关键词：长春高新；开发疫苗；技术咨询；企业策划

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关键词：日本；WTO秘书处；拟修订；麻醉药品；精神药物；控制法

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Neurofibromatosis type 1 patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). Growth factor receptors, particularly EGFR, have been implicated in neurofibroma formation and progression, but their precise roles and relevant signaling pathways remain unknown. We found that EGFR modifies neurofibroma-initiating cell number and promotes transformation to aggressive GEM-PNST. Unbiased insertional mutagenesis screening suggested that these effects were mediated by STAT3 signaling. Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in human and mouse tumors. A specific STAT3 inhibitor blocked neurofibroma-sphere formation in vitro, and reduced neurofibroma growth in vivo; STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduces pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway regulates neurofibroma number and neurofibroma growth, and promotes transformation.

关键词：医药；治疗技术；STAT3；纤维神经瘤

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The goal of this innovator award is to continue to develop and apply RNAi-based screening methods to discover new routes toward breast cancer therapy. The project has three goals. The first is to integrate genomic and genetic information on available breast cancer cell lines to identify tumor- specific vulnerabilities and to understand genetic determinants of therapy resistance. The second is to probe the roles of breast cancer stem cells, with a particular emphasis on microRNAs. The third is to examine genomic regions that determine familial susceptibility to breast cancer using novel, focal re- sequencing methods developed in the laboratory.

关键词：医药；治疗技术；RNAi；乳腺癌

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During the first year of this study, we have completed all case report forms, data collection sheets and informed consent documents. All necessary IRB approvals have been obtained, and all regulatory documents have been submitted to the Baltimore VA Medical Center Research Committee. A local IRB modification has been submitted to clarify exclusion criteria as it relates to the assessment of diabetic subjects. All personnel have obtained appropriate certifications in order to participate in research. Multiple meetings have occurred, both in person and via teleconference in order to coordinate activities between the Baltimore and the Atlanta sites. The research protocols have been initiated, with nine individuals screened and seven progressing to study participation. In Baltimore one participant completed 3 month outcome data assessment and crossed over to the other exercise arm. The other six individuals are in the first exercise arm. Two enrollees at the Baltimore site were withdrawn from the protocol, one because of a burning sensation in the left foot during Lokomat participation, and the other because of asymptomatic blood pressure elevation during Lokomat training. At the end of year one, the research has not as of yet produced any presentations or published reports, but this was not expected.

关键词：医药；治疗技术；脊髓损伤；水生治疗

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关键词：仿制药；一致性评价；原研药

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Histone demethylases are a newly discovered class of non-heme iron enzymes that play an important role in regulating transcription and epigenetic inheritance. We have successfully expressed and purified highly active histone demethylases (HDMs), including the cancerrelevant JMJD2C (GASC1). A detailed enzyme kinetic and inhibition analysis of these HDMs was achieved through a range of fluorescence assays, mass spectrometry, and oxygen consumption measurements. An interesting case of cosubstrate inhibition is observed for these HDMs, with direct relevance to the potential role of alpha-ketoglutarate and HDMs in cancer cells. We have also employed an enzyme-templated approach for specific inhibitor design that takes advantage of the enzyme s substrate specificity. Finally, while the initially tested compounds do not seem to inhibit JMJD2C in MCF7 breast cancer cells, we believe that second generation compounds will be active HDM inhibitors in vivo. The developed specific inhibitors could lead to novel breast cancer therapeutics and can also be used as tools for studying the role of histone demethylases in breast cancer cell proliferation.

关键词：医药；治疗技术；脱甲基酶；乳腺癌

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We have isolated and characterized a population of skeletal muscle- derived stem cells (MDSCs) that display a greatly improved skeletal and cardiac muscle transplantation capacity when compared to skeletal muscle myoblasts. The MDSCs ability to withstand oxidative and inflammatory stresses appears to be the single most important factor for their improved transplantation capacity. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel-derived stem cells suggests their potential origin could be from the vascular wall. We have recently isolated two distinct populations of cells from the vasculature of human skeletal muscle known collectively as human skeletal muscle-derived cells (hMDCs). The two populations are myo-endothelial cells and pericytes and both can repair skeletal and cardiac muscles in a more effective manner than myoblasts, as is observed with murine MDSCs. In the current proposal we intend to evaluate and compare the regeneration capacity of these two hMDC populations after their implantation into the skeletal muscle of immunodeficient/dystrophic (SCID/mdx) mice. We will then investigate the influence that sex has on the regeneration and repair capacity of the hMDCs endowed with the greatest regeneration capacity (either myo-entothelial cells or pericytes). Finally we will investigate the influence that age plays on the regeneration capacity of the cells.

关键词：医药；治疗技术；干细胞疗法

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In response to a request from the public to the Agency for Healthcare Research and Quality (AHRQ) concerning the expanding use of disease-modifying anti-rheumatic drugs (DMARDs) to treat rheumatoid arthritis (RA), a systematic review was undertaken to review the effectiveness and safety of the oral and biologic DMARDs. This summary is based on a systematic review prepared as an update to a review published in 2007. In addition to the material reported in 2007, this update includes articles published after the 2007 report and before January 2011 (a total of 211 studies). This summary, based on the full report of research evidence, is provided to clinicians to inform discussions of options with patients and to assist in decisionmaking along with consideration of a patients values and preferences. Reviews of evidence should not be construed to represent clinical recommendations or guidelines.

关键词：医药；治疗技术；类风湿性关节炎

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Epidemiological evidence has demonstrated an inverse association between serum vitamin D levels and sunlight exposure to prostate cancer incidence. In addition, serum androgen levels and biologically available testosterone decrease significantly in elder men while the incidence rate of prostate cancer increases. These findings lead to the hypothesis that androgen- and vitamin D-mediated signaling events may act together to inhibit prostate tumor initiation and/or development. Using concurrent microarray analyses, we demonstrated that testosterone and 1,25(OH)2D3 co-operate to regulate mRNA and miRNA expression, including some well-defined oncogenes and tumor suppressor genes. Pheno typically, this results in G0/G1 cell cycle arrest and increased neutral lipid accumulation in LNCaP cells, as a consequence of repression of various cell cycle regulators and the up-regulation of PPAR alpha; respectively. This suggests that the cross talk between T and 1,25(OH)2D3 induces cell cycle arrest and promotes cell differentiation in LNCaP cells. It is important ton ote that co-treatment of LNCaP cells with testosterone, 1, 25(OH)2D3 and other standard therapeutics, including bicalutamide, docetaxel and TRAIL did not affect the potencies of these treatments, though there were no synergistic effects either. This suggests that androgen andvitamin D supplementation slow disease progression without affecting the efficacy of standard therapies for prostate cancer. Further analysis is still required to elucidate the underlying mechanisms of T and 1,25(OH)2D3 to modulate key mRNA and miRNA and their significance in prostate tumorigenesis and therapeutic interventions.

关键词：医药；治疗技术；前列腺癌；细胞疗法

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