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Human multi-drug resistant hepatocellular carcinoma induced in nude mice by B-ultrasonographically-directed orthotopic implantation:a new experimental model

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Hepatobiliary & Pancreatic Diseases International 2007年第4期6卷 393-398页

作者： Lei Ding,Xiao-Ping Chen,Zhi-Wei Zhang,Kai Jing and Wan-Guang Zhang Hepatic Surgery center,Affiliated Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,china department of oncology center,beijing shijitan hospital,beijing 100038,china Hepatic Surgery center Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China. dinglei1005@***

BACKGROUND:Present studies on the reversal of multi-drug resistance(MDR) are almost entirely limited to in vitro systems,and are seldom carried out in vivo. In order to study MDR under the in vivo situation,a MDR cell strain was used to establish a model in nude mice via orthotopic implantation directed by B-ultrasonography. This model is expected to provide a good platform for evaluating strategies to reverse the phenomenon of primary hepatocellular carcinoma(HCC) MDR. METHODS:An orthotopic MDR1 hepatoma was obtained by injecting the cell lines HepG2 and HepG2/ADM subserosally into the liver of nude mice(10 control and 20 MDR mice). The injections were made under B-ultrasonographic direction. Ultrasonography and laparotomy were used to assess tumor growth,and the long chain PCR technique was applied to sequence the MDR1 gene from multi-drug resistant human HCC cells,HepG2/ADM,and corresponding implanted tumor tissues. Furthermore,MDR1 mRNA and P-gp protein expression were evaluated by reverse transcriptase-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical methods. RESULTS:The success rates of tumor implantation and induction of MDR were 100%(30/30) and 95%(19/20),respectively. The 3.8kbp MDR1 gene band was detected from the HepG2/ADM cell line and the correspondingimplanted tumor tissues,and the MDR1 gene sequence coincided with that reported in GenBank. The expressions of MDR1 mRNA and P-gp protein in MDR mice were significantly higher than those in the control group. There was a significant difference in P-gp protein expression between MDR and control mice. CONCLUSION:A MDR model has been successfully established in nude mice via orthotopic implantation of multi-drug resistant human HCC cells directed by ultrasonography.

关键词： nude mice orthotopic implantation carcinoma,hepatocellular drug resistance,multiple

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Chinese expert consensus on refined diagnosis,treatment,and management of advanced primary liver cancer(2023 edition)

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肝脏研究（英文） 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu National Clinical Research center for Infectious Diseases Society of Hepatology,beijing Medical Association Translational Medicine Branch,china Association of Gerontology and Geriatrics department of Medical oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University NanjingJiangsuChina department of Hepatobiliary Surgery Southwest HospitalArmy Medical University ChongqingChina Senior department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Senior department of Infectious Diseases The Fifth Medical Center of PLA General HospitalBeijingChina Comprehensive Liver Cancer center The Fifth Medical Center of PLA General HospitalBeijingChina

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in china,accounting for approximately 85％of all cancer cases in the *** guidelines have been used to diagnose and treat liver ***,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual ***,it is necessary to establish a comprehensive and practical expert consensus,specifically for china,to enhance the diagnosis and treatment of HCC using the Delphi *** classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were *** recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment *** findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

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Chinese Journal of Cancer Research 2024年第3期36卷 240-256页

作者： Zaiwei Song Dan Jiang Lingling Yu Yixuan Chen Daobin Zhou Yue Li Depei Wu Lingli Zhang Liyan Miao Jun Ma Jun Zhu Hongmei Jing Rongsheng Zhao the Steering Committee,the Consensus Panel and the Evidence Synthesis Group Evidence-based Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society(CPS) Expert Committee on Lymphoma of Chinese Society of Clinical oncology(CSCO) Expert Committee on Leukemia of Chinese Society of Clinical oncology(CSCO) Society of Integrative Cardio-oncology of china Anti-Cancer Association(CACA) Chinese Society of Hematology of Chinese Medical Association(CMA) hospital Pharmacy Professional Committee of Cross-Straits Medicine Exchange Association(SMEA) department of Pharmacy Peking University Third HospitalBeijing 100191China Institute for Drug Evaluation Peking University Health Science CenterBeijing 100191China Therapeutic Drug Monitoring and Clinical Toxicology center Peking UniversityBeijing 100191China department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbin 150001China department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Pharmacy Evidence-based Pharmacy CenterWest China Second HospitalSichuan UniversityChengdu 610041China department of Pharmacy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Hematology and oncology Harbin Institute of Hematology and OncologyHarbin 150010China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China department of Hematology Peking University Third HospitalBeijing 100191China 不详

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell ***,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased *** evidence-based expert consensus was formulated using an evidence-based approach and the Delphi *** Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,*** consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special *** multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

关键词： Consensus BTK inhibitors safety adverse drug events drug-drug interactions

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Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer

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World Journal of Gastroenterology 2010年第46期16卷 5881-5888页

作者： Fang-Hua Li,Zhuang-Hua Li,Hui-Yan Luo,Miao-Zhen Qiu,Yu-Hong Li,Rui-Hua Xu,State Key Laboratory of oncology in Southern china,department of Medical oncology,Sun YatSen University Cancer center,Guangzhou 510060,Guangdong Province,china Fang-Hua Li,department of Medical oncology,Shengli Oil Field Central hospital,Dongying 257034,Shandong Province,china Lin Shen,department of GI oncology,Peking University School of oncology,beijing Cancer hospital and Institute,beijing 100142,china Hui-Zhong Zhang,State Key Laboratory of oncology in Southern china,department of Pathology,Sun Yat-Sen University Cancer center,Guangzhou 510060,Guangdong Province,china State Key Laboratory of oncology in Southern china Department of Medical Oncology Sun Yat-Sen University Cancer Center Guangzhou 510060 Guangdong Province China.

AIM:To investigate the prognostic value of KRAS mutation,and phosphatase and tensin (PTEN) expression in Chinese metastatic colorectal cancer metastatic colorectal cancer (mCRC) patients treated with ***:Ninety Chinese mCRC patients treated with cetuximab were evaluated for KRAS mutation and PTEN protein expression by DNA sequencing of codons 12 and 13 and immunohistochemistry,*** then selected 61 patients treated with cetuximab,either in combination with chemotherapy,or alone as a second-line or third-line regimen to assess whether KRAS mutation or PTEN protein expression is associated with the response and the survival time of mCRC patients treated with ***:KRAS mutation was found in 30 (33.3%) tumor samples from the 90 patients,and positive PTEN expression was detected in 58 (64.4%) of the 90 *** the 61 patients who were treated with cetuximab as a second-line or third-line regimen,the resistance to cetuximab was found in 22 patients with KRAS mutation and in 39 patients without KRAS mutation,with a response rate of 4.5% and 46.1% respectively (P=0.001),a shorter median progression-free survival (PFS) time of 14 ± 1.3 wk and 32 ± 2.5 wk respectively (P < 0.001),a median overall survival (OS) time of 11 ± 1.2 mo and 19 ± 1.8 mo respectively (P < 0.001),as well as in 24 patients with negative PTEN expression and in 37 patients with positive PTEN expression respectively (P < 0.001),with a responsive rate of 4.2% and 48.6% respectively,a shorter median PFS survival time of 17 ± 2.0 wk and 28 ± 1.9 wk respectively (P=0.07),and a median OS time of 11 ± 1.3 mo and 18 ± 1.9 mo respectively (P=0.004).Combined KRAS mutation and PTEN expression analysis showed that the PFS and OS time of patients with two favorable prognostic factors were longer than those of patients with one favorable prognostic factor or no favorable prognostic factor (P < 0.001).CONCLUSION:KRAS mutation and PTEN protein expression are significantly corr

关键词： Cetuximab Metastatic colorectal cancer KRAS mutation Phosphatase and tensin protein expression

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DNA Damage, Signaling and Repair: Protecting genomic integrity and reducing the risk of human disease

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Chinese Science Bulletin 2011年第30期56卷 3119-3121页

作者： ZHOU PingKun department of Radiation Toxicology and oncology, beijing Institute of Radiation Medicine, beijing 100850, china Special Topic Editor department of Radiation Toxicology and oncology Beijing Institute of Radiation Medicine Beijing China

DNA is the genetic material that contains the 'instructions' to not only guide the continuation of life but also govern the development, metabolism and functioning of living organisms. DNA damage occurs daily due to v... 详细信息

关键词： DNA损伤基因组伤信号人类疾病整性修复风险保护

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Wild-Type KRAS and BRAF Could Predict Response to Cetuximab in Chinese Colorectal Cancer Patients

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Chinese Journal of Cancer Research 2011年第4期23卷 271-275页

作者： Jing Gao, Ting-ting Wang, Jing-wei Yu, Yan-yan Li, Lin Shen* Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), department of Gastrointestinal oncology, Peking University School of oncology, beijing Cancer hospital & Institute, beijing 100142, china Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing 100142 China.

Objective: To analyze the relationship between KRAS, BRAF mutations and the response to Cetuximab in Chinese colorectal cancer patients. Methods: A total of 273 Chinese colorectal cancer patients were evaluated for KRAS and BRAF mutations by Sanger sequencing. Among them, 59 patients with metastatic colorectal cancer (mCRC) were treated with Cetuximab in combination with chemotherapy from August 2005 to July 2009. Statistical analysis was conducted to assess the relationship between KRAS, BRAF mutations and the response or survival of 59 mCRC patients. Results: KRAS and BRAF mutation rates were 38.5% (105/273) and 5.1% (14/273), respectively, and KRAS/BRAF mutations were mutually exclusive. Among 59 patients treated with Cetuximab plus chemotherapy, KRAS and BRAF mutations were identified in 11 and 5 patients, respectively. The response rates and median progression-free survivals (PFS) in KRAS wild-type and mutant patients were 35.4% (17/48) vs. 9.1% (1/11) (P=0.054) and 153 days vs. 99 days (P=0.01), respectively. Also, the response rates and median PFS in BRAF wild-type and mutant patients were 37.2% (16/43) vs. 20% (1/5) (P=0.016) and 138 days vs. 90 days (P=0.036), respectively. Conclusion: Besides KRAS, assessing BRAF mutation should also be required to select patients eligible for Cetuximab. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.

关键词： KRAS BRAF Mutation Cetuximab Colorectal cancer

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A novel aberrant splicing of G_(sa) transcript in human leukemia cell lines

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Chinese Science Bulletin 1999年第4期44卷 340-344页

作者： YE Qinong, YAO Xiao, WANG Hengliang, ZHANG Shu, LIU Huaitian, SU Guofu, HUANG Cuifen and ZHOU Tingchong beijing Institute of Biotechnology, beijing 100071, china department of Biology, Shaanxi Normal College, Xi’an 710062, china beijing Medical University, School of oncology, beijing 100036, china beijing Institute of Microbiology and Epidemiology, beijing 100071, china beijing Institute of Basic Medicine Sciences , beijing 100850, china beijing Institute of Biotechnology Beijing China department of Biology Shaanxi Normal College Xi’an China School of oncology Beijing Medical University Beijing China beijing Institute of Microbiology and Epidemiology Beijing China beijing Institute of Basic Medicine Sciences Beijing China

The α subunit of the stimulatory G protein, Gsα, is involved in the stimulation of adenylate cyclase pathway of signal transduction. The various Gsα mRNAs are generated either by alternative splicing or by using alternative promoter. A novel aberrant splicing of Gsα transcript in human leukemia cell lines is reported. The entire coding region of Gsα gene obtained, referred to as GsαLeu, was amplified by PCR with cDNA from Jurkat human leukemia cDNA library or the reverse-transcribed first strand cDNA from human leukemia cell line HL-60 as a template. The result of DNA sequencing indicated that,compared with originally reported Gsα, GsαLeu has two in-frame deletions, one in amino acid residues 23—249 and the other in amino acid residues 254—260, suggesting that G（sαLeu） may play an important role in leukemia. The complete coding region of GsαLu was inserted downstream of the thrombin site of pGEX-2T fusion protein expression vector and expressed in the form of GST/G(

关键词： Gsa splicing leukemia cloning and expression.

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Low Correspondence of EGFR Mutations in Tumor Tissue And Paired Serum of Non-Small-Cell Lung Cancer Patients

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Chinese Journal of Cancer Research 2010年第1期22卷 27-31页

作者： Guo-hong Song,Jun Ren,Li-jian Zhang,Li-jun Di, Yan-hua Yuan,Jing Yu,Jun Jia Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) department of Medical oncology,Peking University School of oncology,beijing Cancer hospital & Institute,beijing 100142,china Key laboratory of Carcinogenesis and Translational Research (Ministry of Education) department of Medical oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China

Objective： Epidermal growth factor receptor （EGFR） mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer （NSCLC） patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods： The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results： EGFR mutations were detected in 15 （30%） of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 （all were L858R except one was L861Q）, but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion： These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.

关键词： Circulating DNA Epidermal growth factor receptor (EGFR) Mutation Non-small-cell lung cancer (NSCLC)

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Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

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World Journal of Gastroenterology 2012年第4期18卷 368-374页

作者： Meng-Meng Tian,Yu Sun,Zhong-Wu Li,Ying Wu,Ai-Lian Zhao,Ji-You Li,Key Laboratory of Carcinogenesis and Translational Research,department of Pathology,Peking University School of oncology,beijing Cancer hospital and Institute,beijing 100142,china Key Laboratory of Carcinogenesis and Translational Research Department of Pathology Peking University School of Oncology Beijing Cancer Hospital and Institute Beijing 100142 China.

AIM:To investigate the association between single nu-cleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk,biological behavior and prognosis of gastric cancer (GC) in Chinese ***:The study group consisted of 332 GC patients and 380 healthy *** was performed using polymerase chain reaction and the results were confirmed by *** associa-tion of ICAM-1 K469E polymorphisms and the risk of GC were studied,and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was ***:Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios:1.36;95% confidence in-terval (CI):1.01-1.84;P=0.041].GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%,respectively;P=0.002).In addition,patients at stage Ⅳ had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%,re-spectively;P=0.046).Follow-up study showed that the overall cumulative survival rate was 23.7% in AA geno-type group and 42.9% in AG and GG genotypes *** univariate analysis,AA genotype was correlated with the overall cumulative survival (P=0.034).But in multi-variate analysis,ICAM-1 polymorphism was not an inde-pendent prognostic factor for the overall survival (relative risk,1.145;95% CI:0.851-1.540;P=0.370).CONCLUSION:Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC,predicting disease progression,and guiding individualized treatment.

关键词： Intercellular adhesion molecule-i Genepoiymorphism Gastric cancer Risk Prognosis

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Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation of DU-145 cells

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Acta Pharmacologica Sinica 2005年第3期26卷 364-368页

作者： Jin-ming DAI Shu-qun ZHANGl~1 Wei ZHANG Ru-xian LIN Zong-zheng JI~1 Sheng-qi WANG~2beijing Institute of Radiation Medicine,beijing 100850,china 1 department of oncology,the Second hospital of Xi'an Jiaotong University,Xi'an 710004,china beijing Institute of Radiation Medicine Beijing China department of oncology the Second Hospital of Xi'an Jiaotong University Xi'an China

Aim:To investigate the effect of antisense oligodeoxynucleotides （ASODN） tar-geting Pim-2 on cell proliferation of DU-145 ***:Three ASODN target-ing Pim-2 were designed and *** transfection with ASODN,cellproliferation was analyzed using an MTS [3-（4,5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium,inner salt] ***,Pim-2 mRNA,protein levels,and cell cycles were ***:The ASODN designed and synthesized by our laboratory significantly reducedPim-2 mRNA level and protein content in DU-145 *** transfection withASODN for 48 h,a marked reduction in cell viability was observed in DU-145 cellsin a dose-dependent *** remarkable apoptosis occurred in ceils treatedwith ASODN compared with control ***,it should be noted that G1phase arrest was clearly observed in ASODN-treated ***:ASODNtargeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation,andinduction of G1phase cell cycle arrest is one of the important mechanisms forASODN to reduce cell ***,antisense inhibition of Pim-2 expres-sion provides a new promising therapy target for prostate cancer.

关键词： antisense oligodeoxynucleotide Pim-2 cell proliferation: DU-145

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