116 research outputs found

    Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).</p> <p>Methods</p> <p>The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed.</p> <p>Results</p> <p>The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (<it>P </it>= 0.016), tumor size (<it>P </it>= 0.019), T status (<it>P </it>= 0.024), locoregional progression (<it>P </it>= 0.009) and EZH2 expression (<it>P </it>= 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (<it>P </it>= 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (<it>P </it>= 0.048), N0 (<it>P </it>= 0.005) and M0 (<it>P </it>= 0.018) stages as well as in CRT effective group (<it>P </it>= 0.022).</p> <p>Conclusions</p> <p>Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.</p

    Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

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    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma

    Study of the doubly Cabibbo-suppressed decays Ds+K+K+πD^+_s\to K^+K^+\pi^- and Ds+K+K+ππ0D^+_s\to K^+K^+\pi^-\pi^0

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    Based on 7.33 fb1^{-1} of e+ee^+e^- collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, the experimental studies of the doubly Cabibbo-suppressed decays Ds+K+K+πD^+_s\to K^+K^+\pi^- and Ds+K+K+ππ0D^+_s\to K^+K^+\pi^-\pi^0 are reported. We determine the absolute branching fraction of Ds+K+K+πD^+_s\to K^+K^+\pi^- to be (1.230.25+0.28(stat)±0.06(syst){1.23^{+0.28}_{-0.25}}({\rm stat})\pm0.06({\rm syst})) ×104\times 10^{-4}. No significant signal of Ds+K+K+ππ0D^+_s\to K^+K^+\pi^-\pi^0 is observed and the upper limit on its decay branching fraction at 90\% confidence level is set to be 1.7×1041.7\times10^{-4}.Comment: 10 pages, 4 figures, 4 table

    Observation of the Singly Cabibbo-Suppressed Decay Λc+ΣK+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}

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    The singly Cabibbo-suppressed decay Λc+ΣK+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+} is observed for the first time with a statistical significance of 6.4σ6.4\sigma by using 4.5 fb1^{-1} of e+ee^+e^- collision data collected at center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII. The absolute branching fraction of Λc+ΣK+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+} is measured to be (3.8±1.3stat±0.2syst)×104(3.8\pm1.3_{\rm stat}\pm0.2_{\rm syst})\times 10^{-4} in a model-independent approach. This is the first observation of a Cabibbo-suppressed Λc+\Lambda_{c}^{+} decay involving Σ\Sigma^- in the final state. The ratio of branching fractions between Λc+ΣK+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+} and the Cabibbo-favored decay Λc+Σπ+π+\Lambda_{c}^{+}\to \Sigma^- \pi^+\pi^+ is calculated to be (0.4±0.1)sc2(0.4 \pm 0.1)s_{c}^{2}, where scsinθc=0.2248s_{c} \equiv \sin\theta_c = 0.2248 with θc\theta_c the Cabibbo mixing angle. This ratio significantly deviates from 1.0sc21.0s_{c}^{2} and provides important information for the understanding of nonfactorization contributions in Λc+\Lambda_{c}^{+} decays.Comment: 8 pages, 2 figure

    Updated measurements of the M1 transition ψ(3686)γηc(2S)\psi(3686) \to \gamma \eta_{c}(2S) with ηc(2S)KKˉπ\eta_{c}(2S) \to K \bar{K} \pi

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    Based on a data sample of (27.08±0.14)×108 ψ(3686)(27.08 \pm 0.14 ) \times 10^8~\psi(3686) events collected with the BESIII detector at the BEPCII collider, the M1 transition ψ(3686)γηc(2S)\psi(3686) \to \gamma \eta_{c}(2S) with ηc(2S)KKˉπ\eta_{c}(2S) \to K\bar{K}\pi is studied, where KKˉπK\bar{K}\pi is K+Kπ0K^{+} K^{-} \pi^{0} or KS0K±πK_{S}^{0}K^{\pm}\pi^{\mp}. The mass and width of the ηc(2S)\eta_{c}(2S) are measured to be (3637.8±0.8(stat)±0.2(syst))(3637.8 \pm 0.8 (\rm {stat}) \pm 0.2 (\rm {syst})) MeV/c2c^{2} and (10.5±1.7(stat)±3.5(syst))(10.5 \pm 1.7 (\rm {stat}) \pm 3.5 (\rm {syst})) MeV, respectively. The product branching fraction B(ψ(3686)γηc(2S))×B(ηc(2S)KKˉπ)\mathcal{B}\left(\psi(3686) \rightarrow \gamma \eta_{c}(2 S)\right) \times \mathcal{B}(\eta_{c}(2 S) \rightarrow K \bar{K} \pi) is determined to be (0.97±0.06(stat)±0.09(syst))×105(0.97 \pm 0.06 (\rm {stat}) \pm 0.09 (\rm {syst})) \times 10^{-5}. Using BR(ηc(2S)KKˉπ)=(1.860.49+0.68)%\mathcal{BR}(\eta_{c}(2S)\to K\bar{K}\pi)=(1.86^{+0.68}_{-0.49})\%, we obtain the branching fraction of the radiative transition to be BR(ψ(3686)γηc(2S))=(5.2±0.3(stat)±0.5(syst)1.4+1.9(extr))×104\mathcal{BR}(\psi(3686) \to \gamma \eta_{c}(2S)) = (5.2 \pm 0.3 (\rm {stat}) \pm 0.5 (\rm {syst}) ^{+1.9}_{-1.4} (extr)) \times 10^{-4}, where the third uncertainty is due to the quoted BR(ηc(2S)KKˉπ)\mathcal{BR}(\eta_{c}(2S) \to K\bar{K}\pi)

    Asymmetric Synthesis and Absolute Configuration Assignment of a New Type of Bedaquiline Analogue

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    Bedaquiline is the first FDA-approved new chemical entity to fight multidrug-resistant tuberculosis in the last forty years. Our group replaced the quinoline ring with a naphthalene ring, leading to a new type of triarylbutanol skeleton. An asymmetric synthetic route was established for our bedaquiline analogues, and the goal of assigning their absolute configurations was achieved by comparison of experimental and calculated electronic circular dichroism spectra, and was confirmed by the combined use of circular dichroism and NMR spectroscopy
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