87 research outputs found

    Podoplanin in cancer cells is experimentally able to attenuate prolymphangiogenic and lymphogenous metastatic potentials of lung squamoid cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Podoplanin, a mucin-like transmembrane glycoprotein, is reportedly expressed in a variety of malignant cells and is generally regarded as a factor for promoting tumor progression in conventional studies. By contrast, a clinicopathologically conflicting role for podoplanin, namely as a favorable prognostic factor for patients with lung/cervical squamous cell carcinoma (SCC), has recently been reported. Here, we investigated the role of podoplanin expressed in lung squamoid cancer cells (LSCCs) in experimental tumor progression.</p> <p>Results</p> <p>Using EBC-1 cells, a lung SCC cell line without podoplanin expression and with lymphogenous metastatic potential, stable transformants with or without an exogenous human <it>podoplanin </it>gene were established and applied to a mouse tumor implantation model. <it>In vivo </it>examinations revealed that exogenous podoplanin had no influence on tumor growth, whereas it significantly restrained axillary lymph node metastasis associated with the suppression of lymphangiogenesis but not angiogenesis and with the downregulation of EBC-1-derived VEGF-C but not other lymphangiogenesis-related factor mRNAs in implanted tumor tissue. <it>In vitro </it>examinations to clarify the mechanisms underlying the <it>in vivo </it>phenomena revealed that exogenous podoplanin significantly suppressed the expression of VEGF-C mRNA and of the protein, and also increased the level of phosphorylated c-jun N terminal kinase (JNK) in EBC-1 cells. The former effect of exogenous podoplanin was impaired by treatment with either JNK inhibitor sp600125 or podoplanin-siRNA, and the latter effect was impaired by treatment with podoplanin-siRNA, suggesting that podoplanin was able to activate JNK, thereby downregulating VEGF-C gene expression in LSCCs (podoplanin-JNK-VEGF-C axis). Furthermore, supporting evidence in regard to the axis present in LSCCs was obtained from similar experiments using H157 cells, another lung SCC cell line expressing endogenous podoplanin.</p> <p>Conclusions</p> <p>Our findings suggested that LSCC-associated podoplanin was functional and could attenuate the potential for lymph node metastasis, possibly based on the suppression of tumor lymphangiogenesis; thus, podoplanin in cancer cells may become a useful biomarker to measure the malignancy of lung SCC.</p

    Evidence for Solution-Mediated Phase Transitions in Kidney Stones: Phase Transition Exacerbates Kidney Stone Disease

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    Maruyama M., Tanaka Y., Momma K., et al. Evidence for Solution-Mediated Phase Transitions in Kidney Stones: Phase Transition Exacerbates Kidney Stone Disease. Crystal Growth and Design 23, 4285 (2023); https://doi.org/10.1021/acs.cgd.3c00108.In this study, we investigated calcium oxalate (CaOx) kidney stones and showed direct evidence of the solution-mediated phase transition of calcium oxalate dihydrate (COD; the metastable phase) to calcium oxalate monohydrate (COM; the stable phase). We examined the crystal phases, crystal textures, and protein distributions within thin sections of calcium oxalate kidney stones. Observation with a polarized-light microscope showed that the outline of the mosaic texture, in which COM crystals are assembled in a mosaic pattern, roughly coincides with COD’s crystallographically stable face angles. Microfocus X-ray CT measurement captured the intermediate process of the phase transition, starting inside the COD single crystal and gradually transforming to COM crystals. In addition, the distribution of osteopontin and prothrombin fragment-1, common proteins contained in urine and visualized by multicolor fluorescence immunostaining, showed no apparent striations inside the COM single crystals with the mosaic texture, although the striation is apparent inside the COD single crystals. This is probably because the phase transition of mosaic-like COM occurred in a semiclosed system inside the COD single crystal, so the effect of periodic (day-night, seasonal, etc.) urinary protein concentration changes was small. On the other hand, striations were visible in concentrically laminated COM. This indicated that concentrically laminated COM formed in response to the changes in urinary protein concentrations. From the above, we conclude that the COD single crystals and the concentrically laminated COM seen in CaOx stones are primary structures, and the mosaic COM is a secondary structure that is a pseudomorph formed by the solution-mediated phase transition from COD single crystals

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Measurement of the W boson polarisation in ttˉt\bar{t} events from pp collisions at s\sqrt{s} = 8 TeV in the lepton + jets channel with ATLAS

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    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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