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

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

Among 155 clinical respiratory isolates of Haemophilus influenzae in Korea, 6 (3.9%) isolates had reduced levofloxacin susceptibility (MICs > or = 0.5 microg/mL). These six isolates had no significant quinolone resistance-determining region (QRDR) mutations in gyrA, gyrB, parC, or parE. This phenomenon suggests that neither evolution nor spread of any significant QRDRs mutations in clinical isolates occurred in Korea. Therefore, continued surveillance is necessary to observe the evolution of antibiotic-resistance and take measures to avoid the spread of drug-resistant clones.
Anti-Bacterial Agents/*pharmacology ; DNA Gyrase/*genetics ; DNA Topoisomerases, Type II/*genetics ; Haemophilus influenzae/*drug effects/pathogenicity ; Korea ; Microbial Sensitivity Tests ; Mutation ; Ofloxacin/*pharmacology

Among 155 clinical respiratory isolates of Haemophilus influenzae in Korea, 6 (3.9%) isolates had reduced levofloxacin susceptibility (MICs > or = 0.5 microg/mL). These six isolates had no significant quinolone resistance-determining region (QRDR) mutations in gyrA, gyrB, parC, or parE. This phenomenon suggests that neither evolution nor spread of any significant QRDRs mutations in clinical isolates occurred in Korea. Therefore, continued surveillance is necessary to observe the evolution of antibiotic-resistance and take measures to avoid the spread of drug-resistant clones.
Anti-Bacterial Agents/*pharmacology ; DNA Gyrase/*genetics ; DNA Topoisomerases, Type II/*genetics ; Haemophilus influenzae/*drug effects/pathogenicity ; Korea ; Microbial Sensitivity Tests ; Mutation ; Ofloxacin/*pharmacology

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

Synergistic antitumor effects of HB (berberine alpha-hydroxy-beta-decanoylethyl sulfonate, houttuyn berberine) with HCPT (hydroxycamptothecine), and its correlative mechanism were studied in vitro. MTT assay was employed to determine the cytotoxicity of HB combined with HCPT in tumor cells culture in vitro, IC50 and combination index (CI value) were used to evaluate the synergistic effects. The supercoiled DNA relaxation mediated by topoisomerase I & II was measured by agarose gel electrophoresis assay, and influence of HB was detected. The results showed that HB could inhibit the proliferation of tumor cells (SGC-7901, SW1116 and SW480) in vitro, and the inhibition ratio was increased, IC50 was reduced when combining with HCPT. CI value of the two drugs was less than 1 in HepG2, SW480, SGC-7901 and SW1116 cells. The lowest value was 0.447, 0.626, 0.161 and 0.178 in these tumor cells, respectively, further indicating HB has synergistic action with HCPT on suppressing tumor proliferation. The agarose gel electrophoresis assay showed HB can inhibit topoisomerase I & II activity of SW480 cells at the concentration of 2.0-8.0 mg x L(-1). HCPT is a typical inhibitor of topoisomerase I , the synergistic action between HCPT and HB on suppressing tumor proliferation is perhaps related to the congenerous inhibition of topoisomerase.
Antineoplastic Agents, Phytogenic ; pharmacology ; Berberine ; analogs & derivatives ; pharmacology ; Camptothecin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; DNA Topoisomerases, Type II ; metabolism ; Drug Synergism ; Humans ; Topoisomerase I Inhibitors ; pharmacology

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

No abstract available.
DNA Topoisomerases* ; DNA*

PURPOSE: To gain insight on transcriptional repression of Topo II a in HL-60 cells arrested to G2/M and M phase, the levels of Topo IIa mRNA and the binding activity of ATF have been investigated with Northern blot hybridization and DNA mobility shift assay, respectively. MATERIALS AND METHODS: HL-60 cells were grown in RPMI 1640 medium supplemented with 10% heat-mactivated fetal bovine serum and antibiotics in a humidified 5% CO2 at 37C degree. Total RNA was prepared by a modification of the method of Karlinsey et al. Northern blot hybridization was performed by the method of Virca et al. A Xho I-Mlu I fragment of phTOP2 was used as probe for Northern blot analysis of Topo II a mRNA. DNA mobility shift assay was performed by the method of Lim et al. End labeled DNA oligomer (upper strand, 5-TCTCCGCTATGACGCCGAGTGGTG-3) for ATF binding activity was mixed with nuclear extracts in a 20 pl reaction volume containing 60 mM KC1, 12 mM HEPES, pH 7.9, 5 mM MgCl2, 0.2 mM EDTA, 0.2 mM DTT, 12% glycerol, and 2 ug of poly [dI-dC]. RESULTS: HL-60 cells were arrested at G2/M phase and M phase after taxol or nocodazole treatment. The levels of Topo II a mRNA were reduced at 24 hours after exposure with nocodazole or taxol but the unknotting activities were not changed. DNA mobility shift assay using oligonucleotide containing the ATF binding site showed that ATF binding activity was reduced after pretreatment of nododazole or taxol. CONCLUSIONS: These results suggest that the reduction of ATF binding activity may be important to transcriptional repression of Topo II a gene by nocodazole and taxol in HL- 60 cells.
Anti-Bacterial Agents ; Binding Sites ; Blotting, Northern ; Cell Division* ; DNA Topoisomerases, Type I* ; DNA Topoisomerases, Type II* ; DNA* ; Edetic Acid ; Electrophoretic Mobility Shift Assay ; Genes, vif ; Glycerol ; HEPES ; HL-60 Cells ; Humans ; Hydrogen-Ion Concentration ; Magnesium Chloride ; Nocodazole ; Paclitaxel ; Repression, Psychology ; RNA ; RNA, Messenger