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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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Mitochondrial rRNA and tRNA and hearing function

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Cell Research 2007年第3期17卷 227-239页

作者： Guangqian Xing~1 Zhibin chen~1 Xin Cao~2 ~1department of Otolaryngology,the First affiliated hospital of Nanjing medical University,Nanjing 210029,china ~2department of Biotechnology,Nanjing medical University,Nanjing 210029,china department of Otolaryngology the First Affiliated Hospital of Nanjing Medical University Nanjing China department of Biotechnology Nanjing Medical University Nanjing China

The human ear is a delicate sensory apparatus of hearing for normal communication,and its proper functioning is highlydependent on mitochondrial oxidative *** first mitochondrial point mutation for nonsyndromic andaminoglycoside-induced hearing loss was identified in *** then a number of inherited mitochondrial mutationshave been implicated in hearing *** of the molecular defects responsible for mitochondrial disorder-associatedhearing loss are mutations in the 12S rRNA gene and tRNA *** this review,after a short description of normal hear-ing mechanisms and mitochondrial genetics,we outline the recent advances that have been made in the identification ofdeafness-associated mitochondrial mutations,and discuss how mitochondrial dysfunction contributes to hearing loss.

关键词： mitochondrial DNA rRNA tRNA gene mutation aminoglycosides hearing loss

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Effects of multidrug resistance, antisense RNA on the chemosensitivity of hepatocellular carcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2006年第4期5卷 552-559页

作者： Bo Li, Tian Ye, Lei Zhao, De-Hua Li, Xing-Hua Gou, Lan-Ying Zhao, Lei Han, Lin chen, Lu-Nan Yan and Jian-Ping Gong department of Hepatobiliary Surgery, second affiliated hospital, Chongqing University of medical Sciences, Chongqing 400010, china department of Traditional Chinese Surgery, second affiliated hospital, Luzhou medical college, Luzhou 646000, china Genetic Engineering Laboratory, chengdu Di’ao Group Co., Ltd., chengdu 610041, china department of General Surgery, West china hospital, Sichuan University, chengdu 610041, china department of Hepatobiliary Surgery Second Affiliated Hospital Chongqing University of Medical Sciences Chongqing 400010 China.

BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM. METHODS: The recombinant adenoviruses pAdEasy- GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein- producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by flow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis. RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpressionof mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96% respectively. CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.

关键词： antisense nucleic acid multiple drug resistance P-glycoprotein

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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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Effects of aspirin on number,activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood

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Acta Pharmacologica Sinica 2006年第4期27卷 430-436页

作者： Tu-gang chen Jun-zhu chen~2 Xu-dong XIE department of Cardiovascular Disease,First affiliated hospital,medical School of Zhejiang University.Hangzhou 310003,china department of Cardiovascular Disease First Affiliated Hospital Medical School of Zhejiang University Hangzhou China

Aim:To investigate whether aspirin has an influence on endothelial progenitorcells(EPC).Methods:Total mononuclear cells(MNC)were isolated from periph-eral blood by Ficoll density gradient centrifugation,then cells were plated onfibronectin-coated culture *** 7 d of culture,attached cells were stimu-lated with aspirin(to achieve final concentrations of 1,2,5,and 10 retool/L)for 3,6,12,and 24 *** were characterized as adherent cells that were double positivefor 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein(DiLDL)uptake and lectin binding by direct fluorescent *** prolifera-tion and migration were assayed using a 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay and a modified Boyden chamber assay,*** EPC adhesion assay was performed by replating the EPC onfibronectin-coated dishes,and then adherent cells were *** vitrovasculogenesis activity was assayed by using an in vitro vasculogenesis *** nitric oxide synthase(iNOS)was assayed by Western ***:Incubation of isolated human MNC with aspirin decreased the number of *** also decreased the proliferative,migratory,adhesive,and in vitrovasculogenesis capacity of EPC,and also their iNOS levels in a concentration-and time-dependent ***:Aspirin decreases(1)the number ofEPC;(2)the proliferative,migratory,adhesive and in vitro vasculogenesis capaci-ties of EPC;and(3)iNOS levels in EPC.

关键词： aspirin endothelial progenitor cells cell adhesion cell count cell movement cell division physiologic neovascularization

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Clinical analysis of patients with iatrogenic bile duct injury

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Hepatobiliary & Pancreatic Diseases International 2006年第2期5卷 283-285页

作者： Wei-Liang Yang, Dong-Wei Zhang and Xin-chen Zhang department of General Surgery, second affiliated hospital, Harbin medical University, Harbin 150086, china department of General Surgery Second Affiliated Hospital Harbin Medical University Harbin 150086 China. wlyang_2008@***

BACKGROUND: The main cause of iatrogenic bile duct injury is misidentification of the common bile duct as the cystic duct. In this article, we summarize the experience in the treatment of 112 patients with iatrogenic bile duct injury. METHOD: Clinical data of these patients treated at 10 hospitals of Songhua river area, Heilongjiang province, china from January 1978 to January 2005 were analyzed retrospectively. RESULTS: In 55.4% patients (62/112), iatrogenic bile duct injury was due to misidentification of the anatomy of Calot's triangle before cholecystectomy. Their diagnosis was based on clinical features, celiac puncture and imaging examination in which ultrasonography was most sensitive, giving a diagnostic rate of 97. 5%. Six types of injury were identified according to their locations, and type Ⅲ damage was commonly seen ( 92/112 ). The curative rate in this group was 95.5% (107/112). Eighty-seven patients (77.7%) underwent Roux-en-Y choledochojejunostomy with a cure rate of 94.3% (82/87). CONCLUSION: The prevention of iatrogenic bile duct injury lies in identifying the topography of extrahepatic bile ducts. Roux-en-Y choledochojejunostomy is usually the treatment of choice.

关键词： wounds, injury biliary tract diseases surgical procedures operative

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Effect of nitric oxide on toll-like receptor 2 and 4 gene expression in rats with acute lung injury complicated by acute hemorrhage necrotizing pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2005年第4期4卷 609-613页

作者： He-Shui Wu, Lei Zhang, Yan chen, Xing-Jun Guo, Lin Wang, Jian-Bo Xu, Chun-You Wang and Jing-Hui Zhang Center of Pancreatic Surgery Laboratory of General Surgery affiliated Union hospital of Tongji medical college, Hua-zhong University of Science and Technology, wuhan 430022, china Pe-diatric department, affiliated Tongji hospital of Tongji medical college, Huazhong University of Science and Technology, wuhan 430030, china. Center of Pancreatic Surgery Affiliated Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China.

BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS). This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP) and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group ( n = 10) , AHNP group (n = 30) , chloroquine-treated group ( n = 30) , and L-Arg-treated group (n =40). The lungs were dissected for lung histological scoring, and bronchoalveolar lavages were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values in the sham-operated group (0.016±0. 210E-2, 0.112 ±0.750E-2) , but it was markedly increased at 3 hours in the AHNP group (0.787±0.751E-2, 1.512 ±1.794E-2) , peaking at 12 hours (1.113 ±6.141E-2, 2.957±2.620E-2; P <0.05 or P <0.01). When lung injuries were aggravated, TNF-α concentrations in the lungs were increased, but NO concentrations were decreased ( P < 0.05 or P < 0.01 ) . When TLR2/4mRNA was inhibited by CQ (3h: 0.313 ± 5.491E-2, 0.005 ±1.419E-3 ; 6h: 0.488 ±7.442E-2, 0.010 ± 1.518E-3; 12h: 0.883 ± 8.911E-2, 0.024 ± 2.760E-3; P< 0.05 or P <0.01) , lung injuries were relieved. NO concentrations in the lungs were increased but TNF-α concentrations were decreased (P <0. 05 or P <0.01). When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the lungs could be effectively inhibited (50mg-T: 0.656 ±3. 977E-2, 1. 501 ±6.111E-2; 100mg-T: 0.260± 0.891E-2, 0.732 ±5.135E-2; 200mg-T: 0.126 ±0.914E-2, 0.414 ± 1.678E-2; 400mg-T: 0.091 ±0.399E-2, 0.287 ± 0.176E-2; P <0.05 or P <0. 01) and lung injuries were relieved. At the same time, NO concentrations in the lungs were marke

关键词： toll-like receptors acute hemorrhage necrotizing pancreatitis lung nitric oxide chloroquine

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CT examination, clinical situation and experimental characteristics of infants with intracranial hemorrhage induced by delayed vitamin K deficiency

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Neural Regeneration Research 2006年第9期1卷 801-805页

作者： Zhiqing Lin1, Feng Fang1, Min chen2, Guoxiang Cai3 1department of Pediatrics, Tongji hospital affiliated to Tongji medical college, Huazhong University of Science and Technology, wuhan 430030, hubei Province, china 2department of Pediatrics, 3department of Radiation Medicine, Zhongshan hospital affiliated to Xiamen University, Xiamen 361004, Fujian Province, china department of Pediatrics Tongji Hospital Huazhong University of Science and Technology Wuhan 430030 Hubei Province China department of pediatrics Zhongshan Hospital Xiamen University Xiamen 361004 Fujian Province China department of Radiation Medicine Zhongshan Hospital Xiamen University Xiamen 361004 Fujian Province China

BACKGROUND: Delayed vitamin K deficiency is characterized by acute onset, severe illness and high fatality rate. 33%-50% survivors accompany with other various nervous system sequelas. Therefore, diagnosis and treatment of intracranial hemorrhage in time become a key factor for improving healing rate and reducing fatality rate and incidence of sequela. OBJECTIVE: To investigate the clinical situation, experimental characteristics, CT examination and terminative characteristics of infants with intracranial hemorrhage induced by delayed vitamin K deficiency. DESIGN: Case analysis. SETTING: department of Pediatrics, Zhongshan hospital affiliated to Xiamen University. PARTICIPANTS: A total of 17 infants with intracranial hemorrhage induced by delayed vitamin K deficiency aged 1-3 months including 11 boys and 6 girls were selected from department of Pediatrics, Zhongshan hospital affiliated to Xiamen University from January 1994 to December 2005. All infants had drowsiness, rejective milk, spiting milk, gaze of both eyes, tic, coma, full anterior fontanelle, high muscular tension and cerebral hernia, etc. Experimental examination demonstrated that infants had anemia at various degrees; prothrombin time and partial thromboplastin time were prolonged; platelet count was normal. CT examination indicated that screenages of subarachnoid hemorrhage, subdural hematoma, cerebral parenchyma hemorrhage and intraventricular hemorrage were changed. Hemorrhage was stopped by the application of vitamin K. All patients provided informed consent. METHODS: ① Clinical situation and physical sign of infants were observed after hospitalization and scanned with rapid spiral CT scanning system. The thickness and average space of layers were 8-10 mm and the scanning time was 5 s with window width of 30-80 Hu and window position of 28-35 Hu. ② After hospitalization, four items of blood coagulation was measured with Futura meter and biochemical indexes of blood, such as serum calcium, serum alka

关键词： clinical situation and experimental characteristics of infants with intracranial hemorrhage induced by delayed vitamin K deficiency CT examination

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Correlative study on the cognitive dysfunction of patients with myasthenia gravis

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Neural Regeneration Research 2006年第8期1卷 744-746页

作者： Wenli chen1, Wenmin Wang2, Yi Wang3 1department of Neurology, Yunnan First People’s hospital, Kunming 650032, Yunnan Province, china 2department of Neurology, First affiliated hospital of Kunming medical college, Kunming 650032, Yunnan Province, china 3department of Neurology, Huashan hospital affiliated to Shanghai Fudan University, Shanghai 200040, china department of Neurology Yunnan First People's Hospital Kunming 650032 Yunnan Province China department of Neurology Hospital of Kunming Medical College Kunming 650032 Yunnan Province China department of Neurology Huashan Hospital Shanghai Fudan University Shanghai 200040 China

BACKGROUND: Myasthenia gravis (MG) is considered as a peripheral neuromuscular disorder. Some investigations demonstrate that MG affects central nervous system (CNS), and there are disorders in cognitive function, affection, sleep, mental status and others; however, there are also some different standpoints. Some questions are still disputed, such as whether or not MG exists in the CNS and cognitive function is impaired. DATA SOURCES: Using the terms of 'myasthenia gravis, neuropsychological test, memory, central, brain, cognitive dysfunction and so on', we searched the Medline database for the articles about CNS involved in MG, nerve and neuropsychology as well as cognitive function, which were published in the English language between January 1985 and December 2004. Meanwhile, we also searched CNKI database by inputting 'myasthenia gravis, neuropsychology and cognitive function' in Chinese for articles about involved neuropsychology and cognitive function which were published between October 1995 and June 2006 in the Chinese language. STUDY SELECTION: Data were checked in the first trial, and articles about the influences of MG on CNS, neuropsychology, cognitive function and central cholinergic function were selected, then those were obviously unrelated with above criteria were excluded. Articles which expound the influences of MG on neuropsychology and cognitive were included, but those with repeated contents were also excluded. DATA EXTRACTION: A total of 89 related English articles and 34 Chinese articles were collected, including 43 studies on involved CNS and 32 studies on involved central cholinergic function and cholinergic receptor. Sixty-three literatures were about neuropsychology and cognitive function, which were closely related with this article. Seventy-two articles met inclusive criteria and 66 were excluded. Thirty of seventy-two were chosen for analysis. DATA SYNTHESIS: MG is an autoimmune disease of muscular diseased fatigue induced by transmissi

关键词： cognitive function central nervous system cholinergic receptor autoimmune disease English language Chinese language used in

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Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

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World Journal of Gastroenterology 2002年第2期8卷 379-381页

作者： Wei-Xing chen You-Ming Li Chao-Hui Yu Wei-Min Cai Min Zheng Feng-chen,department of Gastroenterology, The First affiliated hospital,medical college of Zhejiang University,Hangzhou 310003,Zhejiang Province,china department of Gastroenterology The First Affiliated Hospital Medical College of Zhejiang University Hangzhou 310003 Zhejiang Province China. weixng121@***

AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P<0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P<0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P<0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.

关键词： Humans Liver Diseases, Alcoholic Male RNA, Messenger Transforming Growth Factor beta

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