No abstract available.
DNA Topoisomerases* ; DNA*

Topoisomerases are nuclear enzymes that regulate the overwinding or underwinding of DNA helix during replication, transcription, recombination, repair, and chromatin remodeling. These enzymes perform topological transformations by providing a transient DNA break, through which the unique problems of DNA entanglement that occur owing to unwinding and rewinding of the DNA helix can be resolved. In mammals, topoisomerases are classified into two types, type I topoisomerase (Top1) and type II topoisomerase (Top2), depending on the number of strands cut in one round of action. Top1 induces single-strand breaks in DNA, and Top2 induces double-strand breaks. In cells from vertebrate species, there are two forms of Top2, designated alpha and beta. Top2α is involved in the cellular proliferation and pluripotency, while Top2β plays key roles in neurodevelopment. In this review, we cover recent advances in structural, mechanistic and functional insights into Top2.
Animals ; Cell Proliferation ; DNA Replication ; DNA Topoisomerases, Type II ; chemistry

BACKGROUND: Topoisomerase II (TOPO II) is an enzyme that separates intertwined chromosomes during DNA synthesis by transiently breaking and joining DNA strands. The level of TOP II is one of the determinants of cellular sensitivity to anti-tumor drugs in non-Hodgkin's lymphoma patients. The alpha form of TOPO II has been recently used as a marker of cellular proliferation. High levels of TOPO IIalpha are expressed in aggressive and proliferative tumors. METHODS: This study was designed to evaluate the relationship between TOPO IIalpha expression and clinicopathological parameters including age, gender, the serum LDH level, the serum beta2-microglobulin level and stage, or expressions, of Ki-67, p53 and p27, in non-Hodgkin's lymphoma. We analyzed forty-one biopsied tissue specimens from patients with non-Hodgkin's lymphoma. RESULTS: The expression of TOPO IIalpha increased with the clinical stage and it was correlated with Ki-67 and p53 expressions. However, TOPO IIalpha expression did not have any significant correlation with age, gender, the serum LDH level, the serum 2-microglobulin level and the p27 expression. CONCLUSIONS: TOPO IIalpha expression is a useful marker of cellular proliferation and it may serve as a prognostic factor of a tumor's progression and aggressiveness in non-Hodgkin's lymphomas.
Cell Proliferation ; DNA Topoisomerases, Type I* ; DNA Topoisomerases, Type II ; DNA* ; Humans ; Ki-67 Antigen ; Lymphoma, Non-Hodgkin*

PURPOSE: Various prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of c-erb B2, Ki-67 and topoisomerase II alpha expression was investigated in relation to prognostic factors for carcinomas of the breast and to the tumor cell growth fraction. METHODS: One hundred eighteen cases of invasive mammary carcinoma were investigated by immunohistochemical staining for c-erb B2, topoisomerase II alpha, and Ki-67. Clinicopathologic parameters were compared with the expression pattern and incidence of c-erb B2, topoisomerase II alpha and Ki- 67 in invasive mammary carcinoma. RESULTS: C-erb B2 showed significant correlation with topoisomerase II alpha (P<0.05), but others were not significant. Topoisomerase II alpha and Ki-67 index closely paralleled each other, indicating that both reflect the proliferate activity of tumor cells and were associated with high nuclear and histological grade, ER and PR expression (P<0.05). CONCLUSION: These results indicate that ki-67 and topoisomerase II alpha proteins might play a role in tumor progression of breast carcinoma. The Ki-67 and topoisomerase II alpha index may be proliferate factors of breast cancer. In addition, the increase expression of Ki-67 and topoisomerase II alpha and hormone receptor were closely correlated each other, and could be used as factors suggesting poor prognosis in breast carcinoma.
Breast ; Breast Neoplasms ; DNA Topoisomerases, Type II* ; Incidence ; Prognosis

PURPOSE: To determine whether the expression of DNA topoisomerase II and P-glycoprotein are of prognostic value. MATERIALS AND METHODS: We evaluated the expression of DNA topoisomerase II and P-glycoprotein immunohistochemically in a retrospective study of samples from 44 patients with breast cancer. Thirty two among 44 patients (72.7%) received chemotherapeutic treatments (CMF or FAC protocol) and/or tamoxifen postoperatively. RESULTS: P-glycoprotein was detected in the 27 samples of 44 patients (61.3%). The expression of P-glycoprotein was increased in the patients older than 50 years, with distant metastases, and with death on follow-up. DNA topoisomerase II was detected in the 34 samples of 44 patients (77.2%). The expression of topoisomerase II was increased in the patients younger than 50 years, with recurrent tumor, with distant metastases, and with death on follow-up. The expression of P-glycoprotein and topoisomerase II was not correlated with other clinico-pathological factors including the size of primary tumor, involvement of lymph node, histologic grade, and clinical stage. The correlation between expression of P-glycoprotein and topoisomerase II was not significant. CONCLUSION: The immunohistochemical evaluation of P-glycoprotein and topoisomerase II before treatment in breast cancer has little clinical prognostic value.
Breast Neoplasms* ; Breast* ; DNA Topoisomerases, Type I* ; DNA Topoisomerases, Type II* ; DNA* ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; P-Glycoprotein* ; Retrospective Studies ; Tamoxifen

PURPOSE: E2F-1 is a transcriptor that converts G1 to S in the cell cycle, and Topoisomerase II-alpha is a key enzyme in the metabolism of DNA, and an indicator of cell replication. The purpose of this study was to evaluate the clinical validity of E2F-1 and Topoisomerase II-alpha as prognostic factors in colorectal cancer. METHODS: The expressions of E2F-1 and Topoisomerase II-alpha were studied immunohistochemically using tumor specimen sections fixed with formalin and paraffin-embedded for 84 cases of colorectal cancer. The correlation between E2F-1 and Topoisomerase II-alpha expressions, and their relationship with the clinicopathological factors, such as tumor differentiation, tumor invasion, lymph node metastasis and tumor stage were investigated. RESULTS: Of the 84 specimens, 43 (51.2%) were immunohistochemically negative for E2F-1, and 41 (48.8%) were positive. The expression of E2F-1 correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The expression of Topoisomerase II-alpha also correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The E2F-1 and Topoisomerase II-alpha expressions indices were significantly correlated. CONCLUSION: These results suggest that the expressions of E2F-1 and DNA Topoisomerase II-alpha may play a role as a prognostic factor for colorectal cancer, but further studies will be required for its comfirmation.
Cell Cycle ; Colorectal Neoplasms* ; DNA ; DNA Topoisomerases, Type I* ; Formaldehyde ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis

OBJECTIVE: The relationship was studied between expression of c-erbB-2 oncoprotein and topoisomerase II-alpha as proliferating marker in precancerous lesions and invasive squamous carcinomas of the uterine cervix. METHODS: Total 81 formalin-fixed, paraffin-embedded sections of low-grade intrasquamous lesion (22 cases), high-grade intraepithelial lesions (42 cases) and invasive squamous cell carcinomas (17 cases) in the uterine cervix were stained by immunohistochemistry for expression of the c-erbB-2 oncoprotein and topoisomerase II-alpha. RESULTS: The expression of c-erbB-2 oncoprotein and staining index (mean+/-S.D) of topoisomerase II-alpha were statistically significant between precancerous lesions and invasive carcinoma. The expression of c-erbB-2 oncoprotein has correlation with staining index (mean+/-S.D) of topoisomerase II-alpha. CONCLUSION: There results suggest that the expression of c-erbB-2 protein has relationship with progression of squamous lesions and topoisomerase II-alpha is an useful proliferating marker in the uterine cervix. And, the expression of c-erbB-2 protein has correlation with expression of topoisomerase II-alpha.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; DNA Topoisomerases, Type I* ; DNA* ; Female ; Immunohistochemistry ; Receptor, erbB-2

The development of drug resistance is a major obstacle in effective cancer chemotherapy. Multidrug resistance(MDR) is a widely studied phenomenon of interest to both clinicians and research workers because many different cancer chemotherapeutic agents are involved and the genetic basis of MDR is understood to a large extent. Several studies show that the P-glycoprotein (P-gp), multidrug resistance-associated protein(MRP), glutathione-s-transferase-pi(GST-pi), and DNA topoisomerase II(topo II) have a complex role for the malignant phenotypes and MDR. Clearly, there is a need to investigate links between the diverse characteristics of tumors and the emergence of drug resistance. We have therefore used reverse transcription-polymerase chain reaction(RT-PCR) assay to analyze expressions of MDR-related genes including the mdr1, MRP, topo II and GST-t gene in normal testis and testis tumors. The results are as follows: 1. The expression levels of topo II and GST-n genes in testis tumors, especially in the nonseminomatous germ cell tumor(NSGCT), were significantly higher than in normal testis(p=0.015 and 0.025, respectively). 2. The MDR-related gene expressions in testis tumors did not appear to be correlated with stage(p>0.05 in each case) and chemotherapy status(p>0.05 in each case). 3. MRP expression levels in primary tumors were much higher than in metastatic tumors. 4. In NSGCT, the coexpressions of the topo II and GST-r or MRP genes were significantly correlated but, seminoma showed no correlation between MDR-related genes in the same sample. Although the mechanism of these connection are not known, the results suggest that these expression patterns and higher GST-rexpression in NSGCF compared to seminoma confer diverse characteristics including difference in the presentation of tumor markers and the responsiveness to chemotherapy on NSGCF and seminoma.
DNA Topoisomerases, Type I ; DNA Topoisomerases, Type II ; Drug Resistance ; Drug Therapy ; Gene Expression* ; Germ Cells* ; Neoplasms, Germ Cell and Embryonal* ; P-Glycoprotein ; Phenotype ; Seminoma ; Testis* ; Biomarkers, Tumor

It is deirable to identify the tumoric factors anticipating the therapeutic failure in breast cancer patients received postoperative adjuvant chemotherapy. So, we studued the tumoric topoisomerase II alpha enzyme, c-erbB-2 oncoprotein, and Pgp expression in breast cancer tissues to identify the roles of these factors as the predictors of chemotherapeutic result. The results were as follows. 1) There wee no significant differences in the average value of topoisomerase II alpha enzyme, c-erb B-2 oncoportein overexpression, and Pgp expression according to stages. 2) CAF chemotherapy was suggested to be more effective than CMF chemotherapy in more advance stages. 3) There was a possible suggestion that the breast cancer with high topoisomerase II alpha enzyme activity might indicate the failure with CMF chemotherapy. 4) C-erbB-2 oncoportein overexperession suggested the possibility of therapeutic failure with CMF chemotherapy and the selection of CAF chemotherapy might improve the survival of advanced breast cancer patients with c-erbB-2 overexpression. In conclusion, it was suggested that c-erb-2 oncopotein overexpression and high topoisomerase II alpha activity might have a meaningful role in the selection of proper chemotherapeutic regimen in setting of adjuvant chemotherapy and predict the therapeutic failure of some chemotherapeutic agents for breast cancer. An expanded study for these factors is required to reveal the clinical significance in chemotherapy for breast cancer patients.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; DNA Topoisomerases, Type II* ; Drug Therapy* ; Humans ; P-Glycoprotein*

Irinotecan (CPT-11) is a chemotherapeutic agent that inhibits topoisomerase I and has shown efficacy against advanced colorectal cancer. Diarrhea is the most common toxicity that has been reported to be as high as 87% in patients treated with irinotecan. However, the serious complications including acute hemorrhagic colitis, intestinal ulceration, and intestinal perforation may be uncommon events with irinotecan therapy. We report the first Korean case of acute hemorrhagic colitis induced by irinotecan administration in the patient with advanced colon cancer.
Colitis* ; Colonic Neoplasms ; Colorectal Neoplasms ; Diarrhea ; DNA Topoisomerases, Type I ; Humans ; Intestinal Perforation ; Ulcer