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

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

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: 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

BACKGROUND: Polymerase chain reacation (PCR)-based methods have been described for rapid detection and identification of Candida spp. Multiplex PCR assay was developed using internal transcribed spacers and topoisomerase II gene for the accurate identification of Candida species. METHODS: We designed Dual Specificity Oligo (DSO) primers for multiplex PCR. Multiplex PCR was followed by agarose gel electrophoresis to test 8 type strains (C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, C. krusei, C. guilliermondii, C. lusitaniae, C. dubliniensis) and 96 clinical isolates (C. albicans 51 isolates, C. parapsilosis 10 isolates, C. glabrata 10 isolates, C. tropicalis 9 isolates, C. krusei 6 isolates, C. guilliermondii 5 isolates, C. lusitaniae 5 isolates) of Candida spp. RESULTS: With multiplex PCR using DSO primers, the eight Candida type strains each could be easily differentiated and all 96 clinical isolates were identified as the same species as were identified by the conventional method. CONCLUSION: Multiplex PCR followed by electrophoresis can be useful for the simple and rapid identification of Candida species in routine laboratories.
Candida* ; DNA Topoisomerases, Type II ; Electrophoresis ; Electrophoresis, Agar Gel ; Multiplex Polymerase Chain Reaction* ; Sensitivity and Specificity

PURPOSE: The mitotic index (MI) and Ki-67 labeling index have been used as cell proliferative markers in the various tumors. Topoisomerase II alpha (Topo II alpha) is also expressed in proliferating cells. The aim of this study was to evaluate the correlations between the MI, Ki-67, and Topo II alpha expression as proliferative markers of breast cancer. METHODS: The cell proliferative activity of 181 breast cancers was measured using MI, Ki-67 labeling index and Topo II alpha expression. The correlation between the measured markers was also analyzed. RESULTS: The MI, Ki-67, and Topo II alpha were significantly correlated with each other(p < 0.000). The MI and Ki-67 labeling index were associated with high histological grade, and absence of hormone receptor (p < 0.000). Topo II alpha expression was correlated with high histological grade (p < 0.000), absence of hormone receptor and HER-2/neu overexpression (p < 0.043). The MI, Ki-67, and Topo II alpha were not associated with any other clinical variables, such as age, tumor size, and lymph node status. CONCLUSION: The three proliferative indices were significantly associated with aggressive features of breast cancer, and significantly correlated with each other.
Breast Neoplasms* ; Breast* ; DNA Topoisomerases, Type II ; Lymph Nodes ; Mitotic Index

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*

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

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.
Adenosine Triphosphatases* ; Adenosine Triphosphate ; Binding Sites ; Cell Proliferation ; DNA Topoisomerases, Type II* ; Heat-Shock Proteins* ; Histidine ; Hot Temperature* ; Humans ; Phosphotransferases

BACKGROUND AND OBJECTIVES: Cholesteatoma is a destructive lesion of the middle ear or mastoid process. The development of human cholesteatoma is due to the altered control of cellular proliferation in part, which tilts the balance toward the aggressive, invasive growth of squamous epithelium within the middle ear. Many efforts were performed to prove overproliferative characteristics of cholesteatoma using various proliferation markers. Nonetheless, trigger site of overproliferation within the overgrowing epithelium of cholesteatoma is still ill defined. MATERIALS AND METHODS: In this study, we used the monoclonal antibody Ki-67 and Topoisomerase II, a marker of active proliferation, on frozen sections obtained from 12 cholesteatoma samples and observed expression of these markers in three different regions, from normal meatal skin, transitional zone and cholesteatoma sac. RESULTS: The results were interpreted on the basis of nuclear staining and percentage of positively stained cells (labeling index). We found that labeling indices of cholesteatoma and transitional zone were significantly increased compared with that of normal meatal skin. CONCLUSION: This result suggested that initiating of overproliliferation of cholesteatoma epithelium started from the transitional zone.
Cell Proliferation ; Cholesteatoma ; Cholesteatoma, Middle Ear* ; DNA Topoisomerases, Type II ; Ear, Middle* ; Epithelium ; Frozen Sections ; Humans* ; Mastoid ; Skin