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Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor

World Journal of gastrointestinal Oncology 2024年第5期16卷 2060-2073页

作者： Jing Zhou Mei-Ying Zhang Ai-Ai gao Cheng Zhu Tao He james g herman Ming-Zhou guo School of Medicine NanKai UniversityTianjin 300071China Department of gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China Departments of Pathology Characteristic Medical Center of The Chinese People’s Armed Police ForceTianjin 300162China The Hillman Cancer Center University of Pittsburgh Cancer InstitutePittsburghPA 15213United States National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100853China

BACKgROUND Targeting DNA damage response(DDR)pathway is a cutting-edge *** has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in ***,the detailed mechanism is *** To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 *** To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse *** Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region ***11 methylation was significantly associated with tumor differentiation and tumor size(both Pgnificant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node *** DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling *** silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in *** SLFN11 is frequently methylated in human *** of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

关键词： Schlafen-11 Esophageal squamous cell carcinoma DNA methylation Synthetic lethality AZD0156

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Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer

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FRONTIERS OF MEDICINE 2024年第4期18卷 721-734页

作者： Yao, Yuanxin Lv, Honghui Zhang, Meiying Li, Yuan herman, james g. Brock, Malcolm V. gao, Aiai Wang, Qian Fuks, Francois Zhang, Lirong guo, Mingzhou Chinese Peoples Liberat Army gen Hosp Med Ctr 1 Dept Gastroenterol & Hepatol Beijing 100853 Peoples R China Zhengzhou Univ Sch Basic Med Sci Dept Pharmacol Zhengzhou 450001 Peoples R China Zhengzhou Univ Henan Inst Adv Technol Zhengzhou 450001 Peoples R China Chinese Peoples Liberat Army gen Hosp Med Ctr 1 Natl Key Lab Kidney Dis Chinese PLA Inst NephrolState Key Lab Kidney Dis Beijing 100853 Peoples R China Univ Pittsburgh UPMC Hillman Canc Ctr Med Ctr Pittsburgh PA 15213 USA Johns Hopkins Sch Med Sch Med Dept Surg Baltimore MD 21287 USA Univ Libre Bruxelles ULB Fac Med Canc Res Ctr U CRC Lab Canc Epigenet B-1070 Brussels Belgium

Synthetic lethality is a novel model for cancer therapy. To understand the function and mechanism of BEN domain-containing protein 4 (BEND4) in pancreatic cancer, eight cell lines and a total of 492 cases of pancreatic neoplasia samples were included in this study. Methylation-specific polymerase chain reaction, CRISPR/Cas9, immunoprecipitation assay, comet assay, and xenograft mouse model were used. BEND4 is a new member of the BEN domain family. The expression of BEND4 is regulated by promoter region methylation. It is methylated in 58.1% (176/303) of pancreatic ductal adenocarcinoma (PDAC), 33.3% (14/42) of intraductal papillary mucinous neoplasm, 31.0% (13/42) of pancreatic neuroendocrine tumor, 14.3% (3/21) of mucinous cystic neoplasm, 4.3% (2/47) of solid pseudopapillary neoplasm, and 2.7% (1/37) of serous cystic neoplasm. BEND4 methylation is significantly associated with late-onset PDAC (> 50 years, P gnostic marker (P gous end joining signaling by interacting with Ku80 and promotes DNA damage repair. Loss of BEND4 increased the sensitivity of PDAC cells to ATM inhibitor. Collectively, the present study revealed an uncharacterized tumor suppressor BEND4 and indicated that methylation of BEND4 may serve as a potential synthetic lethal marker for ATM inhibitor in PDAC treatment.

关键词： BEND4 DNA methylation synthetic lethality NHEJ pathway IDENTIFY MOLECULAR SUBTYPES PATHWAY DOMAIN

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RASSF10 Suppresses Colorectal Cancer growth by Activating P53 Signaling and Sensitizes Colorectal Cancer Cell to Docetaxel

RASSF10 Suppresses Colorectal Cancer Growth by Activating P5...

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遵循诊疗规范、鼓励临床试验——第八届中国肿瘤内科大会、第三届中国肿瘤医师大会、中国抗癌协会肿瘤临床化疗专业委员会2014年学术年会

作者：郭静杨雅阁杨云生詹启敏 james g.herman Malcolm V.Brock 张炳勇郭明洲中国人民解放军总医院消化内科郑州大学第一附属医院中国医学科学院 Johns Hopkins University 河南省人民医院

Objective;To further understand the methylation status,expression,function,and mechanism of RASSFIO in colorectal ***;Eight colorectal cancer cell lines,89 cases of primary colorectal cancer,and 5 cases of normal colorectal mucosa were involved in this *** specific PCR,western blot,colony formation,siRNA,gene expression array,and xenograft mice were ***;Loss of RASSFIO expression and complete methylation were found in LOVO,RKO,and *** or reduced expression and partial methylation were found in LS180,DLD1,HT29,SW480,and SW620 *** or increased expression of RASSFIO was found in these colorectal cancer cells by 5-aza-2’-deoxycytidine *** was methylated in 60.7%(54/89)of primary colorectal cancer *** was associated with tumor stage(Pg2/M phase arrest in RKO and HCT116 ***116 cells tumor xenograft was suppressed by *** expression of MDM2 was revealed by comparison of gene expression profile in RASSFIO expressed and unexpressed RKO *** result was confirmed by RT-PCR and western *** activated P53 signaling in RKO and HCT116 cells after UV ***10 sensitized RKO and HCT116 cells to ***;RASSF10 is frequently methylated in human colorectal cancer and the expression is regulated by promoter region *** of RASSF10 is associated with late tumor stage and ***10 suppresses human colorectal cancer growth by activating P53 signaling in colorectal ***10 sensitizes colorectal cancer to docetaxel.

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肝内和肝外胆管癌肿瘤抑制基因启动子甲基化分析

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胃肠病学和肝病学杂志 2005年第1期14卷 59-65页

作者： YANg Bin Michael g.House gUO Mingzhou james g.herman Douglas P.Clark Department of Patl1ology The Johns Hopkins Medical InstitutionsBaltimoreMaryland The Sidney Kimmel Comprehensive Cancer Center The Johns Hopkins Medical Institutions.BaltimoreMaryland 郑州大学消化疾病研究所 The Sidney Kimmel Comprehensive Cancer CenterThe Johns Hophkins Medical InstitutionsBaltimore Maryland

目的　探讨胆管癌的表遗传学改变。方法　用甲基化特异PCR(MSP)法 ,检测了 12个候选肿瘤抑制基因 (APgE cad herin/CDH1,MgMT ,RASSF1A ,gSTP ,RAR β ,p14 ARF,p15 INK4b,p16INK4a,p73 ,hMLH1,DAPK)启动子在 72例胆管癌中的甲基化情... 详细信息

目的　探讨胆管癌的表遗传学改变。方法　用甲基化特异PCR(MSP)法 ,检测了 12个候选肿瘤抑制基因 (APgE cad herin/CDH1,MgMT ,RASSF1A ,gSTP ,RAR β ,p14 ARF,p15 INK4b,p16INK4a,p73 ,hMLH1,DAPK)启动子在 72例胆管癌中的甲基化情况 ,其中肝内和肝外胆管癌各 3 6例 ,10例良性胆管上皮作为对照。结果　 85 %的胆管癌至少有一个肿瘤抑制基因的甲基化 ,在胆管癌中 ,肿瘤抑制基因的甲基化顺序是 :RASSF1A(65 %) ,p15 INK4b(5 0 %) ,p16INK4a(5 0 %) ,APC(4 6%) ,E cadherin/CDH1(4 3 %) ,p14 ARF(3 8%) ,p73 (3 6%) ,MgMT(3 3 %) ,hMHL1(2 5 %) ,gSTP(14 %) ,RAR β(14 %)和DAPK(3 %)。虽然单个肿瘤抑制基因的甲基化可见于良性胆管上皮 ,但是多个肿瘤抑制基因的甲基化只见于胆管癌。约 70 %(5 0 /72 )的胆管癌有 3个或 3个以上的肿瘤抑制基因的甲基化 ,5 2 %(3 8/72 )有 4个或 4个以上肿瘤抑制基因的甲基化。多个肿瘤抑制基因的协同甲基化 ,和RASSF1A ,p15 INK4b,p16INK4a和 /或hMHL1密切相关。RASSF1A的甲基化在肝外胆管癌 (83 %)较肝内胆管癌更常见 (4 7%) (P =0 . 0 0 3 ) ,而gSTP更多见于肝内胆管癌(肝内 3 1%,肝外 6%,P =0 . 0 12 ) ,本研究提示肿瘤抑制基因启动子Cpg岛的甲基化在胆管癌中是一?

关键词：甲基化肝外胆管癌肿瘤抑制基因肝内 P14^ARF 常见良性启动子 MgMT p16^

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Impaired motor control after sport-related concussion could increase risk for musculoskeletal injury:Implications for clinical management and rehabilitation

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Journal of Sport and Health Science 2021年第2期10卷 154-161页

作者： Terese L.Chmielewski Justin Tatman Shuhei Suzuki MaryBeth Horodyski Darcy S.Reisman Russell M.Bauer james R.Clugston Daniel C.herman TRIA Orthopedic Center BloomingtonMN 55431USA ATP Tour Inc. Ponte Vedra BeachFL 32082USA Department of Orthopaedics and Rehabilitation University of FloridaGainesvilleFL 32607USA Department of Physical Therapy University of DelawareNewarkDE 19716USA Department of Clinical and Health Psychology University of FloridaGainesvilleFL 32611USA Department of Community Health&Family Medicine University of FloridaGainesvilleFL 32603USA

This review presents a conceptual framework and supporting evidence that links impaired motor control after sport-related concussion(SRC)to increased risk for musculoskeletal *** studies have found that athletes who are post-SRC have higher risk for musculoskeletal injury compared to their counterparts.A small body of research suggests that impairments in motor control are associated with musculoskeletal injury *** control involves the perception and processing of sensory information and subsequent coordination of motor output within the central nervous system to perform a motor *** control is inclusive of motor planning and motor *** sensory information is not accurately perceived or there is interference with sensory information processing and cognition,motor function will be altered,and an athlete may become vulnerable to injury during sport *** with SRC show neuroanatomic and neurophysiological changes relevant to motor control even after meeting return to sport criteria,including a normal neurological examination,resolution of symptoms,and return to baseline function on traditional concussion *** conjunction,altered motor function is demonstrated after SRC in muscle activation and force production,movement patterns,balance/postural stability,and motor task performance,especially performance of a motor task paired with a cognitive task(i.e.,dual-task condition).The clinical implications of this conceptual framework include a need to intentionally address motor control impairments after SRC to mitigate musculoskeletal injury risk and to monitor motor control as the athlete progresses through the return to sport continuum.

关键词： Clinical management Concussion Injury Motor control Rehabilitation

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Serious Leisure and Leisure Motivations Among Self-identified Cyclists

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Journal of Tourism and Hospitality Management 2015年第1期3卷 32-40页

作者： Zachary Thomas herman Appalachian State University North Carolina USA

This study examines the leisure motivations among people who participate in cycling as a form of serious leisure. It examines what motivates cyclists to build a life around cycling. This study is a replicative study to Robert g. LaChausse＇s study on leisure motivations among cyclists. This study used the Serious Leisure Inventory and Measure （SLIM） created by james gould. Participants were contacted through a variety of local and national list serves. Potential applications of this study include education, coaching, training, planning, and the creation of programs to encourage long-term cycling among bike users. The primary purpose of this study was to examine the motivations of mountain bikers, commuter cyclists, and other cyclists using the SLIM created by james gould and the Leisure Motivation Scale.

关键词： serious leisure leisure motivations cycling cycling motivations

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麦克斐逊与莫里森小说的后现代豪语、误读与反讽(英文)

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外国文学研究 2006年第5期28卷 13-21页

作者：赫尔曼.比弗斯宾西法尼亚大学英语系

近35年来,随着美国少数族裔作家(包括非洲裔美国作家)在“美国性”定义问题上的重要性日益突显,美国文学研究的重心发生了深刻的变化。到底是什么构成了“非洲裔美国人身份或黑人身份”?这一问题在非洲裔美国文学内部引发了激烈的对话,... 详细信息

近35年来,随着美国少数族裔作家(包括非洲裔美国作家)在“美国性”定义问题上的重要性日益突显,美国文学研究的重心发生了深刻的变化。到底是什么构成了“非洲裔美国人身份或黑人身份”?这一问题在非洲裔美国文学内部引发了激烈的对话,而在诺贝尔文学奖得主托妮·莫里森和普利策小说奖得主詹姆士·阿兰·麦克斐逊的小说中,这类讨论显得尤为深刻。本文通过细读莫里森的小说《柏油娃》和麦克斐逊的两篇短篇小说,即“我为什么喜欢乡村音乐”和“活动空间”,探讨其中隐含的关于种族真实性问题的争论。本文的中心论点是,作品通过旅行而不是通过对种族概念的抽象化,传达出作品人物对自己身份和身份归宿的理解。就本质而言,这些故事是在对一个观念进行言说,即身份是一个过程问题而不是位置问题。

关键词：种族真实性旅行翻译非洲裔美国小说身份

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Meeting report:a hard look at the state of enamel research

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International Journal of Oral Science 2017年第4期9卷 193-199页

作者： ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer program in craniofacial biology and department of orofacial sciences university of californiasan franciscoSan FranciscoUSA department of pediatrics and institute for human genetics university of californiasan franciscoSan FranciscoUSA laboratory of skin biology national institute of arthritis and muscular and skin diseasesnational institutes of healthBethesdaUSA physical science division pacific northwest national laboratoriesRichlandUSA department of basic science and craniofacial biology new york university college of dentistryNewYorkUSA department of materials science and engineering northwestern universityevanstonusaEvanstonUSA center for craniofacial molecular biology herman ostrow school of dentistryuniversity of southern californiaLos AngelesUSA the forsyth institute CambridgeUSA department of developmental biology harvard school of dental medicineBostonUSA department of pediatric dentistry university of north caroline school of dentistryChapel HillUSA departments of dermatology and cel&developmental biology perelman school of medicineand department of anatomy&cell biologyschool of dental medicineuniversity of pennsylvaniaPhiladelphiaUSA functional genomics section national institute of dental and craniofacial researchBethesdaUSA division of biosciences ohio state universitycollege of dentistryColumbusUSA department of periodontics and center for craniofacial research and diagnosis texas a&m university college of dentistryDallasUSA center for children’s oral health research and department of orofacial sciences university of californiasan franciscoSan FranciscoUSA biologic and materials sciences and division of prosthodontics university of michiganAnn ArborUSA

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines （ENAMEL） Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research （NIDCR）. Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.

关键词： enamel mineralized tissue mineralization ameloblast stem cell

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Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases

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Hepatobiliary Surgery and Nutrition 2023年第2期12卷 205-215,I0005页

作者： Tan-To Cheung Rong Liu Federica Cipriani Xiaoying Wang Mikhail Efanov David Fuks gi-Hong Choi Nicholas L.Syn Charing C.N.Chong Fabrizio Di Benedetto Ricardo Robles-Campos Vincenzo Mazzaferro Fernando Rotellar Santiago Lopez-Ben james O.Park Alejandro Mejia Iswanto Sucandy Adrian K.H.Chiow Marco V.Marino Mikel gastaca Jae Hoon Lee TPeter Kingham Mathieu D’Hondt Sung Hoon Choi Robert P.Sutcliffe Ho-Seong Han Chung-Ngai Tang Johann Pratschke Roberto I.Troisi go Wakabayashi Daniel Cherqui Felice giuliante Davit L.Aghayan Bjorn Edwin Olivier Scatton Atsushi Sugioka Tran Cong Duy Long Constantino Fondevila Mohammad Abu Hilal Andrea Ruzzenente Alessandro Ferrero Paulo herman Kuo-Hsin Chen Luca Aldrighetti Brian K.P.goh International robotic and laparoscopic liver resection study group investigators Department of Surgery Queen Mary HospitalThe University of Hong KongHong Kong SARChina Faculty of Hepatopancreatobiliary Surgery The First Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijingChina Hepatobiliary Surgery Division IRCCS San Raffaele HospitalMilanItaly Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Hepato-Pancreato-Biliary Surgery Moscow Clinical Scientific CenterMoscowRussia Department of Digestive Oncologic and Metabolic SurgeryInstitute Mutualiste MontsourisUniversite Paris DescartesParisFrance Division of Hepatopancreatobiliary Surgery Department of SurgerySeverance HospitalYonsei University College of MedicineSeoulKorea Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital and Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong Kong SARChina HPB Surgery and Liver Transplant Unit University of Modena and Reggio EmiliaModenaItaly Department of general Visceral and Transplantation SurgeryClinic and University Hospital Virgen de la ArrixacaIMIB-ARRIXACAMurciaSpain HPB Surgery Hepatology and Liver TransplantationFondazione IRCCS Istituto Nazionale Tumori di MilanoMilanItaly HPB and Liver Transplant Unit Department of General SurgeryClinica Universidad de NavarraUniversidad de NavarraPamplonaSpain Institute of Health Research of Navarra(IdisNA) PamplonaSpain Hepatobiliary and Pancreatic Surgery Unit Department of SurgeryDr.Josep Trueta HospitalIdIBGiGironaSpain Hepatobiliary Surgical Oncology Department of SurgeryUniversity of Washington Medical CenterSeattleWAUSA The Liver Institute Methodist Dallas Medical CenterDallasTXUSA AdventHealth Tampa Digestive Health InstituteTampaFLUSA Hepatopancreatobiliary Unit Department of SurgeryChangi General

Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 ***:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between ***:One hundred RLR and 699 LLR which met study criteria were *** comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median *** PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent *** was no significant difference in perioperative outcomes after RLR or LLR.

关键词： Laparoscopic liver resection(LLR) robotic liver resection(RLR) hepatocellular carcinoma colorectal liver metastases huge

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