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Identification of new genetic risk factors for prostate cancer

Asian Journal of Andrology 2009年第1期11卷 49-55页

作者： Michelle Guy Zsofia Kote-Jarai Graham G. Giles Ali Amin Al Olama Sarah K. Jugurnauth Shani Mulholland Daniel A. Leongamomlert Stephen M. Edwards Jonathan Morrison Helen I. Field Melissa C. Southey Gianluca Severi Jenny L. Donovan Freddie C. Hamdy David R Dearnaley Kenneth R. Muir Charmaine Smith Melisa Bagnato Audrey T. Ardern-Jones Amanda L. Hall Lynne T. O＇Brien Beatrice N. Gehr-Swain Rosemary A. Wilkinson Angela Cox Sarah Lewis Paul M. Brown Sameer G. Jhavar Malgorzata Tymrakiewicz Artitaya Lophatananon Sarah L. Bryant the uk genetic prostate cancer study collaborators British Association of Urological Surgeons＇ Section of Oncology and The uk ProtecT study collaborators Alan Horwich Robert A. Huddart Vincent S. Khoo Christopher C. Parker Christopher J. Woodhouse Alan Thompson Tim Christmas Chris Ogden Cyril Fisher Charles Jameson Colin S. Cooper Dallas R. English John L. Hopper David E. Neal Douglas E Easton Rosalind A. Eeles Section of cancer genetics The Institute of Cancer Research Sutton Surrey SM2 5NG UK cancer Epidemiology Centre The Cancer Council Victoria Carlton VIC 3053 Australia Centre for Molecular Environmental Genetic and Analytic Epidemiology The University of Melbourne Carlton VIC 3053 Australia cancer Research uk genetic Epidemiology Unit University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK Department of Oncology University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK genetic Epidemiology Laboratory Department of Pathology The University of Melbourne Parkville VIC 3052 Australia Department of Social Medicine University of Bristol Bristol BS8 2PR UK Academic Urology Unit University of Sheffield Sheffield SIO 2JF UK The Royal Marsden NHS Foundation Trust Sutton Surrey SM2 5PT and London SW3 6JJ UK University of Nottingham Medical School Queens Medical Centre Nottingham NG7 2UH UK Institute for cancer Studies University of Sheffield Sheffield SIO 2RX UK Surgical Oncology （Uro-Oncology S4） Departments of Oncology and Surgery University of Cambridge Addenbrooke＇s Hospital Cambridge CB2 2QQ UK A full list of authors is provided in the Supplementary Note online Ka Shing Centre Cambridge CB2 ORE UK cancer Research uk Cambridge Research Institute Li Ka Shing Centre Cambridge CB2 ORE UK.

There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

关键词： prostate cancer genetics susceptibility loci SNPs relative risks

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prostate-specific antigen density predicts favorable pathology and biochemical recurrence in patients with intermediate-risk prostate cancer

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Asian Journal of Andrology 2016年第3期18卷 480-484,I0012页

作者： Ho Won Kang Hae Do Jung Joo Yong Lee Jong Kyou Kwon Seong uk Jeh Kang Su Cho Won Sik Ham Young Deuk Choi Department of Urology Chungbuk National University College of Medicine Cheongju Korea Department of Urology Severance Hospital Urological Science InstituteYonsei University College of Medicine Seoul Korea Department of Urology. Inje university Haeundae Paik Hospital Busan Korea Department of Urology Gyeongsang National University School of Medicine Jinju Korea Department of Urology Gangnam Severance Hospital Urological Science Institute Yonsei University Uollege of Medicine Seoul Korea Robot and Minimal Invasive Surgery Center Severance Hospital Yonsei University College of Medicine Seoul Korea.

This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence （BCR） in patients with intermediate-risk prostate cancer （IRPCa）. Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy （RARP） for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score 〈6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients （18.7%） had favorable pathology after RARP. Lower quartile prostate-specific antigen density （PSAD） was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score （odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048）. During a median 37.8 （interquartile range, 24.6-60.2） months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles （log rank, P = 0.003）. Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP （hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036）. The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.

关键词： biochemical recurrence prostatectomy prostate-specific antigen prostate-specific antigen density prostatic neoplasms

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Direct modification of spermatogonial stem cells using lentivirus vectors in vivo leads to efficient generation of transgenic rats

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Asian Journal of Andrology 2019年第2期21卷 190-195页

作者： Bang-Jin Kim Yong-Hee Kim Myeong-Geun Oh Ki-Jung Kim Sang-Eun Jung Ju-Hee Jin Sun-uk Kim Kwan-Sik Min Buom-Yong Ryu Department of Animal Scienee and Technology College of Biotechnology and Natural ResourcesChung-Ang UniversityAnseongGyeonggi-do 17546Korea National Primate Research Center Korea Research Institute of Bioscienee and BiotechnologyCheongjuChungcheongbuk-do 28116Korea Futuristic Animal Resource and Research Center Korea Research Institute of Bioscience and BiotechnologyCheongjuChungcheongbuk-do 28116Korea Animal Biotechnology Graduate School of Future Con verge nee Tech no logyDepartment of Animal Life ScienceInstitute of Genetic Engi neeringHankyong National UniversityAnseongGyeon ggi-do 17579Korea Department of cancer Biology University of PennsylvaniaPhiladelphiaPA 19104USA.

Spermatogonial stem cells(SSCs)transmit genetic information to the next progeny in ***,SSCs are a potential target for germ I i ne modifications to gen erate tran sgenic an *** this study,we report a technique for the gen erati on of tran sgenic rats by in vivo manipulation of SSCs with a high success *** in juvenile rats were transduced in vivo with high titers of lentivirus harbori ng enhan ced green fluoresce nt protei n and mated with wild-type females to create foun der *** founder rats expressed the transgene and passed on the transgene with an overall success rate of 50.0%.Subsequent generations of progeny from the founder rats both expressed and passed on the ***,direct modification of SSCs in juvenile rats is an effective means of generating transgenic rats through the male *** technology could be adapted to larger animals,in which existing methods for gene modificatio n are in adequate or in applicable,resulti ng in the gen eration of tran sge nic an imals in a variety of species.

关键词： germline modification lentivirus spermatogonial stem cell testis transgenic animal

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