger. Seong is also known for his research on the bacterium Orientia tsutsugamushi and his research on immunological adjuvant when he was a student. Since 2013 he has served as Director of the Wide River Institute of Immunology – Seoul National University in conjunction with his Professor position in the Microbiology and Immunology department of Seoul National University College of Medicine.
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As with mice, studies have examined the extent of agreement in assessing pain between rat GS and the use of von Frey filaments. Good agreement has been found between these in relation to three models of pain (intraplantar carrageenan, intraplantar complete Freund's adjuvant and plantar incision). The GS score significantly increased in all pain models and the peak GS score also coincided with the development of paw hypersensitivity, although hypersensitivity persisted after GS scores returned to baseline. For rats, software (Rodent Face Finder®) has been developed which successfully automates the most labour-intensive step in the process of quantifying the GS, i.e.
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Freund's complete adjuvant is effective in stimulating cell-mediated immunity and leads to potentiation of T helper cells that leads to the production of certain immunoglobulins and effector T cells. Its use in humans is forbidden by regulatory authorities, due to its toxicity. Even for animal research there are currently guidelines associated with its use, due to its painful reaction and potential for tissue damage. Injections of FCA should be subcutaneous or intraperitoneal, because intradermal injections may cause skin ulceration and necrosis; intramuscular injections may lead to temporary or permanent muscle lesion, and intravenous injections may produce pulmonary lipid embolism.
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Ammonium thiocyanate is used in the manufacture of herbicides, thiourea, and transparent artificial resins; in matches; as a stabilizing agent in photography; in various rustproofing compositions; as an adjuvant in textile dyeing and printing; as a tracer in oil fields; in the separation of hafnium from zirconium, and in titrimetric analyses. In May 1945, USAAF General Victor E. Betrandias advanced a proposal to his superior General Arnold to use of ammonium thiocyanate to reduce rice crops in Japan as part of the bombing raids on their country. Ammonium thiocyanate can also be used to determine the iron content in soft drinks by colorimetry.
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On January 8, 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma. On May 1, 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF- mutated melanoma. In April 2017, the European Union approved the combination of dabrafenib with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC).
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Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from. It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect. There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications. Cyproheptadine has been studied for the treatment of posttraumatic stress disorder.
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A phase 2 clinical trial for acute myeloid leukemia (AML)Efficacy Study of Anti-KIR Monoclonal Antibody as Maintenance Treatment in Acute Myeloid Leukemia (EFFIKIR) (EFFIKIR) was terminated early ("failed") in 2017.Innate Pharma Leukemia Candidate Lirilumab Fails Phase II Trial. Feb 2017 It was registered for a trial for squamous cell carcinoma of the head and neck (SCCHN),Adjuvant Nivolumab and Lirilumab in Patients With Relapsed, Resectable Squamous Cell Carcinoma of the Head and Neck but it may be abandoned.Bad news for Innate Pharma as BMS-backed drug stumbles nov 2017 nine clinical trials of lirilumab are registered as active.
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Cholangiocarcinoma is considered to be an incurable and rapidly lethal disease unless all the tumors can be fully resected (cut out surgically). Since the operability of the tumor can only be assessed during surgery in most cases, a majority of people undergo exploratory surgery unless there is already a clear indication that the tumor is inoperable. However, the Mayo Clinic has reported significant success treating early bile duct cancer with liver transplantation using a protocolized approach and strict selection criteria. Adjuvant therapy followed by liver transplantation may have a role in treatment of certain unresectable cases.
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Belleruth Naparstek (December 25, 1942, Boston, Massachusetts) is an American social worker, author, teacher and the producer of a guided imagery library of self-administered audio programs. She did her undergraduate and graduate work at University of Chicago in social work, and then worked in hospitals and clinics, then taught at Case Western Reserve University. She eventually developed guided imagery tapes, which have been used in some hospitals and clinics that have adopted alternative medicine practices as adjuvant therapies. Naparstek teaches Guided Imagery on the faculty of the University of Arizona Center for Integrative Medicine's post doctoral Fellowship Program.
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Low-dose IL-2 has been reported to reduce hepatitis C and B infection. IL-2 has been used in clinical trials for the treatment of chronic viral infections and as a booster (adjuvant) for vaccines. The use of large doses of IL-2 given every 6–8 weeks in HIV therapy, similar to its use in cancer therapy, was found to be ineffective in preventing progression to an AIDS diagnosis in two large clinical trials published in 2009. More recently low dose IL-2 has shown early success in modulating the immune system in disease like type 1 diabetes and vasculitis.
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A study of satralizumab as an adjuvant to immunosuppressant treatment for NMOSD included 76 adult participants; 52 were anti-AQP4 positive. Immunosuppressant treatment in combination with satralizumab reduced the rate of relapses in participants who were anti-AQP4 positive by four-fifths compared to immunosuppressant treatment alone. The U.S. Food and Drug Administration (FDA) approved satralizumab based on evidence from two clinical trials (Trial 1/ NCT02073279 and Trial 2/NCT02028884) of 116 participants with NMOSD who were anti-aquaporin-4 (AQP4) antibody positive. The trials were conducted at 62 sites in the Unites States, Canada, Europe and Asia.
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NeuVax is the E75 synthetic peptide initially isolated from HER2/neu proto-oncogene (being HER2/neu p366-379) combined with the immune adjuvant, granulocyte macrophage colony stimulating factor (rhGM-CSF from yeast). NeuVax in Phase II showed effectiveness in early-stage, node-positive breast cancer with low-to-intermediate HER-2 expression, where the five-year recurrence rate dropped from 26% to 6%. The vaccine is now in a Phase III study called PRESENT, short for (Prevention of Recurrence in Early-Stage Node- Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment (ClinicalTrials.gov identifier NCT01479244).
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CEO Garo Armen In October 2013, Agenus CEO Garo Armen issued a press release revealing that after an 18-month follow up on the RTS,S Malaria vaccine using QS21-Stimulon® is working well enough to support a regulatory filing in 2014. This is the first proof of the efficacy of Agenus's patented "QS-21 Stimulon" adjuvant In April 2014, Agenus inked a deal with Merck potentially worth $100 million. Under the terms of that deal, Agenus is using its proprietary Retrocyte Display technology to discover antibodies against a pair of undisclosed checkpoint targets for the treatment of cancer.
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It was historically used as a first-line treatment for hyperthyroidism, as the administration of pharmacologic amounts of iodine leads to temporary inhibition of iodine organification in the thyroid gland, a phenomenon called the Wolff–Chaikoff effect. However it is not used to treat certain autoimmune causes of thyroid disease as iodine-induced blockade of iodine organification may result in hypothyroidism. They are not considered as a first line therapy because of possible induction of resistant hyperthyroidism but may be considered as an adjuvant therapy when used together with other hyperthyroidism medications. Lugol's iodine has been used traditionally to replenish iodine deficiency.
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In patients whose cancer expresses an over-abundance of the HER2 protein, a monoclonal antibody known as trastuzumab (Herceptin) is used to block the activity of the HER2 protein in breast cancer cells, slowing their growth. In the advanced cancer setting, trastuzumab use in combination with chemotherapy can both delay cancer growth as well as improve the recipient's survival. Pertuzumab may work synergistically with trastuzumab on the expanded EGFR family of receptors, although it is currently only standard of care for metastatic disease. Neratinib has been approved by the FDA for extended adjuvant treatment of early stage HER2-positive breast cancer.
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Despite the risk of metastatic spread, there has been little research on the utility of sentinel lymph node biopsy (SLNB). Since periocular tumor have a higher rate of regional metastasis, SLNB is suggested for all ocular SGc tumors greater than 10mm in diameter. Treatment for nodal metastasis confirmed via SLNB involves advanced imaging studies [CT with or without PET scan], followed by removal of the primary tumor and regional lymph nodes, with adjuvant radiotherapy. However, it is important to note there has been no evidence of decreased mortality in those who had SLNB identified lymph node involvement.
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Reg family members such as REG1A and REG1B are associated with various diseases such as diabetes and gastrointestinal cancer. Reg expression has been associated with islet regeneration in pancreas that may be important for islet transplantation and for diabetes therapy and for cancer studies. The mouse Reg1, Reg2, and Reg3δ, expressed by β-cells and acinar cells respectively, have been shown to be linked with pancreatic β-cell regeneration in the mouse by activating cyclin D1 and promoting β-cell cycle progression. Reg2 is substantially up-regulated in the pancreatic islets, particularly in the β-cells following mycobacterial adjuvant treatment.
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The disease free survival is usually used to analyze the results of the treatment for the localized disease which renders the patient apparently disease free, such as surgery or surgery plus adjuvant therapy. In the disease-free survival, the event is relapse rather than death. The people who relapse are still surviving but they are no longer disease-free. Just as in the survival curves not all patients die, in "disease-free survival curves" not all patients relapse and the curve may have a final plateau representing the patients who didn't relapse after the study's maximum follow-up.
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The RTS,S vaccine was engineered using genes from the repeat and T-cell epitope in the pre-erythrocytic circumsporozoite protein (CSP) of the Plasmodium falciparum malaria parasite and a viral envelope protein of the hepatitis B virus (HBsAg), to which was added a chemical adjuvant (AS01) to increase the immune system response. Infection is prevented by inducing humoral and cellular immunity, with high antibody titers, that block the parasite from infecting the liver. The T-cell epitope of CSP is O-fucosylated in Plasmodium falciparum and Plasmodium vivax, while the RTS,S vaccine produced in yeast is not.
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When breast cancer is surgically excised, it can come back (local recurrence) in the remaining breast or on the chest wall in a small proportion of women. Adjuvant radiotherapy is necessary if breast cancer is treated by removing only the cancerous lump with a rim of surrounding normal tissue, as it reduces the chance of local recurrence significantly. When cancer does come back, it most commonly occurs in the tissues surrounding the original cancer (the tumour bed), even though there are multicentric cancers in remote areas of the breast. This suggests that it is most important to treat the tumour bed.
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The inner bark of Quillaja saponaria can be reduced to powder and employed as a substitute for soap, since it forms a lather with water, owing to the presence of a glycoside saponin, sometimes distinguished as quillaia saponin. It's also applied as an agricultural spray adjuvant. The same, or a closely similar substance, is found in soapwort (Saponaria officinalis), in senega root (Polygala senega) and in sarsaparilla; it appears to be chemically related to digitonin, which occurs in digitalis. The wood is used in cabinetry, and scents derived from the tree are used in perfumes and cosmetics.
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In the European sub-group, ejection fraction and NYHA classification improved significantly, and both all-cause and cardiovascular mortality decreased significantly. The researchers concluded that the evidence from the European sub-group analysis re-affirms the evidence of the therapeutic efficacy of the CoQ10 adjuvant therapy despite the greater adherence to guideline-directed therapy in the European sub-group than in the entire group of chronic heart failure patients. The European sub- group study provides confirmatory evidence that the treatment with 300 mg/day of Coenzyme Q10 in additional to conventional heart failure therapy is safe, well tolerated, and effective in improving the symptoms and survival of chronic heart failure patients.
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LY-2140023 is the first drug acting on mGlu receptors that has been studied in humans for the treatment of schizophrenia. It has been proposed as useful treatment of both positive and negative symptoms by acting as a selective agonist at mGlu receptors and modulating glutamatergic neurotransmission. It is suspected that LY-2140023 may balance and normalize dysregulated and hyperactive cortical pyramidal neurons in regions associated with schizophrenia and psychosis such as the thalamus, prefrontal cortex, and limbic system. Clinical trials using LY-2140023 have investigated its use as a therapy when administered alone and as an adjuvant therapy used in addition to atypical antipsychotics.
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Genocea has announced it would shift their strategic efforts to cancer vaccines while at the same time heavily cutting down on research and development of GEN-003 vaccine against genital herpes. Being unable to secure funding or partnering with another company, Genocea's further vaccine development remains to be determined. Vical had been awarded grant funding from the National Institute of Allergy and Infectious Diseases division of the NIH to develop a plasmid DNA-based vaccine to inhibit recurring lesions in patients latently infected with herpes simplex virus type 2 (HSV-2). The plasmid DNA encoding the HSV-2 antigens was formulated with Vaxfectin, Vical's proprietary cationic lipid adjuvant.
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This means that acyclovir cannot be used to cure the virus infection and infected birds will remain infected and become a carrier throughout its lifetime. An autogenous, formalin-inactivated vaccine, with an adjuvant of aluminium, hydroxide gel, has similarly been used in an outbreak, in 1999, to successfully protect psittacine birds from Pacheco’s disease. This vaccine was used to stop the rapid spread of the virus and helped maintain morbidity and mortality rates in psittacine birds within the zoo. By injecting this in the birds, it effectively contained the outbreak, where no herpesvirus was isolated from faecal samples of the many psittacine birds after the outbreak occurred.
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Malignant OGCTs are predominantly unilateral and chemosensitive, which means they are localized in only one side of the ovary. Fertility-preserving surgery is primarily standardized to keep the contralateral ovary and fallopian tube intact, also known as unilateral salpingo-oophorectomy. For Stage II patients with observable metastasis, cytoreductive surgery may be performed to debulk the volume of the tumor, such as hysterectomy (removal of all or part of the uterus) and bilateral salpingo-oophorectomy. A surgical incision at the abdominal cavity after the completion of adjuvant chemotherapy, called second look laparotomy, is best applicable for patients reported with teratomatous elements after previous cytoreductive surgery.
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Some methods that have been attempted include the use of two vaccines, one directed at generating a blood response and the other a liver-stage response. These two vaccines could then be injected into two different sites, thus enabling the use of a more specific and potentially efficacious delivery system. To increase, accelerate or modify the development of an immune response to a vaccine candidate it is often necessary to combine the antigenic substance to be delivered with an adjuvant or specialised delivery system. These terms are often used interchangeably in relation to vaccine development; however in most cases a distinction can be made.
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In 2007, Baum received the St Gallen lifetime achievement award for the treatment of breast cancer. Baum's team was the first to demonstrate the effectiveness of adjuvant tamoxifen for early breast cancer, which has contributed to the 30 per cent reduction in breast cancer mortality and its efficacy in the prevention of breast cancer in susceptible women. Since then, while at UCL, he was responsible for the largest-ever international cancer trial (ATAC - Arimidex, Tamoxifen, Alone or in Combination), which in record time showed anastrozole to be better than tamoxifen. Baum was active in the successful campaign to retain the Royal Marsden's site at Fulham in central London.
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Studies like these resulted in the recommendation to use chemotherapy for grade 2 and 3 tumors. Currently, the use of multi agent chemotherapy for adult patients with ovarian immature teratoma is standard of care except for grade 1, stage I tumors. There is considerable experience with a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) given in an adjuvant setting; however, combinations containing cisplatin, etoposide, and bleomycin (BEP) are now preferred because of a lower relapse rate and shorter treatment time. While a prospective comparison of VAC versus BEP has not been performed, in well-staged patients with completely resected tumors, relapse is essentially unheard of following platinum-based chemotherapy.
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In 2015, it was in clinical trials as an immunotherapy for several types of solid tumors. It was under investigation by Genentech/Roche. In April 2016, Roche announced that atezolizumab had been granted fast track status for lung cancer by the U.S. Food and Drug Administration (FDA). In May 2016, atezolizumab was approved by the FDA for the treatment of people with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within twelve months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In May 2017, atezolizumab failed a phase III trial for second line bladder cancer.
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An adjuvant (from Latin, "adjuvare", meaning "to help") is a pharmacological or immunological agent that improves the immune response of a vaccine. Adjuvants may be added to a vaccine to boost the immune response to produce more antibodies and longer-lasting immunity, thus minimizing the dose of antigen needed. Adjuvants may also be used to enhance the efficacy of a vaccine by helping to modify the immune response to particular types of immune system cells: for example, by activating T cells instead of antibody-secreting B cells depending on the purpose of the vaccine. Adjuvants are also used in the production of antibodies from immunized animals.
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Evidence from longitudinal, cross-sectional, and prospective cohort studies suggests an association between SSRI usage at therapeutic doses and a decrease in bone mineral density, as well as increased fracture risk, a relationship that appears to persist even with adjuvant bisphosphonate therapy. However, because the relationship between SSRIs and fractures is based on observational data as opposed to prospective trials, the phenomenon is not definitively causal. There also appears to be an increase in fracture-inducing falls with SSRI use, suggesting the need for increased attention to fall risk in elderly patients using the medication. The loss of bone density does not appear to occur in younger patients taking SSRIs.
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Chemotherapy (typically utilising the chemotherapeutic agent Mitomycin C) may be infused directly into the abdominal cavity after cytoreductive surgery (curgery removing all visible disease to kill remaining microscopic cancerous tumors and free floating cells. The heated chemotherapy (HIPEC) is perfused throughout the abdominal cavity for an hour or two as the last step in the surgery, or ports are installed to allow circulation and/or drainage of the chemicals for one to five days after surgery, known as early postoperative intraperitoneal chemotherapy (EPIC). EPIC may be given in multiple cycles for several months after surgery. Systemic chemotherapy may be administered as additional or adjuvant treatment.
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While any cancer patient may experience temporary cognitive impairment while undergoing chemotherapy, patients with PCCI continue to experience these symptoms long after chemotherapy has been completed. PCCI is often seen in patients treated for breast cancer, ovarian cancer, prostate cancer, and other reproductive cancers, as well as other types of cancers requiring aggressive treatment with chemotherapy. The clinical relevance of PCCI is significant, considering the increasing number of long-term cancer survivors in the population, many of whom may have been treated with aggressive dosing of chemotherapeutic agents, or with chemotherapy as an adjuvant to other forms of treatment. In some patients, fear of PCCI can impact treatment decisions.
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While herbal remedies are commonly used, a 2016 review found the herbs studied to be no better than placebo. Saw palmetto extract from Serenoa repens, while one of the most commonly used, is no better than placebo in both symptom relief and decreasing prostate size. Other ineffective herbal medicines include beta-sitosterol from Hypoxis rooperi (African star grass), pygeum (extracted from the bark of Prunus africana), pumpkin seeds (Cucurbita pepo) and stinging nettle (Urtica dioica) root. A systematic review of Chinese herbal medicines found that Chinese herbal medicine, either as monotherapy or an adjuvant therapy with Western medicine, was similar to either placebo or Western medicine in the treatment of BPH.
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Neratinib is used as an adjuvant therapy in people with: \- early stage breast cancer in which HER2 is overexpressed, after the person receives treatment with trastuzumab. For label updates see, FDA index page for NDA 208051 \- metastatic HER2-positive breast cancer after 2 or more lines of anti-HER2 therapy (the NALA trial). People should be given drugs to prevent diarrhea (for at least first 56 days) when they are given neratinib. Women who are pregnant should not take it, and women should not become pregnant while taking it, and women who are breast-feeding should not use it, as it causes fetal harm.
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Briefly, they cloned the pertussis toxin, mapped the antigenic epitopes using antibodies from individuals, who had the disease and or were vaccinated with the old whole-cell vaccine, and attached these antigenic peptides onto the diphtheria toxin as a carrier and adjuvant in one. This model is now used to produce other safe acellular vaccines. They also showed that 'toxoidation' of whole bacteria with formaldehyde — the method all manufacturers used to produce the highly neurotoxic pertussis vaccine — did not work on Bordetella pertussis because there are no free amino groups on the toxin of over 200 amino acids. This is both surprising and unlikely, but obviously can happen.
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Its mission is to promote and support basic, translational and clinical studies of the skin in normal and disease states, leading to PDCTC for rheumatic and related diseases. Research is managed under two main areas: Arthritis and Rheumatic Diseases—advance clinical biomedical and biopsychosocial PDCTC research for arthritis and rheumatic diseases. This includes work that advances the understanding of the natural history of these disorders, as well as mechanisms of disease susceptibility and development. The programs support research in rheumatoid arthritis; adjuvant and chemically induced inflammatory arthritis; systemic lupus erythematosus; systemic scleroderma; spondyloarthropathies; dermatomyositis and myositis; vasculitis; fibromyalgia; juvenile arthritis and general autoimmunity; gout; Lyme disease; and infection-related arthritis.
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Lamotrigine is considered a first-line drug for primary generalized tonic-clonic seizures (includes simple partial, complex partial, and secondarily generalized seizures such as focal-onset tonic-clonic seizures). It is also used as an alternative or adjuvant medication for partial seizures, such as absence seizure, myoclonic seizure, and atonic seizures. A 2020 review on the use of Lamotrigine as an add-on therapy for drug resistant generalized tonic-clonic seizures was unable to come to conclusions to inform clinical practice. Although low-certainty evidence suggest that it reduces generalized tonic-clonic seizures by 50% the level of uncertainty indicates that the actual findings could be significantly different.
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The first paper reporting on results of the study was published in 1992, whereupon it generated considerable debate in the scientific community. In February 2014, the BMJ published more results from the study after following up on the participants for twenty-five years, with the authors concluding that "annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available." The study also reported substantial overdiagnosis among women who had been screened, which the authors stated accounted for about 22% of the cancers detected by screening.
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In May 2016, the FDA approved nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) who have relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin. On 20 December 2017, the FDA granted approval to nivolumab for adjuvant treatment of melanoma with involvement of lymph nodes or for metastatic disease with complete resection. On 16 April 2018, the FDA granted approval to nivolumab in combination with ipilimumab for the first- line treatment of intermediate and poor risk advanced renal cell carcinoma patients. On 15 June 2018, China's Drug Administration approved nivolumab, the country's first immuno-oncology and the first PD-1 therapy.
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The Phase I study consists of introducing the vaccine candidate to assess its safety in healthy people. A vaccine Phase I trial involves normal healthy subjects, each tested with either the candidate vaccine or a "control" treatment, typically a placebo or an adjuvant-containing cocktail, or an established vaccine (which might be intended to protect against a different pathogen). The primary observation is for detection of safety (absence of an adverse event) and evidence of an immune response. After the administration of the vaccine or placebo, the researchers collect data on antibody production, on health outcomes (such as illness due to the targeted infection or to another infection).
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In animal studies, a useful immune response was induced and was found to be enhanced ten to a hundred-fold by the company's "Matrix-M" immunologic adjuvant. A study of the response of non-human primate to the vaccine had been initiated. , Novavax had completed two primate studies on baboons and macaques and had initiated a Phase I clinical trial in Australia. The Lipid nanoparticle (LNP)-encapsulated siRNAs rapidly adapted to target the Makona outbreak strain of EBOV and are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at three days post-exposure while animals were viremic and clinically ill.
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Modifying ricin may sufficiently lessen the likelihood that the ricin component of these immunotoxins will cause the wrong cells to internalize it, while still retaining its cell-killing activity when it is internalized by the targeted cells. However, bacterial toxins, such as diphtheria toxin, which is used in denileukin diftitox, an FDA-approved treatment for leukemia and lymphoma, have proven to be more practical. A promising approach for ricin is to use the non- toxic B subunit (a lectin) as a vehicle for delivering antigens into cells, thus greatly increasing their immunogenicity. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines.
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This viral protein not only confers structural stability and homogeneity to virosome-based formulations, but it significantly contributes to the immunological properties of virosomes, which are clearly distinct from other liposomal and proteoliposomal carrier systems. It has been shown that a physical association between the virosome and the antigen of interest is necessary for the full adjuvant effect of virosomes. Such physical association can be achieved by a variety of methods, depending on the properties of the antigen. Antigens can be incorporated into virosomes, adsorbed to the virosome surface, or integrated into the lipid membrane, either via hydrophobic domains or lipid moieties cross-linked to the antigen.
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Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as amitriptyline) and newer antidepressants (such as duloxetine) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using hydroxyzine, promethazine, carisoprodol, or tripelennamine to increase the pain-killing ability of a given dose of opioid analgesic. Adjuvant analgesics, also called atypical analgesics, include orphenadrine, mexiletine, pregabalin, gabapentin, cyclobenzaprine, hyoscine (scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions.
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Tamoxifen treatment is also useful in the treatment of bone density and blood lipids in postmenopausal women. Adverse effects include hot flushes and more serious is two to three times higher relative risk of developing endometrial cancer compared to women of an age-matched population. Toremifene, a chlorinated tamoxifen derivative, causes fewer DNA adducts in liver than seen with tamoxifen in preclinical studies and was developed to avoid hepatic carcinomas. It is used as endocrine therapy in women with ER/PR-positive stage 4 or recurrent metastatic breast cancer and has demonstrated similar efficacy compared to tamoxifen as adjuvant treatment of breast cancer and in the treatment of metastatic breast cancer.
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In April 1981, Giuliani's father died at age 73 of prostate cancer at Memorial Sloan–Kettering Cancer Center. Nineteen years later in April 2000, Giuliani was 55 when diagnosed with prostate cancer on prostate biopsy after an elevated screening PSA. Giuliani chose a combination prostate cancer treatment consisting of four months of neoadjuvant Lupron hormonal therapy, then low dose-rate prostate brachytherapy with permanent implantation of ninety TheraSeed radioactive palladium-103 seeds in his prostate in September 2000, followed two months later by five weeks of fifteen-minute, five-days-a-week external beam radiotherapy at Mount Sinai Medical Center, with five months of adjuvant Lupron hormonal therapy.
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In November 2012, findings from a Phase III trials of an experimental malaria vaccine known as RTS,S reported that it provided modest protection against both clinical and severe malaria in young infants. The efficacy was about 30% in infants 6 to 12 weeks of age and about 50% in infants 5 to 17 months of age in the first year of the trial. The RTS,S vaccine was engineered using a fusion hepatitis B surface protein containing epitopes of the outer protein of Plasmodium falciparum malaria sporozite, which is produced in yeast cells. It also contains a chemical adjuvant to boost the immune system response.
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Advaxis Inc. is an American company devoted to the discovery, development and commercialization of immunotherapies based on a technology platform which uses engineered Listeria monocytogenes (aka Lm). The company is headquartered in Princeton, New Jersey and was incorporated in Delaware in 2006. The Lm-based platform on which the company's products are based involves the use of attenuated Lm which secrete antigen/adjuvant fusion proteins and stimulate a patient's immune system (specifically their T cells) to mount an immune response to the secreted antigen; if the antigen is specifically found on cancerous cells, then the result aims to be an effective immune response targeting and eliminating the cancer.
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In recent studies, human DNA ligase I was used in Computer-aided drug design to identify DNA ligase inhibitors as possible therapeutic agents to treat cancer. Since excessive cell growth is a hallmark of cancer development, targeted chemotherapy that disrupts the functioning of DNA ligase can impede adjuvant cancer forms. Furthermore, it has been shown that DNA ligases can be broadly divided into two categories, namely, ATP- and NAD+-dependent. Previous research has shown that although NAD+-dependent DNA ligases have been discovered in sporadic cellular or viral niches outside the bacterial domain of life, there is no instance in which a NAD+-dependent ligase is present in a eukaryotic organism.
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The efficacy of dendritic cell vaccines may be limited due to difficulty in getting the cells to migrate to lymph nodes and interact with T-cells. Peptide-based vaccines usually consist of cancer specific-epitopes and often require an adjuvant (for example, GM-CSF) to stimulate the immune system and enhance antigenicity. Examples of these epitopes include Her2 peptides, such as GP2 and NeuVax. However, this approach requires MHC profiling of the patient because of MHC restriction. The need for MHC profile selection can be overcome by using longer peptides (“synthetic long peptides”) or purified protein, which are then processed into epitopes by APCs.
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VAS was first recognized at the University of Pennsylvania School of Veterinary Medicine in 1991. An association between highly aggressive fibrosarcomas and typical vaccine location (between the shoulder blades) was made. Two possible factors for the increase of VAS at this time were the introduction in 1985 of vaccines for rabies and feline leukemia virus (FeLV) that contained aluminum adjuvant, and a law in 1987 requiring rabies vaccination in cats in Pennsylvania. In 1993, a causal relationship between VAS and administration of aluminum adjuvanted rabies and FeLV vaccines was established through epidemiologic methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem.
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CYP27A1 converts cholesterol into 27-hydroxycholesterol, an oxysterol that has multiple biological functions including direct, tissue-specific activation of the (it has been characterized as a selective estrogen receptor modulator) and the liver X receptor. 27-Hydroxycholesterol has been found to increase -positive breast cancer cell growth via its estrogenic action, and hence, it has been proposed that bicalutamide and other CYP27A1 inhibitors may be effective as adjuvant therapies to aromatase inhibitors in the treatment of -positive breast cancer. In addition to CYP27A1, bicalutamide has been found to bind to and inhibit CYP46A1 (cholesterol 24-hydroxylase) in vitro, but this has yet to be assessed and confirmed in vivo.
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A cornerstone of surgical treatment of early stage lung cancer is aggressive removal of lymph nodes from the mediastinum; this enhances the likelihood of removing all cancer cells (complete resection) and identifies patients who will require additional treatment (i.e. adjuvant chemotherapy). An important consideration when performing anatomic lung resection is to spare as much lung tissue as possible; while lobectomy and pneumonectomy are equivalent cancer operations, the risk of complications and morbidity is considerably less with lobectomy. Traditionally, pulmonary lobectomy is performed through a poster- lateral thoracotomy incision; over decades, thoracotomy has demonstrated its effectiveness in providing access to structures in the thorax and is in general tolerated by patients.
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Stefán Karl announced in October 2016 that he had been diagnosed with bile duct cancer; a GoFundMe campaign was subsequently created by LazyTown head writer Mark Valenti to pay his living costs when he became too ill to work. The campaign was popularized by various YouTube users uploading parodies of Stefán Karl's work, and linking to the GoFundMe page, which led to the songs "We Are Number One" and "The Mine Song" from LazyTown becoming Internet memes. In August 2017, Stefán Karl stated he was in remission. He clarified on his GoFundMe campaign that while his metastases had been removed after successful liver surgery in June 2017, he still had the disease and had refused further adjuvant therapy.
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The company’s lead candidate, HspE7, is a novel therapeutic vaccine intended for the treatment of HPV-related diseases. HspE7 is derived from Nventa’s patented CoVal fusion platform that uses recombinant DNA technology to covalently fuse heat shock proteins to target antigens, thereby stimulating cellular immune system responses to specific diseases. Nventa is developing HspE7 in combination with the Toll-like receptor 3 (TLR3) agonist adjuvant Poly-ICLC for multiple indications, including Cervical Intraepithelial Neoplasia (also known as cervical dysplasia or CIN), genital warts, cervical cancer, and head and neck cancers. According to the annual information form, for the year ending December 31, 2009, provided on Akela Pharma's website, scientific research funding has ceased for HspE7.
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Because LCLC-RP is so rare, no clinical trials have ever been conducted that specifically address treatment of this lung cancer variant. Because LCLC-RP is considered a form of non-small cell lung carcinoma (NSCLC), most physicians adhere to published NSCLC treatment guidelines in rhabdoid carcinoma cases. When possible, radical surgical resection with curative intent is the primary treatment of choice in early stage NSCLC's, and can be administered with or without adjuvant, neoadjuvant, or palliative chemotherapy and/or radiotherapy, depending on the disease stage and performance status of the individual patient. In numerous clinical trials conducted in NSCLC, several different platinum-based chemotherapy regimens have been shown to be more-or-less equally effective.
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While both groups of patients in the trial deteriorated at equal rates, patients in the Livingston-treated group were reported to have had a "poorer quality of life" at the start of the trial. The study's lead investigator, Barrie Cassileth, acknowledged that "the University of Pennsylvania patients had a significantly better quality of life at all times, including enrollment" and that, quality of life "was different at base line", with Livingston's patients rated worse. Patients in both treatment arms also received conventional therapies in addition to Livingston's therapy. Livingston's patients also received BCG during the trial ---an FDA-approved cancer adjuvant which has been found effective for several cancers, including those of the bladder and colon.
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The "double scalpel" peripheral margin controlled excision method approximates the Mohs method in margin control, but requires a pathologist intimately familiar with the complexity of managing the vertical margin on the thin peripheral sections and staining methods. Some melanocytic nevi, and melanoma-in-situ (lentigo maligna) have resolved with an experimental treatment, imiquimod (Aldara) topical cream, an immune enhancing agent. Some dermasurgeons are combining the 2 methods: surgically excising the cancer and then treating the area with Aldara cream postoperatively for three months. While some studies have suggested the adjuvant use of topical tazarotene, the current evidence is insufficient to recommend it and suggests that it increases topical inflammation, leading to lower patient compliance.
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The receptor status of breast cancers has traditionally been identified by immunohistochemistry (IHC), which stains the cells based on the presence of estrogen receptors (ER), progesterone receptors (PR) and HER2. This remains the most common method of testing for receptor status, but DNA multi-gene expression profiles can categorize breast cancers into molecular subtypes that generally correspond to IHC receptor status; one commercial source is the BluePrint test, as discussed in the following section. Receptor status is a critical assessment for all breast cancers as it determines the suitability of using targeted treatments such as tamoxifen and or trastuzumab. These treatments are now some of the most effective adjuvant treatments of breast cancer.
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Macrophagic myofasciitis (MMF) is a histopathological finding involving inflammatory microphage formations with aluminium-containing crystal inclusions and associated microscopic muscle necrosis in biopsy samples of the deltoid muscle. Based on the presence of aluminium and the common practice of administering vaccines into the deltoid, it has been proposed that the abnormalities are a result of immunisation with aluminium adjuvant-containing vaccines. The findings were observed in a minority of persons being evaluated for "diffuse myalgias, arthralgias or muscle weakness" who underwent deltoid muscle biopsies. The individuals had a history of receiving aluminium- containing vaccines, administered months to several years prior to observation of MMF histopathology, however this link is tenuous and unsustainable.
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Belzer's use of hydrocortisone as an adjuvant to preservation had been suggested by Lotke's work with dog kidney slices, in which hydrocortisone improved the ability of slices to excrete PAH and oxygen after 30 hour storage at 2-4 °C; Lotke suggested that hydrocortisone might be acting as a lysosomal membrane stabiliser in these experiments. The other components of Belzer's model were arrived at empirically. The insulin and magnesium were used partially in an attempt to induce artificial hibernation, as Suomalainen found this regime to be effective in inducing hibernation in natural hibernators. The magnesium was also provided as a metabolic inhibitor following Kamiyama's demonstration that it was an effective agent in dog heart preservation.
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RTS,S attempted to avoid these by fusing the protein with a surface antigen from hepatitis B, hence creating a more potent and immunogenic vaccine. When tested in trials an emulsion of oil in water and the added adjuvants of monophosphoryl A and QS21 (SBAS2), the vaccine gave protective immunity to 7 out of 8 volunteers when challenged with P. falciparum. RTS,S/AS01 (commercial name Mosquirix), was engineered using genes from the outer protein of P. falciparum malaria parasite and a portion of a hepatitis B virus plus a chemical adjuvant to boost the immune response. Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver.
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But many HPV+OPC present with involvement of the lymph nodes in the neck, and hence a higher stage of disease, generally referred to as locally advanced disease. This group is mostly treated with multimodality therapy, with the exception of one of the more favourable subgroups with small primary tumours and lymph node involvement confined to a single node no larger than 3 cm in size, which as noted are considered early stage disease. The three main options for locally advanced but operable disease are resection, neck dissection and adjuvant therapy; chemoradiation (with possible salvage surgery); induction chemotherapy followed by radiation or chemoradiation. However the last option has not been supported in clinical trials that tested it.
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A majority of breast cancers are hormone dependent and most of them express either estrogen receptor and/or progesterone receptor. That is the reason that compounds that inhibit biosynthesis of estrogen have been researched and are now the standard adjuvant therapy for breast cancer in postmenopausal women. It has been proven that breast cancer in postmenopausal women can be treated or prevented by modulating the estrogen receptors or its ligands and as aromatase is part of the final step in estrogen conversion it is a good target for medicine. Because aromatase catalyses the final step in estrogen conversion, inhibiting it does not have any effect on synthesis of other steroids except estrogen.
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One study conducted over 120 Lynch syndrome patients attributing Crohn's like reaction (CLR) associated with MSI to "tumor specific neopeptides generated during MSI-H carcinogenesis." This study further corroborated that the "presence of antimetastatic immune protection in MSI-H CRC patients may explain recent findings that adjuvant 5-FU chemotherapy has no beneficial or even adverse effects in this collective." The researchers assume that there is a protective role of lymphocytes against the MSI-H CRC that prevents tumor metastasis. MSI tumors in 15% of sporadic colorectal cancer result from the hypermethylation of the MLH 1 gene promoter, whereas MSI tumors in Lynch syndrome are caused by germline mutations in MLH 1, MSH 2, MSH 6, and PMS2.
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Started in 2010, Green Ghana Volunteers is a project involving the planting of Moringa Oleifera trees around the region. The tree is arguably one of the world's most useful trees, as almost every part of the moringa tree can be used for food or has some other beneficial property. In the tropics, it is used as forage for livestock, and in many countries, moringa micronutrient liquid, a natural anthelmintic (kills parasites) and adjuvant (to aid or enhance another drug) is used as a metabolic conditioner to aid against endemic diseases in developing countries. Leaves can be eaten fresh, cooked, or stored as dried powder for many months without refrigeration, and reportedly without loss of nutritional value.
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In addition to looking at genetics, Pritchard's research aims to better understand primary and secondary combination treatments, taking into account the patient's age and stage in life. Pritchard's clinical trials have yielded findings that have transformed breast cancer treatment approaches worldwide. Pritchard is published in numerous significant journals of oncology, including The New England Journal of Medicine, Journal of the National Cancer Institute, The Journal of Clinical Oncology, The Lancet, and The Lancet Oncology. One of Pritchard's self-proclaimed "eureka" moments was in a clinical trial concerning the use of the drug Letrozole as an adjuvant therapy in postmenopausal women who had taken tamoxifen for five years as a primary breast cancer treatment.
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Early trials showed a trend towards improved survival among vaccinated test subjects. A direct correlation between the level of antibodies that a vaccinated patient raises against EGF and survival has been observed in several trials, and in one of the largest trials there was also an age-dependence, with only subjects under the age of 60 benefiting in terms of survival. More antibodies are raised when the vaccine is formulated with Montanide ISA 51 rather than aluminum hydroxide as an adjuvant, and when patients receive a low dose of cyclophosphamide three days before vaccine administration. Cyclophosphamide is thought to temporarily block the body's natural immune tolerance to EGF, thereby increasing antibody titers.
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ImPACT is a proposed cancer vaccine based on live, genetically-modified, irradiated human cells which secrete a broad spectrum of cancer-associated antigens as well as an immune adjuvant called gp96. Potential advantages of this product are use as an 'allogeneic', that is, 'off-the-shelf' immunotherapy, and its applicability to a wide range of cancers. It is in phase II trials. ImPACT originated in the late 1990s in work done at the University of Miami which showed that gp96, a heat shock protein resident in the endoplasmic reticulum could be made immunogenic if part of gp96 was replaced with the Fc portion of an IgG1 antibody to engineer a secretory form of gp96.
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The dosing of methylene blue for treatment of ifosfamide neurotoxicity varies, depending upon its use simultaneously as an adjuvant in ifosfamide infusion, versus its use to reverse psychiatric symptoms that manifest after completion of an ifosfamide infusion. Reports suggest that methylene blue up to six doses a day have resulted in improvement of symptoms within 10 minutes to several days. Alternatively, it has been suggested that intravenous methylene blue every six hours for prophylaxis during ifosfamide treatment in people with history of ifosfamide neuropsychiatric toxicity. Prophylactic administration of methylene blue the day before initiation of ifosfamide, and three times daily during ifosfamide chemotherapy has been recommended to lower the occurrence of ifosfamide neurotoxicity.
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Epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence, often a result of environmental or dietary damage to the histone receptors within the cell. Current research has shown that epigenetic pharmaceuticals could be a putative replacement or adjuvant therapy for currently accepted treatment methods such as radiation and chemotherapy, or could enhance the effects of these current treatments. It has been shown that the epigenetic control of the proto-onco regions and the tumor suppressor sequences by conformational changes in histones directly affects the formation and progression of cancer. Epigenetics also has the factor of reversibility, a characteristic that other cancer treatments do not offer.
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Magnesium is absorbed with reasonable efficiency (30% to 40%) by the body from any soluble magnesium salt, such as the chloride or citrate. Magnesium is similarly absorbed from Epsom salts, although the sulfate in these salts adds to their laxative effect at higher doses. Magnesium absorption from the insoluble oxide and hydroxide salts (milk of magnesia) is erratic and of poorer efficiency, since it depends on the neutralization and solution of the salt by the acid of the stomach, which may not be (and usually is not) complete. Magnesium orotate may be used as adjuvant therapy in patients on optimal treatment for severe congestive heart failure, increasing survival rate and improving clinical symptoms and patient's quality of life.
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DAHANCA 9 (2000-06 , 71 pts) - Randomized study of hyperfractionated accelerated vs accelerated radiotherapy in node-negative head and neck carcinoma. DAHANCA 10 (2002-2006 , 522 pts) - Randomized study of the role of EPO in low-Hb patients DAHANCA 11 (2005 – never initiated) - Randomized study of treatment of unknown primary in the neck (Intergroup/EORTC). NCT00047125 DAHANCA 12 (1998-2001, 490 pts) – Retro/prospective evaluation of ipsilateral treatment of tonsillar carcinoma. DAHANCA 13 (2002-2005, 125 pts) - Study of PET in diagnosis of Head and Neck Cancer DAHANCA 14 (2003-2011, 102 pts) – Registration study of chemoradiotherapy in NPC DAHANCA 15 (2003-2004, 28 pts) - Phase I-II study of Zalutumumab (anti-EGFr) as adjuvant to radiotherapy.
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Light therapy has also been suggested in the treatment of non-seasonal depression and other psychiatric mood disturbances, including major depressive disorder, bipolar disorder and postpartum depression. A meta-analysis by the Cochrane Collaboration concluded that "for patients suffering from non-seasonal depression, light therapy offers modest though promising antidepressive efficacy." A 2008 systematic review concluded that "overall, bright light therapy is an excellent candidate for inclusion into the therapeutic inventory available for the treatment of nonseasonal depression today, as adjuvant therapy to antidepressant medication, or eventually as stand-alone treatment for specific subgroups of depressed patients." A 2015 review found that supporting evidence for light therapy was limited due to serious methodological flaws.
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In the United States, ado- trastuzumab emtansine was approved specifically for treatment of HER2-positive metastatic breast cancer (mBC) in patients who have been treated previously with trastuzumab and a taxane (paclitaxel or docetaxel), and who have already been treated for mBC or developed tumor recurrence within six months of adjuvant therapy. Approval was based on the EMILIA study, a phase III clinical trial that compared trastuzumab emtansine versus capecitabine (Xeloda) plus lapatinib (Tykerb) in 991 people with unresectable, locally advanced or metastatic HER2-positive breast cancer who had previously been treated with trastuzumab and taxane chemotherapy. This trial showed improved progression- free survival in patients treated with trastuzumab emtansine (median 9.6 vs. 6.4 months), along with improved overall survival (median 30.9 vs.
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Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti-CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS- mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell activated in vitro reduced IL-4 secretion, while maintaining similar IFN-g secretion. Similarly, CD4+ T cells purified from ICOS-/- mice immunized with the protein keyhole limpet hemocyanin (KLH) in alum or complete Freund's Adjuvant have attenuated IL-4 secretion, but similar IFN-g and IL-5 secretion when recalled with KLH.
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In clinical trials, the term reactogenicity refers to the property of a vaccine of being able to produce common, "expected" adverse reactions, especially excessive immunological responses and associated signs and symptoms, including fever and sore arm at injection site. (Much less frequently, the term has also been applied to therapeutic drug trials.) Other manifestations of reactogenicity typically identified in such trials include bruising, redness, induration, and swelling. The term reactogenicity was coined by the US Food and Drug Administration (FDA). Typically, reactogenicity is observed upon the administration of an adjuvant, which is a chemical additive intended for enhancing the recipient's immune response to the antigen that is present in a vaccine, but can also be observed in non-adjuvanted vaccines.
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A later-appearing metastasis within mediastinal lymph nodes in the same case also showed a durable response to a taxane alone. There have also been reports of rhabdoid carcinomas expressing vascular endothelial growth factor (VEGF), suggesting that targeted molecular therapy with VEGF blocking monoclonal antibodies such as bevacizumab may be active in these variants. However, evidence suggests that caution must be used when treating a cavitated rhabdoid tumor, one that contains significant components of squamous cell differentiation, or large tumors with containing major blood vessels, due to the potential high risk of life-threatening pulmonary hemorrhage. A recent study reported a case wherein 2 courses of adjuvant therapy with cisplatin and paclitaxel, followed by oral gefitinib, were used after complete resection.
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Sandra M. Swain is an American oncologist, breast cancer specialist and clinical translational researcher. She is currently a professor of Medicine at the Georgetown University School of Medicine and the Associate Dean for Research Development at Georgetown University Medical Center (GUMC) and MedStar Health as well as an adjunct professor of Medicine at the F. Edward Hébert School of Medicine of the Uniformed Services University of Health Sciences. She is also a past President of the American Society of Clinical Oncology (ASCO), serving from 2012 through 2013. The focus of Sandra's research includes clinical trials and translational research in metastatic and inflammatory breast cancer, adjuvant treatment of breast cancer, the treatments of metastatic HER2+ breast cancer, cardiotoxicity, as well as health care disparities.
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In December 2014, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved olaparib as monotherapy. The FDA approval is in germline BRCA mutated (gBRCAm) advanced ovarian cancer that has received three or more prior lines of chemotherapy. The EMA public assessment report, which utilized the same phase II trial data, made reference to both "high grade serous ovarian cancers" and to the use of olaparib "not later than 8 weeks after a course of platinum-based medicines, when the tumour was diminishing in size or had completely disappeared". In breast cancer, olaparib is approved for gBRCAm HER2-negative metastatic breast cancer patients who have previously been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting.
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Pharma Nord's coenzyme Q10 preparation is the official reference product for the International Coenzyme Q10 Association (ICQA).HomePage Pharma Nord actively supports scientific research into the health benefits of coenzyme Q10, primarily in relation to cardiology. Q-Symbio, a large multinational study investigating coenzyme Q10's potential as an adjuvant for treating chronic heart failure was published in the Journal of the American College of Cardiology, HEART FAILURE.The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure Results From Q-SYMBIO: A Randomized Double-Blind Trial The Q-Symbio study randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 (ubiquinone) or placebo and followed each patient for a period of two years.
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In the absence of high quality evidence comparing a primary surgical approach to other modalities, decisions are based on consideration of factors such as adequate surgical exposure and anatomically favourable features for adequate resection, post treatment function and quality of life. Such patient selection may enable them to avoid the morbidity of additional adjuvant treatment. In the absence of favourable surgical features the primary treatment of choice remains radiation with or without chemotherapy. Tumor characteristics which favour a non-surgical approach include invasion of the base of the tongue to the extent of requiring resection of 50% or more of the tongue, pterygoid muscle involvement, extension into the parapharyngeal fat abutting the carotid, involvement of the mandible or maxilla or invasion of the prevertebral space.
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Anatomical considerations may also dictate preference for surgical or non- surgical approaches. For instance trismus, a bulky tongue, limited extension of the neck, prominent teeth, torus mandibularis (a bony growth on the mandible) or limited width of the mandible would all be relative contraindications to surgery. Tumour related considerations include invasion of the mandible, base of skull and extensive involvement of the larynx or more than half of the base of tongue. Technical considerations in offering surgery as a primary modality include the presumed ability to achieve adequate margins in the resected specimen and the degree of resulting defect, since close or positive margins are likely to result in subsequent adjuvant therapy to achieve disease control, with resultant increased morbidity.
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Carboplatin-doublet therapy can be combined with paclitaxel for increased efficacy in some cases. Another potential adjuvant therapy for platinum-sensitive recurrences is olaparib, which may improve progression-free survival but has not been shown to improve overall survival. (Olaparib, a PARP inhibitor, was approved by the US FDA for use in BRCA-associated ovarian cancer that had previously been treated with chemotherapy.) For recurrent germ cell tumors, an additional 4 cycles of BEP chemotherapy is the first-line treatment for those tho have been treated with surgery or platins. If the tumor is determined to be platinum-resistant, vincristine, dactinomycin, and cyclophosphamide (VAC) or some combination of paclitaxel, gemcitabine, and oxaliplatin may be used as a second-line therapy.
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A 2010 study concluded that extracts of P. pulmonarius may slow the proliferation of cancer cells with high galectin-3 levels, while at the same time downregulate tumour cell adherence - which is directly related to the progression and spread of cancer. Extracts of P. pulmonarius added to the diet of mice delayed carcinogenesis, suggesting that these extracts may be useful as an adjuvant to cancer therapies. An orally administered hot water extract of P. pulmonarius had a significant antihyperglycemic effect, halted the progression of diabetes, and reduced the mortality of alloxan induced diabetic mice by approximately 50%. It showed a synergistic effect with the antidiabetic drug glibenclamide, supporting the possibility of effective combination therapy of glibenclamide and P. pulmonarius for diabetes.
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However, a large meta-analysis has shown that in individuals with associated risk factors for testicular germ cell tumor, the increase in risk of concurrent diagnosis of testicular germ cell tumor, or testicular carcinoma- in-situ upon biopsy is approximately eight to ten-fold. There is extensive controversy over whether testicular microlithiasis in individuals with testicular germ cell tumor, or risk factors for such, should undergo testicular biopsy to exclude the presence of testicular carcinoma-in-situ, also known as intratubular germ cell neoplasia of unclassified type. Additionally, whether the presence of testicular microlithiasis should influence decision for adjuvant chemotherapy or surveillance in individuals with testicular germ cell tumor remains unclear. A recent review in Nature Reviews Urology has comprehensively evaluated these topics.
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A recent study was carried out with 1,264 patients with stage III colon cancer. The patients were treated with a postoperative weekly adjuvant bolus of 5-fluorouracil/leucovorin (FU/LV) or else with irinotecan+FU/LV and were followed up for 8 years. Eleven percent of the tumors were deficient for DNA repair enzyme MRE11 due to a deletion of a string of thymidines in the DNA sequence of the MRE11 gene. The addition of irinotecan to FU/LV in the treatment protocol resulted in MRE11-deficient patients having better long- term disease free survival than patients with wild-type MRE11 (though the effect was small), indicating some degree of synthetic lethality between irinotecan-induced TOP1 inactivation and MRE11 deficiency.
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SERMs are used for various estrogen-related diseases, including treatment of ovulatory dysfunction in the management of infertility, treatment and prevention of postmenopausal osteoporosis, treatment and reduction in risk of breast cancer and treatment of dyspareunia due to menopause. SERM is also used in combination with conjugated estrogens indicated for the treatment of estrogen deficiency symptoms, and vasomotor symptoms associated with menopause. SERMs are used dependent on their pattern of action in various tissues: Figure 2: Nolvadex (tamoxifen) 20-milligram tablets (UK) Tamoxifen is a first-line hormonal treatment of ER-positive metastatic breast cancer. It is used for breast cancer risk reduction in women at high risk, and as adjuvant treatment of axillary node-negative and node-positive, ductal carcinoma in situ.
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Advances in the understanding of the natural course of breast cancer as well as the development of systemic therapies allowed for the use of breast-conserving surgeries, however, the nomenclature of viewing non-surgical management from the viewpoint of the definitive surgery lends to two adjectives connected with treatment timelines: adjuvant (after surgery) and neoadjuvant (before surgery). The mainstay of breast cancer management is surgery for the local and regional tumor, followed (or preceded) by a combination of chemotherapy, radiotherapy, endocrine (hormone) therapy, and targeted therapy. Research is ongoing for the use of immunotherapy in breast cancer management. Management of breast cancer is undertaken by a multidisciplinary team, including medical-, radiation-, and surgical- oncologists, and is guided by national and international guidelines.
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In addition to identifying genes that correlate to survival, microarray analyses have been utilized to establish gene expression profiles associated with prognosis. It is agreed upon that patients with tumors exhibiting poor prognostic features would benefit the most from adjuvant therapy as these treatments substantially improve overall survival for women with breast cancer. Traditional prognostic factors, however, are inexact as mentioned above. Researchers at the Netherlands Cancer Institute were able to identify "good-prognosis" and "bad-prognosis" signatures based on the expression of 70 genes that was better able to predict the likelihood of metastasis development within five years for breast cancer patients Metastasis involves the spread of cancer from one organ to others throughout the body and is the principal cause of death in cancer patients.
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Both mastectomy and lumpectomy are referred to as "local therapies" for breast cancer, targeting the area of the tumor, as opposed to systemic therapies, such as chemotherapy, hormonal therapy, or immunotherapy. Traditionally, in the case of breast cancer, the whole breast was removed. Currently, the decision to do the mastectomy is based on various factors, including breast size, the number of lesions, biologic aggressiveness of a breast cancer, the availability of adjuvant radiation, and the willingness of the patient to accept higher rates of tumor recurrences after lumpectomy and radiation. Outcome studies comparing mastectomy to lumpectomy with radiation have suggested that routine radical mastectomy surgeries will not always prevent later distant secondary tumors arising from micro-metastases prior to discovery, diagnosis, and operation.
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The American Cancer Society reported that "[t]here is no reliable scientific evidence that Gerson therapy is effective in treating cancer, and the principles behind it are not widely accepted by the medical community. It is not approved for use in the United States." In 1947, the National Cancer Institute reviewed 10 claimed cures submitted by Gerson; however, all of the patients were receiving standard anticancer treatment simultaneously, making it impossible to determine what effect, if any, was due to Gerson's therapy. A review of the Gerson Therapy by Memorial Sloan-Kettering Cancer Center concluded: "If proponents of such therapies wish them to be evaluated scientifically and considered valid adjuvant treatments, they must provide extensive records (more than simple survival rates) and conduct controlled, prospective studies as evidence".
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When the patient is unsatisfied with the outcome of the augmentation mammoplasty; or when technical or medical complications occur; or because of the breast implants’ limited product life, it is likely she might require replacing the breast implants. Common revision surgery indications include major and minor medical complications, capsular contracture, shell rupture, and device deflation. Revision incidence rates were greater for breast reconstruction patients, because of the post-mastectomy changes to the soft-tissues and to the skin envelope of the breast, and to the anatomical borders of the breast, especially in women who received adjuvant external radiation therapy. Moreover, besides breast reconstruction, breast cancer patients usually undergo revision surgery of the nipple-areola complex (NAC), and symmetry procedures upon the opposite breast, to create a bust of natural appearance, size, form, and feel.
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In June 2013, Novavax acquired the Matrix-M adjuvant platform with the purchase of Swedish company Isconova AB and renamed its new subsidiary Novavax AB. In 2015 the company received an $89 million grant from the Bill & Melinda Gates Foundation to support the development of a vaccine against human respiratory syncytial virus for infants via maternal immunization. In March 2015 the company completed a Phase I trial for its Ebola vaccine candidate, as well as a phase II study in adults for its RSV vaccine, which would become ResVax. The ResVax trial was encouraging as it showed significant efficacy against RSV infection. 2016 saw the company's first phase III trial, the 12,000 adult Resolve trial, for its respiratory syncytial virus vaccine, which would come to be known as ResVax, fail in September.
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HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV. 350px The candidate is being developed with a Toll-like receptor 3 (TLR3) agonist adjuvant for multiple indications, including cervical intraepithelial neoplasia (also known as cervical dysplasia or CIN), genital warts, cervical cancer, and head and neck cancers.
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Herberman won numerous awards for his contributions to medicine, including the Governor of Pennsylvania’s Award for Excellence in Science and Medicine, the Lifetime Science Award from the Institute for Advanced Studies in Immunology and Aging, the Award Excellence in Biomedical Research, and the Solomon A. Berson Medical Alumni Achievement Award in Clinical Science from New York University. Herberman served on the Board of Directors of the American Association for Cancer Research. He has also served as interim chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP) from 1994 to 1995, president of the American Association of Cancer Institutes, and president of the Society for Biological Therapy and the Society for Natural Immunity. He was the first recipient of an endowed chair in oncology from the Hillman Foundation.
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FCA is known to stimulate production of tumor necrosis factor, which is thought to kill the T-cells responsible for the autoimmune destruction of the pancreatic beta cells. Still in question is whether the regrowth of functional insulin-producing cells occurs due to differentiation and proliferation of existing pancreatic stem cells, or whether the injected spleen cells re-differentiate to an insulin-producing form. Denise Faustman, whose work has been central to developing the protocol, has suggested that both mechanisms may play a role. However, in experiments to verify and examine her work, Suri reported that DNA-based evidence yielded no sign that spleen cells were needed in pancreatic islet beta cells regeneration after the FCA treatment. In pancreatic islets the β-cells regenerate following Freund’s adjuvant treatment.
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Adjuvants in immunology are often used to modify or augment the effects of a vaccine by stimulating the immune system to respond to the vaccine more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionarily conserved molecules, so called PAMPs, which include liposomes, lipopolysaccharide (LPS), molecular cages for antigens, components of bacterial cell walls, and endocytosed nucleic acids such as double-stranded RNA (dsRNA), single-stranded DNA (ssDNA), and unmethylated CpG dinucleotide-containing DNA. Because immune systems have evolved to recognize these specific antigenic moieties, the presence of an adjuvant in conjunction with the vaccine can greatly increase the innate immune response to the antigen by augmenting the activities of dendritic cells (DCs), lymphocytes, and macrophages by mimicking a natural infection.
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The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called Toll-Like Receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity (T and B lymphocytes) and non-immune cells (epithelial and endothelial cells, and fibroblasts). The binding of ligands – either in the form of adjuvant used in vaccinations or in the form of invasive moieties during times of natural infection – TLR marks the key molecular events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity. As of 2016, several TLR ligands were in clinical development or being tested in animal models as potential adjuvants.
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Biopsies are also used to diagnose diseases other than cancer, including inflammatory, infectious, or idiopathic diseases of the skin and gastrointestinal tract, to name only a few. Surgical resection specimens are obtained by the therapeutic surgical removal of an entire diseased area or organ (and occasionally multiple organs). These procedures are often intended as definitive surgical treatment of a disease in which the diagnosis is already known or strongly suspected. However, pathological analysis of these specimens is critically important in confirming the previous diagnosis, staging the extent of malignant disease, establishing whether or not the entire diseased area was removed (a process called "determination of the surgical margin", often using frozen section), identifying the presence of unsuspected concurrent diseases, and providing information for postoperative treatment, such as adjuvant chemotherapy in the case of cancer.
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In March 2017, the US Food and Drug Administration (FDA) granted accelerated approval to avelumab for the treatment of adults and children twelve years and older with metastatic Merkel-cell carcinoma (MCC).Pfizer, Merck KGaA fourth to market with PD-1/L1 inhibitor In May 2017, the FDA approved avelumab for people with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum- containing chemotherapy or within twelve months of neoadjuvant or adjuvant platinum-containing chemotherapy. In May 2019, the FDA approved avelumab in combination with axitinib for the first-line treatment of people with advanced renal cell carcinoma. In June 2020, the FDA approved avelumab for the maintenance treatment of people with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.
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How chitin interacts with the immune system of plants and animals has been an active area of research, including the identity of key receptors with which chitin interacts, whether the size of chitin particles is relevant to the kind of immune response triggered, and mechanisms by which immune systems respond. Chitin and chitosan have been explored as a vaccine adjuvant due to its ability to stimulate an immune response. Chitin and chitosan are under development as scaffolds in studies of how tissue grows and how wounds heal, and in efforts to invent better bandages, surgical thread, and materials for allotransplantation. Sutures made of chitin have been explored for many years, but , none were on the market; their lack of elasticity and problems making thread have prevented commercial development.
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Rappuoli joined Chiron as head of European vaccines research in 1992 with the acquisition of Italian vaccines company Sclavo SpA, where he served as head of research and development. Rappuoli, was previously the Global Head of Vaccines Research for Novartis Vaccines & Diagnostics (Siena, Italy) Since 2015, Dr. Rappuoli serves as the chief scientist and head of external R&D; at the vaccines division of GlaxoSmithKline and is based in Siena, Italy. Major achievements include development of CRM197 used in Haemophilus influenzae, Neisseria meningitidis, and pneumococcus vaccines; an acellular pertussis vaccine containing a genetically detoxified pertussis toxin; the first conjugate vaccines against meningococcus; MF59 adjuvant for influenza; the meningococcus B genome-derived vaccine. During his career, he has introduced several novel scientific concepts: genetic detoxification in 1987; cellular microbiology in 1996; reverse vaccinology in 2000; pan-genome in 2005.
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The fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase was approved for medical use in the United States in June 2020. The FDA's approval was based on the results of a non-inferiority study in participants with HER2-positive early breast cancer, which demonstrated the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase had comparable efficacy and safety as IV pertuzumab and IV trastuzumab, except for administration-related reactions, which were higher with the fixed-dose combination due to the subcutaneous route of administration. Efficacy was investigated in FeDeriCa (NCT03493854), an open- label, multicenter, randomized trial enrolling 500 participants with operable or locally advanced HER2-positive breast cancer. Participants were randomized to receive neoadjuvant chemotherapy with concurrent administration of either the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies.
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Low, Intermediate and High risk (see Fundakowski and Lango, Table I). Clinical decisions also take into account morbidities, particularly if cancer outcomes are comparable for instance surgery is associated with a risk of bleeding between 5–10%, and a 0.3% risk of fatal postoperative haemorrhage. Surgery may also be complicated by dysphagia, and while most patients can tolerate a diet on the first postoperative day, long term use of a feeding tube has been reported as high as 10%. Patients with larger tumours, involvement of base of tongue and requiring postoperative adjuvant therapy are more likely to require a long term feeding tube. Overall, function and quality of life appear relatively similar between surgery with postoperative radiation, and primary chemoradiation, but HPV+OPC patients tend to have better quality of life at diagnosis than HPV-OPC but may sustain greater loss following treatment.
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Leukocoria in a child with retinoblastoma Ocular oncology, especially retinoblastoma, has been the principal research area of Honavar and he is known to have contributed to the understanding and treatment of various tumors affecting the ocular surface and orbit. Working on retinoblastoma, he developed various therapeutic and management protocols which included high-dose and periocular chemotherapy, adjuvant therapy to mitigate the high risk of metastasis and multimodal management of orbital affection of the disease and he is reported to have treated over 2000 pediatric retinoblastoma patients with a success rate above of 85%. At L. V. Prasad Eye Institute, he was the first to perform intra-ocular brachytherapy procedure, along with Vijay Anand Reddy. His studies have been documented by way of a number of articles of which many have been listed by online article repositories such as Google Scholar and ResearchGate.
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When the woman is unsatisfied with the outcome of the augmentation mammoplasty; or when technical or medical complications occur; or because of the breast implants' limited product life (Class III medical device, in the U.S.), it is likely she might require replacing the breast implants. The common revision surgery indications include major and minor medical complications, capsular contracture, shell rupture, and device deflation. Revision incidence rates were greater for breast reconstruction patients, because of the post-mastectomy changes to the soft-tissues and to the skin envelope of the breast, and to the anatomical borders of the breast, especially in women who received adjuvant external radiation therapy. Moreover, besides breast reconstruction, breast cancer patients usually undergo revision surgery of the nipple-areola complex (NAC), and symmetry procedures upon the opposite breast, to create a bust of natural appearance, size, form, and feel.
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Remsima (infliximab) is a biosimilar monoclonal antibody against tumor necrosis factor alpha (TNF-α), approved by the European Medicines Agency (EMA) for treatment of: # rheumatoid arthritis, # adult Crohn's disease, # pediatric Crohn's disease, # ulcerative colitis, # pediatric ulcerative colitis, # ankylosing spondylitis, # psoriatic arthritis, and # psoriasis. In 2012 Remsima was approved by the Republic of Korea's Ministry of Food and Drug Safety (MFDS), previously known as Korea Food and Drug Administration and in 2013 it became the world's first biosimilar monoclonal antibody (mAb) approved by the EMA. Herzuma is a biosimilar trastuzumab approved by the MFDS for treatment of early and advanced (metastatic) HER2+ breast cancer as well as advanced (metastatic) stomach cancer. Herzuma is a HER2+ breast cancer therapy designed to treat aggressive HER positive metastatic and adjuvant breast cancer, as well as HER2 positive adenocarcinoma of the stomach that has spread (metastatic or advanced gastric cancer).
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Having launched its first vaccine product, Fluad, an adjuvant influenza vaccine, in 1996, the vaccine line was expanded significantly in 1998 with the acquisition of the European vaccine businesses of Behring (Germany) and Sclavo (Italy). This was followed in 2003 by the acquisition of PowderJect, the UK-based vaccines company, making Chiron the second-largest flu vaccines provider and the fifth-largest vaccines business in the world. In 1998, Chiron's nucleic acid testing (NAT) blood-testing business was launched in cooperation with Gen-Probe, followed a year later by the launch of the Procleix system, which detects viral RNA and DNA in donated blood and plasma during the very early stages of infection, when those infectious agents are present but cannot be detected by immunodiagnostic tests. Chiron expanded its cancer drug portfolio in 2002 with the acquisition of Matrix Pharmaceuticals Inc and its product tezacitebine.
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For instance, the 8th-century Zhang zhenren jinshi lingsha lun 張真人金石靈沙論 (The Adept Zhang's Discourse on Metals, Minerals, and Cinnabar) emphasized the poisonous nature of gold, silver, lead, mercury, and arsenic, and described witnessing many cases of premature death brought about by consuming cinnabar. Zhang believed however that the poisons could be rendered harmless by properly choosing and combining adjuvant and complimentary ingredients; for example gold should always be used together with mercury, while silver can only be used when combined with gold, copper carbonate, and realgar for the preparation of the jindan Golden Elixir (tr. Needham and Ho 1970: 331). Many Tang alchemical writers returned to the fashion of using obscure synonyms for ingredients, perhaps because of the alarming number of elixir poisonings, and the desire to dissuade amateur alchemists from experimenting on themselves (Needham et al.
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First ed.1966 In 1963 Zwaveling followed a one-year fellowship at the surgical department of the UW Health University Hospital, Madison, Wisconsin, USA for one year to be familiarized with American surgical procedures and the use of chemotherapy in surgery. Zwaveling became a lector of surgery, specializing in clinical oncology, at Leiden University in 1968 and in 1972 he was appointed a full professor of surgical oncology. In 1971, together with radiotherapist professor Piet Thomas and Emile van Slooten, surgeon at the Antoni van Leeuwenhoekziekenhuis, Zwaveling published the first breast cancer treatment protocol in the Netherlands.”Richtlijnen behandeling mammacarcinoom” Stichting Koningin Wilhelminafonds Nederlandse Organisatie voor de Kankerbestrijding, Amsterdam, 1971 Moreover, in 1973 he initiated the first national multicenter randomized trial on adjuvant chemotherapy in breastcancer.O.J. Repelaer van Driel, PhD thesis Leiden University, 1987 “Adjuvante chemotherapie bij mammacarcinoom” Along with publishing scientific papers, he was actively involved in the training of students, residents and surgeons.
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The Q-Symbio study was a multi-center randomized placebo- controlled double-blind clinical trial that was reported in the Journal of the American College of Cardiology: Heart Failure in September 2014. The purpose of the study was to assess the effect of the adjuvant therapy drug Coenzyme Q10 on several short-term and long-term endpoints in a total of 420 chronic heart failure patients enrolled in 17 cardiology centers in Europe, Asia, and Australia from 2003 to 2010. The trial name Q-SYMBIO reflects the focus on the following elements in the clinical trial: Q = Q10 and SYMBIO = SYMptoms, BIomarker status [Brain-Natriuretic Peptide], and long-term Outcome [hospitalizations/mortality]. Professor Mortensen and a team of researchers assigned 420 patients with moderate to severe chronic heart failure to Coenzyme Q10 100 milligrams three times daily or matching placebos in addition to the patients’ standard heart failure therapies for two years.
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Nivolumab is used as a first-line treatment for inoperable or metastatic melanoma in combination with ipilimumab if the cancer does not have a mutation in BRAF, and as a second-line treatment for inoperable or metastatic melanoma following treatment of ipilimumab and, if the cancer has a BRAF mutation, a BRAF inhibitor. It is also used to treat metastatic squamous non-small cell lung cancer with progression with or after platinum-based drugs and for treatment of small cell lung cancer It also used as a second-line treatment for renal cell carcinoma after anti-angiogenic treatment has failed. Nivolumab is also used for primary or metastatic urothelial carcinoma, the most common form of bladder cancer. It can be prescribed for locally advanced or metastatic form of the condition that experience disease progression during or following platinum-containing chemotherapy or have progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
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Following her service on the NIH panel, President Jimmy Carter appointed Kushner to the National Cancer Advisory Board as the board's first lay member, and she was engaged by the NIH to review grant applications. She took pleasure in the fact that she was working within the system, joking "I'm a full-fledged member of the Establishment." After Kushner's cancer recurred in 1981, she refused chemotherapy, which she considered to be unacceptably toxic, and was treated with tamoxifen. In the 1980s she campaigned against aggressive use of chemotherapy. In a 1984 article "Is Aggressive Adjuvant Chemotherapy the Halsted Radical of the '80s?" she suggested that chemotherapy was being used as indiscriminately as radical mastectomy surgery had been in earlier decades, saying that doctors gave insufficient attention to the serious side effects of chemotherapy, and calling chemotherapy "therapeutic overkill."Barron H. Lerner, Ill Patient, Public Activist: Rose Kushner's Attack on Breast Cancer Chemotherapy, Bulletin of the History of Medicine, Volume 81, Number 1, Spring 2007, pp.
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Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT. The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing the radiation exposure. For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage. For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST.
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The plasmids are often coated with some type of adjuvant prior to delivery to enhance the immune response from the host. Linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia (to which the pathogen responsible for Lyme disease belongs), several species of the gram positive soil bacteria of the genus Streptomyces, and in the gram negative species Thiobacillus versutus, a bacterium that oxidizes sulfur. The linear plasmids of prokaryotes are found either containing a hairpin loop or a covalently bonded protein attached to the telomeric ends of the DNA molecule. The adenine-thymine rich hairpin loops of the Borrelia bacteria range in size from 5 kilobase pairs (kb) to over 200 kb and contain the genes responsible for producing a group of major surface proteins, or antigens, on the bacteria that allow it to evade the immune response of its infected host. The linear plasmids which contain a protein that has been covalently attached to the 5’ end of the DNA strands are known as invertrons and can range in size from 9 kb to over 600 kb consisting of inverted terminal repeats.
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He worked as a Postdoc at the University of Ghent from 1990 until 2004 and he is VIB Project Leader since 2005. His current research focuses on the development and characterisation of novel influenza A and B vaccines. Together with Walter Fiers and their team, he works on the development of an M2e-based vaccine.Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W, A universal influenza A vaccine based on the extracellular domain of the M2 protein, Nat Med. 1999 Oct;5(10):1157-63Saelens X, Vanlandschoot P, Martinet W, Maras M, Neirynck S, Contreras R, Fiers W, Jou WM, Protection of mice against a lethal influenza virus challenge after immunization with yeast- derived secreted influenza virus hemagglutinin, Eur J Biochem 260, 166-175, 1999De Filette M, Min Jou W, Birkett A, Lyons K, Schultz B, Tonkyro A, Resch S, Fiers W, Universal influenza A vaccine: optimization of M2-based constructs, Virology. 2005 Jun 20;337(1):149-61De Filette M, Ramne A, Birkett A, Lycke N, Löwenadler B, Min Jou W, Saelens X, Fiers W, The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection, Vaccine.
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The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity T cells, and B cells, and non immune cells (epithelial and endothelial cells, and fibroblasts). The binding of ligands - either in the form of adjuvant used in vaccinations or in the form of invasive moieties during times of natural infection - to the TLR marks the key molecular events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity. Upon activation, TLRs recruit adaptor proteins (proteins that mediate other protein-protein interactions) within the cytosol of the immune cell in order to propagate the antigen-induced signal transduction pathway. These recruited proteins are then responsible for the subsequent activation of other downstream proteins, including protein kinases (IKKi, IRAK1, IRAK4, and TBK1) that further amplify the signal and ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events.
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