{"title":"Next generation therapies change the landscape in melanoma.","authors":"Keith T Flaherty","doi":"10.3410/M3-8","DOIUrl":"https://doi.org/10.3410/M3-8","url":null,"abstract":"Melanoma is among the leading causes of years of life lost due to cancer. Current chemotherapy and cytokine-based immunotherapy approaches benefit only a small percentage of patients with advanced disease. However, the recent discovery of mutations in the gene encoding the serine-threonine kinase B-RAF (BRAF) raises the possibility that oncogene-targeted therapy may provide a new point of vulnerability. In parallel, a deeper understanding of the molecular mechanisms underlying antitumor T-cell activation and tolerance has provided a basis for developing therapies targeted against these processes. Results from an early phase trial with a BRAF inhibitor and a phase III trial with a novel agent that activates T cells have radically altered the prospects for improving outcomes for patients with this historically treatment-refractory disease.","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/6e/medrep-03-08.PMC3096880.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29922267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vaccines for invasive fungal infections.","authors":"Brad Spellberg","doi":"10.3410/M3-13","DOIUrl":"https://doi.org/10.3410/M3-13","url":null,"abstract":"<p><p>Morbidity and mortality from invasive fungal infections remain unacceptably high despite availability of new antifungal agents, underscoring the need for more effective preventative strategies. Due to our enhanced understanding of the host defense and pathogenetic mechanisms that lead to invasive fungal infections, it should be feasible to develop vaccines targeting these infections. A common immunological theme across many vaccine candidates for invasive fungal infections has been the need to activate a cell-based, pro-inflammatory, Th1 or Th17 immune response to improve phagocytic killing of the fungi. Since neutralization of virulence factor functions has not been required for many active vaccines to function, the antigenic repertoire available for testing should not be limited to virulence factors. With expansion of our fundamental understanding of the immunology of fungal infections, the biggest barrier to development of fungal vaccines is the lack of available capital to translate discoveries made at the bench into biological agents used at the bedside. Continued education on the importance and feasibility of vaccination for such infections, combined with continued development of vaccine antigens and adjuvants, is necessary.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/77/medrep-03-13.PMC3155210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30107819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caroline J Aalbers, Paul P Tak, Margriet J Vervoordeldonk
{"title":"Advancements in adeno-associated viral gene therapy approaches: exploring a new horizon.","authors":"Caroline J Aalbers, Paul P Tak, Margriet J Vervoordeldonk","doi":"10.3410/M3-17","DOIUrl":"https://doi.org/10.3410/M3-17","url":null,"abstract":"<p><p>Gene therapy is a promising new therapeutic strategy that has been explored in a wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders to autoimmune diseases, among others. Proof of concept of gene transfer approaches has been shown in over 100 studies of animal models of disease, although only a few are under development for clinical application. The US Food and Drug Administration and the European Medicines Agency have not approved any viral human gene therapy products for sale so far, but the amount of gene-related research and development occurring in the United States and Europe continues to grow at a fast rate. This review summarizes the current status of developments in the field of viral gene therapy using adeno-associated virus as a vector, with a special focus on arthritis. For rheumatoid arthritis, and to a lesser extent for other immune-related inflammatory disorders, several cell and gene transfer approaches have been investigated at the preclinical level and a few have been implemented in clinical trials. Finally, both the potential and the hurdles that are faced during development of a viral gene therapy through to its clinical application are discussed.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/59/medrep-03-17.PMC3169911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30015826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Illuminating the deleterious effects of light at night.","authors":"Laura K Fonken, Randy J Nelson","doi":"10.3410/M3-18","DOIUrl":"https://doi.org/10.3410/M3-18","url":null,"abstract":"<p><p>Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20(th) century, humans became exposed to bright and unnatural light at night for the first time in their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just \"daytime\" activities now run throughout the night; in many ways Western society now functions on a 24-hour schedule. Recent research suggests that this gain in freedom to function throughout the night may also come with significant repercussions. Disruption of our naturally evolved light and dark cycles can result in a wide range of physiological and behavioral changes with potentially serious medical implications. In this article we will discuss several mechanisms through which light at night may exert its effects on cancer, mood, and obesity, as well as potential ways to ameliorate the impact of light at night.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3410/M3-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30015827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alzheimer's - Looking beyond plaques.","authors":"W Sue T Griffin","doi":"10.3410/M3-24","DOIUrl":"https://doi.org/10.3410/M3-24","url":null,"abstract":"<p><p>Mounting evidence shows that inflammation plays a critical role in causing Alzheimer's disease. Over the last few decades we have gone from a situation where inflammation was generally believed to have no role in the disease to the current picture where chronic activation of IL-1 inflammation has been shown to account for many of the hallmarks of the disease. This review is a personal account of the quest to prove that inflammation plays a critical role in causing Alzheimer's disease.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/db/medrep-03-24.PMC3229272.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30319254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural killer cell-based therapies.","authors":"François Romagné, Eric Vivier","doi":"10.3410/M3-9","DOIUrl":"https://doi.org/10.3410/M3-9","url":null,"abstract":"<p><p>Allotransplantation of natural killer (NK) cells has been shown to be a key factor in the control and cure of at least some hematologic diseases, such as acute myeloid leukemia or pediatric acute lymphocytic leukemia. These results support the idea that stimulation of NK cells could be an important therapeutic tool in many diseases, and several such approaches are now in clinical trials, sometimes with conflicting results. In parallel, recent advances in the understanding of the molecular mechanisms governing NK-cell maturation and activity show that NK-cell effector functions are controlled by complex mechanisms that must be taken into account for optimal design of therapeutic protocols. We review here innovative protocols based on allotransplantation, use of NK-cell therapies, and use of newly available drug candidates targeting NK-cell receptors, in the light of fundamental new data on NK-cell biology.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/2b/medrep-03-09.PMC3096881.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29922269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The challenge of developing universal vaccines.","authors":"Rino Rappuoli","doi":"10.3410/M3-16","DOIUrl":"https://doi.org/10.3410/M3-16","url":null,"abstract":"<p><p>Antigenic variability of immunodominant antigens is a common mechanism used by pathogens to escape the immune response. Frequently, the proposed solution is a universal vaccine based on conserved antigens present on all strains of the pathogen. Indeed, a lot of progress has been made in the development of vaccines that induce broad immune responses. However, truly universal vaccines are not easy to produce and still face many challenges, mostly because in those pathogens that use antigenic variability to escape the immune response, conserved antigens have been selected by evolution to be poorly immunogenic. This review describes the progress made towards the development of vaccines inducing broad protection against Neisseria meningitidis, influenza, HIV, and Candida and the challenges of developing truly universal vaccines.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/8e/medrep-03-16.PMC3155208.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29984301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innate inflammation and cancer: Is it time for cancer prevention?","authors":"Giorgio Trinchieri","doi":"10.3410/M3-11","DOIUrl":"https://doi.org/10.3410/M3-11","url":null,"abstract":"<p><p>Recently, studies have been reported indicating that daily aspirin treatment for a period of 5 years or longer has a significant protective effect against death by colorectal carcinoma (as has previously been shown) and also against death by other solid cancers, both gastrointestinal and otherwise. These studies have reignited interest in the possibility of using nonsteroidal anti-inflammatory drugs for cancer prevention and the possibility that the numerous recent studies identifying the molecular mechanisms of the link between inflammation and cancer may allow the identification of better drugs for cancer prevention. Cancer often originates in tissues that are chronically inflamed, either in response to infections or noninfectious inflammation. Innate inflammation receptors, proinflammatory soluble factors, and inflammation-induced transcription factors have been identified that provide an understanding of some of the molecular pathways underlying the link between inflammation and cancer. However, the important role of the innate inflammatory pathways in host defense against pathogens and tissue damage as well as the maintenance of tissue integrity and homeostasis means that additional careful studies will be needed to identify anti-inflammatory interventions with the beneficial effect of tumor prevention without unacceptable toxic side effects.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/4b/medrep-03-11.PMC3155181.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30107817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Resolvins and inflammatory pain.","authors":"Claudia Sommer, Frank Birklein","doi":"10.3410/M3-19","DOIUrl":"https://doi.org/10.3410/M3-19","url":null,"abstract":"<p><p>Resolvins are a group of molecules derived from omega-3 fatty acids. They are part of a biochemical program that allows inflamed tissues to return to homeostasis once the need for the inflammatory response is over. Resolvins act in very low dose ranges in vitro and in vivo. New data suggest that they might have the potential to become very potent analgesic drugs in inflammatory pain.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3410/M3-19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30211635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ALK and NSCLC: Targeted therapy with ALK inhibitors.","authors":"Bengt Hallberg, Ruth H Palmer","doi":"10.3410/M3-21","DOIUrl":"10.3410/M3-21","url":null,"abstract":"<p><p>For many years treatment for advanced or metastatic non-small cell lung cancer (NSCLC) has employed chemotherapy regimens for patient care, with limited effect. Five-year survival rates for these patients are not encouraging. However, for a subgroup of these patients, there have been radical changes over recent years. Our understanding of the basic pathology behind NSCLC at the molecular level has offered up a host of new molecularly targeted therapies, which are revolutionizing this area of cancer care. Results from recent clinical trials provide hope for NSCLC patients harboring oncogenic translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Just as inhibition of the breakpoint cluster region-ABL complex has changed the face of chronic myeloid leukemia diagnosis, oncogenic ALK fusions offer a step forward in the diagnosis and treatment of ALK-positive NSCLC. This article discusses the current knowledge and potential implications concerning ALK inhibitors and NSCLC.</p>","PeriodicalId":88480,"journal":{"name":"F1000 medicine reports","volume":"3 ","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/6d/medrep-03-21.PMC3206708.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30102832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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