1,056 research outputs found

    Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women

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    Background: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. Methods and Results: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T→C (rs799908:T→C), c.-2265C→T (rs11655505:C→T), c.-2004A→G (rs799906:A→G) and c.-1896(ACA) 1→(ACA) 2 (rs8176071:(ACA) 1→(ACA) 2) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% Cl 0.69 to 0.93; p = 0.003) which was more evident among women aged ≥45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% Cl 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged ≥45 years without a family history of breast cancer (OR = 0.64, 95% Cl 0.46 to 0.89; p = 0.008). Conclusion: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C→T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.published_or_final_versio

    Reaction Chemistry and Kinetics of Corn Stalk Pyrolysis without and with Ga/HZSM-5

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    The bifunctional Ga/HZSM-5 catalyst has been proven having the capability to increase the selectivity of aromatics production during catalytic pyrolysis of furan and woody biomass. However, the reaction chemistry and kinetics of pyrolysis of herbaceous biomass promoted by Ga/HZSM-5 is rarely reported. Pyrolysis–gas chromatography/mass spectrometry (Py–GC/MS) analysis and non-isothermal thermogravimetric analysis at four heating rates were carried out to investigate the decomposition behavior and pyrolysis kinetics of corn stalk without and with Ga/HZSM-5. The effective activation energies for corn stalk pyrolysis were calculated by using the Friedman isoconversional method. The Py–GC/MS analysis results indicated that the Ga/HZSM-5 catalyst had a high selectivity toward producing the aromatic chemicals of xylene, toluene and benzene, whereas the major products from non-catalytic pyrolysis of corn stalk were oxygenated compounds. The presence of Ga/HZSM-5 could significantly reduce the effective activation energies of corn stalk pyrolysis from 159.9–352.4 kJ mol−1 to 41.6–99.8 kJ mol−1 in the conversion range of 0.10–0.85

    Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study

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    INTRODUCTION: Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine. METHODS: Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival. RESULTS: The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00). CONCLUSION: This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted

    Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

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    The decay channel ψπ+πJ/ψ(J/ψγppˉ)\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) is studied using a sample of 1.06×1081.06\times 10^8 ψ\psi^\prime events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the ppˉp\bar{p} invariant mass spectrum. The enhancement can be fit with an SS-wave Breit-Wigner resonance function with a resulting peak mass of M=186113+6(stat)26+7(syst)MeV/c2M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2 and a narrow width that is Γ<38MeV/c2\Gamma<38 {\rm MeV/}c^2 at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

    miR-K12-7-5p Encoded by Kaposi's Sarcoma-Associated Herpesvirus Stabilizes the Latent State by Targeting Viral ORF50/RTA

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    Seventeen miRNAs encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) have been identified and their functions have begun to be characterized. Among these miRNAs, we report here that miR-K12-7 directly targets the replication and transcription activator (RTA) encoded by open reading frame 50. We found that miR-K12-7 targeted the RTA 3′ untranslated region (RTA3′UTR) in a seed sequence-dependent manner. miR-K12-7-5p derived from miR-K12-7 mediates the inhibition of RTA expression, and the mutation of the seed match site totally abrogated the inhibitory effect of miR-K12-7 on RTA3′UTR. The inhibition of RTA expression by miR-K12-7 was further confirmed in the latently KSHV-infected 293/Bac36 cell line through transient transfection of miR-K12-7 expression plasmid or specific inhibitor of miR-K12-7-5p, respectively. The transient transfection of miR-K12-7 into 293/Bac36 cells reduced RTA expression and the expression of the downstream early genes regulated by RTA, and also the production of progeny virus was significantly reduced after treatment with chemical inducers. Our study revealed that another miRNA, miR-K12-7-5p, targets the viral immediate early gene RTA and that this miRNA contributes to the maintenance of viral latency

    IGFBP3 mRNA expression in benign and malignant breast tumors

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    INTRODUCTION: Most previous studies have focused on evaluating the association between circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and breast cancer risk. Emerging evidence over the past few years suggests that IGFBP-3 may act directly on mammary epithelial cells. METHODS: To understand the role of IGFBP-3 in breast tumorigenesis, we investigated IGFBP3 mRNA expression levels in benign and malignant breast tumors and their adjacent normal tissues using real-time quantitative PCR. RESULTS: Cancer tissues had significantly lower IGFBP3 expression than benign tumor tissues (p < 0.001). IGFBP3 expressions in both tumor and adjacent tissues were higher in patients who had proliferative benign tumors than in those who had non-proliferative benign tumors. Among patients with benign breast disease, IGFBP3 expression in the tumor was significantly higher than that in their adjacent normal tissue. There were no apparent associations of IGFBP3 expression in cancer tissues with either overall survival or disease-free survival in a cohort of 521 patients with breast cancer. CONCLUSION: Our findings suggest that the expression level of IGFBP3 in breast tissues may be involved in breast tumorigenesis

    Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

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    Abstract Background We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Methods Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. Results The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p Conclusions Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs.</p
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