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Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

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Cancer Biology & Medicine 2023年第9期20卷 682-688页

作者： Xiaoying Zhao Zhiyu Chen Xiaowei Zhang Xiaodong Zhu Wen Zhang Lixin Qiu Chenchen Wang Mingzhu Huang Zhe Zhang Wenhua Li Lei Yang Weijian Guo Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Shanghai Medical College Fudan UniversityShanghai 200032China Department of Medical Oncology Nantong Tumor HospitalNantong 226006China

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric *** study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)***:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line *** primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and ***:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,*** 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of *** grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

关键词： gastric adenocarcinoma raltitrexed paclitaxel second-line palliative chemotherapy

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-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

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World Journal of Gastroenterology 2006年第34期12卷 5473-5478页

作者： Carina Pereira Hugo Sousa Paula Ferreira Maria Fragoso Luís Moreira-Dias Carlos Lopes Rui Medeiros Mário Dinis-Ribeiro Molecular Oncology Group Portuguese Institute of Oncology of Porto Portugal and ICBAS Abel Salazar Institute for the Biomedical Sciences Porto Portugal Oncology Department Portuguese Institute of Oncology of Porto Portugal Gastroenterology Department Portuguese Institute of Oncology of Porto Portugal and Cintesis / Faculty of Medicine University of Porto Porto Portugal

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

关键词： gastric adenocarcinoma Atrophy Intestinal metaplasia COX-2 Polymorphism PCR-RFLP Pharmacogenomic

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Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide

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Acta Pharmacologica Sinica 2007年第11期28卷 1842-1850页

作者： Mao-tao HUANG~2,Zhi-xin CHEN~3,Bing WEI~4,Bo ZHANG~3,Chun-hui WANG~2,Ming-hui HUANG~5,Rui LIU~5,Cheng-wei TANG~(2,5,6)Departments of ~2 Gastroenterology,~3 Surgery,and ~4 pathology and ~5 Division of Peptides Related with Human Diseases,State Key Laboratoryof Biotherapy of Human Diseases,West China Hospital,Sichuan University Chengdu 610041,China Department of Gastroenterology State Key Laboratory of Biotherapy of Human Diseases West China Hospital Sichuan University Chengdu China Department of Surgery State Key Laboratory of Biotherapy of Human Diseases West China Hospital Sichuan University Chengdu China Department of Pathology State Key Laboratory of Biotherapy of Human Diseases West China Hospital Sichuan University Chengdu China Division of Peptides Related with Human Diseases State Key Laboratory of Biotherapy of Human Diseases West China Hospital Sichuan University Chengdu China

Aim:To gain insight into the histopathological responses and molecular targetsin the inhibition of growth of human gastric cancer treated with celecoxib (acyclooxygenase [COX]-2 inhibitor) combined with ***:Seventyfive patients with gastric cancer undergoing curative gastrectomy or extendedresection were randomly divided into 3 *** apoptosis of tumor cells wasmeasured by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) *** cancer microvessel density (MVD) and the ex-pression of COX-2 were evaluated by immunohistochemical *** expres-sion of somatostatin receptor (SSTR)-2 was detected with the biomolecular inter-action analysis *** transcription of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 was measured by ***:Compared with thecontrol and celecoxib groups,more necrosis in the combination group *** apoptotic rate in the combination group (7.06%±0.67%) was sig-nificantly higher than that in the control group (6.23%±1.29%,Pgastric cancers treated with celecoxib (48%) was significantly higherthan that of control group (12%) after surgery (Pgastric adenocarci-noma through the induction of apoptosis and the reduction of ***-1 andSSTR-2 might be the molecular targets for celecoxib or octreotide.

关键词： gastric adenocarcinoma celecoxib octreo tide non-cytotoxic agent surgery

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Twist 1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression

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World Journal of Gastroenterology 2014年第48期20卷 18306-18315页

作者： Dong-Yuan Zhu Qi-Sen Guo Yan-Liang Li Bin Cui Jun Guo Ji-Xiao Liu Peng Li Department of Medical Oncology Shandong Cancer Hospital and Institute Department of Medical Oncology Zhangqiu City People’s Hospital Department of Medical Oncology Gaomi City TCM Hospital Department of Medical Oncology Wenshang County People’s Hospital Department of Medical Oncology Yantai Yuhuangding Hospital affiliated to Qingdao University

AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression.

关键词： Twist-related protein 1 Fibroblast growth factor receptor 2 gastric adenocarcinoma Cancer differentiation Cancer progression

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Characteristics of cancer susceptibility genes mutations in 282 patients with gastric adenocarcinoma

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Chinese Journal of Cancer Research 2020年第4期32卷 508-515页

作者： Ke Ji Sheng Ao Liu He Li jiao Zhang Li Feng Guoqing Lyu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal SurgeryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal Surgery Peking University Shenzhen HospitalShenzhen 518036China Cadre Health Department Shanxi Provincial Cancer HospitalTaiyuan 030013China Abdominal Surgery Department Affiliated People's Hospital of Inner Mongolia Medical CollegeHohhot 010020China

Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic ***:A total of 282 patients with gastric adenocarcinoma(182 males and 100 females)were enrolled in this study,with peripheral blood genomic DNA *** of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput *** mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics(ACMG)***:In this study,7.1%(20/282)of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility *** detection rate in male patients(3.8%,7/182)was significantly lower than that in female patients(13%,13/100)(P=0.004).The most recurrent mutations were in AT mutated(ATM)(1.1%,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7%(2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EP CAM associated with Lynch syndrome and CDH1 associated with hereditary di ffuse gastric *** detection frequencies were all 0.4%(1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers(median age:58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall(median age:49.3 years old).Conclusions:Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significandy lower than that in female *** known and unidentified mutations

关键词： gastric adenocarcinoma cancer-susceptibility-associated genes pathogenic mutations

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Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries:the impact of decreasing resection rates

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Cancer Communications 2022年第7期42卷 648-662页

作者： Lei Huang Lina Jansen Rob H.A.Verhoeven Jelle P.Ruurda Liesbet Van Eycken Harlinde De Schutter Jan Johansson Mats Lindblad Tom B.Johannesen Vesna Zadnik Tina Zagar Sjoerd M.Lagarde Cornelis J.Hvan de Velde Petra Schrotz-King Hermann Brenner Division of Clinical Epidemiology and Aging Research German Cancer Research Center(DKFZ)Heidelberg 69120Germany Medical Faculty Heidelberg of Heidelberg University Heidelberg 69120Germany German Cancer Consortium German Cancer Research CenterHeidelberg 69120Germany Department of Research&Development Netherlands Comprehensive Cancer OrganizationUtrecht 3501 DBThe Netherlands Department of Medical Oncology Amsterdam University Medical CentersAmsterdam 1105 AZThe Netherlands Department of Surgery University Medical Center UtrechtUtrecht 3508 GAThe Netherlands Belgian Cancer Registry Brussels B-1210Belgium Department of Esophageal and gastric Surgery Lund University HospitalLund 22185Sweden Department of Clinical Science Interventionand TechnologyDivision of SurgeryKarolinska University HospitalStockholm 17176Sweden Registry Department The Cancer Registry of NorwayOslo 0379Norway Epidemiology and Cancer Registry Institute of Oncology LjubljanaLjubljana 1000Slovenia Department of Surgery Erasmus Medical Centre-University Medical Centre RotterdamRotterdam 3015 CEThe Netherlands Department of Surgical Oncology Leiden University Medical CenterLeiden 2300 RCThe Netherlands Division of Preventive Oncology German Cancer Research Center and National Center for Tumor DiseasesHeidelberg 69120Germany

Background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European *** and to what extent these trends affect the trends in overall survival(OS)of patients with non-metastatic GaC at the population level remain *** large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic ***:Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands,Belgium,Sweden,Norway,and Slovenia,and the US Surveillance,Epidemiology,and End Results *** analyzed data for each country *** between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables,with and without including resection and chemotherapy as potential explanatory ***:A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed,with an accumulated follow-up of 172,357 *** adjustment for resection,OS was improved only slightly in the US[hazard ratio(HR)_(per year)=0.99;HR_(≥vs.<2010)=0.96],and no improvement was observed in the investigated European countries,with OS even worsening in Sweden(HR_(per year)=1.03;HR_(≥vs.<2010)=1.17).After adjusting for resection,the increasing OS trend became stronger in the US(HR_(per year)=0.98;HR_(≥vs.<2010)=0.88),and the temporal trend became insignificant in *** Slovenia(HR_(per year)=0.99;HR_(≥vs.<2010)=0.92)and Norway(HR_(per year)=0.97;HR_(≥vs.<2010)=0.86),improved OS over time emerged after resection *** OS in patients undergoing resection was observed in the US,the Netherlands,and *** for chemotherapy did not alter the observed *** analyses by tumor location showedm

关键词： gastric adenocarcinoma resection rate adjusted overall survival temporal trend prognostic factors international population-based cohort study

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Prognostic value of claudin 18.2 expression in gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 343-351页

作者： Erkan Kayikcioglu Ramazan Oğuz Yüceer Bulent Cetin Kamuran Yüceer Nermin Karahan Department of Medical Oncology Suleyman Demirel UniversityIsparta 32260Turkey Department of Pathology Isparta City HospitalIsparta 32360Turkey Department of Internal Medicine Suleyman Demirel UniversityFaculty of MedicineIsparta 32360Turkey Department of Pathology Suleyman Demirel UniversityIsparta 32360Turkey

BACKGROUND Claudin 18.2(CLDN18.2)is a cell surface protein expressed by gastric cancer *** monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death.A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric *** To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric *** This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric *** investigated the effect of CLDN18.2 expression on clinicopathological characteristics(age,sex,histological grade,Lauren classification,family history,metastatic site,HER2 expression)and prognosis for patients with metastatic gastric *** CLDN18.2 expression was positive in 73.8%(48)of the *** the median 17.7-mo follow-up period,89.2%(58)of the patients *** progression-free survival and overall survival(OS)were 6 mo(95%confidence interval:1.6-10.4)and 12 mo(95%confidence interval:7.5-16.5).There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the *** univariate and multivariate Cox regression analysis,there was no correlation between clinicopathological characteristics of patients and progression-free survival or *** CLDN18.2 expression was quite high in patients with gastric adenocarcinoma,identifying the proportion of the patients in whom zolbetuximab would be *** is no statistically significant correlation with clinicopathological characteristics and ***18.2 is not a prognostic marker in patients with gastric adenocarcinoma,although it is predictive.

关键词： gastric adenocarcinoma Claudin 18.2 Overall survival Clinicopathological characteristics

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Adjuvant chemotherapy,p53,carcinoembryonic antigen expression and prognosis after D2 gastrectomy for gastric adenocarcinoma

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World Journal of Gastroenterology 2014年第1期20卷 264-273页

作者： Ming-Ming He Dong-Sheng Zhang Feng Wang Zhi-Qiang Wang Hui-Yan Luo Chao Ren Ying Jin Dong-Liang Chen Rui-Hua Xu State Key Laboratory of Oncology in South China Department of Medical OncologySun Yat-sen University Cancer Center

AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma.

关键词： gastric adenocarcinoma Adjuvant chemotherapy p53 Carcinoembryonic antigen Immunohistochemistry

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MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma

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World Journal of Gastroenterology 2019年第47期25卷 6823-6834页

作者： He-Ying Zhou Chun-Qi Wu En-Xu Bi Department of General Surgery Jinan Seventh People's HospitalJinan 251400Shandong ProvinceChina Department of General Surgery Qingdao West Coast New Area Central HospitalQingdao 266555Shandong ProvinceChina

BACKGROUND gastric adenocarcinoma(GAC)mortality rates have remained relatively changed over the past 30 years,and it continues to be one of the leading causes of cancerrelated *** To search for novel miRNAs related to GAC prognosis and further investigate the effect of miR-96-5p on MGC-803 *** The miRNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed miRNAs(DEMs)and DEMs related to GAC ***,the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by *** target gene,ZDHHC5,of miR-96-5p was predicted using TargetScan,miRTarBase,and miRDB databases and confirmed by luciferase reporter ***,MGC-803 cells were transfected with inhibitor NC,miR-96-5p inhibitor,si-ZDHHC5,or miR-96-5p inhibitor+si-ZDHHC5,and then cell apoptosis was detected by flow *** expression of ZDHHC5,Bcl-2,and COX-2 was detected using western *** A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome *** compared with adjacent normal samples,the levels of miR-96-5p,miR-222-5p,and miR-652-5p were remarkably increased,while miR-125-5p,miR-145-3p,and miR-379-3p levels were reduced in GAC tumor samples(P<0.01),which were consistent with bioinformatics ***,ZDHHC5 was defined as a direct target gene of ***-96-5p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5,Bcl-2,and COX-2 in MGC-803 cells(P<0.01).After ZDHHC5 inhibition,the number of apoptotic cells and the expression of ZDHHC5,Bcl-2,and COX-2 were *** addition of an miR-96-5p inhibitor partly reversed these effects(P<0.01).CONCLUSION Our findings identified six miRNAs related to GAC prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.

关键词： gastric adenocarcinoma Differently expressed miRNAs Prognosis MicroRNA-96-5p Cell apoptosis The Cancer Genome Atlas

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Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1618-1628页

作者： Ze-Feng Yang Zhuan-Xia Dong Chen-Jie Dai Li-Zheng Fu Hong-Mei Yu Yu-Sheng Wang Department of Health Statistics School of Public HealthShanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Shanxi Medical University Taiyuan 030001Shanxi ProvinceChina Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment Taiyuan 030001Shanxi ProvinceChina MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of Oncology Digestive The First Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of Digestive Oncology Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their *** To determine the most effective postoperative chemotherapy regimen for patients with *** We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer ***-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion *** also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate *** subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R *** In all,530 eligible individuals with RGAVCT were enrolled in this *** median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,*** complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ *** Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treat

关键词： Vascular cancer embolism Postoperative chemotherapy regimen gastric adenocarcinoma Risk factors Survival

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