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Enrichment of AT-TA transversion at 5′-CAG-3′ motif is not a unique mutational signature of aristolochic acid

Science China(Life Sciences) 2019年第7期62卷 974-977页

作者： Xin Wang Xinming Qi Jin Ren Center for Drug Safety Evaluation and Research State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China

Aristolochic acids (AA) are the etiologic agents of aristolochic acid nephropathy (AAN) and contribute to the global prevalence of chronic kidney disease and urothelial cancer (Grollman et al.,2007).DNA adducts formed by AA generate a unique A>T transversions mutation spectrum at adenine exclusively on the non-transcribed strand (strand bias).

关键词： Aristolochic acids mutational signature and hepatocellular carcinoma

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IDENTIFICATION OF PARTIAL mutational SITES IN HUMAN MITOCHONDRIAL DNA IN THE CHINESE AND ITS SIGNIFICANCE

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Science China Chemistry 1989年第4期32卷 468-477页

作者：俞民澍邱信芳薛京伦刘祖洞谈家桢李厚钧刘德祥李力余伍忠 Institute of Genetics Fudan University Shanghai Genetics Group Xinjiang Urumqi General Military Hospital Urumqi

A simple method for the identification of mutational sites in human mitochondrial DNA (mtDNA) was described. It was based on the human Cambridge sequence as a relative standard sequence and a single base pair substitution in mtDNA as a unique mutational form. The partial mutational sites can be determined using this method which was characterized by combining the restriction mapping with the analysis for the table of human mtDNA potential mutational sites with rapidity and simplicity. In the meanwhile, six mtDNA mutational sites found in Chinese population were identified by means of this method.

关键词： human mitochondrial DNA mutational sites Chinese population.

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mutational and Phylogenetic Analysis of nfxBGene in Multidrug-Resistant Clinical Isolates of Pseudomonas aeruginosaHyperexpressing MexCD-OprJ Efflux Pump

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Advances in Microbiology 2019年第12期9卷 993-999页

作者： Manju Suresh Nithya Narayanan Kollancheri Puthurath Vimal Pullampara Rajamma Jayasree Panickassery Ramakrishnan Manish Kumar

The present study focused on MexCD-OprJ efflux pump and its regulatory gene nfxB in multidrug resistant (MDR) clinical isolates of Pseudomonas aeruginosa collected from Kerala, South India. Semi-quantitative reverse transcription-PCR technique was employed to detect hyperexpression of the efflux pump gene, mexD. Amplicons from nfxB gene of isolates hyperexpressing the efflux pump were sequenced for mutational and phylogenetic analysis. Among 29 isolates of MDR P. aeruginosa, increased mexD transcription was detected in 10.3% of the isolates when compared with P. aeruginosa reference strain, PAO (MTCC-3541). Various synonymous and non-synonymous mutations in nfxB regulatory gene sequences were detected. Notably, mutations detected in the strains designate Pa6 and Pa7 have been found to be novel and are hitherto unreported in GenBank data base. The genetic divergence and homogeneity of the nfxB regulatory gene sequences of mexCD-oprJ operon were clearly apparent in the phylogram generated employing similar sequences retrieved from the public database.

关键词： Multidrug-Resistant Pseudomonas aeruginosa Efflux Pump Regulatory Gene mutational Variations Phylogenetic Analysis

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Qidong: a crucible for studies on liver cancer etiology and prevention

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Cancer Biology & Medicine 2019年第1期16卷 24-37页

作者： Jianguo Chen Jian Zhu Gaoren Wang John D.Groopman Thomas W.Kensler Department of Epidemiology Qidong Liver Cancer Institute Department of Epidemiology Tumor Hospital Nantong University Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health Public Health Sciences Division Fred Hutchinson Cancer Research Center

Qidong(Jiangsu, China) has been of interest to cancer epidemiologists and biologists because, until recently, it was an endemic area for liver cancer, having amongst the highest incidence rates in the world. The establishment of the Qidong Cancer Registry together with the Qidong Liver Cancer Institute in 1972 has charted the patterns of liver cancer incidence and mortality in a stable population throughout a period of enormous economic, social, and environmental changes as well as of improvements in health care delivery. Updated incidence trends in Qidong are described. Notably, the China age-standardized incidence rate for liver cancer has dropped by over 50% in the past several decades. Molecular epidemiologic and genomic deep sequencing studies have affirmed that infection with hepatitis B virus as well as dietary exposure to aflatoxins through contamination of dietary staples such as corn, and to microcystins–blue-green algal toxins found in ditch and pond water – were likely important etiologic factors that account for the high incidence of liver cancer in this region. Public health initiatives to facilitate universal vaccination of newborns against HBV and to improve drinking water sources in this rural area, as well as economic and social mandates serendipitously facilitating dietary diversity, have led to precipitous declines in exposures to these etiologic factors, concomitantly driving substantive declines in the liver cancer incidence seen now in Qidong. In this regard, Qidong serves as a template for the global impact that a package of intervention strategies may exert on cancer burden.

关键词： Liver cancer incidence hepatitis B virus aflatoxin microcystin screening chemoprevention mutational signature

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Targeted therapy or immunotherapy? Optimal treatment in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2018年第5期10卷 108-114页

作者： Merly Contratto Jennifer Wu Division of Hematology and Oncology Perlmutter Cancer Center New York University School of Medicine

Hepatocellular carcinoma(HCC) is the fifth leading cause of cancer mortality in the United States and the second leading cause of cancer mortality worldwide. Sorafenib is the only food and drug administration(FDA) approved as first line systemic treatment in HCC. Regorafenib and nivolumab are the only FDA approved second line treatment after progression on sorafenib. We will discuss all potential first and second line options in HCC. In addition, we also will explore sequencing treatment options in HCC, and examine biomarkers that can potentially predict benefits from treatments such as immune checkpoint inhibitor. This minireview summarizes potential treatments in HCC based on clinical trials that have been published in manuscript or abstract format from 1994-2018.

关键词： Sequencing treatment Sorafenib Hepatocellular carcinoma treatments Nivolumab Regorafenib Lenvatinib Cabozantinib Immunotherapy Biomarker Pembrolizumab Ramucirumab Alpha-fetoprotein Neoantigen Tumor mutational burden Interferon-gamma

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SEPT10Expression in Chronic Lymphocytic Leukemia. Correlation with Clinical and Biological Prognostic Factors

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Open Journal of Blood Diseases 2013年第3期3卷 11-16页

作者： Ana Travella Julieta Panero Carmen Stanganelli Raimundo Bezares Irma Slavutsky División Patología Molecular Instituto de Investigaciones Hematológicas Academia Nacional de Medi- cina Buenos Aires Argentina Laboratorio de Genética de Neoplasias Linfoides Instituto de Medicina Experimental CONICET-Academia Nacional de Medicina Buenos Aires Argentina Servicio de Hematología Hospital General de Agudos “Dr Teodoro álvarez” Buenos Aires Ar- gentina.

Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Microarray studies allowed highlight genes differentially expressed in this pathology. In this study, we have evaluated the prognostic significance of SEPT10 expression in CLL patients. Results were correlated with immunoglobulin heavy-chain variable (IGHV) genes mutational status, genomic rearrangements and clinical parameters. SEPT10 mRNA levels were determined by quantitative real-time PCR in 70 newly diagnosed CLL patients consecutively referred to our Institution. A wide heterogeneity for SEPT10 expression was found. Gene upregulation was observed in 18.5% of cases. The univariate analysis showed a positive association between gen expression and platelet count (p 0.0001) and a negative correlation with hemoglobin levels (p = 0.0094). Although no significant differences were observed, mean treatment free survival was shorter in patients with high expression (31 months) with respect to those with low mRNA levels (72 months). Cases with abnormal karyotypes had increased expression compared to those with normal karyotypes and no association between gene expression and FISH (fluorescence in situ hybridization) risk groups and IGHV mutational status was found. Cases using IGHV3-23 gene rearrangement had low SEPT10 expression. Our results showed an association between SEPT10 expression and features of adverse outcome but without independent prognostic value. The study of SEPT10 expression may be important for a better understanding of disease heterogeneity, adding further information to those provided by established prognostic factors.

关键词： Chronic Lymphocytic Leukemia SEPT10 Expression FISH Cytogenetics IGHV mutational Status

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