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The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2065-2076页

作者： Xiaojiao Wang Xi Luo Chuan Chen Ye Tang Lian Li Banghui Mo houjie liang Songtao Yu Department of Oncology Southwest HospitalArmy Medical University30 Gaotanyan StreetChongqing 400038People’s Republic of China Cancer Center Daping Hospital and Research Institute of SurgeryArmy Medical UniversityChongqing 402560People’s Republic of China Department of Oncology Tong Liang District HospitalChongqing 402560People’s Republic of China

The inhibitory receptor signal regulatory protein-α(Sirpα)is a myeloid-specific immune checkpoint that engages the“don’t eat me”signal CD47,which is expressed on tumor and normal tissue ***,the profile and regulatory mechanism of Sirpαexpression in tumor-associated macrophages(TAMs)are still not ***,we found that the expression of Sirpαin TAMs increased dynamically with colorectal cancer(CRC)***,CRC cell-derived lactate induced the nuclear translocation of the transcription factor Ap-2αfrom the cytoplasm in ***-2αfunctioned as a transcription factor for Elk-1 by binding to the conserved element GCCTGC located at−1396/−1391 in the mouse Elk-1 ***,the Elk-1 protein bound to two conserved sites,CTTCCTACA(located at−229/−221)and CTTCCTCTC(located at−190/−182),in the mouse Sirpαpromoter and promoted Sirpαexpression in ***,the macrophage-specific knockout of Ap-2αnotably promoted the phagocytic activity of TAMs and suppressed CRC progression,whereas these effects were prevented by the transgenic macrophage-specific expression of Elk-1,which regulated TAM phagocytosis and CRC development in a Sirpα-dependent ***,we showed that Elk-1 expression was positively correlated with Sirpαexpression in TAMs and was associated with poor survival in CRC *** together,our findings revealed a novel mechanism through which CRC evades innate immune surveillance and provided potential targets for macrophage-based immunotherapy for CRC patients.

关键词： colorectal cancer promoted

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The real-world study of the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer in China

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Journal of Pancreatology 2024年第1期7卷 1-9页

作者： Jiujie Cui Qihan Fu Xiaobing Chen Yanling Wang Qi Li Feng Wang Zhihua Li Guanghai Dai Yusheng Wang Hongmei Zhang houjie liang Jun Zhou Liu Yang Fenghua Wang Leizhen Zheng Xiaofeng Chen Ping Gong Jiang Liu Ying Yuan Lin Wang Yuejuan Cheng Jun Zhang Yuhong Zhou Weijian Guo Xianbao Zhan Zhengyun Zou Da Li Shan Zeng Enxiao Li Zhiwei Li Zan Teng Dan Cao Jie Kan Jianping Xiong Ming Quan Jiayu Yao Haiyan Yang Liwei Wang Department of Medical Oncology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Medical Oncology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina Department of Medical Oncology Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina Department of Medical Oncology Shanghai General HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Medical Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Medical Oncology Sun Yat-sen Medical Hospital Sun Yat-sen UniversityGuangzhouChina Medical Oncology Chinese PLA General HospitalBeijingChina Department of Gastrointestinal Oncology Shanxi Provincial Cancer HospitalAffiliated to Shanxi Medical UniversityTaiyuanChina Department of Clinical Oncology Xijing HospitalAir Force Medical UniversityXi’anChina Department of Oncology and Southwest Cancer Center Southwest HospitalThird Military Medical University(Army Military Medical University)ChongqingChina Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital&InstituteBeijingChina Cancer Center Department of Medical OncologyZhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhouChina Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongChina Oncology Department Xin Hua Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghaiChina Department of Oncology the First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology The First Affiliated HospitalSchool of MedicineShihezi UniversityShiheziChina Department of Oncology People’s Hospital of Xinjiang Uygur Autonomous RegionXinjiangChina Department of Medical Oncology t

Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are *** such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center ***:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a *** entire course of real-world pancreatic cancer management was ***:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this *** carbohydrate antigen(CA)19-9 is one of the most common tumor *** the present study,2562 patients underwent first-line *** median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 *** major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS ***:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in *** revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported *** intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

关键词： Advanced pancreatic cancer China Pancreas Data Center Chinese First-line regimens Real-world study

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Role of integrin oV in sensitivity to radiotherapy of human NPC

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The Chinese-German Journal of Clinical Oncology 2009年第2期8卷 86-89页

作者： Haihui Huang Wei Luan Jianjun Li houjie liang Department of Oncology Southwest Hospital Third Military Medical University Chongqing 400038 China

Objective： To investigate whether the cell adhesion molecule integrin αV could influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells via effecting intercellular effect. Methods： Human NPC cell line CNE-2Z was cultivated as three dimensional model using liquid overlay technique. Cell counting was employed to detect the radiosensitivity of CNE-2Z cells by blood cell counter before and after blocking integrin aV function; cell apoptosis was detected by flow cytometry using Annexin V/PI label. Results： Three dimensional culture model of human NPC cell line CNE-2Z cells were successfully established. The integrin αV expression of CNE-2Z multicellular spheroids elevated as the dosage of radiotherapy increased. Blocking of integrin aV function leaded to higher radiosensitivity and more apoptotic cells of CNE-2Z multicellular spheroids. Conclusion： Cell adhesion molecules integrin aV can influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells and the inhibition of cell apoptosis might be its mechanism, proved by three dimensional culture model to mimic solid tumor in vivo.

关键词： human NPC cell line CNE-2Z multicellular spheroids integrin αV radiosensitivity apoptosis

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胃肠胰神经内分泌肿瘤的诊断与治疗

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中华消化外科杂志 2014年第10期13卷 756-759页

作者：梁后杰第三军医大学西南医院肿瘤科重庆400038

胃肠胰神经内分泌肿瘤（GEP-NENs）是一种罕见肿瘤,近年来发病率不断增加.神经内分泌肿瘤（NENs）的诊断依据包括提示NENs的临床表现、生化标志物、基因检测、影像学检查、组织学诊断等.GEP-NENs按临床表现可分为功能性和非功能性GEP-NE... 详细信息

胃肠胰神经内分泌肿瘤（GEP-NENs）是一种罕见肿瘤,近年来发病率不断增加.神经内分泌肿瘤（NENs）的诊断依据包括提示NENs的临床表现、生化标志物、基因检测、影像学检查、组织学诊断等.GEP-NENs按临床表现可分为功能性和非功能性GEP-NENs.手术是局限期GEP-NENs的主要治疗手段.然而,大多数GEP-NENs患者确诊时已发生远处转移,难以接受根治性手术,最合适的治疗模式是多学科综合治疗,包括手术、化疗、生物治疗、分子靶向治疗以及肽受体放射性核素治疗.分子靶向治疗有望成为标准的一线治疗方案.

关键词：神经内分泌肿瘤胃肠胰腺

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Changes of NF-κB activity in colon carcinoma cells treated with different crude extracts of abrotani herba

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The Chinese-German Journal of Clinical Oncology 2008年第8期7卷 465-468页

作者： Feng Pan Yuying Chen Li Yang Zhiheng Bian houjie liang Department of Oncology South West Hospital The Third Military Medical University Chongqing 400038 China

Objective: To study changes of NF-κB activity in colon carcinoma cell lines treated with different crude extracts of abrotani herba obtained through solvent extraction methods. Methods: Crude extracts of abrotani herba were extracted with ligarine, chloroform, acetoacetate and n-butanol in separating funnel. Exposure concentration of crude extracts were obtained through detecting viability of HT-29 cells by MTT. Then HT-29 cells and Lovo cells were treated with different crude extracts respectively. Changes of NF-κB activity in HT-29 cells and Lovo cells using different crude extracts were observed by EMSA. Results: Successfully extracted different crude extracts of abrotani herba and called them ligarine extract, chloroform extract, acetoacetate extract, n-butanol extract and remaining extract for short. NF-κB activity was significantly inhibited in HT-29 cells treated with chloroform extract, there were no significant differences in other groups compared with the control. The same change of NF-κB activity was observed in Lovo cells using different crude extracts of abrotani herba. Conclusion: NF-κB activity can be inhibited in colon carcinoma HT-29 cells and Lovo cells treated with chloroform extract obtained from abrotani herba through the method of solvent extraction.

关键词： abrotani herba solvent extraction colon carcinoma NF-κB

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6-磷酸果糖-2-激酶在结直肠癌中的表达及临床意义

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第三军医大学学报 2017年第10期39卷 983-989页

作者：魏莱王喆梁后杰第三军医大学西南医院肿瘤科重庆400038

目的检测6-磷酸果糖-2-激酶(6-phosphofructokinase-2,PFKFB)在结直肠癌及癌旁组织中的表达,并探讨其临床意义。方法应用组织芯片结合免疫组化技术检测本院90例结直肠癌组织标本和相应90例癌旁组织中PFKFB1、PFKFB2、PFKFB3、PFKFB4及... 详细信息

目的检测6-磷酸果糖-2-激酶(6-phosphofructokinase-2,PFKFB)在结直肠癌及癌旁组织中的表达,并探讨其临床意义。方法应用组织芯片结合免疫组化技术检测本院90例结直肠癌组织标本和相应90例癌旁组织中PFKFB1、PFKFB2、PFKFB3、PFKFB4及缺氧诱导因子-1(HIF1-α)的表达。结果 PFKFB1、PFKFB2、PFKFB3、PFKFB4和HIF1-α在90例结直肠癌组织中高表达例数分别为57、59、59、51和60,表达均显著高于相应癌旁组织(P0.05)。PFKFB3的表达同HIF-1α的表达呈正相关(r=0.627,P0.05)。结论 PFKFB家族在结直肠癌中高表达,且结直肠癌患者中PFKFB3高表达者比低表达者预后差,并且其作用同HIF1-α的表达密切相关。

关键词：结直肠癌组织芯片 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶缺氧诱导因子-1

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胆红素上调PPARα/CPT1A降低Huh7细胞对索拉非尼的敏感性

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陆军军医大学学报 2022年第16期44卷 1606-1612页

作者：谭君张弛董严梁后杰陆军军医大学(第三军医大学)第一附属医院肿瘤科重庆400038

目的观察胆红素(bilirubin,Bil)对索拉非尼(sorafenib,Sor)治疗肝癌效果的影响,并探讨其可能机制。方法体外实验:用不同浓度的Sor(0、2、4、8、16、32μmol/L)、Bil(0、2.5、5、10、20、40μmol/L)及不同浓度Sor+Bil(20μmol/L)培养Huh7细胞系不同时间(24、48、72 h)后,通过CCK-8法检测细胞活力。采用Sor(4μmol/L)、Bil(20μmol/L)、Sor(4μmol/L)+Bil(20μmol/L)处理Huh7细胞,48 h后用流式细胞仪检测细胞周期,14 d后通过克隆形成实验检测药物对细胞增殖的影响。体内实验:取16只裸鼠构建Huh7细胞异种移植瘤模型,按S型抽样方法将裸鼠分为Con组、Bil组(25 mg·kg^(-1)·d^(-1))、Sor(15 mg·kg^(-1)·d^(-1))组、Bil(25 mg·kg^(-1)·d^(-1))+Sor(15 mg·kg^(-1)·d^(-1))组,每组各4只,并进行相应处理。通过Western blot和实时荧光定量PCR(RT-qPCR)检测各组过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPARα)、肉毒碱棕榈酰基转移酶1A(carnitine palmityl transferase 1A,CPT1A)的表达量。加入CPT1A抑制剂乙莫克舍(etomoxir,Eto)后,通过CCK-8、克隆形成实验验证Bil削弱Sor对肝癌细胞的增殖抑制与PPARα/CPT1A的相关性。结果CCK-8结果显示,Sor对Huh7细胞的增殖抑制效应呈现剂量和时间依赖(P0.05)。与单独Sor处理组相比,Bil+Sor组细胞增殖活力增加,细胞克隆数目较多(P<0.05),细胞在S期的数目减少(P<0.05)。体内实验结果显示:Sor组肿瘤体积和质量小于Con组(P<0.05),Bil+Sor组肿瘤体积和质量大于Sor组(P<0.05)。Western blot和RT-qPCR结果显示:与Sor组相比,Bil+Sor组PPARα、CPT1A的表达增多(P<0.05)。与Bil+Sor组相比,加入Eto后,Bil+Sor+Eto组细胞增殖活力降低(P<0.05),细胞克隆数目减少(P<0.05)。结论胆红素通过PPARα/CPT1A介导脂肪酸氧化削弱索拉非尼的抗肿瘤效果。

关键词：肝癌索拉非尼胆红素脂肪酸氧化 PPARα/CPT1A

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结肠癌术后辅助化疗的共识与争议

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第三军医大学学报 2012年第1期34卷 1-4页

作者：梁后杰李建军第三军医大学西南医院肿瘤科重庆400038

根据美国1992-2004年130 762例结肠癌(不包括转移性结肠癌)的统计资料,不同分期(AJCC 2010年)的5年生存率分别为:Ⅰ期97.1%,ⅡA期87.5%,ⅡB期79.6%,ⅡC期58.4%,ⅢA期87.2%,ⅢB期64.9%,ⅢC期32.9%[1-2],结果显示分期较早的患者,其疗效并... 详细信息

根据美国1992-2004年130 762例结肠癌(不包括转移性结肠癌)的统计资料,不同分期(AJCC 2010年)的5年生存率分别为:Ⅰ期97.1%,ⅡA期87.5%,ⅡB期79.6%,ⅡC期58.4%,ⅢA期87.2%,ⅢB期64.9%,ⅢC期32.9%[1-2],结果显示分期较早的患者,其疗效并不一定优于分期较晚者,ⅢA期5年生存率明显高于ⅡC期,也高于ⅡB期,与ⅡA期相似,

关键词：辅助化疗结肠肿瘤

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AMPK的激活调节COX-2对HT-29细胞增殖和凋亡的影响

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中国肿瘤临床 2009年第14期36卷 823-826页

作者：陈琦邹岚梁后杰第三军医大学西南医院肿瘤科重庆市400038

目的:研究AMPK的激活在结肠癌HT-29细胞中对COX-2表达的影响,并探讨其对细胞增殖和凋亡的作用。方法:用Western Blot方法检测AMPK的激活对COX-2表达的影响,MTT法检测不同浓度、时间的AMPK激活剂AICAR和选择性COX-2抑制剂塞来昔布作用下... 详细信息

目的:研究AMPK的激活在结肠癌HT-29细胞中对COX-2表达的影响,并探讨其对细胞增殖和凋亡的作用。方法:用Western Blot方法检测AMPK的激活对COX-2表达的影响,MTT法检测不同浓度、时间的AMPK激活剂AICAR和选择性COX-2抑制剂塞来昔布作用下的细胞存活率,流式细胞术检测细胞凋亡率,用MTT法检测二者联合对细胞增殖的影响。结果:AMPK被激活后COX-2蛋白表达减少,随着AICAR和塞来昔布作用浓度、时间增加,细胞存活率呈剂量和时间依赖性下降,塞来昔布组和AICAR组凋亡细胞增多,早期凋亡细胞及晚期凋亡细胞比例均高于对照组(P<0.05),AICAR和塞来昔布联用后细胞的存活率为(23.0±0.82)%,均低于AICAR组(54.0±2.86)%和塞来昔布组(57.0±2.54)%。结论:AMPK激活可以抑制COX-2表达对人结肠癌HT-29细胞产生增殖抑制和凋亡诱导效应,AICAR和塞来昔布二者联用具有协同作用。

关键词： AMPK AICAR COX-2 塞来昔布结肠癌

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三种DNA甲基转移酶在肝细胞癌组织中的表达及其临床意义

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中国肿瘤临床 2009年第6期36卷 333-336页

作者：李宏涛肖文华梁后杰第三军医大学西南医院肿瘤科解放军总医院第一附属医院肿瘤科北京市100037

目的:探讨肝细胞癌组织中三种甲基转移酶(DNMT)蛋白表达的差异及其临床意义。方法:收集38例肝癌标本,取癌区组织各3块,制作组织芯片,应用免疫组化SP法分析肝癌组织中DNMT蛋白的表达,并分析其与肝癌各临床、病理参数间的关系。结果:在38... 详细信息

目的:探讨肝细胞癌组织中三种甲基转移酶(DNMT)蛋白表达的差异及其临床意义。方法:收集38例肝癌标本,取癌区组织各3块,制作组织芯片,应用免疫组化SP法分析肝癌组织中DNMT蛋白的表达,并分析其与肝癌各临床、病理参数间的关系。结果:在38例肝癌组织中,DNMT1、DNMT3a和DNMT3b蛋白的表达阳性率分别为55.3%、48.5%和65.8%。DNMT蛋白质着色主要分布在细胞核,散在分布于胞浆。DNMT1蛋白质表达与门脉癌栓和肿瘤无包膜等参数显著相关;组织中DNMT1表达与DNMT3b表达具有相关性,二者同时表达与门脉癌栓和肿瘤无包膜等参数显著相关。但三种DNMT蛋白的阳性表达与患者的年龄、性别、肿瘤分化程度和淋巴结转移无显著相关性(P>0.05)。结论:肝细胞癌组织中存在三种DNMT蛋白的过表达,DNMT1和DNMT3b的高表达与门脉癌栓和肿瘤无包膜等参数显著相关,二者协同作用可能在肝癌的发生和发展中起重要作用。

关键词：肝细胞癌 DNA甲基转移酶免疫组织化学

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