1,721,057 research outputs found

    Effects of gliadin stimulation on bone marrow-derived dendritic cells from HLA-DQ8 transgenic MICE

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    Gliadin presentation by HLA-DQ2/8 molecules to T cells plays a crucial role in triggering the inflammatory cascade in coeliac disease. We aimed to study the immunological effects of gliadin stimulation on dendritic cells (DCs) from HLA-DQ8 transgenic and BALB/c mice

    Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells

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    In recent years, numerous studies have supported the use of topical blood components to improve wound healing and tissue regeneration. Platelet gel (PG), a hemocomponent obtained from mix of activated platelets (PLTs) and cryoprecipitate,1 is currently being used clinically in reconstructive, cosmetic, orthopedic, cardiovascular, oral maxillofacial, and dermatologic surgery in an attempt to improve tissue healing.2,3 PLTs have concentrated levels of naturally occurring growth factors and other substances that have the potential to accelerate tissue repair4-6 by influencing several cellular processes including chemotaxis, cell proliferation, cell differentiation, angiogenesis, matrix deposition, and tissue remodeling.7,8 Previous studies have demonstrated that the healing process might be accelerated by the use of PG. Compared with lesions of patients treated by conventional methods, the sternal dehiscent wounds and skin necrotic ulcers of patients treated with PG recovered more rapidly.9 Moreover, patients treated by partial mandibulectomies for malignant tumors experienced satisfactory mandibular reconstructions when PLT-rich plasma was combined with autologous bone grafts.10 Despite the promising clinical results, PG use has proceeded in a totally empirical way, mainly grounding on experience of individual doctors, and the most effective PG concentration to promote wound healing has not yet been determined. In this study, the effects of PG-released supernatant at different concentrations on angiogenesis (process involved in tissue reparation mechanism) were investigated using different in vitro assays (proliferation, migration, invasion, cord formation, and wound healing)

    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

    Cathepsin B mediates the pH-dependent proinvasive activity of tumor-shed microvesicles

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    Vesicles shed by cancer cells are known to mediate several tumor-host interactions. Tumor microenvironment may, in turn, influence the release and the activity of tumor-shed microvesicles. In this study, we investigated the molecular mediators of the pH-dependent proinvasive activity of tumor-shed vesicles. Gelatinase zymography showed increased microvesicle activity of matrix metalloproteinases 9 and 2 as a result of acid exposure (pH 5.6) compared to pH 7.4. Thus, we reasoned that the cysteine protease cathepsin B might play a role in mediating the pH-dependent activation of gelatinases. Cathepsin B expression in tumor-shed microvesicles was confirmed by Western blot analysis and zymography. The activity of vesicle-associated cathepsin B measured using Z-Arg- Arg-pNA as substrate was significantly increased at acidic pH values. Inhibition of protease activity by the cysteine protease inhibitor, E-64, and treatment of ovarian cancer cells with small interfering RNA against cathepsin B suppressed the ability of tumor-shed microvesicles to stimulate both gelatinase activation and the invasiveness of endothelial cells observed at low pH values. We conclude that microvesicle shedding is a major secretory pathway for cathepsin B release from tumor cells. Hence, the acidic microenvironment found in most solid tumors may contribute to cathepsin B–mediated proinvasive capabilities of tumor-shed vesicle

    Akt down-modulation induces apoptosis of human prostate cancer cells and synergizes with EGFR tyrosine kinase inhibitors

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    BACKGROUND. PTEN is a well-characterized tumor suppressor that negatively regulates cell growth and survival through the modulation of PI3K/Akt pathway. METHODS. In this paper, we investigated the effects of an PI3K/Akt inhibitor, perifosine, in human prostate cancer (PCa) cells analyzing cell proliferation, apoptosis, and the synergy with EGFR inhibitors. RESULTS. Clinically achievable concentrations of perifosine, as well as Akt gene knockdown, induced a G0/G1 arrest and apoptosis in PTEN defective PCa cells. Although PTEN introduction was able to restore the control of Akt activity and to reduce cell proliferation, the manipulation of PTEN gene was not able alone to influence apoptosis. Perifosine induced apoptotic program also in PTEN positive cells when Akt activity was augmented by EGF suggesting the possibility that this drug could be used in combination with EGFR inhibitors. The combination treatment between erlotinib and pharmacological or molecular Akt knockdown, indeed, showed synergistic effects. This is the first demonstration that a pharmacological compound against Akt activity can restore the efficacy against EGFR inhibitors in PCa and has important therapeutic fallout since EGFR inhibitors have demonstrated very low effectiveness in PCa patients. CONCLUSIONS. Taken together our data have an important clinical relevance in the treatment of advanced prostate tumors. However, further studies in the setting of combination therapies in advanced PCas are necessary
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