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World Journal of Gastroenterology 2001年第1期7卷 143-148页

作者： Edgar Staren Takeshi Iwamura Hubert Appert John Howard Department of Surgery Medical College of Ohio Toledo Ohio USA Department of Surgery Miyazaki Medical College Miyazaki Japan

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

关键词： Carcinoma Pancreatic Neoplasms Taxoids Antineoplastic Agents, Phytogenic Biocompatible Materials Collagen drug Combinations drug resistance, multiple drug resistance, Neoplasm Fluorescent Dyes Humans In Vitro Laminin Neoplasm Invasiveness P-Glycoprotein Paclitaxel derivatives Phenotype Proteoglycans RNA, Neoplasm Research Support, Non-U.S. Gov't Rhodamine 123 Tumor Cells, Cultured

Coagulase-negative staphylococcus and enterococcus as predominant pathogens in liver transplant recipients with Gram-positive coccal bacteremia

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Chinese Medical Journal 2010年第15期123卷 1983-1988页

作者： SHI Shao-hua KONG Hai-shen JIA Chang-ku XU Jian ZHANG Wen-jin WANG Wei-lin SHEN Yan ZHANG Min ZHENG Shu-sen Department of Hepatobiliary Surgery and Center of Liver Transplantation First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003 China

Background Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant （LT） recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant （MDR） Gram-positive coccal bacteremia after *** A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT *** In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 （17%） patients. Seventy-five （77%） bacteremic episodes occurred in the first post-LT *** most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus （CoNS, 46 isolates）,methicillin-resistant Staphylococcus aureus （MRSA, 13） and enterococcus （34, E. faecium 30, E. faecalis 4）. In all Gram-positive bacteremic isolates, 59 of 98 （60%） were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were： LT candidates with encephalopathy grades Ⅱ-Ⅳ （P=0.013, OR： 16.253, 95% CI：1.822-144.995）, pre-LT use of empirical antibiotics （P=0.018, OR： 1.029, 95% CI： 1.002-1.057）, post-LT urinary tract infections （P 〈0.001, OR： 20.340, 95% CI： 4.135-100.048） and abdominal infection （P=0.004, OR： 2.820, 95% CI：1.122-10.114）. The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative ***

关键词： drug resistance, multiple Gram-positive coccus risk factors bacteremia liver transplantation

Ligustrazine as a salvage agent for patients with relapsed or refractory non-Hodgkin＇s lymphoma

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Chinese Medical Journal 2010年第22期123卷 3206-3211页

作者： YANG Xi-gui JIANG Chao Department of Internal Medicine Oncology Shandong Cancer Hospital Shandong Academy of Medical Sciences Jinan Shandong 250117 China Department of Internal Medicine Oncology Shandong Cancer Hospital (East District) Shandong Academy of Medical Sciences Jinan Shandong 250031 China

Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin＇s lymphoma （NHL）. The main reason for poor prognosis is multidrug resistance （MDR）, for which the main phenotype is overexpression of P-glycoprotein （P-gp）. This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression. Methods Sixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression. Results In the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival （PFS） in the two groups （P=0.0651）, but the reversal agent group had a higher overall response rate （ORR） than did the control group （P=0.048）. Forty-one of 56 patients had P-gp（＋） tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed （CR＋CRu） reflecting a significant advantage in the reversal agent group （P=0.048）. Patients with P-gp（＋） tumor cells in the reversal agent group had a higher overall response rate （ORR） than did the control group （11/18 vs. 6/23, P=0.024）. Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp（＋） tumor cells in the reversal agent group had longer progression-free survival than did the control group （P=0.0464）. A small number of patients who received ligustrazine had a decrease in blood pressure. Conclusion Ligustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.

关键词： lymphoma, non-Hodgkin drug resistance, multiple ligustrazine treatment efficacy toxicity

Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1

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Chinese Medical Journal 2007年第8期120卷 703-707页

作者： CHEN Yong-bing YAN Mao-lin GONG Jian-ping XIA Ren-pin LIU Li-xin LI Ning LU Shi-chun ZHANG Jing-guang ZENG Dao-bing XIE Jian-guo YANG Jia-yin YAN Lü-nan Department of General Surgery Second Hospital Chongqing University of Medical Sciences Chongqing 400010 China Department of General Surgery West China Hospital Sichuan University Chengdu 610041 China Liver Transplantation Centre Beijing You-an Hospital Capital University of Medical Sciences Beijing 100069 China Liver Transplantation Centre General Hospital of People＇s Liberation Army Beijing 100852 China

Background The multidrug resistance （MDR） associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell （HCC） patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein （Pgp） in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were （59.7±7.9）% and （12.28±2.09）%, respectively, compared with （16.9±3.2）% and （3.07±1.06）% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide th

关键词： drug resistance, multiple P-glycoprotein carcinoma, hepatocellular

Reversal effect of bufalin on multidrug resistance in K562/VCR vincristine-resistant leukemia cell line

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Journal of Traditional Chinese Medicine 2014年第6期34卷 678-683页

作者： Xiaofeng Zhai Jianying Lu Ying Wang Fanfu Fang Bai Li Wei Gu Department of Traditional Chinese Medicine Changhai Hospital Affiliated to the Second Military Medical University Department of Onology Anhui Jingan Hospital of Integrative Medicine

OBJECTIVE: To probe insights into the reversal effect of bufalin on vincristine-acquired multidrug resistance(MDR) in human leukemia cell line K562/***: Proliferative inhibition rate and the reversal index(RI) of bufalin were determined by Methyl thiazolyl tetrazolium assay. The uptake of Adriamycin(ADM) in K562/VCR cells, cell cycle and apoptosis rate were determined by flow cytometry(FCM). Cell morphologic changes were observed with Wright-Giemsa staining. The expression of P-glycoprotein(P-gp), multidrug-associated protein-1(MRP1), Bcl-x L and Bax protein were measured by ***: The human leukemia multidrug resistant K562/VCR cells showed no cross-resistance to bufalin. The RIs of bufalin at concentrations of 0.0002,0.001 and 0.005 μmol/L were 4.85, 6.94 and 14.77,respectively. Preincubation of 0.001 μmol/L bufalin for 2 h could increase intracellular ADM fluorescence intensity to 28.07%(P<0.05) and down-regulate MRP1 expression simultaneously, but no remarkable effect was found on P-gp protein. Cell cycle analysis indicated increased apoptosis rate and apparent decreased G2/M phase proportion after treatment with bufalin. When exposed to 0.01μmol/L bufalin, typical morphological changes of apoptosis could be observed. Down-regulation of Bcl-x L and up-regulation of Bax expression in K562/VCR cells could be detected by ***: Bufalin could partly reverse the MDR of K562/VCR cells, with a possible mechanism of down-regulating MRP1 expression and activating apoptosis pathway by altering Bcl-x L/Bax ratio.

关键词： Bufalin drug resistance, multiple Apoptosis Multidrug resistance-associated protein1 Human leukemia cell line K562/VCR

Enterococcal urinary tract infections: eight years experience at a regional hospital in Trinidad, West Indies

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Chinese Medical Journal 2001年第1期114卷 90-92页

作者： Fitzroy A.Orrett Ehlich Connors Faculty of Medical Sciences Department of ParaClinical SciencesThe University of the West IndiesSt.AugustineTrinidad and TobagoWest Indies San Fernando General Hospital San FernandoTrinidad and TobagoWest Indies

OBJECTIVE: To investigate the prevalence of significant enterococcal isolates from urine and determine what factors are associated with the increased prevalence, with particular reference to antibiotic susceptibilities. METHODS: Retrospective analysis over an 8-year period of hospital laboratory records of urinary isolates of enterococci was done. Species were identified via colony morphology, growth in 6.5% sodium chloride and their ability to hydrolyze esculin in the presence of 40% bile salts. Susceptibility testing via the disc diffusion technique with 9 commonly used antibiotics was also done as defined by the National Committee for Clinical Laboratory Standards. RESULTS: From 39,881 urine specimens, 9116 (22.9%) were culture positive. Of this 9116, 1001 (11.0%) were enterococci, the 4th most common urinary isolate. E. coli was the most common (36.2%). Most enterococci were from pediatric patients (28.4%) and the urology unit (24.5%). All enterococci were fully sensitive to ampicillin and augmentin (amoxicillin-clavulanic acid). Sensitivity to gentamicin decreased significantly from 79% in 1990 to 58% in 1997 (P

关键词： drug resistance, multiple Enterococcus Gram-Positive Bacterial Infections Humans Microbial Sensitivity Tests Prevalence Retrospective Studies Urinary Tract Infections West Indies

Correlation between Cyclin A Gene Expression in Adult Patients with Acute Leukemia and drug resistance

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第3期23卷 245-248页

作者：马劼徐世荣赖永榕卢玉英姚尔固 Department of Hematology

In order to investigate the relationship between the expression of cyclin A and drug resistance in adult patients with acute leukemia (AL), the mRNA expression of cyclin A, mdr1, TopⅡ α , bcl-2 was detected in 64 adult patients with AL and 20 normal controls by semi-reverse transcription polymerse chain reaction (semi-RT-PCR). It was found that the cyclin A and TopⅡ α mRNA expression levels in drug resistant group were significantly lower than in sensitive group ( P drug resistant group there was a negative correlation between the gene expression levels of cyclin A and mdr1 ( r s =-0.337, P=0.029 ). The 10 AL patients with positive lower expression of both cyclin A and TopⅡ α were all resistant to drugs. Logistic regression of Binary analysis showed the correlation between the lower expression of cyclin A and drug resistance. It was concluded that lower expression of cyclin A gene might be an unfavorable prognostic factor for patients with AL, and detection of both cyclin A and TopⅡ α gene expression would predict drug resistance in AL patients.

关键词： acute leukemia cyclin A drug resistance, multiple

A novel myeloma cell line identified for multidrug resistant study

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The Chinese-German Journal of Clinical Oncology 2009年第5期8卷 296-299页

作者： Hui Xiao Qi Xiao Kejian Zhang Xuelan Zuo Department of Hematology Zhongnan Hospital of Wuhan University Wuhan 430071 China Department of Internal Medicine Yanqiao Hospital of Yunyang Medical College Shiyan 442000 China

Objective:To find out how to overcome resistance during multiple myeloma(MM) treatment through establishing a multidrug resistant human multiple myeloma cell line and investigating its biological ***:The parent cell line MOLP-2 was exposed to different concentrations of melphalan and a melphalan-resistant cell line MOLP-2/R was identified by continuous stepwise *** cell morphology and growth curves were *** levels of P-gp, MRP and FANCD2 monoubiquitination were checked by Western *** IC50 of melphalan and resistance index(RI) were detected by MTT ***:A melphalan-resistant cell line MOLP-2/R was finally *** RI of MOLP-2/R cells to melphalan was *** melphalan it was cross resistant to other chemotherapeutic agents, including ADM, CTX, DDP and *** multiplication time was postponed(P drug resistance in MOLP-2/R cell line.

关键词： multiple myeloma (MM) FANCD2 drug resistance, multiple

Clinical relationship between MDR1 gene and gallbladder cancer

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Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 296-299页

作者： Bai-Lin Wang, Hai-Ying Zhai, Bing-Yi Chen, Shu-Ping Zhai, Hai-Yan Yang, Xiao-Ping Chen, Wen-Tao Zhao and Lei Meng Guangzhou, China Third Department of Surgery, First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China Depart- ment of Surgery, First People’s Hospital, Jining 272100, China Department of Surgery, General Hospital of PLA, Beijing 100853, China and Hepatic Surgery Center, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Third Department of Surgery First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine Guangzhou 510405 China. wbl672000@***

BACKGROUND: The most common mechanisms of mul- tidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene ex- pression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDR1 mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 ca- ses of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDRlmRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin against Nevin , (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteris- tics , takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.

关键词： gallbladder neoplasms gene drug resistance, multiple