Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis / 中国医学科学杂志(英文版)

Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

Expression of SIRT1 protein in gastric cancer and its relationship with P-gp and Top-Ⅱ alpha / 中国现代普通外科进展

Objective:Explore the expression of SIRT1 protein in gastric cancer tissues and cells.Analyze the correlation of SIRT1 protein expression and multidrug resistance protein P-gp and Top-Ⅱ alpha.Methods:Immunohistochemical to detect SIRT1,P-gp and Top-Ⅱ alpha protein in 15 cases of gastric cancer tissue and 15 cases of normal gastric mucosa tissues.Western blot test the expression of SIRT1 protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45,MKN28,HGC27,AGS and MGC803.Western blot test the expression of SIRT1,P-gp and Top-Ⅱ alpha protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45.After siRNA-SIRT1/liposome transfection gastric cancer cells SGC7901,western blot test the changes of expression of SIRT1,P-gp and Top-Ⅱ alpha protein and MTT test the changes of SGC7901 cells proliferation in vitro and the sensitivity of chemotherapy drugs 5-Fu.Results:In 15 cases of gastric cancer tissue have the positive expression of 15 cases of SIRT1 protein,13 cases of P-gp protein and 3 cases of Top-Ⅱ alpha protein.In 15 cases of normal gastric mucosa tissues have the positive expression of 6 cases of SIRT1 protein,5 cases of P-gp protein and 0 cases of Top-Ⅱ alpha protein.The relative quantity of SIRT1 protein expression average were 0.385,0.827,0.009,0.232,0.275,0.159,0.275 in GES-1,SGC7901,MKN45,MKN28,HGC27,AGS and MGC803,respectively.The relative quantity of P-gp protein expression average were 0.339,0.526,1.03 in GES 1,SGC7901 and MKN45 and Top-Ⅱ alpha protein were 0.093,0.889,and 0.158,respectively,siRNA-SIRT1 transfected SGC7901 for 8 hours and after 72 hours to test the relative quantity of SIRT1 protein expression average were 0.965,0.937,0.958,0.567,0.253,0.083 in control,BC-V,negative,siRNA-1,2,3 SIRT1,P-gp were 1.893,1.905,1.932,0.465,0.006,0.465 and Top-Ⅱ alpha were 0.09,0.07,0.073,0.085,0.168,0.085.MTT results showed that after SIRT1 protein expression was inhibited the SGC7901 proliferation has no obvious change in vitro and cell sensitivity to the chemotherapy drugs 5-Fu was increased significantly.Conclusion:SIRT1 expression in gastric cancer tissues and the expression of SIRT1 in gastric cancer tissue and cell carcinoma factors role,SIRT1 protein overexpression can promote P-gp protein expression lower Top-Ⅱ alpha protein expression in gastric cancer cells to chemotherapy of multiple drug resistance increase.

Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomeraseⅠ and topoisomeraseⅡ / 中国药理学与毒理学杂志

OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms. METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexinⅤ-FITC/PI staining, and comet assay. Effects of lapachol on topoisomerase I (TOP I) and topoi?somerase Ⅱ (TOP Ⅱ) activities were detected by TOP Ⅰ and TOP Ⅱ mediated supercoiled pBR322 DNA relaxation assays and molecular docking. TOPⅠ and TOPⅡ expression levels in C6 cells were also determined. RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats (P<0.05). It was showed that lapachol could inhibit proliferation, induce apoptosis and DNA damage of C6 cells in dose dependent manners. Lapachol could inhibit the activities of both TOPⅠ and Ⅱ. Lapachol-TOPⅠ showed relatively stronger interaction than that of lapachol-TOPⅡ in molecular docking study. Also, lapachol could inhibit TOPⅡ expression levels, but not TOPⅠ expression levels. CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro, which might be related with inhibiting TOPⅠ and TOPⅡ activities, as well as TOPⅡ expression.

Expression of excision repair cross-complementing 1, topoisomeraseⅡ, ribonucleotide reductase M1,β3-tubulin and thymidylate synthase in lung cancer / 肿瘤研究与临床

Objective To analyze the expression characteristics of excision repair cross-complementing 1 (ERCC1), topoisomeraseⅡ (TOPOⅡ), ribonucleotide reductase M1 (RRM1), β3-tubulin and thymidylate synthase (TS) in lung cancer and their associations with the pathological types. Methods The immunohistochemical EnVision method was used to determine the expression of ERCC1, TOPOⅡ, RRM1,β3-tubulin and TS in 548 patients who were diagnosed as lung cancer from January 2011 to December 2014. Variance analysis was performed to analyze their expression characteristics among different pathological types and correlation. Results The expression positive rates of ERCC1, TOPOⅡ, RRM1, β3-tubulin and TS were 61.86 % (339/548), 91.06 % (499/548), 62.59 % (343/548), 73.18 % (401/548) and 70.44 % (386/548), respectively. The expression of ERCC1 was weak positive mostly (P<0.05), meanwhile the expression of TOPOⅡ was medium-strong positive mostly (P<0.05). In ERCC1 group, the positive rate of squamous cell carcinoma was higher than that of adenocarcinoma [57.39 % (167/291) vs. 42.61 % (124/291), P=0.000]. In weak positive of TOPOⅡ group, the proportion of adenocarcinoma was higher than that of squamous cell carcinoma [23.58 % (100/137) vs. 8.73 % (37/137), P=0.000]. In medium-strong positive of TOPOⅡ group, the proportion of squamous cell carcinoma was higher than that of adenocarcinoma [47.41 % (201/287/) vs. 20.28%(86/287), P=0.000]. The expressions of ERCC1, TOPOⅡ, RRM1,β3-tubulin and TS were irrelevant (r=0.4, P=0.397). Conclusions The expressions of ERCC1 and TOPOⅡ are higher in squamous cell carcinoma than those in adenocarcinoma. The expression of ERCC1 is weak positive mostly, meanwhile the expression of TOPOⅡis medium-strong positive mostly. There is no correlation between them.

Ki-67 and DNA topoisomerase Ⅱ a predict survival in patients with primary hepatocellular carcinoma after liver transplantation / 中华肝胆外科杂志

Objective To investigate whether Ki-67 and DNA topoisomerase Ⅱ α (Topo Ⅱ α) are effective prognostic markers in patients with primary hepatocellular carcinoma (HCC) after liver transplantation.Methods This retrospective cohort study included 105 patients with HCC who underwent liver transplantation in a single center from 2001 to 2012.The demographic features,clinicopathological data,expressions of Topo I c and Ki-67 as detected by immunohistochemistry.The long-term survival and the potential prognostic factors,together with standard histologic parameters,were analyzed by univariate and multivariate analyses.Results A positive correlation was found between Topo II α and Ki-67 levels in HCC (r ＝ 0.469,P ＜ 0.01).Multivariate analyses showed that Ki-67 was an independent prognostic risk factor of recurrencefree survival (HR ＝ 2.296,P ＜ 0.05).The 5-year overall survival rate was related to tumor size (HR ＝ 1.743,P ＜ 0.05),AFP (HR ＝ 2.291,P ＜ 0.05),histological grade (HR ＝ 0.283,P ＜ 0.01),and high expressions of Ki-67 (HR ＝ 1.977,P ＜ 0.05) and Topo Ⅱ α levels (HR ＝ 1.883,P ＜ 0.05).The KaplanMeier analysis showed that there was a significant difference in the 5-year recurrence-free survival rate (40.4％ vs.57.6％) between patients with high and low expressions of Ki-67,which were significantly lower in the high Topo Ⅱ α expression patients (13.5％ vs.63.8％) (P ＜0.01).The 5-year overall survival rates were significantly lower in the high Ki-67 expression patients (12.7％ vs.61.1％,P ＜0.01) when compared with the low Ki-67 expression patients,which were significantly lower in the high Topo Ⅱ α-and Ki-67 expression patients (10.7％ vs.54.5％,P ＜0.01) than the low Topo Ⅱ α-or Ki-67 patients.Conclusions Ki-67 was associated with recurrence and metastasis in patients with primary hepatic carcinoma after liver transplantation.High expression of both Ki-67 and Topo Ⅱ α were associated with poor prognosis in these patients.

Expressions of P53,topoisomerase Ⅱ and multi-drug resistance associated protein in tissues of colorectal cancer of patients combined with chronic schistosomiasis / 中华消化外科杂志

Objective To investigate the expressions of P53,topoisomeraseⅡ(TopoⅡ)and multidrug resistance associated protein(MRP)in tissues of colorectal cancer of patients combined with chronic schistosomiasis.Method The retrospective case-control study was adopted.The clinicopathological data of 338 colorectal cancer patients who were admitted to the Zhejiang Cancer Hospital between January 2008 and December 2010 were collected.Cancer tissue specimens from surgical resection were collected.Among 338 patients,80 were combined with chronic schistosomiasis and 258 were combined with non-chronic schistosomiasis.The expressions of P53,TopoⅡand MRP were dectected using immunohistochemistry(IHC).Ranked data were presented as percentage and analyzed using the non-parametric test.Results The negative,weak positive,positive and strong positive expressions of P53 were respectively 5.00％(4/80),87.50％(70/80),3.75％(3/80),3.75％(3/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 28.68％(74/258),19.38％(50/258),16.67％(43/258),35.27％(91/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-2.962,P＜0.05).The negative,weak positive,positive and strong positive expressions of TopoⅡwere respectively 8.75％(7/80),51.25％(41/80),22.50％(18/80),17.50％(14/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 12.01％(31/258),55.43％(143/258),22.48％(58/258),10.08％(26/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with no statistically significant difference(Z=-1.551,P＞0.05).The negative,weak positive,positive and strong positive expressions of MRP were respectively 7.50％(6/80),40.00％(32/80),28.75％(23/80),23.75％(19/80)in issues of colorectal cancer of patients combined with chronic schistosomiasis and 24.42％(63/258),38.37％(99/258),24.03％(62/258),13.18％(34/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-3.408,P＜0.05).Conclusion There are abnormal expressions of P53 and MRP in tissues of colorectal cancer of patients combined with chronic schistosomiasis,which may be involved in the hypothetical mechanism of chronic schistosomiasis inducing carcinogenesis of colorectal cancer.

Research progress of dual topoisomerase Ⅰ and Ⅱ inhibitors / 药学实践杂志

DNA topoisomerases (Tops) are essential enzymes that regulate the cellular processes such as replication , transcription ,recombination and repair .DNA Tops can be classified into two types ,topoisomerase Ⅰ (TopⅠ ) and topoi-somerase Ⅱ (TopⅡ) .They catalyze the breakage and religation of DNA ,maintaining the topological changes of DNA and va-rious DNA metabolic processes .Due to their important role in DNA metabolism ,the ability to interfere with the functions of Tops or generating Top-mediated DNA damage is an effective strategy for cancer chemotherapy .Tops have been considered as the most important targets for tumor chemotherapy .In this review ,we used examples to describe the development of dual to-poisomerase Ⅰ and Ⅱ inhibitors .

Correlation between expression of TOP2A and HER2 signaling pathway in breast cancer / 西安交通大学学报(医学版)

Objective To study the correlation of expression of DNA topoisomerase Ⅱ alpha (TOP2A)with expressions of human epidermal growth factor receptor 2 (HER2)and phosphatase and tensin homolog (PTEN)and gene mutation of phosphatidylinositol 3-kinase (PI3K)in breast cancer so as to provide reference for prognosis of the cancer and evaluation of drug efficiency.Methods This study enrolled totally 96 breast cancer patients. Tumor specimens were resected.The gene expressions of TOP2A,HER2 and PTEN were analyzed using branched DNA-liquid-chip,and PI3K gene mutation was detected by xTAG-liquid-chip.Correlations between gene expressions and gene mutation were further explored by Spearman correlation analysis so as to clarify the relationship between TOP2A and HER2 signaling pathway gene.Results Co-expression of TOP2A and HER2 was strong,and TOP2A tended to be highly expressed in the presence of high expression of HER2 (P =0.01).The expression of PTEN was not significantly correlated with the expression of TOP2A,whereas the mutation of PI3K had a positive association with the high expression of TOP2A (P =0.004).Conclusion Anthracycline drug resistance factor TOP2A may be related to the critical factors of HER2 signaling pathway,suggesting that HER2 expression and PI3K mutation may be key factors in regulation of TOP2A expression,which would provide important evidence for chemotherapeutic resistance.

Expression of glutathione-S-transferase-π, P-glycoprotein, topoisomerase Ⅱ and thymidylate synthase in gastric adenocarcinoma tissues and their clinical significances / 肿瘤研究与临床

Objective To explore the expression of glutathione-S-transferase-π(GST-π),P-glycoprotein (P-gp),topoisomerase Ⅱ (Topo Ⅱ) and thymidylate synthase (TS) in gastric adenocarcinoma tissues and the clinical significance.Methods Envision method of immunohistochemistry was used to detect the expression of GST-π,P-gp,Topo Ⅱ and TS in sample of 64 gastric adenocarcinoma tissues and 12 normal gastric mucosas,and their corresponding clinical data were comprehensive analyzed.Results The expression positive rates of GST-π,P-gp,Topo Ⅱand TS were respectively 76.6 ％(49/64),64.1％ (41/64),84.4 ％ (50/64) and 53.1％ (34/64),that were all higher than in gastric mucosa [8.3 ％ (1/12),8.3 ％(1/12),16.7 ％ (2/12),0],the differences were statistically significant respectively (P ＜ 0.01).Their positive expression rates were closely relevant to the degree of differentiation (P ＜ 0.05),but not to the patients' gender,age,tumour size,clinical staging,invasive depth and lymph node metastasis (P ＞ 0.05).The expressions of GST-π,P-gp and TS in high and middle differentiation adenocarcinoma were high.er than in low differentiation,but the expression of Topo Ⅱ in high and middle differentiation adenocarcinoma was lower than in low differentiation (P ＜ 0.05).Conclusion GST-π,P-gp,Topo Ⅱ and TS are over-expressed in gastric adenocarcinoma,which is related to the multidrug resistance of gastric adenocarcinoma.The joint detection of the expression of GST-π,P-gp,Topo Ⅱ and TS in gastric adenocarcinoma can be looked as an important symbol for guiding its chemotherapy drug and prognosis.

Expression and significance of EGFR, Her-2 and TOPO Ⅱ in esophageal canceration course / 肿瘤研究与临床

Objective To investigate the expression of EGFR, Her-2 and TOPO Ⅱ in esophageal canceration course, analyze the correlation between the expression and clinical pathological parameters and the correlation of the three genes. Methods EGFR, Her-2 and TOPO Ⅱ were detected by Tissue microarray technology and Envision immunohistochemistry method in 107 cases of esophageal carcinoma, including normal esophageal epithelium, esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma. Results The positive expression rates of EGFR and TOPO Ⅱ display an improving trend from normal esophageal epithelium, intraepithelial neoplasia to carcinoma (P =0.031) in the above four groups. The positive expression rates of EGFR were 8.41 %, 7.94 %, 27.27 %, 50.47 %, and TOPO Ⅱ were 3.74 %, 4.76 %, 20.45 %, 43.93 %. Furthermore, the expression showed gradually incresing with histological grades advance (P =0.009). There was no correlation between EGFR or TOPO Ⅱ and gender, age, lymph node or distant metastasis (P >0.05). There was a positive correlation between EGFR and TOPO Ⅱ (r 1=0.410, P 0.05), no correlation was obtained between Her-2 and gender, age, the depth of invasion or lymph node metastasis (P >0.05), no relationship between Her-2 and EGFR or TOPO Ⅱ either. Conclusion EGFR and TOPO Ⅱ are closely related to the occurrence and development of esophageal squamous cell carcinoma, their expressions all make a qualitative change in the esophageal high-grade intraepithelial neoplasia. The role of Her-2 in the development of esophageal squamous cell carcinoma is still not definite in Shanxi province.

Expression and clinical significance of Topo Ⅱα , COX-2 in breast cancer tissues / 肿瘤研究与临床

Objective To explore the expression of Topo Ⅱα and COX-2 in breast cancer tissues and investigate their correlations to clinicopathologic feature of breast cancer. MethodsThe expression of Topo Ⅱα and COX-2 in 50 specimens of breast cancer and their normal tissues were detected by immunohistochemistry. Their correlation to clinicopathologic features of breast cancer were analyzed.ResultsThe positive rates of Topo Ⅱα were 64 % (32/50) and 22 % (11/50) and COX-2 were 68 % (34/50) , 14 %(7/50) in breast cancer and normal tissue (P＜0.05). The expression of Topo Ⅱα was correlated to degree of differentiation (P ＜0.05), not correlated to patient age, tumor size, clinical stage and lymph node metastasis(P ＞0.05). The expression of COX-2 was correlated to tumor size, degree of differentiation, clinical stage and lymph node metastasis (P ＜0.05), not correlated to patient age (P ＞0.05). Conclusion Topo Ⅱα and COX-2 expression can be used as an indicator for predicting the differentiation, infiltration and metastasis characteristics of breast cancer.

Study on the efficacy of neoadjuvant chemotherapy with TTC and FTC regimens for the treatment of breast cancer / 肿瘤研究与临床

Objective To investigate the efficacy of TTC and FTC regimens as neoadjuvant chemotherapy in breast cancer. Methods Collecting clinical data of 325 patients received neoadjuvant chemotherapy with TIC and FTC regimens from June 2004 to April 2008, among them 138 patients received neoadjuvant chemotherapy with TTC regimen in one group, and 187 patients received neoadjuvant chemotherapy with CTF regimen in the other group. The expression of Topo Ⅱ a in specimen of 325 patients before neoadjuvant chemotherapy were detected by immunohistochemical method. Results Among the 325 cases of neoadjuvant chemotherapy, the overall response rate (RR) was 87.7 % in TIC arm and 67.4 % in FTC arm (P=0.000), but in the group of Topo Ⅱ a(+) Her-2(-), the overall response rate (RR) was 87.8 % in TTC arm and 79.4 % in FTC arm (P=0.266), and in the groups of Topo Ⅱ a(-), there was statistical significance; the pathologic complete response rate (pCR) was 13.7 % in TIC ann and 11.2 % in CTF ann (P=0.491). Conclusion TIC regimen is superior to FTC regimen in the response rate of neoadjuvant chemotherapy, but patients with negative expression of Topo Ⅱ a may get more benefits from 9eoadjuvant taxane and anthracycline chemotherapy.

Correlation of Expressions of P170,TOPⅡ and Proliferation in Gliomas / 中国康复理论与实践

@#Objective To investigate the correlation of the expressions of P170,topoisomerase Ⅱ(TOPⅡ)and the proliferation in gliomas.Methods Ki-67 was used as the marker of the proliferation in gliomas.The expressions of P170,TOPⅡ and Ki-67 were tested by S-P immunohistochemical technique using monoclonal antibody to their protein in 54 cases of low-grade gliomas(WHO Ⅰ～Ⅱ grade)and 54 cases of high-grade gliomas(WHO Ⅲ～Ⅳ grade),analysis of the clinical and follow-up were performed.Results The expressions of P170,TOPⅡ and Ki-67 had significant differences between low-grade and high-grade gliomas(P<0.01).Correlation analysis showed that the expression of P170 was negatively related with Ki-67(r=-0.276,P=0.019);the expression of TOPⅡ was positively related with Ki-67(r= 0.637,P<0.001);there was no correlation between the expressions of P170 and TOPⅡ.Conclusion The expressions of P170 and TOPⅡ are associated with the malignant prognosis in gliomas.

Enhancement of cisplatin on cytocidal effect of tineposide against small cell lung cancer cell line / 基础医学与临床

Objective To investigate the mechanism of cisplatin enhanceing the effect of tineposide killing small cell lung cancer cell line by combination of the two drug.Methods The microculture tetrazolium(MTT) assay was used to determine the inhibition rates of CDDP combined with VM-26.Acridine orange/ethidium bromide(AO/EB) fluorescent staining was used to show the cell vitality rates,DNA disruption ladder were applied to reveal cell apoptosis.The mRNA and protein level of topoisomerase Ⅱ(Topo Ⅱ) and transcript factor SP1 were measured by semi-quantitative RT-PCR and western blot.Results There is synergistic effect between the two drug.The cell vitality rates were decreased in combination group than that of CDDP or VM-26 used alone.the combination treatment group resulted in more serious DNA strand breakage.The expression of Topo Ⅱ?,? and SP1 mRNA and protein both increased in CDDP treatment group,while the Topo Ⅱ?,? expression decreased and(the SP1 expression) has no obviously change in VM-26 treatment group.In combination group,Topo Ⅱ? expressionwere decreased comparing with CDDP used alone,SP1 expression increased comparing with VM-26 used alone,but has no obviously change as comparing with CDDP used alone.Conclusion CDDP could enhance Topo Ⅱ expression through up-regulating SP1 expression,which offer more target for Topo Ⅱ inhibitor VM-26 to act on killing small cell lung cancer cell.

Expression of TopoⅡ gene in human bladder cancer multidrug-resistant cells / 中国癌症杂志

Purpose:To study the expression of TopoⅡ gene in multidrug resistant cells of human bladder cancer. Methods:The degree of drug resistance was detected by MTT method ;the expression of TopoⅡ gene in cell lines BIU 87/ADM and BIU 87 was detected with reverse transcriptase polymerase chain reaction. Results:The cell lines BIU 87/ADM were 56.4 times more resistant to ADM than the cell lines BIU 87;the expression of TopoⅡ gene was poorly positive in BIU 87/ADM but strongly positive in BIU 87 cells. Conclusions: The decreased expression of TopoⅡ gene in BIU 87/ADM cells might contribute to the development of multidrug resistance of human bladder cancer.

The expression of P-gp, GST-? and TopoⅡ in breast cancer and their clinical significance / 肿瘤研究与临床

Objective To investigate the expression and their clinical significance of P?- glycoprotein (P?- gp), glutathione?- S?- transferase?- ?(GST?- ?)and DNA topoisomerase Ⅱ(TopoⅡ)in breast cancer. Methods The expressions of P?- gp, GST?- ? and TopoⅡ were detected in 60 cases of untreated primary breast cancer by using immunohistochemical S?- P method. Results The positive expression rates of P?- gp, GST?- ? and TopoⅡ in breast cancer were 37.1 %, 66.7 % and 55.0 % respectively. The expression of P?- gp and TopoⅡ had positive correlation with degree of differentiation(P