关键词：乙肝疫苗；天坛生物

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In response to a request from a national professional society regarding the use of procalcitonin in the clinical management of adult and pediatric patients with suspected local or systemic infection, a systematic review of comparative studies (randomized controlled trials and nonrandomized studies) was conducted. The patient populations included critically ill adults with suspected sepsis or other serious bacterial infections, neonates with suspected early neonatal sepsis, patients with upper and lower respiratory tract infections, children with fever of unknown origin, and postoperative patients at risk of infection. Pregnant women, patients with absolute neutropenia and other immunocompromised populations (solid organ and stem-cell transplant recipients, patients with advanced HIV infection/AIDS), and patients with chronic infections such as infective endocarditis were excluded from this review. The systematic review included 18 reports of eligible studies in over 6,000 patients published between January 1, 1990, and December 16, 2011. Outcomes including antibiotic usage, mortality, morbidity, adverse drug effects of antibiotic therapy, and hospital or intensive care unit (ICU) length of stay were assessed. This summary, based on the full report of research evidence, is provided to assist in decisionmaking along with consideration of a patients values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

关键词：医药；治疗技术；抗生素治疗；降钙素原

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Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm microscopically similar to undifferentiated nasopharyngeal carcinoma. It is typically nonaggressive and is treated with wide local excision. However, we present a case of a patient with a regional recurrence and more aggressive LELCS with perineural invasion and positive margins for which he was treated with wide local excision followed by chemoradiation. We discuss the use of chemoradiation for this patient and review the literature, specifically pertaining to treatment of more aggressive cases of LELCS.

关键词：医药；治疗技术；皮肤淋巴上皮癌

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This study was an open-label, single-group, treatment-development project aimed at developing and testing a method for applying virtual reality exposure therapy (VRET) to active duty service members diagnosed with combat post-traumatic stress disorder (PTSD). Forty-two service members with PTSD were enrolled, and 20 participants completed treatment. The PTSD Checklist-Military version, Patient Health Questionnaire-9 for depression, and the Beck Anxiety Inventory were used as outcome measures. Of those who completed post-treatment assessment, 75had experienced at least a 50reduction in PTSD symptoms and no longer met DSM-IV criteria for PTSD at post treatment. Average PSTD scores decreased by 50.4, depression scores by 46.6, and anxiety scores by 36. Intention-to-treat analyses showed that statistically significant improvements in PTSD, depression, and anxiety occurred over the course of treatment and were maintained at follow up. There were no adverse events associated with VRET treatment. This study provides preliminary support for the use of VRET in combat-related PTSD. Further study will be needed to determine the wider utility of the method and to determine if it offers advantages over other established PTSD treatment modalities.

关键词：医药；治疗技术；应激障碍；暴露疗法

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Tuberous Sclerosis Complex (TSC) is a genetic disorder resulting from mutations in either the TSC1 or TSC2 genes. TSC is characterized by abnormal skin pigmentation and tumor formation in multiple organ systems. TheTSC1andTSC2gene products are involved in cell signaling; in particular they are involved in the mammalian target of rapamycin (mTOR) signaling pathway. In TSC, the epidermal basal cells contain a mutant copy of either theTSC1orTSC2gene. A loss of heterozygosity results in constitutive activation of mTOR leading to production of epidermal cells at a faster rate than the ability to slough the dead cells. This overproduction of skin cells, in conjunction with angiogenesis, results in the formation of visible facial angiofibromas over time.

关键词：医药；治疗技术；雷帕霉素；皮肤结节性硬化综合症

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This is the final report that shows the results obtained during the funding. The aim of this study was identify combinations of currently approved drugs that would be effective for treating MPNST. The resources attained along the first phase of this project were valuable for the subsequent drug screen performed in human MPNST cells and in vivo experiments. The inhibition of mammalian target of rapamycin (mTOR) by drugs (Rapamycin and RAD001) or RNA interference shows synergism with ionizing radiation decreasing human MPNST cell proliferation. Cell-based drug screen in combination with mTOR inhibitiors uncovers three potential candidates (toremifene, riluzole and bortezomib) with different mechanism of action. We further characterized the interaction between bortezomib, a proteasome inhibitor, and mTOR signaling inhibition in MPNST cells proliferation, cell cycle and apoptosis. Finally, dual targeting of proteasome and mTOR signaling associated with radiotherapy delay MPNST tumor growth in xenograft nude mice.

关键词：医药；治疗技术；纤维瘤；临床前测试

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Project 1: Dilated cardiomyopathy affects approximately 1 in 2,500 individuals in the United States and is the 3rd most common cause of heart failure and the most frequent cause of heart transplantation. Patients that suffer from various muscle diseases, including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty, which involves the transplantation of exogenous cells into the heart, is a possible approach by which to repair diseased or injured myocardium and improve cardiac function. Though there are a number of drugs prescribed to treat dilated cardiomyopathy, there is no cure and individuals eventually require a heart transplant; therefore the use of cardiomyoplasty to repair the hearts of individuals suffering from cardiomyopathy could possibly be an effective alternative to heart transplantation. Technical Objective No. 1: To investigate the effect of cell survival, proliferation, and differentiation on the regeneration/repair capacity of various human MDSC populations implanted into the heart of mdx/SCID mice. Technical Objective No. 2: To investigate the role that angiogenesis plays in the regeneration/repair capacity of human MDSCs injected into the hearts of mdx/SCID mice. Project 2: This project will determine the extent to which novel sources of hepatocytes can be used for regeneration and repair of injuries to the liver and liver failure. A more complete understanding of the extent to which donor liver cells can be resuscitated from non-traditional sources and expanded for application to reduce liver injury and toxin and/or cancer risk should enhance the number of areas where hepatic stem cell transplantation might be effectively applied. Technical Objectives: (1) to characterize and expand hepatocytes from patients with cirrhosis and end-stage liver disease in immune deficient hosts whose livers permit extensive repopulation with donor cells; (2); to determine the extent to which transplant.

关键词：医药；治疗技术；肌肉干细胞疗法；心肌病

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Long bone fractures resulting from high impact trauma can result in delayed healing. Photodynamic therapy (PDT) is a non-surgical, non-ionizing minimally invasive local treatment currently used to treat cancer and skin diseases. Surprisingly, recent findings from studying the effect of PDT on spinal metastases have shown that PDT improved the strength and stiffness of the vertebrae. Although variability in fracture generation led to inconclusive findings with respect to bone generation in the closed tibia fracture model (n=17), higher local levels of VEGF were found in PDT treated animals. A critical size defect fracture of the femur was generated in 20 adult female Sprague-Dawley rats. PDT treatment was applied either 1d (n=6) or 7d (n=6) after fracture generation. Qualitatively, a larger callus was seen in the 7d- PDT group, suggesting an important effect of timing on PDT administration. Both PDT treated groups showed evidence of healing and closing of the fracture gap in this critical defect model. Preliminary, quantitative CT measurements support the qualitative findings. Additional CT based imaging and stereological analysis are underway. Histologic processing and analysis of the serum will also be conducted on these animals.

关键词：医药；治疗技术；光动力疗法；骨折

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The research goals of this grant proposal are to: (1) investigate the effect of ETS gene fusions on radiation phenotype in pre-clinical models of prostate cancer, (2) to explore the mechanism of interaction between ERG (the predominant ETS gene fusion product) and the DNA repair protein DNA-PK, and (3) to determine if ETS gene fusion status is a clinical biomarker of radioresistance for prostate cancer. The training goals of this grant proposal included a series of regular meetings with mentors, research seminars, journal clubs, and workshops, all of which are intended to help Dr. Feng develop as a translational scientist. This grant proposal was approved as a five-year award; the current annual report summarizes accomplishments over the second year of the grant, from July 15, 2011 to July 15, 2012. Overall, the first two years of this grant have been very successful. The work accomplished as a result of this grant resulted in two publications in very high impact journals, four national presentations, and three grants (two from the Prostate Cancer Foundation and one from Celgene). Additionally, Dr. Feng has met the training achievements specified in his original grant. The research proposed in this training grant represents an important area within the field of prostate cancer research. Because ETS gene fusions are thought to be driver alterations in over half of all prostate cancers, understanding the mecha-nistic and potential clinical implications of these gene fusions has significant ramifications, particularly in the context of radiation therapy, which represents a primary treatment modality for localized prostate cancer. In the second year of this grant period, we have generated bioluminescent ETS+ and ETS- cells in three different prostate cancer cell lines, and we havereceived institutional approval to proceed with the proposed animal studies and human biomarker tissue studies.

关键词：医药；治疗技术；生物标记；前列腺癌

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Trastuzumab, a monoclonal antibody (mAb) targeting HER-2/neu, kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including natural killer (NK) cells, may improve trastuzumab s efficacy. NK cells that encounter trastuzumabcoated, HER2-overexpressing breast cancer cells become activated and express CD137, a costimulatory receptor. CD137 activation, which is dependent on the Fc RIII receptor, occurred both in vitro and in the peripheral blood of women with HER2- expressing breast cancer following trastuzumab treatment. Stimulation of trastuzumab-activated NK cells with an agonistic mAb against CD137 killed breast cancer cells more efficiently in vitro.

关键词：医药；治疗技术；曲妥单抗疗法；乳腺癌

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