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Oncogenesis of RON receptor tyrosine kinase:a molecular target for malignant epithelial cancers

Acta Pharmacologica Sinica 2006年第6期27卷 641-650页

作者： ming-hai wang~(2,3,4)hang-ping yao~2 yong-qing zhou~2 2 laboratory of chang-kung scholars program for tumor biology,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003.china 3 Cancer biology Center and Department of Pharmaceutical Sciences,Texas Tech university Health Sciences Center school of Pharmacy,Amarillo,TX 79106,USA laboratory of chang-kung scholars program for tumor biology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China Cancer biology Center and Department of Pharmaceutical Sciences Texas Tech University Health Sciences Center School of Pharmacy Amarillo USA

Recepteur d’origine nantais(RON)belongs to a subfamily of receptor tyrosinekinases(RTK)with unique expression patterns and biological *** isactivated by a serum-derived growth factor macrophage stimulating protein(MSP).The RON gene transcription is essential for embryonic development and critical inregulating certain physiological *** studies have indicated thataltered RON expression contributes significantly to cancer progression *** primary tumors,such as colon and breast cancers,overexpressionof RON exists in large numbers and is often accompanied by the generation ofdifferent splicing *** RON variants direct a unique program thatcontrols cell transformation,growth,migration,and invasion,indicating that al-tered RON expression has the ability to regulate motile/invasive *** activities were also seen in transgenic mice,in which targeted expression ofRON in lung epithelial cells resulted in numerous tumors with pathological fea-tures of human bronchioloalveolar ***,abnormal RON activation isa pathogenic factor that transduces oncogenic signals leading to uncontrolledcell growth and subsequent malignant *** these facts,RON and its variants can be considered as potential targets for *** using small interfering RNA and neutralizing mono-clonal antibodies demonstrated that suppressing RON expression and activationdecreases cancer cell proliferation,increases apoptotic death,prevents tumorformation in nude mice,and reduces malignant ***,blocking RONexpression and activation has clinical significance in reversing malignant pheno-types and controlling tumor growth.

关键词： growth factor receptor signal transduction tumorigenesis monoclonal antibody small molecule inhibitor therapeutics

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Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1198-1207页

作者： hai-Dong Zhu hai-Liang Li ming-Sheng Huang Wei-Zhu Yang Guo-Wen Yin Bin-Yan Zhong Jun-Hui Sun Zhi-Cheng Jin Jian-Jian Chen Nai-Jian Ge Wen-Bin Ding Wen-Hui Li Jin-Hua Huang Wei Mu Shan-Zhi Gu Jia-ping Li Hui Zhao Shu-Wei Wen Yan-ming Lei Yu-Sheng Song Chun-wang Yuan Wei-Dong wang ming Huang Wei Zhao Jian-Bing Wu Song wang Xu Zhu Jian-Jun Han Wei-Xin Ren Zai-ming Lu Wen-Ge Xing yong Fan hai-Lan Lin Zi-Shu Zhang Guo-Hui Xu Wen-Hao Hu Qiang Tu Hong-Ying Su Chuan-Sheng Zheng yong Chen Xu-Ya Zhao Zhu-Ting Fang Qi wang Jin-Wei Zhao Ai-Bing Xu Jian Xu qing-Hua Wu Huan-Zhang Niu Jian wang Feng Dai Dui-ping Feng qing-Dong Li Rong-Shu Shi Jia-Rui Li Guang Yang hai-Bin Shi Jian-Song Ji Yu-E Liu Zheng Cai Po Yang Yang Zhao Xiao-Li Zhu Li-Gong Lu Gao-Jun Teng Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjing 210009China Department of Minimally invasive Intervention The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008China Department of Interventional Radiology the Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Interventional Radiology Union Hospital of Fujian Medical UniversityFuzhou 350001China Department of Interventional Radiology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Department of Interventional Radiology The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Hepatobiliary and Pancreatic Interventional Treatment Center Division of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Interventional Radiology Eastern Hospital of Hepatobiliary SurgeryNavy Medical University(Second Military Medical University)Shanghai 200438China Department of Interventional Radiology Nantong First People’s HospitalNantong 226001China Department of Interventional Radiology Yancheng Third People’s HospitalYancheng 224008China Department of Minimally Invasive Interventional Therapy Sun YatSen University Cancer CenterGuangzhou 510060China Department of Vascular Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China. Department of Interventional Radiology Hunan Cancer HospitalChangsha 410031China Department of Interventional Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Interventional Radiology The Hospital of Nantong UniversityNantong 226001China Department of Interventional Therapy Shanxi Tumor HospitalTaiyuan 030001China Department of Interventional Radiology Tibet Autonomous Region People’s

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world *** this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May *** primary endpoint was progression-free survival(PFS)according to modified *** secondary outcomes included overall survival(OS),objective response rate(ORR),and *** performed propensity score matching approaches to reduce bias between two *** matching,228 pairs were included with a predominantly advanced disease *** PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,*** results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

关键词： hepatocellular targeted matching

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Malnutrition and Quality of Life in Chinese Cancer Patients: a Clinical Study of 23,994 Subjects

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Journal of Nutritional Oncology 2021年第1期6卷 16-32页

作者： Hong Xia Xu Chun Hua Song Zhen ming Fu chang wang Zeng qing Guo Yuan Lin Ying Ying Shi Wen Hu Yi Ba Su Yi Li Zeng Ning Li Kun Hua wang Jing Wu Ying He Jia Jun Yang Cong Hua Xie Fu Xiang zhou Xin Xia Song Gong Yan Chen Wen Jun Ma Su Xia Luo Zi Hua Chen ming Hua Cong Hu Ma Chun Ling zhou Wei wang Qi Luo yong Mei Shi Yu Mei Qi hai ping Jiang Wen Xian Guan Jun Qiang Chen Jia Xin Chen Yu Fang Lan zhou yong Dong Feng Rong Shao Tan Tao Li Jun Wen Ou qing Chuan Zhao Jian Xiong Wu Min Weng qing Hua yao Jiu Wei Cui Wei Li Han ping Shi the Investigation on Nutrition Status and Clinical Outcome of Common Cancers(INSCOC)Group Department of Nutrition Daping Hospital&Research Institute of SurgeryThird Military Medical UniversityChongqing 400042China Department of Epidemiology College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Cancer Center Renmin Hospital of Wuhan UniversityWuhan 430060HubeiChina Cancer Center of the first hospital of Jilin university Changchun 130021JilinChina Department of Medical Oncology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhou 350014FujianChina Department of Gastrointestinal Surgery Cancer Hospital Affiliated to Guangxi Medical UniversityNanning 530021GuangxiChina Department of Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080GuangdongChina Department of Clinical Nutrition West China Hospital of Sichuan UniversityChengdu 610041SichuanChina Department of Gastrointestinal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin Key Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Nutrition and Metabolism of Oncology Affiliated Provincial Hospital of Anhui Medical UniversityHefei 230031AnhuiChina Department of Clinical Nutrition the First Hospital of Hebei Medical UniversityShijiazhuang 050031HebeiChina Department of Gastrointestinal Surgery Institute of Gastroenterologythe First Affiliated Hospital of Kunming Medical University 650032KunmingYunnanChina Department of Clinical Nutrition the First People's Hospital of KashiKashi 844000XinjiangChina Department of Clinical Nutrition Chongqing General HospitalChongqing 400014China Department of Colorectal and Anal Surgery Huizhou Municipal Central HospitalHuizhou 516001GuangdongChina Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityWuhan 430071HubeiChina Department of Oncology Xingtai People’s HospitalHebei Medical UniversityXingtai 054031HebeiChina Harbin Medical university Cancer hospital Harbin 150085HeilongjiangChina

Background Malnutrition is common in patients with cancer,and can negatively impact their quality of life(QoL)and even ***,there is currently no large data available on the prevalence of malnutrition in Chinese cancer *** study evaluated the prevalence of malnutrition and the QoL of Chinese patients with locoregional,recurrent or metastatic *** We conducted a nationwide observational,multi-center,hospital-based cross-sectional study within the Chinese Society of Nutritional Oncology(CSNO)*** of the patients were diagnosed with one of the following 18 different types of malignant tumors:lung cancer,gastric cancer,liver cancer,colorectal cancer,breast cancer,esophageal cancer,cervical cancer,endometrial cancer,nasopharyngeal carcinoma,malignant lymphoma,leukemia,pancreatic cancer,ovarian cancer,prostate cancer,bladder cancer,brain cancer,biliary tract malignant tumors or gastrointestinal stromal *** patients were enrolled from 72 hospitals located in different regions of *** patients’nutritional status was evaluated based on the body mass index(BMI),loss of bodyweight,laboratory measurements and patient generated-subjective global assessment(PG-SGA)*** cancer patients’physical status and QoL were assessed by the Karnofsky Performance Status(KPS)questionnaire and the European Organization for Research and Treatment of Cancer(EORTC)QLQ-C30 questionnaire,*** From December 2013 to April 2016,23,994 patients hospitalized for cancer treatment(such as surgery,chemotherapy or radiotherapy)were enrolled in the *** patients included 12,494(52.9%)males and 11,124(47.1%)*** mean age was 55.8±13.7 *** proportions of patients in cancer stagesⅠ,Ⅱ,Ⅲ,Ⅳand uncertain were 11.5%,20.3%,27.5%,30.2%and 10.5%,*** the 23,994 inpatients,the proportions of patients who were underweight(BMI2),normal(18.5 kg/m224 kg/m2),overweight(24 kg/m2≤BMI28 kg/m2)and obese(BMI≥2

关键词： Nutritional status Nutritional assessment Malnutrition Patient generated subjective global assessment Body mass index Body weight loss Karnofsky Performance Status score Quality of life

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Extension Protocol for the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in china(INSCOC)Study:2021 update

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Journal of Nutritional Oncology 2022年第2期7卷 64-74页

作者： Hong Xia Xu Chun Hua Song Liang Yu Yin chang wang Zhen ming Fu Zeng qing Guo Yuan Lin Ying Ying Shi Wen Hu Yi Ba Su Yi Li Zeng Ning Li Kun Hua wang Jing Wu Ying He Jia Jun Yang Cong Hua Xie Fu Xiang zhou Xin Xia Song Gong Yan Chen Wen Jun Ma Su Xia Luo Zi Hua Chen Zhi Kang Chen ming Hua Cong Hu Ma Chun Ling zhou Wei wang Qi Luo yong Mei Shi Yu Mei Qi hai ping Jiang Wen Xian Guan Jun Qiang Chen Xiang Hua Wu Jia Xin Chen Yu Fang Lan zhou yong Dong Feng Rong Shao Tan Tao Li Jun Wen Ou qing Chuan Zhao Jian Xiong Wu Min Weng qing Hua yao Ya Yin Yu Quan Jun Lyu Hong Qiu ming Liu Wei Li Han ping Shi The Investigation on Nutrition Status and Clinical Outcome of Common Cancers(INSCOC)Group Department of Nutrition Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Department of Epidemiology College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Cancer Center of the first hospital of Jilin university Changchun 130021Jilin China Cancer Center Renmin Hospital of Wuhan UniversityWuhan 430060HubeiChina Department of Medical Oncology Fujian Cancer HospitalFujian Medical University Cancer HospitalFuzhou 350014FujianChina Department of Gastrointestinal Surgery Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Department of Surgery The First Affiliated Hospital of SunYat-Sen UniversityGuangzhou 510080GuangdongChina Department of Clinical Nutrition West China Hospital of Sichuan UniversityChengdu 610041SichuanChina Department of Gastrointestinal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin Key Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Nutrition and Metabolism of Oncology The First Affiliated Hospital of University of Science and Technology of ChinaAnhui Provincial Cancer HospitalHefei 230031AnhuiChina Department of Clinical Nutrition The First Hospital of Hebei Medical UniversityShijiazhuang 050031HebeiChina Department of Gastrointestinal Surgery Institute of GastroenterologyThe First Affiliated Hospital of Kunming Medical UniversityKunming 650032YunnanChina Department of Clinical Nutrition The First Affiliated Hospital of Zhejiang Chinese Medical UniversityZhejiang Provincial Hospital of Traditional Chinese MedicineHangzhou 310006ZhejiangChina Department of Clinical Nutrition Chongqing General HospitalChongqing 400014China Department of Colorectal and Anal Surgery Huizhou Municipal Central HospitalHuizhou 516001GuangdongChina Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityWuhan 430071HubeiChina Department of Oncology Xingtai Peo

Background Malnutrition is common in patients with cancer,and this adversely affects the survival and quality of life of *** Society for Nutritional Oncology issued a multi-center,large-scale,long-term follow-up prospective study,the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in china(INSCOC study)since *** is an extension to the previous 2013-2020 study *** study still sought to:①address the prognostic impact of nutritional factors and quality of life on cancer patient survival;②describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of *** and study design This is an observational,multi-centered,hospital-based prospective cohort *** collection will be performed at baseline(within 48 hours after patient admission),during the hospital stay and 30 days after hospital ***-up will be conducted for 1-20 years after *** primary outcome will be the all-cause mortality/overall survival,and secondary outcomes will be the length of hospital stay and costs of *** factors will include demographic characteristics,tumor characteristics,information about chronic diseases,hematological measurements(e.g.,red blood cell count,total lymphocyte counts,hemoglobin,albumin,prealbumin,creatinine,C-reactive protein,IL-6),anthropometric measurements(e.g.,height,weight,arm circumference,arm muscle circumference,triceps skinfold thickness,and waist circumference),body composition parameters,PG-SGA scores,quality of life(as indicated by the QLQ-C30 questionnaire),muscle mass(as indicated by the calf circumference),muscle strength(as indicated by the handgrip strength),muscle function(as indicated by the six-meter walking speed test)and physical status assessments(as indicated by the Karnofsky Performance Status scores).This clinical study protocol was approved by local Ethics Committees of

关键词： Cancer Malnutrition Nutritional status Nutritional assessment Survival Patient-Generated Subjective Global Assessment

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