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Identification of a new target region on the long arm of chromosome 7 in gastric carcinoma by loss of heterozygosity

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World Journal of Gastroenterology 2006年第15期12卷 2437-2440页

作者： de-sheng weng Jin-Tian Li Shi-Juan Mai Zhi-Zhong Pan Bing-Jian Feng Qi-sheng Feng Li-Xi Huang Qi-Jing Wang Yong-Qiang Li Xing-Juan Yu Shi-Ping Chen Jia He Jian-Chuan Xia Research Section of Oncopathology State Key Laboratory of Oncology in Southern china Cancer CenterZhongshan University Guangzhou 510064 Guangdong ProvinceChina

AIM： To define the common deleted region on the long arm of haman chromosome 7q linked to primary gastric carcinomas in Chinese by loss of heterozygosity （LOH） and its clinical significance. METHODS： Nine microsatellite markers distributed over chromosome 7q with an average marker density of 10cM were used to examine 70 primary gastric carcinomas for LOH by PCR amplification. The PCR products were separated by electrophoresis on polyacrylamide gel. Genescan and Genotyper softwares were used to analyze LOH. RESULTS： LOH with at least one marker on 7q occurred in 34.3% （12/50） of the tumors. Among them, LOH at D7S486 and D7S798 was higher in 24.0% （24/70） and 29.2% （5/26）, respectively. By statistical analysis we also observed an obvious genotype-phenotype correlation on 7q （P〈0.05）. The frequency of LOH at D7S486 in patients with lymph node metastasis was significantly higher than that in those without lymph node metastasis （P=0.015）. CONCLUSION： The high incidence of LOH at D7S486 and its correlation with poorer prognosis suggest that there might be putative tumor suppressor genes in this region involved in the tumorigenesis and progression of gastric carcinoma.

关键词： LOH Chromosome 7 Gastric cancer

TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis

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Cancer Communications 2019年第1期39卷 14-27页

作者： Dan-dan Wang Yi-bing Chen Jing-jing Zhao Xiao-fei Zhang Guang-chao Zhu de-sheng weng Ke Pan Lin Lv Qiu-zhong Pan Shan-shan Jiang Lei-lei Wang Jian-chuan Xia Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060GuangdongP.R.China department of Biotherapy Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Shandong Medicinal Biotechnology Centre Back and Neck Pain HospitalShandong Academy of Medical SciencesJinan 250062ShandongP.R.China Genetic and Prenatal Diagnosis Center Department of Gynecology and ObstetricsFirst Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanP.R.China Key Laboratory for Applied Microbiology of Shandong Province Ecology Institute of Shandong Academy of SciencesJinan 250014ShandongP.R.China

Background: In our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC. Methods: We explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation-based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prog-nostic significance of TES and Mena in GC. Results: TES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena-dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression. Conclusions: We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prog-nostic marker and potential target for GC

关键词： Gastric cancer TES Tumor suppressor Mena Lamellipodin

Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies

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Chinese Journal of Cancer 2013年第12期32卷 661-666页

作者： Fei Zhang Xiao-Fei Sun Yong-Qiang Li Zi-Jun Zhen Hai-Xia Zheng Jia Zhu Qi-Jing Wang Su-Ying Lu Jia He Juan Wang Ke Pan Rui-Qing Cai Yan Chen de-sheng weng Fei-Fei Sun Jian-Chuan Xia State Key Laboratory of Oncology in South China department of Pediatric Oncology department of Biotherapy Sun Yat-sen University Cancer Center

In vitro amplified human leukocyte antigen(HLA)-haploidentical donor immune cell infusion(HDICI)is not commonly used in ***,our study sought to evaluate its safety for treating childhood *** September 2011 and September 2012,12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer *** median patient age was 5.1 years(range,1.7-8.4 years).Of the 12 patients,9 had high-risk neuroblastoma(NB)[7 showed complete response(CR),1 showed partial response(PR),and 1 had progressive disease(PD)after multi-modal therapies],and 3 had Epstein-Barr virus(EBV)-positive lymphoproliferative disease(EBV-LPD).The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×108immune cells/kg body weight:71 infusions with natural killer(NK)cells,8 with cytokine-induced killer(CIK)cells,and 13 with cascade primed immune cells(CAPRIs);83 infusions with immune cells from the mothers,whereas 9 with cells from the *** cases(21.7%)of fever,including 6 cases(6.5%)accompanied with chills and 1(1.1%)with febrile convulsion,occurred during infusions and were alleviated after symptomatic *** cases(5.4%)of mild emotion changes were *** other adverse events occurred during and after the completion of *** acute nor chronic graft versus host disease(GVHD)was observed following *** a median of 5.0 months(range,1.0-11.5 months)of follow-up,the 2 NB patients with PR and PD developed PD during *** the other 7 NB patients in CR,2 relapsed in the sixth month of HDICIs,and 5 maintained CR with disease-free survival(DFS)ranging from 4.5 to 11.5 months(median,7.2months).One EBV-LPD patient achieved PR,whereas 2 had stable disease(SD).Our results show that HDICI is a safe immunotherapy for childhood malignancies,thus warranting further studies.

关键词：免疫细胞恶性肿瘤体外扩增安全性 HLA 儿童人类白细胞抗原移植物抗宿主病

Tripartite *** 3(TRIM3)inhibits tumor growth and metastasis of liver cancer

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Chinese Journal of Cancer 2017年第9期36卷 407-419页

作者： Xu.Qiong Huang Xiao.Fei Zhang Jin.Hua Xia Jie Chao Qiu.Zhong Pan Jing.Jing Zhao Zi.Qi Zhou Chang.Long Chen Yan Tang de.sheng weng Jian.Hua Zhang Jian.Chuan Xia department of Biotherapy State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China department of Epidemiology and Health Statistics Guangdong Pharmaceutical UniversityGuangzhou 510010GuangdongP.R.China Guangzhou Health Science College Guangzhou 510925GuangdongP.R.China Shanxi Entry-Exit Inspection and Quarantine Bureau Xi’an 710068ShanxiP.R.China.

Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human *** our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC ***,the role of TRIM3 in liver cancer remains *** study aimed to investigate the function of TRIM3 in liver cancer ***:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western ***2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were *** effect ofTRIM3 on tumor growth and metastases in nude mice was also ***:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell *** cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 ***,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing ***,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and *** vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and ***:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest a

关键词： Tripartite motif-containing 3 (TRIM3) Liver cancer Tumor suppressor Cell cycle

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-sheng Zhang Li-Ping Wang Wen-Wei Hu de-sheng weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China department of Stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

Minimally Invasive Treatment Combined With Cytokineinduced Killer Cells herapy Lower the Short-termRecurrence Rates of Hepatocellular Carcinomas

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Minimally Invasive Treatment Combined With Cytokineinduced K...

Targeting Liver Cancer Stem-Like Cells with Annexin A3-Specific Cytotoxic T Lymphocytes

中国(第七届)肿瘤微创治疗学术大会暨世界影像导引下肿瘤微创治疗学会成立筹备大会

作者： de-sheng weng,Jun Zhou,Qi-Ming Zhou,Ming Zhao,Qi-Jing Wang, Xi Huang,Yong-Qiang Li,Shi-Ping Chen,Pei-Hong Wu,and Jian-Chuan Xia

Summary:The recurrence of hepatocellular carcinoma(HCC)after minimally invasive therapy is *** immu-notherapy is thought to be an effective method to lowerecurrence and metastasis rates of malignant tumors. Therefore,85 HCC patients after transcatheter arterial chemoembolizationand radiofrequency ablation therapy were randomized tommunotherapy group and no adjuvant therapy ***-ogous cytokine-induced killer(CIK) cells were transfused viahepatic artery to the *** alteration of levels ofymphocyte subsets in peripheral blood of patients wasexamined by flow *** patients were screened bycomputed tomography every 2 months to observe the tumor ecurrent *** CIK cell infusions,the percentages of CD3+,CD4+,CD56+,CD3+CD56+ cells, and CD4+ /CD8+ ratio increased from 68.6±11.0%,31.1±9.0%,15.6±7.9%,5.2±3.1%,and 1.1±0.5 to 70.7±10.1%, 33.5±8.0%,18.4±9.4%,5.9±2.8%,and 1.3±0.7,respec- ively(Pdecreased from 31.1=1=7.8%to 28.6±8.3%(P<0.05).The 1-year and 18-month recurrence rates of the study group were 8.9%and 15.6%,compared with 30.0%and 40.0%of the control group(both P value <0.05).The data suggest that CIK cell transfusion is an e-ective *** can boost the mmunologic function in HCC patients and plays an important ole in reducing the recurrence rate of HCC.

关键词： hepatocellular carcinoma cytokine-induced killer cells T-lymphocyte subsets NK cells immunologic function J Immunother 2008 31-71)

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Targeting Liver Cancer Stem-Like Cells with Annexin A3-Speci...

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

第九届全国免疫学学术大会

作者： Qiu-Zhong Pan Ke Pan de-sheng weng Jing-Jing Zhao Hai-Xia Zheng Xiao-Fei Zhang Shan-Shan Jiang Lin Lv Yan Tang Chang-Long Chen Hong-Xia Zhang Jian-Chuan Xia Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oneology in South ChinaSun Yat-Sen University Cancer Center department of Biotherapy Sun Yat-Sen University Cancer Center

Background:Cancer stem-like cells/cancer initiating cells(CSCs/CICs)are considered to represent a small population of cancer cells that is resistant to conventional cancer treatments and responsible for tumor recurrence and ***:The aim of the present study was to establish CSGCIC-targeting ***:Microarray was performed to identify the differential expression gene between CD133and CD 133-Huh7cell *** identified gene was electroporated to dendrite cells(DCs)to generate the specific cytotoxic T lymphocytes(CTLs).The cytotoxic activity of these CTLs was determined in vitro and in ***:In this study,we found that Annexin A3(ANXA3)was preferentially expressed in CSCs/CICs derived from hepatocellular carcinoma(HCC)cells compared to non-CSCs/*** of ANXA3 increased the proportion of CD133cells representing CSCs/CICs in HCC cells,enhancing their *** the contrary,knockdown of ANXA3decreased CD133cells and inhibited *** ANXA3 as a target,ANXA3-transfected DCs could induce more functionally active T cells and these effector T cells could superiorly kill CD133HCC CSCs/CICs in vitro and in ***:Taken together,our findings suggest that ANXA3 plays a role in HCC CSC/CIC maintenance,and that ANXA3 may represent a potential CSC/CIC-specific therapeutic target for improving the treatment of HCC.

关键词： Cancer stem-like cell cancer immunotherapy ANXA3 hepatocellular carcinoma cytotoxic T lymphocytes

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Adjuvant cellular immunotherapy in patients with resected pr...

Overview of in-situ oxygen production technologies for lunar resources

第十四届全国肿瘤生物治疗大会

作者： Qiu-Zhong Pan Yan Tang Qi-Jing Wang Yong-Qiang Li Li Zhang Xiao-Dong Li Jing-Jing Zhao de-sheng weng Qing Liu Li-Xi Huang Jia He Shi-Ping Chen Miao-La Ke Yi-Xin Zeng Jian-Chuan Xia Collaborative Innovation Center for Cancer Medicine State Key Laboratory of Oncology in South China Sun Yat-Sen University Cancer Center department of Biotherapy Sun Yat-Sen University Cancer Center

Postoperative non-small cell lung cancer(NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of cellular immunotherapy(CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy;33 cases received chemotherapy and sequential CIT with cytokine-induced killer(CIK) cells;and 27 cases received chemotherapy and sequential CIT with alternate CIK cells and natural killer(NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK cells and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 year old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with combined application of CIK cells and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients ≤60 years old with positive lymph nodes.

关键词： cellular immunotherapy cytokine-induced killer cells natural killer cells non-small cell lung cancer benefit

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 233-255页

作者： Youpeng Xu sheng Pang Liangwei Cong Guoyu Qian Dong Wang Laishi Li Yusheng Wu Zhi Wang College of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China CAS Key Laboratory of Green Process and Engineering National Engineering Research Center for Green Recycling of Strategic Metal ResourcesInstitute of Process EngineeringChinese Academy of SciencesBeijing 100190China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China

The rich resources and unique environment of the Moon make it an ideal location for human expansion and the utilization of extraterrestrial ***,crucial for supporting human life on the Moon,can be extracted from lunar regolith,which is highly rich in oxygen and contains polymetallic *** oxygen and metal extraction can be achieved using existing metallurgical ***,the ample reserves of water ice on the Moon offer another means for oxygen *** paper offers a detailed overview of the leading technologies for achieving oxygen production on the Moon,drawing from an analysis of lunar resources and environmental *** delves into the principles,processes,advantages,and drawbacks of water-ice electrolysis,two-step oxygen production from lunar regolith,and one-step oxygen production from lunar *** two-step methods involve hydrogen reduction,carbothermal reduction,and hydrometallurgy,while the one-step methods encompass fluorination/chlorination,high-temperature decomposition,molten salt electrolysis,and molten regolith electrolysis(MOE).Following a thorough comparison of raw materials,equipment,technology,and economic viability,MOE is identified as the most promising approach for future in-situ oxygen production on the *** the corrosion characteristics of molten lunar regolith at high temperatures,along with the Moon's low-gravity environment,the development of inexpensive and stable inert anodes and electrolysis devices that can easily collect oxygen is critical for promoting MOE technology on the *** review significantly contributes to our understanding of in-situ oxygen production technologies on the Moon and supports upcoming lunar exploration initiatives.

关键词： lunar resources in-situ oxygen production space metallurgy molten lunar regolith electrolysis