1,822 research outputs found

    NEFL mRNA Expression Level Is a Prognostic Factor for Early-Stage Breast Cancer Patients

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    Neurofilament, light polypeptide (NEFL) was demonstrated to be ectopically expressed in breast cancer tissues and decreased in lymph node metastases compared to the paired primary breast cancers in our previous study. Moreover, in several studies, NEFL was regarded as a tumor suppressor gene, and its loss of heterozygosity (LOH) was related to carcinogenesis and metastasis in several types of cancer. To explore the role of NEFL in the progression of breast cancer and to evaluate its clinical significance, we detected the NEFL mRNA level in normal breast tissues, primary breast cancer samples and lymph node metastases, and then analyzed the association between the NEFL expression level and several clinicopathological parameters and disease-free survival (DFS). NEFL mRNA was found to be expressed in 92.3% of breast malignancies and down-regulated in lymph node metastases compared to the paired primary tumors. NEFL mRNA level was lower in primary breast cancers with positive lymph nodes than in cancers with negative lymph nodes. Moreover, a low expression level of NEFL mRNA indicated a poor five-year DFS for early-stage breast cancer patients. Thus, NEFL mRNA is ectopically expressed in breast malignancies and could be a potential prognostic factor for early-stage breast cancer patients

    Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface

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    Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623

    The Effect of Polyhydramnios on Cervical Length in Twins: A Controlled Intervention Study in Complicated Monochorionic Pregnancies

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    Objective: To test the hypothesis that cervical shortening in polyhydramnios reflects the degree of excess amniotic fluid, and increases with normalisation of amniotic fluid volume. Study Design: Prospective cohort study of 40 women with monochorionic twins undergoing interventional procedures between 16-26 weeks. Cervical length was assessed via transvaginal sonography pre-procedure, 1 and 24 hours postprocedure, and results compared between amnioreduction and control procedures. Amniotic fluid index (AFI) was measured pre- and post-procedure. Results: Pre-procedural cervical length correlated with AFI (linear fit = 5.07 -0.04x, R2 = 0.17, P = 0.03) in patients with polyhydramnios (n = 28). Drainage of 2000ml fluid (range 700-3500ml), reduced AFI from 42cm to 21cm (P>0.001). Their pre-procedural cervical length did not change at one (mean Δ:-0.1cm, 95%CI, -0.4 to 0.2) or 24 hours (0.2cm, -0.1 to 0.6) after amnioreduction. There was no change in cervical length at control procedures. Conclusion: Cervical shortening in twins with polyhydramnios does not appear to be an acute process; cervical length can be measured before or after therapeutic procedures. © 2008 Engineer et al

    Measurement of the Relative Branching Fraction of Υ(4S)\Upsilon(4S) to Charged and Neutral B-Meson Pairs

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    We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ -> J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) -> B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- = 0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Y(4S) resonance.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

    First Observation of the Decays B0→D∗−ppˉπ+B^{0}\to D^{*-}p\bar{p}\pi^{+} and B^{0}\to D^{*-}p\bar{n}$

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    We report the first observation of exclusive decays of the type B to D^* N anti-N X, where N is a nucleon. Using a sample of 9.7 times 10^{6} B-Bbar pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B^0 \to D^{*-} proton antiproton \pi^+) = ({6.5}^{+1.3}_{-1.2} +- 1.0) \times 10^{-4} and B(B^0 \to D^{*-} proton antineutron) = ({14.5}^{+3.4}_{-3.0} +- 2.7) times 10^{-4}. Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

    Study of the Decays B0 --> D(*)+D(*)-

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    The decays B0 --> D*+D*-, B0 --> D*+D- and B0 --> D+D- are studied in 9.7 million Y(4S) --> BBbar decays accumulated with the CLEO detector. We determine Br(B0 --> D*+D*-) = (9.9+4.2-3.3+-1.2)e-4 and limit Br(B0 --> D*+D-) < 6.3e-4 and Br(B0 --> D+D-) < 9.4e-4 at 90% confidence level (CL). We also perform the first angular analysis of the B0 --> D*+D*- decay and determine that the CP-even fraction of the final state is greater than 0.11 at 90% CL. Future measurements of the time dependence of these decays may be useful for the investigation of CP violation in neutral B meson decays.Comment: 21 pages, 5 figures, submitted to Phys. Rev.

    A Search for B→τνB\to \tau\nu

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    We report results of a search for B→τνB\to\tau\nu in a sample of 9.7 million charged BB meson decays. The search uses both πν\pi\nu and ℓννˉ\ell\nu\bar\nu decay modes of the τ\tau, and demands exclusive reconstruction of the companion Bˉ\bar B decay to suppress background. We set an upper limit on the branching fraction B(B→τν)<8.4×10−4{\cal B}(B\to \tau\nu) < 8.4\times 10^{-4} at 90% confidence level. With slight modification to the analysis we also establish B(B±→K±ννˉ)<2.4×10−4{\cal B}(B^\pm\to K^\pm\nu\bar\nu) < 2.4\times 10^{-4} at 90% confidence level.Comment: 10 ages postscript, also available through http://w4.lns.cornell.edu/public/CLN

    Measurements of B --> D_s^{(*)+} D^{*(*)} Branching Fractions

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    This article describes improved measurements by CLEO of the B0→Ds+D∗−B^0 \to D_s^+ D^{*-} and B0→Ds∗+D∗−B^0 \to D_s^{*+} D^{*-} branching fractions, and first evidence for the decay B+→Ds(∗)+Dˉ∗∗0B^+ \to D_s^{(*)+} \bar{D}^{**0}, where Dˉ∗∗0\bar{D}^{**0} represents the sum of the Dˉ1(2420)0\bar{D}_1(2420)^0, Dˉ2∗(2460)0\bar{D}_2^*(2460)^0, and Dˉ1(j=1/2)0\bar{D}_1(j=1/2)^0 L=1 charm meson states. Also reported is the first measurement of the Ds∗+D_s^{*+} polarization in the decay B0→Ds∗+D∗−B^0 \to D_s^{*+} D^{*-}. A partial reconstruction technique, employing only the fully reconstructed Ds+D_s^+ and slow pion πs−\pi_s^- from the D∗−→Dˉ0πs−D^{*-} \to \bar{D}^0 \pi^-_s decay, enhances sensitivity. The observed branching fractions are B(B0→Ds+D∗−)=(1.10±0.18±0.10±0.28){\mathcal B} (B^0 \to D_s^+ D^{*-}) = (1.10 \pm 0.18 \pm 0.10 \pm 0.28)%, B(B0→Ds∗+D∗−)=(1.82±0.37±0.24±0.46){\mathcal B} (B^0 \to D_s^{*+} D^{*-}) = (1.82 \pm 0.37 \pm 0.24 \pm 0.46)%, and B(B+→Ds(∗)+Dˉ∗∗0)=(2.73±0.78±0.48±0.68){\mathcal B} (B^+ \to D_s^{(*)+} \bar{D}^{**0}) = (2.73 \pm 0.78 \pm 0.48 \pm 0.68)%, where the first error is statistical, the second systematic, and the third is due to the uncertainty in the Ds+→ϕπ+D_s^+ \to \phi \pi^+ branching fraction. The measured Ds∗+D_s^{*+} longitudinal polarization, ΓL/Γ=(50.6±13.9±3.6)\Gamma_L/\Gamma = (50.6 \pm 13.9 \pm 3.6)%, is consistent with the factorization prediction of 54%.Comment: 26 pages (LaTeX), 15 figures. To be submitted to PR

    Improved Measurement of the Pseudoscalar Decay Constant fDsf_{D_{s}}

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    We present a new determination of the Ds decay constant, f_{Ds} using 5 million continuum charm events obtained with the CLEO II detector. Our value is derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of 0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6 +/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN
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