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Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer

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Cancer Communications 2024年第8期44卷 855-878页

作者： Jian Xiao Shuqing Cao Jiawei Wang Pengyu Li Quan Cheng Xinyi Zhou Jiacheng Dong Yuan Li Xinyu Zhao zekuan xu Li Yang Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China

Background:Lymph node metastasis(LNM)is the primary mode of metastasis in gastric cancer(GC).However,the precise mechanisms underlying this process remain *** cells necessitate lipid metabolic reprogramming to facilitate metastasis,yet the role of lipoprotein lipase(LPL),a pivotal enzyme involved in exogenous lipid uptake,remains uncertain in tumor ***,the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this ***:Intracellular lipid levels were quantified using oil red O staining,BODIPY 493/503 staining,and flow *** analysis was employed to identify alterations in intracellular lipid composition following LPL *** expression levels were assessed through immunohistochemistry,Western blotting,and enzyme-linked immunosorbent *** mouse popliteal LNM model was utilized to investigate differences in *** and mass spectrometry were employed to examine protein *** vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4(ANGPTL4)***:We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive(N+)GC and further demonstrated that a high-fat diet can expedite *** was found to be significantly overexpressed in N+GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC ***,an obesity-related hormone,intercepted the effect exerted by ANGPTL4/Furin on LPL *** leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1(IRE1)kinase,leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with ***,our research revealed that LPL disrupted lipid homeostasis by elevating intrace

关键词： angiopoietin-like protein 4 leptin lipoprotein lipase lymph node metastasis prostaglandin E2

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胃癌切除消化道重建话今昔

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中华胃肠外科杂志 2024年第10期27卷 1004-1011页

作者：王林俊王森徐泽宽南京医科大学第一附属医院普通外科胃肿瘤中心南京

胃癌消化道重建历经百年, 逐渐形成了相对完整成熟的体系。合理的消化道重建是改善胃切除术后功能障碍、提高生命质量的关键因素之一。因此, 本文针对中国及国际消化道重建的历史及现状进行了梳理归纳, 按照远端胃切除消化道重建、全胃... 详细信息

胃癌消化道重建历经百年, 逐渐形成了相对完整成熟的体系。合理的消化道重建是改善胃切除术后功能障碍、提高生命质量的关键因素之一。因此, 本文针对中国及国际消化道重建的历史及现状进行了梳理归纳, 按照远端胃切除消化道重建、全胃切除消化道重建、近端胃切除消化道重建及保留幽门的胃切除术消化道重建进行了总结, 以寻求未来消化道重建的发展方向, 造福广大胃癌患者。

关键词：胃肿瘤胃切除手术消化道重建

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近端胃切除消化道重建方式实施的质量化控制

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中华胃肠外科杂志 2024年第2期27卷 153-157页

作者：徐泽宽王林俊李沣员葛晗南京医科大学第一附属医院普通外科南京210029

随着食管胃结合部癌发病率的增高,近端胃切除术的应用率逐年上升。近端胃切除后消化道重建的方式种类繁多,部分重建方式问世时间尚短,存在术者临床经验较少、重建方式欠规范的情况。此状况势必会带来近端胃切除消化道重建后临床疗效参... 详细信息

随着食管胃结合部癌发病率的增高,近端胃切除术的应用率逐年上升。近端胃切除后消化道重建的方式种类繁多,部分重建方式问世时间尚短,存在术者临床经验较少、重建方式欠规范的情况。此状况势必会带来近端胃切除消化道重建后临床疗效参差不齐的后果。为促进近端胃切除消化道重建的规范化实施,从而提高近端胃切除术的临床疗效,降低术后并发症发生率,本文针对在《近端胃切除消化道重建中国专家共识(2020版)》中专家推荐率最高的双通道吻合、食管管型胃吻合、食管残胃侧壁吻合(side overlap)和双肌瓣吻合(double flaps)4种消化道重建方式,从适应证选择、手术步骤及技术要点分别进行阐述,以期为施行近端胃切除消化道重建的质量化控制提供参考。

关键词：胃肿瘤近端胃切除消化道重建质量化控制

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Cytosolic TGM2 promotes malignant progression in gastric cancer by suppressing the TRIM21-mediated ubiquitination/degradation of STAT1 in a GTP binding-dependent modality

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Cancer Communications 2023年第1期43卷 123-149页

作者： Lu Zhang Qingya Li Jing Yang Penghui xu Zhe xuan Jianghao xu zekuan xu Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029P.R.China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166P.R.China

Background:Previous studies have revealed the critical role of transglutaminase 2(TGM2)as a potential therapeutic target in cancers,but the oncogenic roles and underlying mechanisms of TGM2 in gastric cancer(GC)are not fully *** this study,we examined the role and potential mechanism of TGM2 in ***:Western blotting,immunohistochemistry,CCK8,colony formation and transwell assays were used to measure TGM2 expression in the GC cells and tissues and to examine the in vitro role of TGM2 in *** and in vivo metastasis experiments were performed to examine the in vivo role of TGM2 in *** set enrichment analysis,quantitative PCR and western blotting were conducted to screen for potential TGM2 targets involved in ***/loss-offunction and rescue experiments were conducted to detect the biological roles of STAT1 in GC cells in the context of ***-immunoprecipitation,mass spectrometry,quantitative PCR and western blotting were conducted to identify STAT1-interacting proteins and elucidate their regulatory *** in TGM2 and two molecules(ZM39923 and A23187)were used to identify the enzymatic activity of TGM2 involved in the malignant progression of GC and elucidate the underlying ***:In this study,we demonstrated elevated TGM2 expression in the GC tissues,which closely related to pathological grade,and predicted poor survival in patients with ***2 overexpression or knockdown promoted(and inhibited)cell proliferation,migration,and invasion,which were reversed by STAT1 knockdown or *** studies showed that TGM2 promoted GC progression by inhibiting STAT1 ubiquitination/***,tripartite motif-containing protein 21(TRIM21)was identified as a ubiquitin E3 ligase of STAT1 in ***2 maintained STAT1 stability by facilitating the dissociation of TRIM21 and STAT1 with GTP-binding enzymatic activity.A23187 abolished the role of TGM2 in STAT1 and reversed the pro-tumor role of TGM2 in vitro and

关键词： TGM2 STAT1 TRIM21 ubiquitination degradation gastric cancer

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胃癌手术质量控制数据的公布推动胃癌手术水平的提高:基于2020—2022年江苏省胃癌质量控制数据分析

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肿瘤 2024年第02期44卷 136-145页

作者：王林俊夏义文李铮李清雅张殿彩徐皓杨力宋军管文贤徐泽宽南京医科大学第一附属医院胃肿瘤中心徐州医科大学附属医院普通外科南京大学医学院附属鼓楼医院胃肠外科

目的:收集并分析2020—2022年江苏省胃癌手术质量控制的相关数据,研究胃癌手术质量控制数据的公布在推动中国胃癌手术水平提升中的作用。方法:以江苏胃癌联盟(Jiangsu Gastric Cancer Union,JSGCU)为平台,采用调查问卷的形式,在线创建... 详细信息

目的:收集并分析2020—2022年江苏省胃癌手术质量控制的相关数据,研究胃癌手术质量控制数据的公布在推动中国胃癌手术水平提升中的作用。方法:以江苏胃癌联盟(Jiangsu Gastric Cancer Union,JSGCU)为平台,采用调查问卷的形式,在线创建相关问卷后,由各联盟成员单位根据要求在线填写相关问卷内容。收集资料内容包括:医院基本情况、早期胃癌诊治、局部进展期胃癌诊治、晚期胃癌诊治、消化道重建、手术安全性以及经济学指标等。结果:连续收集并分析了2020—2022年江苏省胃癌手术质量控制的相关数据。数据分析结果显示,2020—2022年Ⅰ期胃癌患者的比例逐年上升,胃癌早筛、早诊、早治工作的成果得到了很好的体现;腹腔镜手术率逐年上升,已成为江苏省胃癌根治术的主流方式;胃癌淋巴结清扫数目≥30枚的医院比例逐年上升;不同部位的胃癌根治术后消化道重建方式的选择各有特点;胃癌腹腔镜手术Ⅲ级以上并发症的发生率略低于开放性手术,其中发生并发症患者的术后住院时间明显延长,术后住院费用也明显提高。胃癌手术中选择关闭系膜间隙的医院比例逐年上升。结论:江苏省胃癌手术质量控制数据的公布推动了中国胃癌手术水平的提高。

关键词：胃癌手术质量控制手术质量

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N6-methyladenosine modification of CENPF mRNA facilitates gastric cancer metastasis via regulating FAK nuclear export

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Cancer Communications 2023年第6期43卷 685-705页

作者： Penghui xu Jing Yang Zetian Chen Xing Zhang Yiwen Xia Sen Wang Weizhi Wang zekuan xu Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsuP.R.China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsuP.R.China

Background:N6-methyladenosine(m^(6)A)modification is the most common modification that occurs in *** substantial effort has been made in the prevention and treatment of gastric cancer(GC)in recent years,the prognosis of GC patients remains *** regulatory mechanism between m^(6)A modification and GC development needs to be *** this study,we examined m^(6)A modification and the downstream mechanism in ***:Dot blotting assays,The Cancer Genome Atlas analysis,and quantitative real‑time PCR(qRT-PCR)were used to measure the m^(6)A levels in GC *** RNA-immunoprecipitation sequencing and RNA sequencingwere performed to identify the targets ofm^(6)*** blotting,Transwell,wound healing,and angiogenesis assays were conducted to examine the role of centromere protein F(CENPF)in GC in ***,immunohistochemistry,and in vivo metastasis experiments were conducted to examine the role of CENPF in GC in *** RNA-immunoprecipitation-qPCR,RNA immunoprecipitation-qPCR and RNA pulldown assays were used to verify the m^(6)A modification sites of ***/loss-of-function and rescue experiments were conducted to determine the relationship between CENPF and the mitogen-activated protein kinase(MAPK)signaling pathway in GC ***,mass spectrometry,qRT-PCR,and immunofluorescence assays were performed to explore the proteins that interact with CENPF and elucidate the regulatory mechanisms between ***:CENPF was upregulated in GC and facilitated the metastasis of GC both in vitro and in ***,increasedm^(6)A modification of CENPF was mediated by methyltransferase 3,and this modified molecule could be recognized by heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1),thereby promoting its mRNA *** addition,the metastatic phenotype of CENPF was dependent on the MAPK signaling ***,CENPF could bind to FAK and promote its local

关键词： CENPF epithelial-mesenchymal transition FAK gastric cancer MAPK metastasis N6-methyladenosine

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Gastric cancer: Epidemiology, risk factors and prevention strategies

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Chinese Journal of Cancer Research 2020年第6期32卷 695-704页

作者： Lei Yang Xiangji Ying Shuo Liu Guoqing Lyu zekuan xu Xi Zhang Huichao Li Qingyu Li Ning Wang Jiafu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Beijing Office for Cancer Prevention and ControlPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal Surgery Peking University Shenzhen HospitalShenzhen 518036China Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 210029China

Gastric cancer(GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in Helicobacter pylori(H. pylori) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors. H. pylori infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.

关键词： Gastric cancer epidemiology risk factor prevention strategy

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全机器人下根治性全胃切除+食管空肠Roux-en-Y吻合术（Overlap法）

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手术电子杂志 2024年第2期11卷 18-19页

作者：李沣员刘宏达汪未知王林俊张殿彩杨力徐泽宽徐皓南京医科大学第一附属医院胃肿瘤中心

2000年获得临床应用许可的达芬奇外科手术系统（da Vinci surgical system）作为一种创新的微创手术平台，提供了高清晰度的裸眼3 D成像功能、有效的震颤过滤技术以及高精度灵活的模拟机械臂。根据目前研究证明，达芬奇机器人手术系统... 详细信息

2000年获得临床应用许可的达芬奇外科手术系统（da Vinci surgical system）作为一种创新的微创手术平台，提供了高清晰度的裸眼3 D成像功能、有效的震颤过滤技术以及高精度灵活的模拟机械臂。根据目前研究证明，达芬奇机器人手术系统在胃癌手术治疗方面具有其安全性和可行性。灵活的机械臂，在胃周淋巴结清扫中更具优势，对周围器官的损伤更小，术后胰瘘发生率更低；缝合优势能更便利完成全机器人完全缝合重建，缩短腹腔暴露时间、减少腹腔体液丢失、降低手术对患者内环境稳态的干扰。

关键词：全机器人下根治性全胃切除 Roux-en-Y吻合术

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Establishment of simultaneous pancreas and kidney transplantation (SPK) model with cuff technique and portal venous drainage in rats

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Journal of Nanjing Medical University 2007年第1期21卷 8-10页

作者： Shuguang Han zekuan xu xuan Zhang Yi Miao Department of General Surgery the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

To establish a simultaneous pancreas and kidney transplantation （SPK） model in the rat. Methods： SD rats served as donors and recipients. The donor portal vein and the recipient superior mesenteric vein were anastomosed and the donor renal veins and recipient renal veins were anastomosed by cuff method. Arterial reconstruction was carried out by end to side anastomosis of the donor abdominal aorta to the recipient abdominal aorta. Enteric drainage was performed by side to side anastomosis between donors＇ duodenum and recipients＇ jejunum. The donor ureter -bladder valve was anastomosed to the bladder of recipients. Results： Out of 30 cases of SPK transplantation, 24 had normal serum glucose and serum creatinine after operation. The successful rate was 80 %. Conclusion： This model of SPK in rats is stable and reliable, which could be applied for further scientific research.

关键词： simultaneous pancreas and kidney transplantation rat model

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Growth hormone receptor expression in human primary gastric adenocarcinoma

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The Journal of Biomedical Research 2012年第5期26卷 307-314页

作者： Xiaodong Yang Ping Huanga Feng Wang zekuan xu Xiaonin Wang Department of General Surgery the First Affiliated Hospital the Nanjing Medical University Nanjing Jiangsu 210029 China Department of General Surgery Jiangsu Hospital of Integrated Traditional Chinese and Western Medicine Nanjing Jiangsu 210028 China

The aim of this study was to determine the expression of growth hormone receptor（GHR） in patients with pri-mary gastric *** investigated 48 specimens of primary gastric adenocarcinoma and their cor-responding normal gastric *** and reverse transcription-polymerase chain reaction（RT-PCR） were used to detect the expression of *** analyses revealed that GHR was expressed in human primary gastric adenocarcinoma（36/48,75.0%） and appeared to be upregulated,compared to the normal mucosa（28/48,58.3%,P 〈 0.001）.A significant correlation was found between GHR expression and tumor stage（P 〈 0.001） and tumor differentiation（P 〈 0.001）.The average positive rate of ki-67 in GHR-positive tumors was 16.06%,while the positive rate in GHR-negative tumors was 6.17%（P 〈 0.01）.The average apoptosis index（AI） of GHR-positive tumors was 3.36%,which was significantly lower than that（7.33%） of GHR-negative *** addition,27 of 48 cases of tumors had GHR mRNA expression,while only 17 of all 48 cases of normal mucosa did *** results indicate that the frequency of GHR was significantly higher in primary gastric adeno-carcinoma than that in normal gastric *** expression was significantly correlated with tumor differen-tiation and tumor *** finding supported a possible role of growth hormone in primary gastric adenocarci-noma pathophysiology.

关键词： growth hormone receptor primary gastric cancer proliferative index apoptosis index

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