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Identification of Global DNA Methylation Signatures in Glioblastoma-Derived Cancer Stem Cells

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journal of Genetics and Genomics 2015年第7期42卷 355-371页

作者： Eun-joon Lee Prakash Rath jimei Liu Dungsung Ryu Lirong Pei Satish K.Noonepalle Austin Y.Shull Qi Feng N.Scott Litofsky Douglas C.Miller Douglas C.anthony Mark D.Kirk john Laterra Libin Deng Hong-Bo Xin Xinguo Wang jeong-Hyeon Choi Huidong Shi GRU Cancer Center Georgia Regents University Department of Biology College of Art and SciencesUniversity of Missouri Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological HealthFood and Drug Administration Department of Biochemistry and Molecular Biology Georgia Regents University Division of Neurological Surgery University of Missouri School of Medicine Department of Pathology and Anatomical Sciences University of Missouri School of Medicine Department of Pathology and Laboratory Medicine Brown University and Lifespan Academic Medical Center Department of Neurology The Hugo W.Moser Research Institute at Kennedy Krieger Inc.and The Johns Hopkins University School of Medicine Institute of Translational Medicine Nanchang University David H.Murdock Research Institute Department of Biostatistics and Epidemiology Georgia Regents University

Glioblastoma （GBM） is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM- derived cancer stem ceils （GSCs）. Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls （a neural stem cell （NSC） line and normal brain tissue） identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary GBMs, and their counterpart GSC lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT, AjAP1 and PTPRN2. These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.

关键词： Glioblastoma Cancer stem cells DNA methylation SPINT2

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软组织密度差异的显示——腹水中的肝脏

成都中医药大学学报 1978年第2期 101-105页

作者： anthony V.Proto,M.D. Edward j.Lane,M.D. 余朝骏

在100例腹水患者的平片中,有54例肝侧缘被显示。无论边界被显示或不显示,腹水的原因,液体的比重和蛋白总含量是相似的。由于肝脏和它周围液体之间接触的结果,使腹水中肝侧缘在右上腹的断层摄影中被显示出来。浸泡在液体中的尸解的肝脏的... 详细信息

在100例腹水患者的平片中,有54例肝侧缘被显示。无论边界被显示或不显示,腹水的原因,液体的比重和蛋白总含量是相似的。由于肝脏和它周围液体之间接触的结果,使腹水中肝侧缘在右上腹的断层摄影中被显示出来。浸泡在液体中的尸解的肝脏的X线照片己证实,液体和肝脏之间的密度差异是可以区分的,在平片的密度测试中肝脏和液体的交界处密度差异被揭示。平均肝的比重与平均腹水液体比重的比较,表示出5％的差异,这些

关键词：腹水水肿肝脏侧缘密度差异

X-Linked Dominant Congenital Ptosis Cosegregating with an Interstitial Insertion of a Chromosome 1p21.3 Fragment into a Quasipalindromic Sequence in Xq27.1

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Open journal of Genetics 2014年第6期4卷 415-425页

作者： David j. Bunyan David O. Robinson anthony G. Tyers Shuwen Huang Vivienne K. Maloney Francis H. Grand Sarah Ennis Samantha R. de Silva john A. Crolla Tristan F. W. McMullan Wessex Regional Genetics Laboratory Salisbury District Hospital Salisbury UK Human Genetics Division Southampton University School of Medicine Southampton UK Ophthalmology Department Salisbury District Hospital Salisbury UK Manchester Centre for Genomic Medicine Saint Mary’s Hospital Manchester UK Genetic Epidemiology and Genomic Informatics Group Faculty of Medicine University of SouthamptonSouthampton UK Oxford Eye Hospital John Radcliffe Hospital Oxford UK Ophthalmology Department Northampton General Hospital Northampton UK

Blepharoptosis (ptosis) is defined as the abnormal drooping of the upper eyelid and is a feature of many conditions. It can be in isolated or syndromic form, bilateral or unilateral and congenital or acquired. Previously we have carried out linkage analysis on a family with dominantly inherited congenital bilateral isolated ptosis and found the condition to be linked to a region of approximately 20 megabases of chromosome Xq24-Xq27.1 with a cumulative LOD score of 5.89. We now describe further analysis using array comparative genomic hybridisation (array CGH), fluorescence in situ hybridisation (FISH), long range PCR and sequencing. This has enabled us to identify and characterise at the level of DNA sequence an insertional duplication and rearrangement involving chromosomes 1p21.3 and a small quasipalindromic sequence in Xq27.1, disruption of which has been associated with other phenotypes but which is cosegregating with X-linked congenital bilateral isolated ptosis in this family. This work highlights the significance of the small quasipalindromic sequence in genomic rearrangements involving Xq27.1 and the importance of comprehensive molecular and molecular cytogenetic investigations to fully characterise genomic structural complexity.

关键词： Ptosis X-Linked Dominant Insertional Duplication

The Relationship between Human Papillomavirus and Oesophageal Squamous Cell Carcinoma in China—A Review of the Evidence

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Advances in Infectious Diseases 2013年第1期3卷 17-34页

作者： Surabhi S. Liyanage Qian Li Yang Zheng Holly Seale Philip j. Crowe anthony T. Newall Bayzidur Rahman Eva Segelov Chenxu Qu Fanghui Zhao junfeng Liu Zhanhai Gao Weixian Shi Peng Yang Aye Moa Chandini Raina MacIntyre Centre for Disease Control and Prevention Beijing China Department of Cancer Epidemiology Cancer Institute Chinese Academy of Medical Sciences Peking Union Medical College Beijing China Department of Medicine St. Vincent’s Hospital Clinical School The University of New South Wales Sydney Australia Department of Surgery Fourth Hospital Shijiazhuang China Department of Surgery Prince of Wales Hospital Clinical School The University of New South Wales Sydney Australia School of Public Health and Community Medicine The University of New South Wales Medicine The University of New South Wales Sydney Australia

Background: China has one of the highest incidence rates of oesophageal cancer in the world. The role of human papillomavirus (HPV) has been extensively researched in oesophageal squamous cell carcinoma (OSCC) with indeterminate results. The majority of these studies have been conducted in the Chinese population. Evidence for a definitive HPV-OSCC association could potentially support prophylactic vaccination in target populations, highlighting the need for ongoing investigation. The aim of this review is to summarise the findings of HPV DNA in OSCC tissue in Chinese subjects, with a view to informing further research in this area. Methods: A systematic literature search of the Chinese National Knowledge Infrastructure (CNKI) database, Medline, Embase and PubMed was conducted for all studies in English and Chinese language, examining OSCC tissue for HPV DNA in China. Reference lists of retrieved articles were reviewed and hand searches of relevant, key journals were conducted, to source articles which were not electronically indexed. Sixty-four studies met our selection criteria. Data from case-control and cross-sectional studies were analysed separately for any HPV-OSCC association, using the Epi InfoTM 3.5.3 software program. Results: From all studies conducted in the Chinese population, 2166/5953 (36%) of all OSCC tissue and 478/1684 (28%) of healthy control tissue, tested positive for HPV. We found that 11/16 case-control and cross-sectional studies had a statistically significant crude odds ratio, which supported a potential HPV-OSCC association. The largest study, carried out in the high incidence County of Anyang in Henan Province, reported 207/265 (78%) OSCC tissues testing positive for HPV DNA against 203/357 (57%) controls and had an unadjusted odds ratio of 2.71 (p-value Conclusion: A rigorous meta-analysis would improve interpretation of the data and a well-designed large-scale case-control study is warranted. If a link is found between HPV and OSCC, pro

关键词： Human Papillomavirus Oesophageal Carcinoma Squamous Cell Carcinoma HPV Vaccine China

Development of an in vitro macrophage screening system on the immunomodulating effects of feed components

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journal of Animal Science and Biotechnology 2021年第2期12卷 639-648页

作者： S.E.Sivinski L.K.Mamedova R.A.Rusk C.C.Elrod T.H.Swartz j.M.McGill B.j.Bradford Department of Animal Sciences and Industry Kansas State UniversityManhattan 66506USA Department of Diagnostic Medicine/Pathobiology Kansas State UniversityManhattan 66506USA Natural Biologics NewfieldNY 14867USA 2265K anthony Hall 474 S.Shaw LaneEast LansingMI 48824USA

Background:While feed components capable of modulating the immune system are highly sought after and marketed,often little evidence is available to support functional immune response ***,a high-throughput in vitro cell screening system was developed to test these compounds for innate immune signaling effects,using Saccharomyces cerevisiae and its cell wall components in addition to lauric acid and its esters as models in two separate *** screening system utilized RAW 264.7 murine macrophages to assess live *** cells and ***-derived cell wall componentsβ-glucan,mannan,and zymosan(a crude cell wall preparation containing bothβ-glucan and mannan).D-mannose was also evaluated as the monomer of *** also examined the effect of a saturated fatty acid(C12:0,lauric acid)and its esters(methyl laurate and glycerol monolaurate)on innate immune cell activation and cellular *** cells were transfected with a vector that drives expression of alkaline phosphatase upon promoter activation of nuclear factorκ-light-chain-enhancer of activated B cells(NFκB),a major inflammatory/immune transcription *** cells were incubated with 0.01,0.1 or 1 mg/mL of yeast compounds alone or RAW cells were challenged with LPS and then incubated with yeast *** a separate experiment,RAW cells were incubated with 0,0.5,2.5,12.5,62.5,and 312.5μmol/L of lauric acid,methyl laurate,or glycerol monolaurate alone,or RAW cells were challenged with LPS and then incubated with fatty acid ***:Treatment with zymosan orβ-glucan alone induced NFκB activation in a dose-dependent manner,whereas treatment with D-mannose,mannan,or live *** cells did ***-treatment with mannan after an LPS challenge decreased NFκB activation,suggesting that this treatment may ameliorate LPS-induced *** increases in NFκB activation were found when fatty acid treatments were applied in the absence of LPS,yet substantial reductio

关键词： Inflammation In vitro screening system NFκB

Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

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World journal of Hepatology 2016年第20期8卷 858-862页

作者： Yaakov Hasin Shimon Shteingart Harel Dahari Inna Gafanovich Sharon Floru Marius Braun Amir Shlomai anthony Verstandig Ilana Dery Susan L Uprichard Scott j Cotler Yoav Lurie Liver Unit Digestive Disease Institute Shaare Zedek Medical Center the Program for Experimental and Theoretical Modeling Division of Hepa-tology Department of Medicine Loyola University Medical Center "Bat Yamon" Internal Medicine Day Care Clalit Health Care Organization Liver Institute Rabin Medical Center Beilinson Hospital Petah-Tiqwa Affiliated with the Sackler Faculty of Medicine Invasive Radiology Unit Shaare Zedek Medical Center

The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.

关键词： Direct antiviral agent Drug-induced liver injury Hepatitis C Mathematical modeling Sustained virolog

Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors

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World journal of Gastroenterology 2015年第8期21卷 2450-2459页

作者： jonathan R Strosberg George A Fisher Al B Benson Lowell B anthony Bulent Arslan john F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William j Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center and Research Institute Department of Medicine Division of Oncology Stanford University Medical Center Stanford Robert H. Lurie Comprehensive Cancer Center of Northwestern University Department of Internal Medicine Division of Medical Oncology University of Kentucky Markey Cancer Center Rush University Medical Center Department of Surgery University at Buffalo - State University of New York Department of Medicine Division of Hematology Oncology and Transplantation University of Minnesota Department of Medical Oncology Roswell Park Cancer Institute Department of Medicine Gastroenterology Mount Sinai School of Medicine Mission Health System Asheville Department of Oncology Karmanos Cancer Institute Partnership for Health Analytic Research LLC

AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment ***:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic *** this time,there is little data to guide treatment selection and *** therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment *** appropriateness ratings were collected using the RAND/UCLA modified Delphi *** studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 *** were done both before and after an extended discussion of the *** measurements of agreement were made and consensus statements developed from the second round ***:Specialties represented were medical and surgical oncology,interventional radiology,and *** had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)*** the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were *** statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be *** patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated u

关键词： Unresectable Neuroendocrine carcinomas Neuroendocr

人为控制的暴露于烹饪炉空气污染对血压的急性影响

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中华高血压杂志 2019年第12期27卷 1178-1178页

作者：刘青(译) 叶鹏(摘/审校) Fedak KM Good N Walker ES Balmes j Brook RD Clark ML Cole-Hunter T devlin R L'Orange C Luckasen G Mehaffy j Shelton R Wilson A Volckens j Peel jL 不详

使用固体燃料的住宅炉灶造成的空气污染被认为是全球疾病的主要环境风险因素,但这一关系的证据在很大程度上是根据吸烟、二手烟和环境细颗粒物(particulate matter≤2.5μm,PM2.5)的文献中推断出来的。研究者进行了一项人为控制的人体... 详细信息

使用固体燃料的住宅炉灶造成的空气污染被认为是全球疾病的主要环境风险因素,但这一关系的证据在很大程度上是根据吸烟、二手烟和环境细颗粒物(particulate matter≤2.5μm,PM2.5)的文献中推断出来的。研究者进行了一项人为控制的人体暴露研究[STOVES(the subclinical tests on volunteers exposed to smoke)],以研究暴露于炉灶空气污染后的血压急性反应。

关键词：空气污染收缩压烹饪炉

Tumor-associated methylation of the putative tumor suppressor AjAP1 gene and association between decreased AjAP1 expression and shorter survival in patients with glioma

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Chinese journal of Cancer 2011年第4期30卷 247-253页

作者： David Cogdell Woonbok Chung Yuexin Liu j. Matthew McDonald Kenneth Aldape jean-Pierre j. Issa Gregory N. Fuller Wei Zhang Department of Pathology The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA.

Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers,most frequently in *** our previous studies,we evaluated 177 oligodendroglial tumor samples and identified the AjAP1 gene(formerly Shrew1) in the consensus region of ***1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and *** a putative tumor suppressor gene,we did not detect AjAP1 gene *** subsequent studies,we found that AjAP1 was underexpressed in oligodendrogliomas relative to normal brain *** analysis revealed the presence of CpG islands in the promoter of *** analysis of the AjAP1 promoter identified hypermethylation in 21% of oligodendrogliomas(n = 27),and the degree of methylation correlated with low levels of AjAP1 expression(P = 0.045).The AjAP1 promoter was also highly methylated in a wide spectrum of cell lines(n = 22),including cell lines of *** of the National Cancer Institute's REMBRANDT dataset,which contains 343 glioma samples,indicated that low AjAP1 gene expression was associated with decreased ***,both genetic(gene deletion) and epigenetic alterations(promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AjAP1 in gliomas,which contributes to poor prognosis.

关键词：甲基化分析脑胶质瘤抑癌基因 P1基因肿瘤患者协会少突胶质细胞