1,720,998 research outputs found

    The Role Of Nitric Oxide After Repeated Low Dose Photodynamic Treatments In Prostate Carcinoma Cells

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    Photodynamic therapy (PDT) is a clinically approved treatment that causes a selective cytotoxic effect in cancer cells. In addition to the production of singlet oxygen and reactive oxygen species, PDT can induce the release of nitric oxide (NO) by up-regulating nitric oxide synthases (NOS). Since non-optimal PDT often causes tumor recurrence, understanding of the molecular pathways involved in the photoprocess is a challenging task for scientists. The present study has examined the response of the PC3 human metastatic prostate cancer cell line, following repeated low-dose pheophorbide a treatments, mimicking non-optimal PDT treatment. The analysis was focused on the NF-kB/YY1/RKIP circuitry as it is (i) dysregulated in cancer cells (ii) modulated by NO and (iii) correlated with the epithelial to mesenchymal transition (EMT). We hypothesized that a repeated treatment of non-optimal PDT induces low levels of NO that lead to cell growth and EMT via regulation of the above circuitry. The expressions of gene products involved in the circuitry and in EMT were analyzed by western blot. The findings demonstrate the cytoprotective role of NO following non-optimal PDT treatments that was corroborated by the use of l-NAME, an inhibitor of NOS

    Repeated sub-optimal photodynamic treatments with pheophorbide a induce an epithelial mesenchymal transition in prostate cancer cells via nitric oxide

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    Photodynamic therapy (PDT) is a clinically approved treatment that causes a selective cytotoxic effect in cancer cells. In addition to the production of singlet oxygen and reactive oxygen species, PDT can induce the release of nitric oxide (NO) by up-regulating nitric oxide synthases (NOS). Since non-optimal PDT often causes tumor recurrence, understanding the molecular pathways involved in the photoprocess is a challenging task for scientists. The present study has examined the response of the PC3 human metastatic prostate cancer cell line following repeated low-dose pheophorbide a treatments, mimicking non-optimal PDT treatment. The analysis was focused on the NF-kB/YY1/RKIP circuitry as it is (i) dysregulated in cancer cells, (ii) modulated by NO and (iii) correlated with the epithelial to mesenchymal transition (EMT). We hypothesized that a repeated treatment of non-optimal PDT induces low levels of NO that lead to cell growth and EMT via the regulation of the above circuitry. The expressions of gene products involved in the circuitry and in EMT were analyzed by western blot. The findings demonstrate the cytoprotective role of NO following non-optimal PDT treatments that was corroborated by the use of L-NAME, an inhibitor of NOS

    Emerging Role of NO-Mediated Therapeutics

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    The free radical nitric oxide (NO) is fundamental in the neoplastic environment. At low concentrations, the gasotransmitter manifests a pathological phenotype characterized by uncontrolled proliferation, increased invasion and metastasis, stimulation of angiogenesis and inhibited apoptosis. Paradoxically, at superphysiological concentrations, a less aggressive phenotype exists, where tumor cells are less likely to metastasize, angiogenesis is inhibited, and apoptotic machinery operates appropriately. This dichotomy of response to NO has created a divergence in the field, with some researchers set on interfering with NO signaling in cancer cells, and others endeavoring to boost it. The purpose of this chapter is to examine the activity of NO in oncology, and to highlight the recent advances in NO-mediated therapeutics. We have focused on emerging strategies that act either by promotion of or interference with NO signaling, including genetic therapies, and have largely limited topics discussed to discoveries from the past 18 months. Attention is paid to agents that have been or are being assessed at clinical trial, and the chapter concludes with a cautionary note on the appropriate use of NO-mediated therapies in oncology.<br/

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Therapeutic Impact of Immune Responses in Cancer

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    Therapeutic targeted oncoimmunology has a long history reaching back to the nineteenth century and represents the basis of modern tumor immunology. Cell biological and molecular genetic techniques have uncovered crucial cellular and molecular mechanisms underlying effective cancer immunotherapies used in the clinic. To illustrate the scientific way that led to actual insights into the molecular and cellular approaches realized in recent cancer therapies, this chapter introduces into the history of oncoimmunology. Experimental findings of adoptive cell transfer-based cancer therapy are summarized under functional, immunological aspects. An actual overview of the antitumor prosperity of all genetically engineered tumor cells expressing recombinant cytokines which were characterized by animal experiments is given. The application of antigen-presenting cells which are triple transgenic for immune stimulatory cytokines, tumor specific antigens, and the correlated major histocompatibility complex class I necessary for tumor antigen presentation is explained exemplarily. A recent experimental animal model characterizing critical parameters for preconditioning the host prior to ACT of transgenic T cells and essential therapeutic conditions is described

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Leukoregulin transmembrane signals and regulation of cell growth

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    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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