1,145 research outputs found

    Hypertension and reduced renal function: a rebuttal

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    An Exact Solution for the Lattice Gas Model in One Dimension

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    A simple method to obtain a canonical partition function for one dimensional lattice gas model is presented. The simplification is based upon rewriting a sum over all possible configurations to a sum over numbers of clusters in the system.Comment: 6 pages, LaTe

    Infection by high-risk human papillomaviruses, epithelial-to-mesenchymal transition and squamous pre-malignant or malignant lesions of the uterine cervix: a series of chained events?

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    : Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor

    Dissociation of CH Species on Ni(111):A HREELS Study

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    The isothermal dissociation rate of CCH and CH on Ni(111) was measured by following, with HREEL spectroscopy, the intensity of the CH stretching peak as a function of time. By repeating the experiment at several different temperatures we obtained an activation energy of 8±3 kcal/mol for the CCH dissociation reaction and of 12±3 kcal/mol for the CH dissociation reaction. Pre-exponential factors were found to be 10^3±1 s-1 in both cases. Independent thermal desorption spectra show a feature at 470 K and a tail extending up to 600 K which can be assigned to the CCH dissociation and the CH dissociation respectively. The two experiments are quantitatively consistent

    2D-DIGE analysis of ovarian cancer cell responses to cytotoxic gold compounds

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    Cytotoxic gold compounds hold today great promise as new pharmacological agents for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2D-DIGE analysis to identify differential protein expression in a cisplatin-sensitive human ovarian cancer cell line (A2780/S) following treatment with two representative gold(III) complexes that are known to be potent antiproliferative agents, namely AuL12 and Au2Phen. Software analysis using DeCyder was performed and few differentially expressed protein spots were visualized between the three examined settings after 24h exposure to the cytotoxic compounds, implying that cellular damage at least during the early phases of exposure is quite limited and selective reflecting the attempts of the cell to repair damage and to survive the insult. The potential of novel proteomic methods to disclose mechanistic details of cytotoxic metallodrugs is herein further highlighted. Different patterns of proteomic changes were highlighted for the two metallodrugs with only a few perturbed protein spots in common. Using MALDI-TOF MS and ESI-Ion trap MS/MS, several differentially expressed proteins were identified. Two of these were validated by western blotting: Ubiquilin-1, responsible for inhibiting degradation of protein such as p53 and NAP1L1, a candidate marker identified in primary tumors. In conclusion, we performed a comprehensive analysis of proteins regulated by AuL12 and Au2Phen, providing a useful insight into their mechanisms of action

    In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.

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    Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21- Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT- 61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer

    Network Planning for Disaster Recovery

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