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Objective:To investigate the function of breast cancer susceptibility gene variants in predicting breast cancer risk and guid-ing clinical treatment through DNA sequencing. Methods:This study involved 146 patients, 71 high-risk cases, and 55 healthy people, totaling 272 cases. The subjects were treated in Tianjin Medical University Cancer Institute and Hospital from November 2013 to July 2015. Genomic DNA was sequenced by a second generation sequencing platform. All exon areas of six common breast cancer suscepti-bility genes (BRCA1, BRCA2, PTEN, STK11, TP53, and RAP1) were sequenced through amplicon sequencing method. Meaningful vari-ants including single nucleotide variants (SNVs), insertion-deletions (InDels) and nonsense mutations were selected and statistical methods, such as t test andχ2 test, were used to analyze the statistical differences in incidence rates among three groups. Results:A total of 177 meaningful variants were confirmed, including 50 SNVs, 8 nonsense mutations, and 9 InDels. Among the variants, 31 were recorded in the Exome Aggregation Consortium (ExAC), 40 were noted in ClinVar database, and 21 were not encoded in the present da-tabase, which were defined as new variants in this study. Conversely, 57 variants (85.1%) were found in breast cancer patients and high-risk cases, and the incidence of axillary lymph node metastasis (P=0.010) and pathological stages (P=0.002) in mutation positive patients were both higher than mutation negative patients. Moreover, the percentage of family history of cancer (P=0.005) and triple negative breast cancer (P=0.009) were both higher in patients carrying pathogenic mutations than in nonpathogenic patients. Conclu-sion:Breast cancer susceptibility gene variants may not only be a tool used to predict the risk of getting breast cancer but also a mean-ingful guideline for the clinical treatment and prognosis evaluation.
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<p><b>OBJECTIVE</b>To establish and evaluate a hypercoagulable animal model for the assessment of anticoagulants.</p><p><b>METHODS</b>Forty mice, thirty-two rats, and twenty-four rabbits were randomly and equally divided into control group (saline) and three ellagic acid (EA)-treated groups (low, middle, and high doses). In the mice, bleeding time (BT) was estimated with tail transaction, and clotting time (CT) with template method. Prothrombin time (PT) and the activated partial thromboplastin time (APTT) in rats and rabbits were measured by means of Quick's one-stage assay and modified APTT assay respectively. In addition, thrombin activity was estimated in rats with PT assay using a hemagglutination analyzer. The circulating platelet aggregates were detected in rabbits through platelet counting and presented as the circulating platelet aggregate ratio (CPAR).</p><p><b>RESULTS</b>EA shortened BT and CT in mice, PT and APTT in rats, and increased thrombin activity and CPAR, all in a dose-dependent manner. EA also brought reduction of PT and APTT in rabbits in dose- and time-dependent manners.</p><p><b>CONCLUSION</b>EA could induce hypercoagulable state through activating coagulation system and platelets in mice, rats, and rabbits.</p>