Biobanks are collections of biological samples (e.g. tissues, blood and derivatives, other body fluids, cells, DNA, etc.) and their associated data. Consequently, human biobanks represent collections of human samples and data and are of fundamental importance for scientific research as they are an excellent resource to access and measure biological constituents that can be used to monitor the status and trends of both health and disease. Most -omics data trust on a secure access to these collections of stored human samples to provide the basis for establishing the ranges and frequencies of expression. However, there are many open questions and future challenges associated with the large amounts of heterogeneous data, ranging from pre-processing, data integration and data fusion to knowledge discovery and data mining along with a strong focus on privacy, data protection, safety and security.

关键词：生物库；个性化医药；大数据

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Autism is an extremely common and heterogeneous neurodevelopmental disorder. While genetic factors are known to play a critical role in the etiologies of autism, the underlying genes and mechanisms remain unknown in approximately 70-75% of cases. Advances in technology and our understanding of the causes of autism are occurring at a rapid pace, affecting standards for clinical patient care. The purpose of the central Ohio registry for autism (CORA) is to develop a comprehensive autism registry for genetic and other studies for military and civilian families in central Ohio. Congressionally- supported funding for the project was secured, beginning in late 2009 (total $2.77 million, September 30, 2009-December 31, 2012). The specific aims of the project are to support (1) development of the CORA registry; (2) expansion of diagnostic and treatment services for WPAFB families through a collaboration with Dayton Children's Medical Center (DCMC); (3) molecular studies to identify novel autism susceptibility genes; and (4) cost and satisfaction analyses for the military services components in Aim 2.

关键词：遗传图谱；染色体；发育生物学

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Our research program is to study the role and underlying mechanisms of breast cancer stem/progenitor cells in antiestrogen resistance. One central subject is to understand the function of a novel estrogen receptor variant, ER- 36, in antiestrogen resistance. In the past year, we have accomplished most of the tasks proposed. We demonstrated that antiestrogen treatment enriched breast cancer stem/progenitor cells and antiestrogens positively regulated the selfrenewal of breast cancer stem/progenitor cells. ER-negative breast cancer cells with knocked-down levels of ER- 36 have less cancer stem/progenitor cells and are sensitive to antiestrogens. We found that ER- 36 mediates agonist activities of antiestrogens such as activation of the PI3K/AKT signaling pathway. In addition, we discovered a novel anticancer agent Broussoflavonol that is able to down-regulate ER- 36 expression, induce differentiation of ER- negative breast cancer stem cells and inhibit growth of these cells. Our results thus demonstrated that ER- 36 plays an important role in the resistance of breast cancer stem/progenitor cells to antiestrogens and provided a rational to development of novel therapeutic approaches by targeting ER- 36, which will ultimately revolutionize current therapeutic approaches.

关键词：乳腺癌；雌激素类；干细胞；阻值

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A retrospective statistical analysis of data obtained from the Janus Program at Argonne National Laboratory was conducted. We assessed the cancerous and non-cancerous tissue toxicities induced by low dose rate fractionated gamma or neutron irradiation and the way in which gender modulates their accumulation. The statistical analysis was done of the data from a study done on mice irradiated with either 2-40 cGy of Janus reactor fission neutrons or 100-600 cGy of 60 Cobalt gamma rays, given in 60 fractions. Dose rates varied between 0.002 0.034 cGy/min for neutrons or 0.083 0.5 cGy/min for gamma rays.

关键词：毒性；组织（生物学）；积累；癌

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This research proposal will provide important insights into cancer mechanisms and blood biomarkers to assess progression and stratification of human glioblastoma. We have collected several tumor specimens to date and have made excellent progress in establishing primary tumor cell cultures from individual tissue samples. These parental cell lines have successfully been used for the generation of quantized tumor cell populations for general molecular characterization, and for evaluating the effectiveness of drug candidates in targeting these cell populations. This program will significantly advance genomic, proteomic and single-cell technologies, which will be generally applicable to all cancer-based studies.

关键词：癌症细胞（生物学）；基因组学；蛋白质组学

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Year one involved hiring and training staff, preparing all regulatory documents and submitting them for approval, initiating participant recruitment, baseline assessment, and follow- up. Year two focused on recruiting for and completing the feasibility phase of the study, and making necessary protocol amendments prior to the full-trial phase of the study. Year three focused on recruitment and data collection for the full trial phase. Year four continued to focus on recruitment and data collection including implementing a mass mailing to aid in the final recruitment push. We were also approved for a one year No Cost Extension.

关键词：临床医学；可行性研究；发病率

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The central hypothesis of this proposal is that changes in the expression of nuclear envelope proteins such as lamins or lamin B receptor (LBR) may contribute to the characteristic irregular morphology of cancer cell nuclei and directly modulate cellular functions relevant to cancer progression. Nuclear lamins, particularly lamins A and C, are important determinants of nuclear shape and stiffness.1-3 At the same time, these proteins also interact with various transcription factors, thereby affecting important signaling pathways.1, 4 The purpose of this study is to conduct a systematic analysis of the functional consequences of changes in the expression of lamins (A, B1, B2, and C) and lamin B receptor on nuclear morphology and stiffness, as well as the functional consequences of such changes on cell migration through confined spaces (where more deformable nuclei may facilitate enhanced passage), proliferation, and epithelial-to-mesenchymal transition (EMT). In addition, we proposed to conduct an analysis of samples derived from breast cancer patients and orthotopic mouse models of the disease to assess changes in the expression of nuclear envelope proteins in breast cancer samples.

关键词：乳腺癌细胞（生物学）；核结构；蛋白质类

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Staphylococcus aureus methicillin-resistant and methicillin- susceptible (MRSA/MSSA) is a leading cause of infections in military personnel, but there are limited data regarding baseline colonization of individuals while deployed. We conducted a pilot study to screen non-deployed and deployed healthy military service members for MRSA/MSSA colonization at various anatomic sites and assessed isolates for molecular differences.

关键词：菌落（生物学）；金黄色葡萄球菌；解剖学

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The vascular endothelial growth factor (VEGF) family of cytokines promotes vascularization, tumorigenesis and metastasis in many cancers. Our goal is to develop computational models that combine mechanistic topological data on the VEGF protein interaction network with gene expression datasets for a large population of prostate cancers. We have assembled databases of prostate cancer gene expression data, and analyzed the data using bioinformatic techniques, identifying key VEGF-based subgroups of prostate cancer plus biomarkers that identify these groups. We have also created new computational models to simulate prostate cancer, based on the individualized gene expression data. These models will be used to simulate therapies that target the pathway. The therapies to be tested include anti-ligands such as bevacizumab but also anti-receptors and small molecules such as tyrosine kinase inhibitors. In this way, we can build on both the successes and the failures of anti-VEGF trials to date in order to develop more effective therapies for prostate cancer. This progress will continue, and we will be able to develop models of therapies including bevacizumab and other drugs, in order to design improved therapeutic approaches (both for individuals and for the population).

关键词：转移；前列腺癌；飞行速度；生长（生理学）

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Protein kinase C epsilon (PKCe), a member of the PKC family of phorbol ester/diacylglycerol receptors, is up-regulated in many human cancers, including prostate cancer. We recently demonstrated that PKCe is an essential mediator of NF-kB activation in prostate cancer (Garg et al., JBC, 287, 37570 37582, 2012). In this research, we wish to determine if PKCe regulates TNFa- signaling to mediate its effect on NF-kB activation. Using a specific PKCe antagonist, we demonstrated that PKCe plays essential role in the TNFa-induced phosphorylation of TNF receptor in prostate cancer cells. We have previously identified that PKCe regulates NF-kB responsive genes in prostate cancer cells, including cyclooxygenase-2 (COX-2) (JBC, 2012). COX-2 has been reported to be up-regulated in metastatic prostate cancer. As PKCe plays an important role in prostate cancer cell survival and cooperates with other oncogenic insults, herein we aim to determine if PKCe regulates COX-2 activation during prostate tumorigenesis. We observe that PKCe RNAi depletion diminishes constitutive and stimulated COX-2 mRNA expression and PGE2 levels in prostate cancer cells. Conversely, PKCe overexpression by adenoviral means potentiates COX-2 expression in LNCaP cells. Thus, our study characterizes a novel molecular link between PKCe and NF-kB/COX-2 and its implication in survival pathways in prostate cancer.

关键词：前列腺癌；细胞（生物学）；酯类；基因

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