Advanced prostate cancers (PCa) treated with first line androgen-deprivation therapy (ADT) eventually relapse in a hormone refractory or castration-resistant (CR) form. 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. We have shown that PP2A downregulation promotes 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. Furthermore, we delineated the molecular mechanisms involved in the PP2A-mediated growth and aggressive phenotypes of PCa cells. We observed PP2A downregulation facilitates castration-resistant growth of PCa cells in both androgen receptor (AR)-dependent and independent manners in AR expressing (LNCaP and C4-2) cells. Moreover, we identified that PPP2CA downregulation favors EMT, migration and invasion of PCa cells through Akt-dependent activation of catenin and NF-B pathway. 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；雄激素；细胞（生物学）

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Based on our published data we propose that specific patterns of genomic copy number alterations (CNAs) occur in prostate cancer in African American (AA) men which are associated with different levels of disease aggressiveness.

关键词：前列腺癌；非洲裔美国人；基因；基因组学

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Apoptin-containing nanocapsules have been shown to be efficiently internalized by mammalian cells and induce tumor-specific apoptosis in vitro and in vivo. Identification of targeting moieties can further improve the efficacy of these nanoparticles. Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. We demonstrated a targeting strategy by conjugating nanoparticles with a tumor-penetrating peptide, iRGD. The results showed that iRGD could facilate the binding and cellular uptake of nanoparticles. Colocalization data revealed that iRGD-conjugated nanoparticles entered cells via the clathrin- mediated pathway, followed by endosome-lysosome transport. In addition, we were able to demonstrate that the biofunctional chelator AmBaSar could be used in the 64Cu labeling of nanoparticles and the positron emission tomography-based images of particle distribution could be obtained at several time points after intravenous administration of nanoparticles. Our data support the further experiment to use iRGD for targeting nanocapsules and to use PET imaging for investigating bioditribution of nanocapsule in vivo.

关键词：乳腺癌；凋亡细胞（生物学）；肿瘤；蛋白质

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Bone tumor metastasis is the major cause of mortality and morbidity in advanced prostate cancer patients. These patients frequently suffer from moderate to severe chronic bone pain. However, the current treatments for these patients are ineffective and non-curative, because metastatic tumors are resistant to most of the current anti-cancer treatments, and the currently used pain therapeutic medications or analgesics often do not provide effective relief from pain due to the development of tolerance upon chronic use, and also have serious side effects. Thus, it is imperative to develop novel approaches that can both effectively block tumor growth in bones and relieve the associated bone cancer pain. This proposal aims to define the key role of the G subunits of heterotrimeric G proteins in the development of prostate tumor bone metastasis and the associated bone pain. Our studies by far have demonstrated that G signaling plays a key role in mediating proliferation of several prostate cancer cell lines, including LNCaP, PC3, DU145 and 22Rv1. Blocking G signaling decreases prostate cancer cell growth by increasing apoptosis. Moreover, we show that G mediates the effect of multiple G protein-coupled receptorstimulated tumor cell migration and invasion. Finally, we have identified several signaling pathways, including PI3K/AKT, ERK and calcium signaling that are activated downstream of G and could potential contribute to prostate tumor progression.

关键词：骨头；前列腺癌；止痛药；细胞（生物学）

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Alternative lengthening of telomeres (ALT) is a mechanism utilized by several cancer types to maintain telomeres.

关键词：乳腺癌细胞（生物学）；遗传学；基因组

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Human liver prolidase, a metal-dependent dipeptidase, is being tested as a potential catalytic bioscavenger against organophosphorus (OP) chemical warfare nerve agents. The purpose of this study was to determine whether persistent and high-levels of biologically active and intact recombinant human (rHu) prolidase could be introduced in vivo in mice using adenovirus (Ad). Here, we report that a single intravenous injection of Ad containing the prolidase gene with a 6x histidine-tag (Ad-prolidase) introduced high-levels of rHu prolidase in the circulation of mice which peaked on days 5 7 at 159 129 U/ mL. This level of prolidase is approximately 120 times greater than that of the enzyme level in mice injected with Ad-null virus. To determine if all of Ad- prolidase-produced rHu prolidase was exported into the circulation, enzyme activity was measured in a variety of tissues. Liver contained the highest levels of rHu prolidase on day 7 (5647 454 U/g) compared to blood or any other tissue. Recombinant Hu prolidase hydrolyzed DFP, a simulant of OP nerve agents, in vitro. In vivo, prolidase overexpression extended the survival of 4 out of 6 mice by 4 8 h against exposure to two 1 x LD50 doses of DFP. In contrast, overexpression of mouse butyrylcholinesterase (BChE), a proven stoichiometric bioscavenger of OP compounds, protected 5 out of 6 mice from DFP lethality and surviving mice showed no symptoms of DFP toxicity. In conclusion, the results suggest that gene delivery using Ad is capable of introducing persistent and high levels of human liver prolidase in vivo. The gene-delivered prolidase hydrolyzed DFP in vitro but provided only modest protection in vivo in mice, delaying the death of the animals by only 4 8 h.

关键词：腺病毒；基因表达；肝；含量测定

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Among prominent mechanisms thought to impede the anticancer response is the accumulation of pro-tumor myeloid populations. However, there is a fundamental gap regarding the mechanisms that drive their accumulation. To that end, we originally hypothesized that tumor-derived granulocyte-colony stimulating factor (G-CSF) production in ovarian cancer facilitates this aberrant myelopoietic response. However, during year-1, we made the discovery implicating tumor-derived IL-8 in the mechanism of ovarian cancer-mediated immune suppression. Accordingly, this observation prompted us to further evaluate the potential clinical significance of IL-8. To do so, we analyzed the relationship between blood IL-8 levels and newly acquired de-identified patient survival data and, unfortunately, found no significant connection between these clinical factors. Consequently, we reassessed the potential clinical merit of five other myelopoietic factors we had previously identified. Interestingly, only IL-6 fulfilled three important clinical criteria. Altogether, we found that the levels of IL-6: (1) were significantly higher in patients than matched healthy donors; (2) strongly correlated with the accumulation of myeloid populations commonly observed in ovarian cancer patients; and (3) were inversely associated with patient outcome; that is, rising IL-6 levels portended worse overall survival. Although the tumor factor identified is different from the original premise, the conceptual advances made are still consistent with the original hypothesis.

关键词：卵巢癌；免疫抑制；免疫治疗；肿瘤

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Green technologies have been around since the first public health projects were set up in cities to provide people with clean drinking water. To date, a new generation of green technologies is expected to arrive, as pressures on resources grow and investors see healthy profit in a wide range of innovative products. Moreover, in an attempt to alleviate fossil fuel usage and CO_2 emissions, fuels, heat or electricity must be produced from biological sources in a way that is economic (and therefore efficient at a local scale), energetically (and greenhouse gas) efficient, environmentally friendly and not competitive with food production. Aims to advance the development of clean technologies using nanotechnology, to minimize potential environmental and human health risks associated with the manufacture and use of nanotechnology products in general, to apply nano to solve legacy environmental problems, and to encourage replacement of existing products with new nanoproducts, bionanotechnology, a new crosscutting technology platform, will build an environmentally sustainable society in the 21st century. Therefore, aim to provide vital information about the growing field of nanomaterials formed by green nanotechnology for bioapplication to minimize the potential human health and environmental risk, the technologies included author's own research (such as nanoparticles/NPs, carbon nanotubes/CNTs, and membranes) based on bionanotechnology for the friendly environment are reviewed. Furthermore, the current development and future prospects related to the significantly feasible world's eco-bionanotechnology for the foreseeable future are also pointed out.

关键词：色纳米技术；生物纳米技术；人类健康；生态环境

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Text is a very important type of data within the biomedical domain. For example, patient records contain large amounts of text which has been entered in a non-standardized format, consequently posing a lot of challenges to processing of such data. For the clinical doctor the written text in the medical findings is still the basis for decision making -neither images nor multimedia data. However, the steadily increasing volumes of unstructured information need machine learning approaches for data mining, i.e. text mining. This paper provides a short, concise overview of some selected text mining methods, focusing on statistical methods, i.e. Latent Semantic Analysis, Probabilistic Latent Semantic Analysis, Latent Dirichlet Allocation, Hierarchical Latent Dirichlet Allocation, Principal Component Analysis, and Support Vector Machines, along with some examples from the biomedical domain. Finally, we provide some open problems and future challenges, particularly from the clinical domain, that we expect to stimulate future research.

关键词：文本挖掘；自然语言处理；非结构化信息；生物医学

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Fanconi anemia (FA) is a rare disease characterized by developmental defects, progressive bone marrow failure (BMF) and pronounced cancer susceptibility. The FA proteins and the major breast cancer susceptibility gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have demonstrated that the FA-BRCA pathway plays an important role in the response of hematopoietic stem and progenitor cells to cellular stresses, and in particular oxidative stress caused by elevated levels of reactive oxygen species (ROS). In our research proposal, we have hypothesized that the FA-BRCA pathway may play an important role in the prevention of genome-wide de novo copy number variation. Chromosome copy number variation refers to gains or losses of large (>10 kb) genomic DNA segments. While copy number variation is a feature of normal genetic variation it is also strongly associated with genetic disease, including autism and psychiatric disorders. In addition, several recent studies have demonstrated that hematological malignancies show large numbers of de novo somatically acquired copy number variants (CNVs).

关键词：贫血细胞（生物学）；染色体；遗传性疾病

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