The purpose of this study was to determine the role of Notch in lymphatic endothelial cell (LEC) behavior and to determine the effects on tumor vasculature upon Notch inhibition.

关键词：血管生成；淋巴结；肿瘤；活化

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Carbon-coated magnetite nanoparticles (NPs) were synthetized by the mechanochemical method with hematite as precursor and amorphous carbon as inorganic reductor. After 18 hours of milling in an inert atmosphere, a nanocomposite material of magnetite and carbon was obtained. Structural and magnetic properties of the NPs were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and vibrating sample magnetometry. XRD patterns, refined with the Rietveld method, show that magnetite is present in samples milled from 6 hours onward and that after milling for 18 hours and annealing in Ar, the sample contains a single crystalline phase. Magnetization curves for samples with different milling times show saturation magnetization values that range from 34.1 emu/g after 1 h to 78.0 emu/g after 18 h. Coercive fields are about 500 Oe for all samples. TEM studies reveal that the samples are made of amorphous carbon clusters with magnetite NPs of 20 nm. The obtained NPs, associated to electrochemical transducers, show an improved enhancement of the charge transfer for redox processes involving different bioanalytes. Thus, these NPs offer unique properties as a catalyst in biosensing strategies for the electrochemical detection of high-impact markers and the development of theranostics smart-devices for biomedical applications.

关键词：磁性纳米粒子；过氧化氢；生物医学

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Aneuploidy is a hallmark of virtually all ovarian cancer cells and is thus indicative of chromosome instability (CIN). CIN may be a preprogrammed strategy of cancer cells to generate enormous genetic and biochemical diversity in a single cell division. CIN therefore allows cancer cells to rapidly evolve and survive suboptimal growth conditions that include drug treatments. The molecular basis of CIN is unclear but we discovered that Aurora B kinase is unable to phosphorylate proteins that are critical for preventing CIN. Restoring Aurora B function can reduce chromosome missegregation in ovarian cancer cells. This strategy should limit their ability to evolve and thus should increase chemosensitivity. We conducted a screen of clinically relevant kinase inhibitors to identify compounds that exhibits off-target effects on the DNA damage checkpoint. Most chemotherapies damage DNA which arrests cells to provide time to repair the damage. Crippling the checkpoint is known to enhance drug sensitivity because cells are forced to enter mitosis with damaged DNA. We identified Bostunib, an FDA approved src/abl inhibitor, as a new checkpoint inhibitor. As compounds specifically designed to inhibit Chk1 were toxic in patients, Bosutinib may provide the first clinically tolerable chemosensitizing agent that targets the DNA damage checkpoint.

关键词：细胞（生物学）；染色体；化疗

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Basal-like breast cancers (BLBCs) generally become resistant to cytotoxic agents and resistance has been attributed to the presence of tumor initiating cancer stem cells (CSCs). Furthermore, LRP6/Wnt appears to play a crucial role in BLBC and CSC progression, and may represent an excellent therapeutic target. We have previously described that TRA-8, a monoclonal antibody specific to death receptor 5, kills both the CSCs and non-CSC population of BLBCs. This study examined two questions: whether niclosamide (an FDA approved antihelminthic, that inhibits Wnt/ -catenin signaling) is cytotoxic to BLBCs and its CSC population; and whether niclosamide in combination with TRA-8 produces synergistic cytotoxicity. We characterized non- adherent tumorsphere enriched (NATE) cells as a CSC enriched population from BLBC cell lines. Both Adherent and NATE cells from 2LMP, SUM159, HCC1187, HCC1143 cell lines and patient pleural effusion samples showed that niclosamide inhibited Wnt/ -catenin pathway activation, down regulated LRP6, and decreased downstream - catenin signaling. The combination of TRA-8 and niclosamide showed additive to synergistic cytotoxicity and further reduced Wnt/ -catenin activity. In vivo studies also showed that intraperitoneal administration of niclosamide in combination with TRA-8 suppressed growth of established 2LMP orthotopic tumor xenografts. Treatment with niclosamide in combination with TRA- 8 may be an effective therapy against BLBC.

关键词：乳腺癌；干细胞；将细胞（生物学）；细胞毒素

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Through this collaborative research effort, we intend to develop quantitative tools with direct applications for patients with glioblastoma. We will pursue new strategies for genome sequencing and new technologies for the genetic analyses of cancer mechanisms, as well as methods for assessment of progression and stratification of human glioblastoma. This proposal will significantly advance genomic, proteomic and single-cell technologies, and the proposed tools will be generally applicable to all cancer-based studies to identify and quantify DNA, RNAs, proteins and cells, challenges ubiquitous to all human disease systems.

关键词：癌症细胞（生物学）；基因组学；蛋白质组学

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Nonmedical use of prescription drugs ranks as the second most common class of illicit drug use in the United States. Recent data indicate that the rate of use declined slightly between 2010 and 2011 and suggest that National, State, and local efforts to reduce prescription drug misuse may be beginning to have an impact. However, with an annual average of 15.7 million people aged 12 or older having misused prescription drugs between 2005 and 2011, there is still much work left to be done. State and local public health authorities are better able to understand and effectively serve their communities if they know the prevalence of nonmedical use of prescription drugs in various types of counties (e.g., metropolitan, urbanized non-metropolitan, and rural). Access to drugs and the delivery of prevention and treatment services may differ by county type.

关键词：药物滥用；非法药物；医药

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Although prostate cancers are initially responsive to androgen deprivation therapy, castration resistant prostate cancer demands alternative treatment options. It has been reported that the apoptotic protease, caspase 2 (C2) is critical for prostate cancer cell death in several settings. Several reports have also indicated that fatty acid synthesis is critical for maintaining prostate cancer cell viability and that inhibition of fatty acid synthesis can lead to apoptosis. Finally, C2 is suppressed by high intracellular NADPH and this is not due to the redox effects of NADPH, suggesting that the synthetic role of NADPH (e.g., in fatty acid synthesis) may account for its ability to suppress apoptosis. Our new data suggest that manipulating metabolism, particularly inhibiting fatty acid synthesis, can alter chemosensitivity in prostate cancer cells.

关键词：脂肪酸；前列腺癌；氨基酸；雄激素

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Research indicates that privately insured, rural adults have lower use of office-based mental health services, but higher use of prescription medicines than their urban counterparts. Similar studies for rural children have been limited to specific populations, diagnoses, or to single states. Patterns for rural children may be different than those of urban children and adults generally because of their high enrollment in Medicaid and the State Children's Health Insurance Program, which tend to have more generous behavioral health benefits than private coverage and may equalize rural-urban treatment patterns. On the other hand, the more limited supply of specialty mental health providers in rural areas, particularly for children, could lead to lack of access and lower utilization of some types of mental health services in rural areas versus urban.

关键词：心理健康服务；农村地区；儿童；心理健康护理

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We have identified NuSAP as prognostic marker up-regulated in recurrent prostate tumors. Our grant aimed at identifying the role of NuSAP in promoting proliferation and invasion in Prostate Cancer and identify genes that upregulate NuSAP expression. To characterize the role and regulation of NuSAP in prostate cancer, we expanded our investigation into looking at critical regulatory elements within the NuSAP promoter region. We identified 2 non- canonical MYC binding sites within the 1000bp of NuSAP promoter. Luciferase expression studies using wildtype and deletion constructs suggested no direct response of MYC on NuSAP promoter region. We also carried out studies to understand whether NuSAP expression is regulated by RB1/E2F1 axis. We found NuSAP expression increased upon knockdown of RB1 and a further reduction of E2F1 resulted in reduction of NuSAP gene and protein suggesting that NuSAP is regulated by the RB1/E2F1 axis.

关键词：前列腺癌；基因；生长（生理学）

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Tobacco use continues to be the leading cause of preventable death in the United States. Despite increased evidence provided in the 2010 Surgeon Generals report that cigarette smoking causes disease and that no level of cigarette use is safe, rates of cigarette use among certain groups of Americans remain high. One group with cigarette use that has garnered both increased attention and concern over the past decade is persons with mental illness. Previous research has shown that rates of cigarette use among persons with mental illness have been significantly higher than rates among persons who do not have mental illness. This report uses data from the 2009 to 2011 National Surveys on Drug Use and Health (NSDUH) to provide up-to-date information on the relationship between smoking and mental illness.

关键词：吸烟；精神障碍；医药

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