Advances and challenges in basic and translational research on clusterin.
Ontology highlight
ABSTRACT:
SUBMITTER: Trougakos IP
PROVIDER: S-EPMC2848483 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
Publications
Advances and challenges in basic and translational research on clusterin.
Trougakos Ioannis P IP Djeu Julie Y JY Gonos Efstathios S ES Boothman David A DA
Cancer research 20090101 2
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Project description:The current gap between basic science research and the development of new analgesics presents a serious challenge for the future of pain medicine. This challenge is particularly difficult in the search for better treatment for comorbid chronic pain conditions because: (i) animal 'pain' models do not simulate multidimensional clinical pain conditions; (ii) animal behavioral testing does not assess subjective pain experience; (iii) preclinical data provide little assurance regarding the direction of new analgesic development; and (iv) clinical trials routinely use over-sanitized study populations and fail to capture the multidisciplinary consequences of comorbid chronic pain. Therefore, a paradigm shift in translational pain research is necessary to transform the current strategy from focusing on molecular switches of nociception to studying pain as a system-based integral response that includes psychosocial comorbidities. Several key issues of translational pain research are discussed in this review.
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Project description:This review summarizes key developments in the heparanase field obtained 20 years prior to cloning of the HPSE gene and nearly 20 years after its cloning. Of the numerous publications and review articles focusing on heparanase, we have selected those that best reflect the progression in the field as well as those we regard important accomplishments with preference to studies performed by scientists and groups that contributed to this book. Apart from a general 'introduction' and 'concluding remarks', the abstracts of these studies are presented essentially as published along the years. We apologize for not being objective and not being able to include some of the most relevant abstracts and references, due to space limitation. Heparanase research can be divided into two eras. The first, initiated around 1975, dealt with identifying the enzyme, establishing the relevant assay systems and investigating its biological activities and significance in cancer and other pathologies. Studies performed during the first area are briefly introduced in a layman style followed by the relevant abstracts presented chronologically, essentially as appears in PubMed. The second era started in 1999 when the heparanase gene was independently cloned by 4 research groups [1-4]. As expected, cloning of the heparanase gene boosted heparanase research by virtue of the readily available recombinant enzyme, molecular probes, and anti-heparanase antibodies. Studies performed during the second area are briefly introduced followed by selected abstracts of key findings, arranged according to specific topics.
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Project description: Not available
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Project description:ProblemUnderstanding and communicating medical advances driven by basic research, and acquiring foundational skills in critically appraising and communicating translational basic research literature that affects patient care, are challenging for medical students to develop.ApproachThe authors developed a mandatory course from 2012 to 2018 at Texas A&M University College of Medicine to address this problem. Medical Student Grand Rounds (MSGR) trains first-year students to find, critically assess, and present primary research literature about self-selected medically relevant topics. With basic science faculty mentoring, students completed milestones culminating in oral presentations. Students learned to search literature databases and then choose a clinical subject using these skills. They outlined the clinical subject area background and a mechanistic research topic into a clinical problem based on deeper evaluation of primary research literature. "Mechanistic" was defined in this context as providing experimental evidence that explained the "how" and "why" underlying clinical manifestations of a disease. Students received evaluations and feedback from mentors about discerning the quality of information and synthesizing information on their topics. Finally, students prepared and gave oral presentations, emphasizing the primary literature on their topics.OutcomesIn the early stages of the course development, students had difficulty critically assessing and evaluating research literature. Mentored training by research-oriented faculty, however, dramatically improved student perceptions of the MSGR experience. Mentoring helped students develop skills to synthesize ideas from basic research literature. According to grades and self-evaluations, students increased proficiency in finding and interpreting research articles, preparing and delivering presentations, and understanding links among basic and translational research and clinical applications.Next stepsThe authors plan to survey fourth-year students who have completed MSGR about their perceptions of the course in the context of clinical experiences in medical school to guide future refinements.
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Project description:BackgroundAdoptive immunotherapies are among the pillars of ongoing biological breakthroughs in neuro-oncology, as their potential applications are tremendously wide. The present literature review comprehensively classified adoptive immunotherapies in neuro-oncology, provides an update, and overviews the main translational challenges of this approach.MethodsThe PubMed/MEDLINE platform, Medical Subject Heading (MeSH) database, and ClinicalTrials.gov website were the sources. The MeSH terms "Immunotherapy, Adoptive," "Cell- and Tissue-Based Therapy," "Tissue Engineering," and "Cell Engineering" were combined with "Central Nervous System," and "Brain." "Brain tumors" and "adoptive immunotherapy" were used for a further unrestricted search. Only articles published in the last 5 years were selected and further sorted based on the best match and relevance. The search terms "Central Nervous System Tumor," "Malignant Brain Tumor," "Brain Cancer," "Brain Neoplasms," and "Brain Tumor" were used on the ClinicalTrials.gov website.ResultsA total of 79 relevant articles and 16 trials were selected. T therapies include chimeric antigen receptor T (CAR T) cell therapy and T cell receptor (TCR) transgenic therapy. Natural killer (NK) cell-based therapies are another approach; combinations are also possible. Trials in phase 1 and 2 comprised 69% and 31% of the studies, respectively, 8 of which were concluded. CAR T cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) was demonstrated to reduce the recurrence rate of glioblastoma after standard-of-care treatment.ConclusionAdoptive immunotherapies can be classified as T, NK, and NKT cell-based. CAR T cell therapy redirected against EGFRvIII has been shown to be the most promising treatment for glioblastoma. Overcoming immune tolerance and immune escape are the main translational challenges in the near future of neuro-oncology.
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