335 research outputs found

    Successful remission of extensive liver metastases in a breast cancer patient with acute liver failure using a combined chemotherapy regimen with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU)

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    Liver failure due to disseminated hepatic secondaries represents a therapeutic dilemma in patients with metastatic breast cancer (MBC). Reduced liver function and non-assessable toxicity are limiting factors in the selection of chemotherapeutic agents. Currently, there is no standard treatment after failure of anthracycline-and taxane-based first-line therapies, although there is a variety of well evaluated drugs such as capecitabine

    High emission rate of sulfuric acid from Bezymianny volcano, Kamchatka

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    High concentrations of primary sulfuric acid (H2SO4) in fumarolic gases and high emission rate of sulfuric acid aerosol in the plume were measured at Bezymianny volcano, an active dome-growing andesitic volcano in central Kamchatka. Using direct sampling, filter pack sampling, and differential optical absorption spectroscopy measurements, we estimated an average emission of H2SO4 at 243 ± 75 t/d in addition to an average SO2 emission of 212 ± 65 t/d. The fumarolic gases of Bezymianny correspond to arc gases released by several magma bodies at different stages of degassing and contain 25-92% of entrained air. H2SO4 accounts for 6-87 mol% of the total sulfur content, 42.8 mol% on average, and SO2 is the rest. The high H2SO4 in Bezymianny fumaroles can be explained by catalytic oxidation of SO2 inside the volcanic dome. Because sulfate aerosol is impossible to measure remotely, the total sulfur content in a plume containing significant H2SO4 may be seriously underestimated

    Research on atmospheric volcanic emissions: An overview

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    The project Research on Atmospheric Volcanic Emissions is a unique effort by NASA and university scientists to investigate the detailed chemical nature of plumes from volcanic eruptions. The major goals of the project are to: 1) understand the impact major eruptions will have on atmospheric chemistry processes, 2) understand the importance of volcanic emissions in the atmospheric geochemical cycles of selected species, 3) use knowledge of the plume chemical composition to diagnose and predict magmatic processes. Project RAVE\u27S first mission used the NASA Lockheed Orion P-3 outfitted with equipment to measure concentrations of the gases SO2, OCS, H2S, CS2, NO, O3and trace elements in particles in Mt. St. Helens\u27 plume on September 22, 1980. Measurements of SO2 column densities in the plume permitted calculations of SO2 fluxes. This article is an overview of the first experimental design factors and performance of the initial RAVE experiment

    Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

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    Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

    Tono-Pen XL tonometry during application of a suction ring in rabbits

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study is to evaluate the use of Tono-Pen XL in measuring IOP during the application of a suction ring in rabbit eyes with manometrically controlled IOP.</p> <p>Methods</p> <p>Tono-Pen XL was calibrated against direct manometry in 10 rabbit eyes. A suction ring was then applied in 4 rabbit eyes and the IOP was determined manometrically during suction ring application at 350 mmHg vacuum pressure. Finally, in 6 catheterized rabbit eyes the IOP was measured with Tono-Pen XL during suction ring application at suction vacuum from 350 to 650 mmHg, while keeping actual IOP stable at 30 mmHg and 60 mmHg.</p> <p>Results</p> <p>Linear regression analysis revealed that the Tono-pen XL was reliable for IOPs between 10 and 70 mmHg (R<sup>2 </sup>= 0.9855). Direct manometry during suction ring application showed no statistically significant variation of Tono-Pen XL readings when the incanulation manometry intraocular pressure changed from 30 mmHg to 60 mmHg and no statistically significant correlation between suction vacuum and IOP measurements.</p> <p>Conclusion</p> <p>Tono-Pen XL measurements are unreliable during the application of a suction ring on living rabbit eyes even when the actual IOP is forced to be within the validated range of Tono-Pen XL measurements. This inaccuracy is probably related to altered corneal and scleral geometry and stress.</p

    JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression

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    Oncogenic KRAS has been difficult to target and currently there is no KRASbased targeted therapy available for patients suffering from KRASdriven lung adenocarcinoma (AC). Alternatively, targeting KRASdownstream effectors, KRAScooperating signaling pathways or cancer hallmarks, such as tumorpromoting inflammation, has been shown to be a promising therapeutic strategy. Since the JAKSTAT pathway is considered to be a central player in inflammationmediated tumorigenesis, we investigated here the implication of JAKSTAT signaling and the therapeutic potential of JAK1/2 inhibition in KRASdriven lung AC. Our data showed that JAK1 and JAK2 are activated in human lung AC and that increased activation of JAKSTAT signaling correlated with disease progression and KRAS activity in human lung AC. Accordingly, administration of the JAK1/2 selective tyrosine kinase inhibitor ruxolitinib reduced proliferation of tumor cells and effectively reduced tumor progression in immunodeficient and immunocompetent mouse models of KRASdriven lung AC. Notably, JAK1/2 inhibition led to the establishment of an antitumorigenic tumor microenvironment, characterized by decreased levels of tumorpromoting chemokines and cytokines and reduced numbers of infiltrating myeloid derived suppressor cells, thereby impairing tumor growth. Taken together, we identified JAK1/2 inhibition as promising therapy for KRASdriven lung AC.(VLID)510233

    Age-related gene expression in luminal epithelial cells is driven by a microenvironment made from myoepithelial cells

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    Luminal epithelial cells in the breast gradually alter gene and protein expression with age, appearing to lose lineage-specificity by acquiring myoepithelial-like characteristics. We hypothesize that the luminal lineage is particularly sensitive to microenvironment changes, and age-related microenvironment changes cause altered luminal cell phenotypes. To evaluate the effects of different microenvironments on the fidelity of epigenetically regulated luminal and myoepithelial gene expression, we generated a set of lineage-specific probes for genes that are controlled through DNA methylation. Culturing primary luminal cells under conditions that favor myoepithelial propogation led to their reprogramming at the level of gene methylation, and to a more myoepithelial-like expression profile. Primary luminal cells' lineage-specific gene expression could be maintained when they were cultured as bilayers with primary myoepithelial cells. Isogenic stromal fibroblast co-cultures were unable to maintain the luminal phenotype. Mixed-age luminal-myoepithelial bilayers revealed that luminal cells adopt transcription and methylation patterns consistent with the chronological age of the myoepithelial cells. We provide evidence that the luminal epithelial phenotype is exquisitely sensitive to microenvironment conditions, and that states of aging are cell non-autonomously communicated through microenvironment cues over at least one cell diameter
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