34 research outputs found

    Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

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    Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    Search for the associated production of the Higgs boson with a top-quark pair

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    A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb &#8722;1 and 19.7 fb &#8722;1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H &#8594; hadrons, H &#8594; photons, and H &#8594; leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, &#956; = &#963;/&#963; SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is &#956; = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

    Measurement of prompt Jψ\psi pair production in pp collisions at \sqrt s = 7 Tev

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    Production of prompt J/ &#968; meson pairs in proton-proton collisions at s s&#8730; = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb &#8722;1 . The two J/ &#968; mesons are fully reconstructed via their decays into &#956; + &#956; &#8722; pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ &#968; pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ &#968; transverse momentum ( p T J/ &#968; ) and rapidity (| y J/ &#968; |): | y J/ &#968; | 6.5 GeV/ c ; 1.2 4.5 GeV/ c . The total cross section, assuming unpolarized prompt J/ &#968; pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ &#968; polarization imply modifications to the cross section ranging from &#8722;31% to +27%

    Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone

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    International Journal of Gynecology and Obstetrics573305-311IJGO

    Transcatheter aortic valve implantation: Implications for Asian patients

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    10.1177/0218492312454123Asian Cardiovascular and Thoracic Annals214396-401ACTA

    Clinical predictors of stent thrombosis in the "real world" drug-eluting stent era

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    10.1016/j.ijcard.2009.05.038International Journal of Cardiology1453422-425IJCD
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