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Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

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World Journal of Transplantation 2024年第3期14卷 120-131页

作者： William Chung Kevin Wong Noel Ravindranayagam lauren tang Josephine Grace Darren Wong Danny Con Marie Sinclair Avik Majumdar Numan Kutaiba Samuel Hui Paul Gow Vijayaragavan Muralidharan Alexander Dobrovic Adam Testro Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology Monash HealthClayton 3168VictoriaAustralia Department of Surgery University of MelbourneAustin HealthHeidelberg 3048VictoriaAustralia Department of Surgery Beacon LaboratoryAustin PrecinctThe University of MelbourneAustin HospitalHeidelberg 3048VictoriaAustralia

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced *** is increasing interest in chemoprophylaxis to improve HCC-related outcomes *** To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following *** This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian *** use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival *** measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related *** analysis was performed to account for immortality time bias and statin *** Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 *** of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)*** a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related ***,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)*** dosing was not associated with statist-ically significant differences in HCC-related ***

关键词： Liver transplantation Hepatocellular carcinoma Transplant oncology Statins HMG-Co-A reductase Aspirin Metformin Mammalian target of rapamycin

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Large tumor suppressor 2,LATS2,activates iNK in kinase-independent mechanism through ASK1

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Journal of Molecular Cell Biology 2018年第6期10卷 549-558页

作者： lauren Rusnak Cong tang Qi Qi Xiulei Mo Haian Fu Graduate Program in Cancer Biology Emory UniversityAtlantaGA 30322USA Department of Pharmacology and Emory Chemical Biology Discovery Center Emory UniversityAtlantaGA 30322USA The First Affiliated Hospital Medical School of Xi'an Jiaotong UniversityXi'an 710061China Winship Cancer Institute Emory UniversityAtlantaGA 30322USA Department of Hematology and Medical Oncology Emory UniversityAtlantaGA 30322USA

Apoptosis signal-regulating kinase 1 (ASK1)is an important mediator of the cell stress response *** of its central role in regulating cell death,the activity of ASK1 is tightly regulated by protein-protein interactions and post-translational *** of ASK1 activity has been linked to human diseases,such as neurological disorders and *** we describe the identification and characterization of large tumor suppressor 2 (LATS2)as a novel binding partner for ***2 is a core kinase in the Hippo signaling pathway and is commonly downregulated in *** found that LATS2 interacts with ASK1 and increases ASK1-mediated signaUng to promote apoptosis and activate the iNK mitogen-activated protein kinase (MAPK).This change in MAPK signaling is dependent on the catalytic activity of ASK1 but does not require LATS2 kinase activity. This work identifies a novel role for LATS2 as a positive regulator of the ASK1-MKK-JNK signaling pathway and establishes a kinase-independent function of LATS2 that may be part of the intricate regulatory system for cellular response to diverse stress signals.

关键词： ASK1 LATS2 kinase regulation signal transduction mitogen-activated protein kinase

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Feasibility of differentiating T3 from T4a gastric cancer in different lauren classification by determining serosa invasion：Diagnostic performance of high enhanced serosa sign

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Chinese Journal of Cancer Research 2018年第2期30卷 263-271页

作者： Rui-Jia Sun Lei tang Ying Chen Xiao-Ting Li Yu Sun Zi-Yu Li Ying-Shi Sun Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Department of Radiology Beijing 100142 China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Departrnent of Pathology Beijing 100142 China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Center of Gastrointestinal Surgery Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： To study the value of high enhanced serosa sign on contrast-enhanced computed tomography（CT）in differentiating T3 from T4a gastric cancer in different lauren ***： This study included 276 consecutive patients with surgically confirmed p T3 or p T4a gastric *** pre-operative CT images were reviewed by two radiologists blinded. The demonstration of the high enhanced serosa on CT between T3 and T4a was compared with chi-square test. The diagnostic performance of this sign on CT in the differentiation of T4a from T3 in different lauren classification was ***： The accuracy, sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for the judgement of serosa invasion using the high enhanced serosa sign on CT was 74.6%, 63.7%, 83.6%,76.0% and 73.8% by one radiologist and 76.4%, 66.1%, 84.9%, 78.1% and 75.4% by the other *** to the intestinal-type, the sensitivity of the judgement of serosa invasion using the high enhanced serosa sign on CT in diffuse-type was significant higher（80% in both readers）, while the specificity trended to be lower（65.9% and 80.5%, respectively）. There is no significant difference in the accuracy of diagnosis between intestinaltype and diffuse-type of gastric cancers（the P-values of two radiologists were 0.968, 0.591, respectively）. The combination of the high enhanced serosa sign with conventional CT signs is significant different in diagnosis of T3 and T4a（P〈0.001）. The diagnostic accuracy was increased in both radiologists after the combination. The two readers achieved substantial agreement, with Kappa coefficient of 0.63, P〈***： The high enhanced serosa sign on CT is associated with serosa involvement. The sensitivity of the judgement of serosa invasion using this sign on CT in diffuse-type was significant higher than that in intestinal-type.

关键词： Computed tomography gastric cancer staging serosa invasion imaging

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Multidisciplinary team for the diagnosis and treatment of 2cases of primary intestinal yolk sac tumor

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Cancer Biology & Medicine 2018年第4期15卷 461-467页

作者： Qiujuan Huang Changxu Liu Ruijun tang Jie Li Wei Li Lei Zhu Yuhong Guo Lin Zhang Tongyuan Qu Lingyi Yang Lingmei Li Yalei Wang Baocun Sun Bin Meng Jie Yan Wengui Xu Huilai Zhang Dengfeng Cao Wenfeng Cao Department of Pathology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin Medical UniversityMinistry of EducationTianjin 300060China Department of Pathology Guilin TCM Hospital of ChinaGuilin 541002China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Molecular Image and Nuclear Medicine Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Pathology Tianjin Central Hospital of Gynecology ObstetricsTianjin 300110China The lauren V Ackerman Laboratory of Surgical Pathology Division of Anatomic and Molecular PathologyDepartment of Pathology and ImmunologyWashington University School of MedicineSaint LouisMO 63110USA

Extragonadal primary yolk sac tumor of the intestinal tract origin is exceedingly rare. Through a multiple disciplinary team, the diagnosis and treatment of primary intestinal yolk sac tumor were further defined. We report 2 such cases with detailed histologic and immunohistochemical analysis. The two patients were a 7-year-old girl and a 29-year-old woman. Both of them preoperatively had an elevated serum alpha fetoprotein(AFP) level(≥ 1,210 ng/mL). The tumors are located in the intestine and imaging examination indicated the rectum as the primary site. Grossly the mass was grey-white and crisp texture. Microscopic examination featured reticular, microcystic, macrocystic, papillary, solid, and some glandular patterns. Immunohistochemically,tumor cells of both cases were positive for SALL4, AFP, pan-cytokeratin(AE1/AE3), and glypican-3. Simultaneously, a stain for EMA, OCT4, CD30, HCG, vimentin and CK20 were negative in all 2 neoplasms. The features of morphology,immunohistochemistry, laboratory examinations and imaging studies consist of the diagnosis of primary yolk sac tumor of the intestine.

关键词： Yolk sac tumor intestine extragonadal immunohistochemistry multidisciplinary team (MDT)

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Runx3基因CpG岛甲基化与胃癌发生的关系

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中华病理学杂志 2012年第5期41卷 314-319页

作者：唐国华孙少卫贺修胜南华大学生命科学研究中心湖南衡阳421001 南华大学肿瘤所湖南衡阳421001

目的通过研究Runx3基因CpG岛甲基化对胃癌病变的影响，探讨甲基化特异性聚合酶链反应（MSP）法与焦磷酸测序（PS）法对Runx3基因甲基化检测的特异性。方法选取150例胃癌患者胃切除标本及50例无癌变胃黏膜标本，以MSP法和Ps法同时检测其R... 详细信息

目的通过研究Runx3基因CpG岛甲基化对胃癌病变的影响，探讨甲基化特异性聚合酶链反应（MSP）法与焦磷酸测序（PS）法对Runx3基因甲基化检测的特异性。方法选取150例胃癌患者胃切除标本及50例无癌变胃黏膜标本，以MSP法和Ps法同时检测其Runx3启动子的甲基化程度。结果与正常胃黏膜相比，胃癌组织Runx3的甲基化程度差异有显著性意义（MSP法：67．3％比40．0％，P=0．002；PS法：76．0％比30．0％，P〈0．01）。MSP法显示Runx3甲基化只与肿瘤大小相关（P〈0．05）。而Ps法分析显示进展期胃癌的Runx3甲基化率高于早期胃癌（P〈0．05）；且其甲基化状态与肿瘤的大小（P=0．004）、lauren分型（P=0．043）、浸润的深度（P〈0．01）、淋巴结转移（P=0．021）及肿瘤TNM临床分期（P=0．045）等临床病理特征之间存在相关性。结论Runx3启动子甲基化与胃癌临床病理特征包括肿瘤大小、lauren分型、浸润的深度、淋巴结转移以及肿瘤TNM临床分期密切相关；与MSP法相比，Ps法敏感性更高，且检测结果与临床病理学结果之间有显著相关性，对于胃癌的早期诊断和治疗有着重要意义。

关键词：胃肿瘤 DNA甲基化核心结合因子仪3亚基

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Nomogram for predicting the overall survival of patients after D2/R0 resection and chemoradiotherapy for stage Ⅲ gastric cancer or gastroesophageal junction cancer

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Radiation Medicine and Protection 2023年第3期4卷 130-135页

作者： Jinming Shi Wenzhe Kang Songlin Gao Wenyang Liu Yuan tang Ning Li Qiang Zeng Huiying Ma Haoyue Li Yantao Tian Jing Jin Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijing 100021China Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Department of Herpetological SurgeryBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences100730 BeijingChina State Key Laboratory of Molecular Oncology and Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China The VIPII Gastrointestinal Cancer Division of Medical Department Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116China

Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and establish and validate a nomogram model to predict the OS in this patient ***:A total of 569 stage Ⅲ GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this *** patients were randomly divided into training and validation cohorts in a 3:1 *** the training cohort,univariate and multivariate analysis were conducted to identify clinical factors associated with OS,and a nomogram model was established on the basis of the independent *** concordance index(C-index)and the calibration curve were used to validate the prediction power of the ***:Overall,427 and 142 patients were enrolled in the training and validation cohorts,*** the univariate and multivariate analyses,age,lauren's classification,TNM stage,and administration of adjuvant CRT were independent factors for OS to construct the *** C-index values were 0.654 and 0.613 in the training and validation cohorts,*** calibration curves were identical to the actual *** stratification based on the nomogram model showed good risk stratification for OS in both ***:Our study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant *** nomogram could facilitate more individualized prediction of OS in clinical practice.

关键词： Gastric cancer Gastroesophageal junction cancer Nomogram Overall survival

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比较MSP法与PS法检测胃癌组织中Runx3启动子甲基化

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中南医学科学杂志 2012年第1期40卷 24-30页

作者：唐国华孙少卫南华大学生命科学研究中心湖南衡阳421001

目的探讨甲基化特异性聚合酶链法(MSP)和焦磷酸测序法(PS)检测Runx 3基因甲基化的特异性。方法选取150例胃癌患者[依据美国癌症联合委员会(AJCC)分期标准,分肿瘤的早期,进展期两组]胃切除的胃癌标本及50例无癌变胃黏膜标本。分别以MSP法... 详细信息

目的探讨甲基化特异性聚合酶链法(MSP)和焦磷酸测序法(PS)检测Runx 3基因甲基化的特异性。方法选取150例胃癌患者[依据美国癌症联合委员会(AJCC)分期标准,分肿瘤的早期,进展期两组]胃切除的胃癌标本及50例无癌变胃黏膜标本。分别以MSP法和PS法同时检测其Runx3启动子甲基化程度。结果胃癌组织与正常胃黏膜相比,其Runx3基因甲基化程度的差异均有显著性(MSP法:67.3%,40.0%,P=0.002;PS法:76.0%,30.0%,Plauren分级(P=0.043)、浸润的程度(P<0.001)、淋巴结转移(P=0.021)及肿瘤TNM临床分期(P=0.045)等临床病理特征之间存在相关性。结论 PS法与MSP法相比,敏感性更高,PS检测结果与临床病理学结果之间存在显著相关性。

关键词：甲基化 Runx3基因胃癌 PS法 MSP法

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基于数据挖掘分析COL1A1在胃腺癌中的表达及意义

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现代肿瘤医学 2021年第9期29卷 1543-1546页

作者：唐效成吴君辉林昌伟中南大学湘雅三医院胃肠外科湖南长沙410000

目的:通过生物信息数据库挖掘分析胃腺癌中COL1A1基因的表达并探讨其临床意义。方法:使用Oncomine数据库分析COL1A1基因在胃腺癌中的表达水平;通过Oncomine数据库摘录数据信息,进行COL1A1基因表达程度与临床病理参数及胃腺癌生存期的相... 详细信息

目的:通过生物信息数据库挖掘分析胃腺癌中COL1A1基因的表达并探讨其临床意义。方法:使用Oncomine数据库分析COL1A1基因在胃腺癌中的表达水平;通过Oncomine数据库摘录数据信息,进行COL1A1基因表达程度与临床病理参数及胃腺癌生存期的相关性分析;最后使用STRING数据库分析COL1A1蛋白-蛋白互作网络,并进行GO基因富集和KEGG通路富集分析。结果:通过Oncomine数据库分析显示,在mRNA水平上,COL1A1在胃腺癌中高表达(Plauren弥漫型胃腺癌COL1A1表达水平高于肠型胃腺癌(P<0.05)。通过STRING数据库分析显示与COL1A1相关的蛋白有COL6A3、COL5A1、COL6A1、COL5A2等,互作基因的GO基因富集及KEGG信号通路富集分析显示其蛋白涉及的生物学过程、分子功能及细胞定位等方面均与细胞外基质的调控有关,互作基因涉及的主要信号通路为细胞外基质通路、PI3K-AKT等与胃癌的发生发展有关的信号通路。结论:通过对肿瘤基因数据库Oncomine进行数据挖掘分析发现,COL1A1在胃腺癌组织中显著高表达且与患者预后负相关,为胃腺癌的致病机制研究和抗肿瘤靶向治疗提供了理论依据。

关键词：胃腺癌 COL1A1 数据库分析

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贲门癌淋巴结外软组织转移的临床病理特征及预后分析

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中华外科杂志 2013年第10期51卷 882-886页

作者：张洪典唐鹏段晓峰于振涛天津医科大学附属肿瘤医院食管肿瘤科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室 300060

目的探讨贲门癌淋巴结外软组织转移（EM）与各种临床病理特征的相关性及其对患者预后的影响.方法回顾性分析2002年1月至2007年1月行根治性手术切除并经病理诊断明确的323例贲门癌患者的临床病理资料.其中男性272例,女性51例；年龄22... 详细信息

目的探讨贲门癌淋巴结外软组织转移（EM）与各种临床病理特征的相关性及其对患者预后的影响.方法回顾性分析2002年1月至2007年1月行根治性手术切除并经病理诊断明确的323例贲门癌患者的临床病理资料.其中男性272例,女性51例；年龄22～85岁,中位年龄63岁,分析EM阳性与患者临床病理因素的相关性及其对患者术后复发和生存的影响.结果 323例患者中有67例（20.7％）术后检出EM阳性,EM阳性与肿瘤lauren分型、分化程度、浸润深度及淋巴结转移相关（x2 =4.647 ～27.216,P ＜0.05）.EM阳性与阴性患者的5年生存率和中位生存时间分别为12.3％、34.1％和20、39个月,5年生存率差异有统计学意义（x2=23.936,P=0.000）.多因素分析表明,肿瘤浸润深度、淋巴结转移和EM是贲门癌患者预后的独立危险因素.至随访截止,EM阳性患者的累积复发率高于EM阴性患者（59.7％比35.9％,x2=12.409,P=0.000）.分层分析显示,有淋巴结转移患者中,EM阳性患者累积复发率高于EM阴性患者（60.9％比40.0％,x2=8.410,P=0.004）,EM阳性患者5年生存率低于EM阴性患者（12.9％比30.1％,x2=12.939及P=0.000）.结论 EM是贲门癌患者独立预后因素.EM阳性患者术后复发风险高,生存时间短.

关键词：胃肿瘤肿瘤转移预后肿瘤复发局部

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Wnt7a蛋白在胃癌组织中的表达及其与预后的关系

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中国普通外科杂志 2019年第4期28卷 449-455页

作者：刘博赵建国夏爱辉唐晶刘洋李永峰刘俊华中科技大学同济医学院附属协和医院胃肠外科湖北武汉430022

目的:Wnt7a在胃癌组织中的表达及其与胃癌患者临床病理因素及预后的关系。方法:收集胃癌切除术组织样本135例,用Western blot和免疫组化染色检测Wnt7a蛋白在胃癌组织及癌旁组织中的表达。分析Wnt7a表达与胃癌患者临床病理因素以及与胃... 详细信息

目的:Wnt7a在胃癌组织中的表达及其与胃癌患者临床病理因素及预后的关系。方法:收集胃癌切除术组织样本135例,用Western blot和免疫组化染色检测Wnt7a蛋白在胃癌组织及癌旁组织中的表达。分析Wnt7a表达与胃癌患者临床病理因素以及与胃癌患者无瘤生存率及总生存率的关系。结果:Wnt7a在胃癌组织中的表达量高于癌旁组织,其在胃癌组织中的高表达率也明显高于癌旁组织(χ~2=30.5,P=0.000)。Wnt7a蛋白表达与患者性别、年龄、HP感染、分化程度和lauren分型无关(P>0.05),而与TNM分期、远处和淋巴结转移有关(P<0.05)。Wnt7a高表达胃癌患者1、5年无瘤生存率及总生存率均明显低于Wnt7a低表达胃癌患者(均P<0.01)。Wnt7a高表达(P=0.01)与远处转移(P=0.02)及为影响胃癌患者无瘤生存率的独立危险因素,而Wnt7a高表达(P=0.02)与TNM分期(P=0.03)、远处转移(P<0.01)为影响胃癌患者总生存率的独立危险因素。结论:Wnt7a蛋白在胃癌组织中高表达,且与患者恶性病理特征显著相关。Wnt7a蛋白表达可作为胃癌患者术后生存预后评估的指标之一。

关键词：胃肿瘤 Wnt蛋白质类因素分析,统计学预后

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