PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Teniposide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1992

The effect of topoisomerase inhibitors on the expression of differentiation markers and cell cycle progression in human K-562 leukemia cells.

Treatment of human K-562-J leukemia cells for 1 h with the topoisomerase II-reactive drugs VP-16, VM-26, or mAMSA resulted in a dose-dependent inhibition of proliferation and in an increase in the percentage of cells staining positive for hemoglobin, a marker of erythroid differentiation. Staining for hemoglobin of up to about 60% of the cells was observed at 20 microM VP-16, 1 microM VM-26, and 8 microM mAMSA. Such treatment also caused a G2/M arrest in the cell cycle. Incubation of the cells with radiolabeled VP-16 indicated that the induced erythroid differentiation was not due to continuous cell exposure to a residual amount of the drug. VP-16-induced erythroid differentiation was also not affected by DNA, RNA, or protein synthesis inhibitors. Differentiation induction and the G2/M arrest evoked by VP-16, VM-26, and mAMSA were, however, reduced in the presence of novobiocin. Our results indicate that topo-reactive drugs that cause G2/M arrest in the K-562-J cell cycle can induce in these cells erythroid differentiation after a short and irreversible interaction with their target molecule(s).

Amsacrine↗
PubMed1986

Topoisomerase II cleavage in chromatin.

We have examined the effect of the anti-tumor drug VM-26 on purified Drosophila topoisomerase II, and used this drug to map (putative) topoisomerase II cleavage sites in chromatin. These studies indicate that VM-26 interferes with the strand breakage-rejoining catalytic cycle. VM-26 appears to stabilize the topoisomerase-II-cleavable complex and markedly enhances the formation of double-strand breaks in naked DNA. VM-26 also stimulates the formation of double-strand breaks in isolated Drosophila nuclei. Analysis of the parameters of the VM-26-stimulated cleavage reaction in nuclei strongly suggests that the double-strand scissions are generated by endogenous topoisomerase II. Finally, we have examined the distribution of (putative) cleavage sites for endogenous topoisomerase II in the chromatin of the 87A7 heat shock locus and the histone repeat unit. We have found that there are prominent VM-26-induced cleavage products from the 5' ends of the 87A7, the two heat shock protein 70 genes, and in the intergenic spacer separating these genes. Moreover, the pattern of VM-26-induced cleavage products is altered in nuclei prepared from heat-shocked cells. In the case of the histone repeat unit, only minor VM-26-induced cleavage products are observed in nuclei (in spite of the fact that experiments on naked DNA indicate that the histone repeat contains many major cleavage sites for purified topoisomerase II). These findings suggest that the nucleoprotein organization of different DNA segments may be important in determining whether specific sites are accessible to endogenous topoisomerase II in nuclei.

Adenosine Triphosphate↗
PubMed1990

Effects of the DNA topoisomerase II inhibitor, VM26, on transcriptional initiation in vitro.

Inhibitors of DNA topoisomerase II have been shown to influence the expression of specific genes in vivo, leading investigators to suggest that the topological state of certain genes may affect their expression. In the present study, we have examined the effects of the topoisomerase II inhibitor, VM26, on transcriptional initiation in vitro. VM26 inhibited transcriptional initiation from the rat prolactin and adenovirus major late promoters in an in vitro transcription assay using rat pituitary tumor GH3 cell nuclear extracts. Transcriptional initiation from both supercoiled and linear DNA templates was equally inhibited by VM26 in a dose dependent manner. In order to identify sequences around the prolactin promoter recognized by topoisomerase II, we have mapped topoisomerase II cleavage sites using GH3 cell nuclear extracts as a source for the endogenous enzyme. Using a 910 bp genomic DNA fragment containing 423 bp of 5'-flanking sequences from the prolactin gene, we observed five VM26-enhanced topoisomerase II cleavage sites. Some of these sites map to positions near or within previously described regulatory DNA elements, and thus, may provide the structural basis for the sensitivity of prolactin gene expression to topoisomerase II inhibitors in vivo. These data suggest that inhibition of transcriptional initiation was a consequence of VM26 induced cleavage in the promoter region.

Animals↗
PubMed1991

Ewing's sarcoma: metastatic tumor to the jaw.

Metastatic tumors to the jaw are a rare occurrence. The incidence of metastatic Ewing's sarcoma to the jaw has been reported to be less than 2% of all cases of Ewing's sarcoma. Early detection of such lesions is difficult because the signs and symptoms do not appear until the lesion has progressed considerably. The treatment options are therefore limited to palliative care of the patient rather than cure. This article reports a case of Ewing's sarcoma that had metastasized to the mandible and reviews the literature.

Carboplatin↗
PubMed1995

DNA topoisomerase II isozymes involved in anticancer drug action and resistance.

DNA topoisomerase II is a major protein of the nuclear matrix. The enzyme appears to have a central role in both DNA organization and replication. The importance of nuclear matrix topoisomerase II alpha as a target for certain anticancer agents was evaluated in CEM human leukemia cells. Studies were done to determine the extent to which the alpha (170 kDa) and beta (180 kDa) isozymes of topoisomerase II form covalent enzyme-DNA complexes in whole cells and in the nuclear matrix and nonmatrix fractions of CEM cells that are either sensitive or resistant to topoisomerase II-active anticancer agents. Topoisomerase II alpha was detected in both the high salt-soluble (nonmatrix) and matrix fractions of nuclei from parental CEM cells. Most of the matrix topoisomerase II alpha was tightly bound to DNA in cells incubated with VM-26. In contrast, topoisomerase II beta was detected only in the high salt-soluble (nonmatrix) fraction of the nucleus. The subnuclear distribution of the alpha and beta topoisomerase II isozymes in CEM/VM-1 cells resistant to topoisomerase-active drugs was similar to that in drug-sensitive CEM cells. However, the amount and activity of topoisomerase II alpha in nuclear matrices of CEM/VM-1 cells were decreased 3- to 6-fold relative to that of CEM cells. The differences observed in the subnuclear distribution and DNA binding pattern of the topoisomerase II isozymes support the hypotheses that each isozyme has a distinct cellular function. Furthermore, these results provide evidence that topoisomerase II alpha is the nuclear matrix target for VM-26, and that depletion of the nuclear matrix isozyme contributes to cellular resistance to this anticancer agent.

Adenosine Triphosphate↗
PubMed1981

Late results of multimodality therapy of high-grade supratentorial astrocytomas.

Fifty-one patients with histologically proved astrocytomas grades III and IV treated with postoperative irradiation and chemotherapy were evaluated with serial computerized tomographic (CT) scans and with special regard to their functional state 30 months after operation. Fourteen patients (27.4%) are still alive, but only 7 of them have a good performance status. The impaired functional state of 6 (11.7%) of the other 7 patients was caused by a secondary progressive dementia with radiological signs of diffuse cerebral atrophy and leukoencephalopathy, but no signs of recurrent tumors. The best explanation for this is a synergistic toxic action of whole brain irradiation and chemotherapy. Measuring survival time for evaluation of brain tumor therapy is of limited value without examination of the performance status and sequential CT scans.

Adult↗
PubMed1981

VM-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: preliminary report.

Twenty-five adults with recurrent supratentorial malignant gliomas were treated with VM-26 in a monochemotherapy schedule, the antiblastic region covering a period of 24 weeks. Five cases were excluded from the final evaluation, 4 because of protocol violations and 1 due to intolerance to the drug. In the group of 20 patients who met the criteria for evaluation, 7 (35%) showed a partial or complete response, with clinical or radiological tumor aggression, and the conditions of 7 (35%) were unchanged at the end of the chemotherapy courses. The progression-free intervals turned out to be 10.4 months and 8.5 months, respectively. Six patients (30%) complained of tumor progression despite the treatment. Most of the patients are still alive, and the actuarial survival rate is encouraging. Toxicity was mainly hematologic, but usually moderate and easily reversible.

Anemia↗