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LncRNA-CCAT5-mediated crosstalk between Wnt/β-Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity

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Cancer Communications 2024年第1期44卷 76-100页

作者： Chenchen Liu Aiwen Shen Junquan Song Lei Cheng Meng Zhang yanong wang Xiaowen Liu Department of Gastric Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Nephrology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP.R.China Department of Pulmonary Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China

Background:Although the constitutively activated Wnt/β-catenin signaling pathway plays vital roles in gastric cancer(GC)progression,few Wnt inhibitors are approved for clinical ***,the clinical significance of long non-coding RNAs(lncRNAs)in GC intraperitoneal dissemination(IPD)remains ***,we investigated the function and therapeutic potential of Wnt-transactivated lncRNA,colon cancer-associated transcript 5(CCAT5),in GC ***:LncRNA-sequencing assay was performed to document abun-dance changes of lncRNAs induced by Wnt family member 3A(Wnt3a)and degradation-resistantβ-catenin(S33Y mutated)in ascites-derived GC cells with low Wnt *** reporter,Chromatin immunoprecipitation(ChIP)-re-ChIP assays were performed to determine how CCAT5 was *** clinical significance of CCAT5 was examined in 2 cohorts of GC *** biological function of CCAT5 was investigated through gain-and loss-of-function *** molecular mechanism was explored through RNA-sequencing,mass spectrometry,and CRISPR/Cas9-knocknout *** therapeutic potential of CCAT5 was examined through RNAi-based cell xenograft model and patient-derived xenograft(PDX)model of ***:WeidentifiedanovelWnt-regulatedlncRNA,CCAT5,whichwastrans-activated by theβ-catenin/transcription factor 3(TCF3)***5 was significantly upregulated in GC and predicted poor *** studies confirmed the promotive role of CCAT5 in GC growth and ***-tically,CCAT5 bound to the C-end domain of signal transducer and activator of transcription 3(STAT3)and blocks Src homology 2 domain-containing protein tyrosine phosphatase 1(SHP-1)-mediated STAT3 Y705 dephosphorylation,leading to STAT3 nuclear entry and transactivation,thus accelerating GC ***,we demonstrated that both Wnt3a andβ-catenin acted as activa-tor of STAT3 signaling pathway,and the interplay between CCAT5 and STAT3 was functionally essential for Wnt-

关键词： CCAT5 gastric cancer intraperitoneal dissemination STAT3 Wnt/β-catenin

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Construction and evaluation of a polygenic hazard score for prognostic assessment in localized gastric cancer

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Fundamental Research 2024年第5期4卷 1331-1338页

作者： Jing Ni Mengyun wang Tianpei wang Caiwang Yan Chuanli Ren Gang Li Yanbing Ding Huizhang Li Lingbin Du Yue Jiang Jiaping Chen yanong wang Dazhi Xu Meng Zhu Juncheng Dai Hongxia Ma Zhibin Hu Hongbing Shen Qingyi Wei Guangfu Jin Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineChina International Cooperation Center for Environment and Human HealthNanjing Medical UniversityNanjing 211166China Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefei 230032China Cancer Institute Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Public Health Institute of Gusu School The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006China Department of Immunology School of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Department of Laboratory Medicine Clinical Medical College of Yangzhou UniversityYangzhou 225001China Department of General Surgery Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Department of Gastroenterology the Affiliated Hospital of Yangzhou UniversityYangzhou 225001China Zhejiang Provincial Office for Cancer Prevention and Control The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China Department of Gastric Cancer and Soft Tissue Sarcomas Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Laboratory of Molecular and Translational Cancer Research Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Institute for Precision Cancer Prevention and Medicine Great Bay Area Institutes of Precision MedicineGuangzhou 511466China Department of Population Health Sciences Duke University School of MedicineDurh

To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survival in the Jiangsu(N=1049)and Shanghai(N=1405)*** using a TCGA dataset,we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated ***,we constructed a weighted polygenic hazard score(PHS)and developed a nomogram in combination with clinical *** also evaluated prognostic accuracy with the time-dependent receiver operating characteristic(ROC)curve,net reclassification improvement(NRI)and integrated discrimination improvement(IDI).We identified a single nucleotide polymorphism(SNP)of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12×10^(-8),and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA *** PHS derived from these 26 SNPs(PHS-26)was an independent prognostic factor for GC survival(all P<0.001).The 5-year AUC of PHS-26 was 0.68,0.66 and 0.67 for Jiangsu,Shanghai and their pooled cohorts,respectively,which increased to 0.80,0.82 and 0.81,correspondingly,after being integrated into a nomogram together with variables of the clinical *** PHS-26 could improve the NRIs by 16.20%,4.90%and 8.70%,respectively,and the IDIs by 11.90%,8.00%and 9.70%,*** 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.

关键词： Stomach neoplasm Survival Genome-wide association study Polygenic hazard score Nomogram

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Clinical Prognostic Factors and Survival Analysis of Gastric Stump Cancer

Clinical Prognostic Factors and Survival Analysis of Gastric...

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第9届全国胃癌学术会议暨第二届阳光长城肿瘤学术会议

作者： Hua Huang Wei wang Zhong Chen Jiejie Jin Ziwen Long Hong Cai Xiaowen Liu Ye Zhou yanong wang Department of Gastric Cancer and Soft Tissue Sarcoma Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University Department of General Surgery Affiliated Hospital of Nantong University

Objective To elucidate the clinicopathologic characteristics and prognostic factors of patients with gastric stump *** The clinical data of ninety-two gastric stump cancer patients were collected at Fudan University Shanghai Cancer *** prognostic factors were analyzed by Cox’s proportional hazard *** GSC occurs mainly 25 years after primary surgery which initial disease was benign,and occurs mostly in the first 15 years after operation for gastric *** who had regular follow-up after primary surgery had a better *** Cox regression analysis showed that Borrmann Ⅰ/Ⅱ type（HR:3.165,95%CI:1.055-9.500,P=0.040） and radical resection（HR:1.780,95%CI:1.061-2.987,P=0.029） were independent prognostic factor for *** overall 1-,3- and 5-year survival of 92 patients were 78.3%,45.6%and 27.6%,***1-,3- and 5-year survival rates of those accepted radical resection were 79.3%,52.2%,37.8%,*** 5-year survival rates for stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 85.7%,47.4%,16.0%and13.3%,respectively（P=0.005）.Conclusion Gastric stump cancer has its unique clinicopathologic characteristics,the appearance of GSC is earlier in the primary malignant cases than in the primary benign *** regular follow-up after primary surgery is *** overall survival of GSC is poor and curative resection can improve prognosis.

关键词： Gastric stump cancer Clinicopathologic characteristics Prognosis

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Three-port laparoscopic exploration is not enough for patients with T4 gastric cancer

Three-port laparoscopic exploration is not enough for patien...

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第9届全国胃癌学术会议暨第二届阳光长城肿瘤学术会议

作者： Hua Huang Jiejie Jin Ziwen Long Wei wang Hong Cai Xiaowen Liu Hongmei Yu Liwen Zhang yanong wang Department of Gastric Cancer and Soft Tissue Sarcoma Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University Department of General Surgery Affiliated Hospital of Nantong University

Background and Objective Gastric cancer continues to be a leading cause of cancer *** majority of patients with gastric adenocarcinoma in China present with advanced *** out unresectable cancers patients from an unnecessary "open" exploration is very *** aim of this study was to assess the value of five-port anatomical laparoscopic exploration in T4gastric cancer in comparison with three-port laparoscopic exploration and laparotomy *** We conducted a retrospective study on 126 patients with T4 stage scheduled for D2curative gastrectomy based on computed tomography（CT） staging at Department of Gastric Cancer and Soft Tissue Sarcoma,Fudan University Shanghai Cancer Center,from Apr.2011 to *** exploration（Group I）,three-port laparoscopic exploration（Group II） or five-port anatomical laparoscopic exploration（Group IS） were performed prior to radical *** Accuracy rate for feasibility of D2 curative gastrectomy in laparotomy exploration group and five-port anatomical laparoscopic exploration group is higher than that in three-port laparoscopic exploration ***-port anatomical laparoscopic exploration group had the highest accuracy resection rate（Group Ⅰ vs Group Ⅱ vs Group Ⅲ,92.6%vs78.6%vs 97.7%;P＜0.05） and shorter length of hospitalization（Group Ⅰ vs Group Ⅱ vs Group Ⅲ,9.58±4.17 vs6.13±2.85 vs 5.00±1.81;P＜0.001）Conclusions Three-port laparoscopic exploration has low accuracy rate for feasibility of D2curative ***-port anatomical laparoscopic exploration has higher accurate in assessment for feasibility of D2 curative ***-port anatomical laparoscopic exploration should be performed on patients with T4 gastric cancer.

关键词： Gastric cancer Anatomical laparoscopic exploration

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基于K-SVD算法的数字图像自适应修复方法

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现代电子技术 2024年第13期47卷 15-18页

作者：王彦龙高俊杰杨阳山西大学山西太原030006

为了提升数字图像的完整性和清晰度,提出一种基于K-SVD算法的数字图像自适应修复方法。通过FCM算法将数字图像划分成不同的图像块,将不同类别的数字图像依据K-SVD算法的稀疏编码和字典更新模块进行训练,获取各个不同类别数字图像块的字... 详细信息

为了提升数字图像的完整性和清晰度,提出一种基于K-SVD算法的数字图像自适应修复方法。通过FCM算法将数字图像划分成不同的图像块,将不同类别的数字图像依据K-SVD算法的稀疏编码和字典更新模块进行训练,获取各个不同类别数字图像块的字典,求出其稀疏系数,结合字典和稀疏系数更新数字图像中的每一类图像块,完成数字图像中每一类图像块的修复或重构,将修复好的图像块放回原数字图像中,实现数字图像的自适应修复。实验结果表明,该方法能够有效地恢复图像的细节和结构,修复后的数字图像均方根误差低,并且具有较高的峰值信噪比,同时,修复后的数字图像与原图像的结构相似性高达0.95,且在数字图像修复效率方面具备显著优势。

关键词： FCM算法 K-SVD算法稀疏编码更新字典数字图像图像细节图像聚类图像修复

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表柔比星联合奥沙利铂及氟尿嘧啶的化疗方案提高局部进展期胃癌根治性手术机会的研究

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中国癌症杂志 2017年第11期27卷 890-895页

作者：刘晓文龙子雯蔡宏王亚农复旦大学附属肿瘤医院胃外科复旦大学上海医学院肿瘤学系上海200032

背景与目的:转化性化疗能使肿瘤降期,提高胃癌根治性手术的切除率,改善胃癌患者的预后。本研究旨在探讨EOF方案是否可以提高局部晚期胃癌根治性手术切除率,同时评价转化性化疗的安全性和耐受性。方法:30例经病理证实为胃癌的患者,影像... 详细信息

背景与目的:转化性化疗能使肿瘤降期,提高胃癌根治性手术的切除率,改善胃癌患者的预后。本研究旨在探讨EOF方案是否可以提高局部晚期胃癌根治性手术切除率,同时评价转化性化疗的安全性和耐受性。方法:30例经病理证实为胃癌的患者,影像学评估为潜在可根治的局部进展期胃癌入组。采用EOF方案进行治疗,具体为奥沙利铂130 mg/m2,静脉注射(2 h),第1天;表柔比星50 mg/m2,静脉注射(2 h),第1天;氟尿嘧啶2 400 mg/m2,静脉注射(48 h),每3周重复1次,共行2~4个周期。化疗结束后进行临床疗效及不良反应的评估。结果:30例局部进展期胃癌患者接受了EOF方案的化疗,完全缓解(complete response,CR)为3.3%(1/30),部分缓解(partial response,PR)为26.7%(8/30),疾病稳定(stable disease,SD)为46.7%(14/30),疾病进展(progressive disease,PD)为23.3%(7/30),临床总有效率(CR+PR)为30%(9/30)。66.7%(20/30)的患者行手术切除,其中46.7%(14/30)获得根治性切除,20%(6/30)行姑息性手术。主要的化疗不良反应为白细胞减少53.3%(16/30),中性粒细胞减少53.3%(16/30),食欲减退43.3%(13/30),无化疗相关死亡。结论:EOF方案在局部进展期胃癌的治疗中是安全有效且耐受良好的方案。

关键词：局部晚期胃癌转化性化疗奥沙利铂表柔比星氟尿嘧啶

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前哨淋巴结活检在中国皮肤和肢端恶性黑色素瘤患者诊治中的临床意义

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中国癌症杂志 2018年第11期28卷 819-826页

作者：徐宇朱蕙燕陈勇王亚农王春萌郑必强师英强复旦大学附属肿瘤医院骨软组织外科复旦大学上海医学院肿瘤学系上海200032 复旦大学附属肿瘤医院胃外科复旦大学上海医学院肿瘤学系上海200032

背景与目的:恶性黑色素瘤近年来在中国发病率呈上升趋势。前哨淋巴结活检(sentinel lymph node biopsy,SLNB)在欧美是皮肤恶性黑色素瘤外科诊治规范的重要环节,但在中国却未广泛开展。中国黑色素瘤具有多肢端亚型、浸润深度厚、溃疡率... 详细信息

背景与目的:恶性黑色素瘤近年来在中国发病率呈上升趋势。前哨淋巴结活检(sentinel lymph node biopsy,SLNB)在欧美是皮肤恶性黑色素瘤外科诊治规范的重要环节,但在中国却未广泛开展。中国黑色素瘤具有多肢端亚型、浸润深度厚、溃疡率高和预后差等特点。但中国黑色素瘤外科治疗后的预后仍未明确。该研究旨在分析中国黑色素瘤患者的临床数据,评价SLNB的可行性及其对预后的影响。方法:回顾性分析2009—2017年在复旦大学附属肿瘤医院治疗的无临床淋巴转移和远处转移征象的黑色素瘤患者。每例患者在接受原发病灶扩大切除的同时,进行相应区域淋巴结的SLNB。前哨淋巴结(sentinel lymph node,SLN)的定位通过美兰染色和同位素示踪完成。所有患者术后均进行随访。结果:本研究共纳入452例黑色素瘤患者。平均Breslow浸润深度为3.29 mm,66.4%为肢端病灶,溃疡率达59.7%。SLN阳性率为26.8%,假阴性率为4%,淋巴结总转移率为30.8%。本组患者5年总生存率(overall survival,OS)和无病生存率(disease-free survival,DFS)分别为66.6%和55.8%。SLN状态是显著影响患者预后的独立危险因素,而Breslow浸润深度是预测SLN转移状态的独立危险因素。结论:对于无临床大体转移的中国黑色素瘤患者,应常规开展SLNB。SLN状态是影响复发和总体生存的重要因素,SLNB能提高淋巴结微转移患者的生存,提供准确的临床分期。

关键词：肢端恶性黑色素瘤前哨淋巴结活检预后

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局部进展期胃癌术前化疗与术前放化疗的对比研究

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中国癌症杂志 2018年第10期28卷 762-768页

作者：刘晓文龙子雯蔡宏章真王亚农复旦大学附属肿瘤医院胃外科复旦大学上海医学院肿瘤学系上海200032 复旦大学附属肿瘤医院放疗科复旦大学上海医学院肿瘤学系上海200032

背景与目的:术前化疗和术前放化疗都是胃癌治疗指南推荐的针对局部进展期胃癌患者的治疗方法。然而,由于缺乏对比性的研究证据,两者的优劣性不详。本研究将对比术前放化疗与术前化疗在临床疗效及毒性反应之间的差异。方法:2007年6月—2... 详细信息

背景与目的:术前化疗和术前放化疗都是胃癌治疗指南推荐的针对局部进展期胃癌患者的治疗方法。然而,由于缺乏对比性的研究证据,两者的优劣性不详。本研究将对比术前放化疗与术前化疗在临床疗效及毒性反应之间的差异。方法:2007年6月—2012年10月期间,30例局部进展期胃癌患者入组一项术前化疗的Ⅱ期临床试验,采用EOF(表柔比星+奥沙利铂+氟尿嘧啶)方案进行3～4个周期的术前化疗,对于能手术的患者予以手术,术后给于2～3个周期的EOF方案化疗。2012年4月—2014年8月,40例局部晚期胃癌患者入组一项术前放化疗的Ⅱ期临床试验,患者接受1个周期的SOX[替吉奥(S-1)+奥沙利铂]方案化疗,继续行同步放化疗,再进行1个周期的SOX方案化疗,对于能手术的患者予以手术,术后给于4个周期的SOX方案化疗。比较两项临床试验患者的临床病理特点、术前治疗的效果、R0手术切除率、预后及不良反应。结果:术前化疗临床试验定义为化疗组,有30例胃癌患者入组,且完成了所有的术前化疗,都可评估。术前放化疗临床试验定义为放化疗组,有40例胃癌患者入组,其中36例(90%)患者可评估。两组间的基线参数,如性别、年龄、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分、临床T分期、临床N分期及肿瘤部位,差异无统计学意义。化疗组的临床有效率(CR+PR)为30%(9/30),放化疗组的临床有效率(CR+PR)为41.7%,两者间的差异无统计学意义(P>0.05)。化疗组与放化疗组间的R0手术切除率差异无统计学意义(46.7% vs 66.7%)。放化疗组的病理有效率高于化疗组,且差异有统计学意义(50.0% vs 23.3%)。术前放化疗组的毒性反应较化疗组明显。放化疗组的3年总生存率为41%,高于化疗组的20%(P=0.009)。结论:放化疗组的病理有效率及3年总生存率高于化疗组。急性毒性反应也较化疗组明显,但无严重的毒性反应。

关键词：局部晚期胃癌术前化疗术前放化疗预后

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YC气层水锁损害及预防

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石油钻采工艺 2002年第4期24卷 20-22页

作者：薛芸袁萍姚峰朱伟民王亚农江苏油田石油工程技术研究院江苏扬州225009

YC气田是江苏油田至今发现的储量最大的气田。通过对YC地区气层的储层特征分析及试验研究 ,表明该气藏属低渗气藏 ,该地区气层水锁严重 ,尤其是入井液水锁严重。进行了气层保护技术的研究 ,提出了使用氧化剂消除钻井液在井壁表面形成的... 详细信息

YC气田是江苏油田至今发现的储量最大的气田。通过对YC地区气层的储层特征分析及试验研究 ,表明该气藏属低渗气藏 ,该地区气层水锁严重 ,尤其是入井液水锁严重。进行了气层保护技术的研究 ,提出了使用氧化剂消除钻井液在井壁表面形成的滤饼堵塞 ,使用高抑制性低界面张力型的水基钻井液、完井液及加速储层中入井流体的返排等预防措施。建议采用氧化和酸化复合解堵方法 ,以提高酸化效果。

关键词：预防措施保护技术 YC气田 YC气层水锁损害

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柔性钻具水力导向射流喷嘴流场分析

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石油矿场机械 2024年第2期53卷 26-33页

作者：张强王文强车阳任宪可马群汪彦龙东北石油大学机械科学与工程学院黑龙江大庆163318 中国石油集团工程技术研究院有限公司北京102206

现有柔性钻具钻井技术和水力喷射径向钻井技术在控制钻进方向上存在困难或有局限性。为实现钻井导向可控,设计了一种能够水力导向的高压射流喷嘴结构。建立导向喷嘴流体数值模型,利用数值模拟的方法进行流场分析,研究喷嘴倾角、喷嘴直... 详细信息

现有柔性钻具钻井技术和水力喷射径向钻井技术在控制钻进方向上存在困难或有局限性。为实现钻井导向可控,设计了一种能够水力导向的高压射流喷嘴结构。建立导向喷嘴流体数值模型,利用数值模拟的方法进行流场分析,研究喷嘴倾角、喷嘴直径、喷嘴开启个数等参数对导向力、射流速度的定量关系,给出了导向力方向确定方法。结果表明:随着关闭喷嘴个数的增加,喷嘴导向力呈指数逐渐增大;轴向倾角越大,喷嘴导向力和最大喷射速度越大;喷嘴内径减小时,导向力和喷射速度都显著增大。通过数值模拟验证了射流喷嘴水力导向的可行性,分析结果和导向力的拟合公式对水力导向喷嘴钻进方向的研究具有指导意义。

关键词：水力径向钻井高压射流导向喷嘴导向力数值模拟

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