Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines and cancer lesions as compared to the adjacent normal/benign tumor tissues. Under this project, we have utilized multiple approaches to demonstrate a functional role of PP2A in human prostate cancer progression. Specifically, we have generated and characterized stable PPP2CA overexpression (C4-2 and PC3) and knockdown (LNCaP) transfectants and obtained experimental evidence (in vitro) for the role of PP2A downregulation in growth, androgen depletion- resistance and aggressive behavior of prostate cancer cells. We have also developed in vivo experimental support for a suppressor role of PP2A in prostate cancer progression using orthotopic mouse model. Our data strongly suggest that downregulation of PP2A is associated with human prostate cancer progression and restoration of PP2A activity may be an effective approach for the treatment of the advanced disease.

关键词：前列腺癌激素;磷酸酶;;蛋白质;行为;细胞(生物学);疾病;增长(生理学)

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Depression is a complex mental illness associated with disability and reduced quality of life for the person with depression, as well as substantial societal burden. Major depressive disorder (MDD) is the second leading medical cause of long-term disability, the fourth leading cause of global burden of disease, and is predicted to become the second highest cause of disability by 2020. Depression exerts a negative impact on physical health; it reduces adherence to medical treatment, reduces participation in preventive activities, and increases the likelihood of risk factors such as obesity, smoking, and sedentary lifestyles. MDD may be associated with immune dysfunction and cardiovascular disease, endocrine and neurological diseases, and a general increase in chronic disease incidence. The primary goal of this comparative effectiveness review is to examine the evidence guiding clinical treatment decisions and ultimately to aid clinicians in their care of patients when selective serotonin reuptake inhibitors (SSRIs) therapy for an index episode does not result in an adequate treatment response.

关键词：临床治疗;抑郁;搜索策略;患者;治疗反应;数据提取

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This summary describes chronic pelvic pain and explains research about therapies for women with this condition. It can help you talk with your doctor about treating or managing chronic pelvic pain.

关键词：慢性疼痛;骨盆疼痛;女性;治疗;医疗保险

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Horizon scanning is an activity undertaken to identify technological and system innovations that could have important impacts or bring about paradigm shifts. In the health care sector, horizon scanning pertains to identification of new (and new uses of existing) pharmaceuticals, medical devices, diagnostic tests and procedures, therapeutic interventions, rehabilitative interventions, behavioral health interventions, and public health and health promotion activities. In early 2010, the Agency for Healthcare Research and Quality (AHRQ) identified the need to establish a national Healthcare Horizon Scanning System to generate information to inform comparative-effectiveness research investments by AHRQ and other interested entities. AHRQ makes those investments in 14 priority areas. For purposes of horizon scanning, AHRQs interests are broad and encompass drugs, devices, procedures, treatments, screening and diagnostics, therapeutics, surgery, programs, and care delivery innovations that address unmet needs. Thus, we refer to topics identified and tracked in the AHRQ Healthcare Horizon Scanning System generically as interventions. The AHRQ Healthcare Horizon Scanning System implementation of a systematic horizon scanning protocol (developed between September 1 and November 30, 2010) began on December 1, 2010. The system is intended to identify interventions that purport to address an unmet need and are up to 7 years out on the horizon and then to follow them for up to 2 years after initial entry into the health care system. Since that implementation, more than 7,000 leads about topics have resulted in identification and tracking of more than 900 topics across the 14 AHRQ priority areas.

关键词：消化性溃疡疾病、消化不良的治疗干预措施,鞭虫,蠕虫治疗,溃疡性结肠炎

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Bone is the most common site of metastasis for human breast cancer (BCa), which results in significant morbidity and mortality in patients with advanced disease. A vicious cycle, arising due to the interaction of BCa cells and cells in the bone microenvironment results in the activation of osteoclasts and increased osteolytic bone destruction. The major treatment to reduce the burden of bone metastasis in BCa patients is bisphosphonate therapy. Despite significant efforts to improve the potency of bisphosphonates, the complications are only retarded but not prevented. Thus, development of newer therapies that can both ameliorate the threshold of bone destruction and increase survival of patients with metastatic breast disease will be highly beneficial. The central hypothesis of the proposed work is bone-targeted delivery of genetically-engineered MSC, over-expressing OPG, will prevent osteolytic bone damage and restore skeletal remodeling. Further, based on the requirement of angiogenesis for tumor growth in primary and metastatic sites, in combination with a systemically stable anti-angiogenic therapy, long-term survival will significantly increase. These hypotheses will be tested in this proposal using an immnocompetent, preclinical mouse model of BCa dissemination to all major bones as in human patients.

关键词：骨头;乳腺癌;转移;临床医学;发病率;死亡率

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In the second year of this training grant, 11 faculty members, 7 postdocs, 4 graduate and 6 undergraduate students from 6 departments at the Howard University have been trained in the use of nanoparticles as targeted drug delivery vehicles for cancer diagnosis and therapy. Ten seminars and workshops in cancer, molecular imaging, and nanomedicine have been offered. The trainees have received hands-on training in MRI, optical imaging, cell biology lab techniques, and small animal handling. The two research projects have progressed well. We have improved controlling the size of liposome with a heat sonic method. We studied the stability of surface coating of quantum dots as a model for studying potential toxicity of nanoparticles. We have shown that A- dmDT(390)-scfbDb(PSMA), a single chain Fv fragments of antibody with diphtheria toxin, demonstrates good dual targeted imaging and therapeutic properties. We have shown that a contrast agent encapsulated in liposome with transferrin as a targeting ligand has higher uptake in breast cancer cells and in tumor bearing animals. This year, there are 11 research projects utilizing the facility of the Nanomedicine Core. The Core has become a synergy center, drawing multidisciplinary research using nanotechnology for cancer research.

关键词：乳腺癌;细菌毒素;细胞(生物学);白喉杆菌;诊断(医学)

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Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a systems biology; approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the bodys response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

关键词：外星辐射生物效应;;辐射剂量;辐射防护;放射化学;治疗;防辐射药物

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The objective of this report is to update a 2007 systematic review on the effectiveness and safety of treatments to prevent fractures in persons with low bone density or osteoporosis and factors affecting adherence to these treatments, and to assess whether monitoring helps identify those most likely to benefit from treatment and the benefits of long-term treatment.

关键词：骨折;骨质疏松;疾病预防;治疗

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This future research needs (FRN) report is based on an Agency for Healthcare Research and Quality (AHRQ) comparative effectiveness review (CER) titled First- and Second-Generation Antipsychotics for Children and Young Adults. The purpose of the CER was to review and synthesize the evidence regarding the benefits and harms of first- and second-generation antipsychotics (FGAs and SGAs) (see Tables A and B) for the treatment of various psychiatric and behavioral conditions in individuals 24 years of age or younger. Table C shows the key questions from this CER.

关键词：抗精神病药物;儿童;成年人;药物;研究需求;行为障碍

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America's investment in cancer research has vastly expanded and deepened our understanding of the many diseases called cancer. Some of the genetic and environmental factors and biologic mechanisms that cause or contribute to cancer development, progression, and spread have been elucidated. This knowledge has led to the development of diverse interventions to reduce risk of cancer and more effectively treat some cancers, enabling many individuals to survive diseases that previously were almost universally fatal. Although notable, these achievements do not obscure the fact that cancer prevention and cure remain largely elusive. Given the complex nature of cancer and the lack of screening methods to detect most types of cancer, progress against some cancers has been slower than for others. Between September 2010 and, February 2011, the President's Cancer Panel (the Panel) convened four meetings to evaluate opportunities to accelerate the development of Innovations with the potential to dramatically improve cancer outcomes. The Panel received testimony from 47 experts from the academic, industnal. not-for-profit, and public sectors. The speakers Included basic, translational. clinical. and population science researchers and research program administrators; voluntary sector research sponsors; health and science policy specialists; representatives from the cancer advocacy community; professional and industry association representatives; and Federal Government regulators and administrators.

关键词：癌症;医学研究;会议;科技创新;流行病学;基因

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