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An information theoretic method to identify combinations of genomic alterations that promote glioblastoma

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分子细胞生物学报:英文版 2015年第3期7卷 203-213页

作者： Rachel D.melamed j.guang Wang Antonio Iavarone Raul Rabadan Department of Systems Biology Columbia University College of Physicians and SurgeonsNew YorkNYUSA Department of Biomedical Informatics Columbia University College of Physicians and SurgeonsNew YorkNYUSA Institute for Cancer Genetics Columbia University College of Physicians and SurgeonsNew YorkNYUSA Department of Pathology and Cell Biology Columbia University College of Physicians and SurgeonsNew YorkNYUSA Department of Neurology Columbia University College of Physicians and SurgeonsNew YorkNYUSA

Tumors are the result of accumulated genomic alterations that cooperate synergistically to produce uncontrollable cell *** identifying recurrent alterations among large collections of tumors provides a way to pinpoint genes that endow a selective advantage in oncogenesis and progression,it fails to address the genetic interactions behind this selection process.A non-random pattern of co-mutated genes is evidence for selective forces acting on tumor cells that harbor combinations of these genetic *** existing methods have successfully identified mutually exclusive gene sets,no current method can systematically discover more general genetic *** develop Genomic Alteration Modules using Total Correlation(GAMToC),an information theoretic frameworkthat integrates copynumberandmutation datato identify genemodules with any non-randompattern of j.int ***,wepresent theSeed-GAMToCprocedure,which uncoversthe mutational context of any putative cancer *** software is publicly *** to glioblastoma multiforme samples,GAMToC results show distinct subsets of co-occurring mutations,suggesting distinct mutational routes to cancer and providing new insight into mutations associated with proneural,proneural/G-CIMP,and classical types of the *** results recapitulate known relationships such as mutual exclusive mutations,place these alterations in the context of other mutations,and find more complex relationships such as conditional mutual exclusivity.

关键词： genomics sequencing entropy copy number cancer cancer genetics

SELECTIVE LASER TRABECULOPLASTY (SLT) AS PRIMARY TREATMENT FOR OPEN ANGLE GLAUCOMA. A PROSPEC-TIVE NON -RANDOMIZED PILOT STUDY

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国际眼科杂志 2003年第1期3卷 99-100页

作者： S.melamed G.j.Ben Simon H.Levkovitz-Verbin The Gold-scheleger Eye Institute Sheba Medical Center IsraelThe Gold-scheleger Eye Institute Sheba Medical Center IsraelThe Gold-scheleger Eye Institute Sheba Medical Center Israel

Purpose: To examine the safety and efficacy of Selective Laser Trabeculoplasty (SLT) as primary treatment for patients with Open Angle Glaucoma. Patients and Methods: Forty-five eyes of 31 patients with Open Angle Glaucoma (IOP323mmHg on two consecutive measurements) underwent selective laser trabeculo-plasty as primary treatment All patients underwent

关键词：开角型青光眼初步治疗 SLT 随机试点研究

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雷沙吉兰作为左旋多巴的辅助用药治疗帕金森病和运动波动患者(LARGO研究,雷沙吉兰每日1次辅助治疗的持久影响):一项随机、双盲、平行分组试验

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世界核心医学期刊文摘(神经病学分册) 2006年第1期 1-2页

作者： Rascol O. Brooks D.j. melamed E. 郭俊 Department of Clinical Pharmacology Faculty of Medicine University Hospital 37 Allees Jules Guesde Toulouse 31073 France Prof.

Background: Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. Methods: In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. Findings: 88 (13%)patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4h; p=0.0001, p < 0.0001, respectively) and increased daily on-time without troublesome dyskinesia (0.85 h vs placebo 0.03 h; p=0.0005 for both). We recorded significant mean improvements in CGI scores (-0.86 rasagiline and -0.72 entacapone vs -0.37 placebo; p < 0.0001, p=0.0002, respectively). Changes in UPDRS scores also significantly improved for activities of daily living during off-time (-1.71 and -1.38 vs placebo; p < 0.0001, p=0.0006, respectively) and motor function during on-time (-2.94 and -2.73 vs placebo; both p < 0.0001). Frequency of adverse events was similar for all treatments. Interpretation: Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

关键词：左旋多巴帕金森病 LARGO 恩他卡朋雷沙吉兰双盲患者波动

SCANNING LASER DOPPLER FLOWMETRY OF NON PERFUSED REGIONS OF THE OPTIC NERVE HEAD IN GLAUCOMATOUS PATIENTS

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国际眼科杂志 2003年第1期3卷 15-15页

作者： G.j.Ben Simon I.Moroz M.Goldenfeld S.melamed Goldschleger Eye Institute IsraelGoldschleger Eye Institute IsraelGoldschleger Eye Institute IsraelGoldschleger Eye Institute Israel

Purpose: To examine the reliability of scanning laser-doppler flowmetry (SLDF) in measuring capillary flow in regions of the optic nerve head which are manifested differently by con-focal tomographic angiography. Perfused and non-perfused regions of glaucomatous optic nerves and documented related altitudinal visual field defects were compared using SLDF. Methods: The optic nerve head capillary blood flow was measured in 16 eyes of 13 glaucoma patients with moderate to severe visual field defect.

关键词：青光眼视神经非灌流区扫描激光多普勒流速计检测

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乏脂肪血管平滑肌脂肪瘤:采用常规MR技术能否与肾透明细胞癌鉴别?

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国际医学放射学杂志 2013年第1期 64-64页

作者： N.Hindman L.Ngo E.M.Genega j.melamed j.Wei j.M.Braza 赵博峰 Department of Radiology University of Texas Southwestern Medical Center5323 Harry Hines BlvdDallasTX 75390-8896

目的回顾性评估MR反相位和同相位GRE序列与MR特征分析对于乏脂肪血管平滑肌瘤(AML)和肾透明细胞癌(RCC),特别是直径<3cm病灶的鉴别诊断能力。材料与方法本研究得到单位伦理委员会批准,无需病人的知情同意,符合HIPAA要求。收集两个学术... 详细信息

目的回顾性评估MR反相位和同相位GRE序列与MR特征分析对于乏脂肪血管平滑肌瘤(AML)和肾透明细胞癌(RCC),特别是直径<3cm病灶的鉴别诊断能力。材料与方法本研究得到单位伦理委员会批准,无需病人的知情同意,符合HIPAA要求。收集两个学术机构的108例病人(其中RCC88例,乏脂肪AML20例;男64例,女44例)经病理证实肾肿物的MR影像资料。测量每例肾肿物和脾在同相位和反相位像中的信号强度(SI),用于计算SI指数和肿物/脾SI比率。2位放射科医师采用盲法独立主观评价是否存在体素内脂肪(如反相位SI较同相位减低)、T1WI和T2WI的SI、囊变、坏死、出血、腹膜后侧支循环和肾静脉血栓的表现。对于所有的肾肿物和小病灶的数据进行秩和检验、双尾Fisher确切检验和多因素logistic回归分析。P<0.05认为差异具有统计学意义。结果在全部肾脏肿物和小病灶中,乏脂肪AML与RCC的SI指数(8.05±14.46%和14.99±19.9%;P=0.146)和肿物/脾SI比率(-8.96±16.6%和-15.8±22.4%;P=0.227)间差异无统计学意义。SI指数和肿物/脾SI比率的诊断正确度(ROC曲线下面积)为0.59。对于所有病变,肿瘤内坏死和大病灶提示RCC的诊断(P<0.001),而T2WI上低SI(相对于肾实质)、小病灶和女性则与乏脂肪AML存在相关性(P<0.001)。结论同相位和反相位序列对于鉴别诊断乏脂肪AML和RCC的准确性较差。本研究中T2WI上相对肾实质的低SI和小病灶提示乏脂肪AML,而瘤内坏死和大病灶则不支持此诊断。

关键词：肾透明细胞癌反相位 AML 脂肪 RCC MR

扩散峰值模型对外周带前列腺癌检出与侵袭性评估的可行性及初步研究

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国际医学放射学杂志 2012年第5期 474-474页

作者： A.B.Rosenkrantz E.E.Sigmund G.j.hnson j.S.Babb T.C.Mussi j.melamed 盛会雪 Department of Radiology New York University Langone Medical Center 550 First AveTCH-HW202New YorkNY 10016

摘要目的将扩散峰值成像(DKI)与标准DWI进行比较,评价两者对区别前列腺外周带良恶性病变、高低级别前列腺癌的可行性。材料与方法这项符合HIPAA标准的回顾性研究得到伦理委员会的批准,无需病人知情同意。47例前列腺癌病人使用盆腔相控... 详细信息

摘要目的将扩散峰值成像(DKI)与标准DWI进行比较,评价两者对区别前列腺外周带良恶性病变、高低级别前列腺癌的可行性。材料与方法这项符合HIPAA标准的回顾性研究得到伦理委员会的批准,无需病人知情同意。47例前列腺癌病人使用盆腔相控阵线圈行3TMRDWI(最大b值2000s/mm2)得到ADC图(高斯扩散)、代表非高斯扩散度的度量DK图(K)、补偿非高斯扩散后的校正扩散图(D)。

关键词：前列腺癌病人高低外周带