Intravesical chemotherapy of superficial bladder cancer.
Explore the source record for details and available documents.
Absorption↗
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.
Pulsed-field gel electrophoresis analysis of higher-order chromatin structures of Zea mays. Highly methylated DNA in the 50 kb chromatin structure.
We have investigated the presence of higher-order chromatin structures in different maize tissues. Taking advantage of the pulsed-field gel electrophoresis technique to analyse large DNA fragments from intact nuclei and cells, we have determined the size distribution of the high-molecular-weight DNA fragments obtained from chromatin degradation by endogenous nucleases in isolated nuclei. Chromatin digestion leads to the appearance of stable DNA fragments of about 50 kb in all the tissues examined, suggesting the folding of DNA in higher-order chromatin domain structures. It has been reported that such chromatin domains are formed by loops of the 30 nm fibers anchored to the nuclear matrix by a complex set of proteins, including DNA topoisomerase II. Treatment of maize protoplasts with the calcium ionophore A23187 and the antitumour drug VM-26, which specifically inhibit the religation of the cleaved DNA in the topoisomerase II reaction, also produces the 50 kb structure. Analysis of the DNA contained in the 50 kb chromatin structure shows a higher degree of methylation than in bulk maize chromosomal DNA. The role of methylated DNA in the chromatin folding is discussed.
Calcimycin↗
Induction of sister chromatid exchanges by inhibitors of topoisomerases.
To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10(-6) M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.
Amsacrine↗
The podophyllotoxin derivatives VP16-213 and VM26.
VP16-213 and VM26 are compounds with definite anticancer activity in specific tumor types. Despite 10 years of clinical development the full impact of these compounds in current cancer therapy requires further study. There is no conclusive evidence that one compound is superior to the other in any specific tumor type. The composite activities suggest possible differences in certain cancers such as small cell anaplastic lung cancer, lymphoma, leukemia, bladder and ovarian cancer, but sufficiently adequate studies to determine this have not been reported for any tumor. Understanding the basic pharmacology of these compounds should also be considered of high priority since it is obvious that there is much to learn in this area and further clarification should allow improved clinical utilization. It is hoped that the presentations and discussions of the First International Symposium will generate a new wave of interest in future podophyllotoxin research and development.
Animals↗
VM26: phase I and II studies.
Explore the source record for details and available documents.
Drug Evaluation↗
VP16-213 and podophyllotoxin. A study on the relationship between chemical structure and biological activity.
VP16-213, a semi-synthetic derivative of podophyllotoxin, is an effective antitumor agent in the treatment of a variety of leukemias and solid tumors. A comparison of the mechanism of action of VP16-213 and podophyllotoxin has revealed that although both drugs inhibit the uptake of nucleosides into HeLa cells, they exhibit other biological properties which are quite distinct. Podophyllotoxin is a potent inhibitor of microtubule assembly in vitro, while VP16-213 has no effect in this system. VP16-213 induces single stranded breaks in HeLa cells DNA, an effect which may be related to its antitumor activity. In contrast to VP16-213 treated cells, podophyllotoxin-treated cells maintain DNA integrity. Structure-activity relationship studies have identified some of chemical sites of VP16-213 and podophyllotoxin responsible for each of their biological properties. These studies illustrate that chemical modification of podophyllotoxin can generate derivatives which possess new and unique biological properties.
Animals↗
The clinical pharmacology of VM26 and VP16-213. A brief overview.
Explore the source record for details and available documents.
Biotransformation↗
VM26 therapy in children with drug-refractory lymphocytic leukemia.
Explore the source record for details and available documents.
Child↗
VM26 in malignant hematological diseases. A phase II study.
From August 1979 to April 1981, 33 consecutive patients with malignant hematological diseases, entered this phase II study. Sixteen patients had NHL, eight CLL, four Myeloma, three HD, one ALL, and one Polycythaemia vera. Two patients were unevaluable because of early death. The median age was 67 years. Eight patients were not pretreated with drugs. Two CR (5+, 20+ weeks) were obtained among NHL patients, whereas five PR were observed among two NHL, one CLL, one Myeloma, and one HD patients, respectively. Toxicity was almost exclusively hematologic and occurred in ten patients, in one of them causing severe myelosuppression. Moreover, severe asthenia, attributable to VM26, was encountered in three patients, in one requiring the suspension of the treatment.
Drug Evaluation↗
Cooperative studies of chemoprophylaxis after transurethral resection of bladder tumors.
Large cooperative trials are more likely than series studied by small groups to bring about significant progress in the field of intravesical adjuvant chemotherapy of superficial bladder tumor. Multicenter randomized trials involving large numbers of patients have been conducted in Europe by the EORTC Urological Group. The Group's main objectives were to compare the efficacy of thio-TEPA, VM-26, epodyl, Adriamycin, and cisplatin, against no treatment, and to study the prophylactic effect of oral pyridoxine and evaluate the main prognostic factors. The results obtained so far are reported. Preliminary information is also given about the Blinst study, a multicenter open investigation of local chemotherapy with doxorubicin (Adriamycin), with special reference to evaluation of the importance of different modalities of treatment with a single drug.
Antineoplastic Agents↗
Some effects of chemotherapeutic drugs on bone marrow stem cells. II. Effect on non-Hodgkin lymphoma chemotherapy on various hemopoietic compartments of the mouse.
The non-Hodgkin lymphoma chemotherapy protocol used at the Gustave-Roussy Institute was adapted, in terms of drug doses and interval between doses, to normal CBA mice. The numbers of pluripotential stem cells (CFU-S), unipotential stem cells (CFC), differentiated bone marrow cells, and circulating white cells were determined. Eight hours after each drug of the first chemotherapy cycle the number of pluripotent stem cells decreased while the proportion of these cells in DNA synthesis increased. Six hours after the end of each complete cycle, the stem cell compartments were found to be considerably depleted, and they were not completely restored when the next cycle was begun, while the other hematologic compartments were completely restored at this time.
Animals↗
A comprehensive protocol for management of cancer of the bilharzial bladder.
A randomized clinical trial for the management of bilharzial bladder cancer is presented. A multidisciplinary approach is adopted. The objective of the study is to evaluate the role of adjuvant radiotherapy in improving the results of surgery in deeply infiltrating tumours, and to screen a number of chemotherapeutic agents for their effectiveness in bladder cancer. A large number of cases will be admitted into the study and the results will hopefully help to achieve better results in the management of this disease.
Altretamine↗
Chemotherapy of bladder tumours.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Pharmacokinetic study of VM26 given as a prolonged IV infusion to ovarian cancer patients.
Plasma levels of VM26 were assayed by HPLC in six ovarian cancer patients with normal renal and liver function who received the drugs as an initial 1-h IV infusion of 80 mg/m2 followed by a 24-h IV infusion of 120 mg/m2. These doses and infusion rates were chosen on the basis of mean VM26 clearance values found in a previous study, with the aim of reaching plasma steady-state levels of approximately 6 micrograms/ml in a short time. Plasma steady-state levels of 4-10 micrograms/ml, close to those predicted theoretically, were in fact attained at 4-9 h during the second, slower infusion. Mean half-lives and clearance values were 8.6 +/- 1.1 h and 0.78 +/- 0.08 l/h/m2. Six percent of the VM26 dose was recovered as unchanged drug in the urines collected up to 24 h after the end of infusion. The glucuronide of VM26 aglycone (4'-demethylepipodophyllotoxin) was identified in the urine of all patients, in amounts corresponding to about 8% of the drug dose.
Animals↗
Effective treatment of lymphomas of Burkitt's type and B-ALL in adults.
Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.
Adolescent↗
Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation.
The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for greater than 20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4-11.8) for VP-16 and 3.4 (2.5-4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6-10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo.
Animals↗
A quantitative microdensitometric and autoradiographic study of the effect of 4'-demethyl-epipodophyllotoxin-beta-D-thenylidene glucoside (VM-26) on the cell cycle of cultured fibroblasts.
The effect of 4'-demethyl-epipodophyllotoxin-beta-D-thenylidene glucoside (VM-26) , a semi-synthetic derivative of podophyllotoxin, on the cell cycle was studied with chick embryo fibroblasts cultivated in vitro. DNA, RNA and protein content, as well as NADH-diaphorase activity were determined by quantitative microdensitometry and cytofluorometry. The incorporation of [3H]thymidine and [3H]leucine into DNA and proteins were analysed by autoradiography. These metabolic data correlated with morphological observation showed that VM-26 blocks the cell cycle at different moments of its kinetics depending on both the dose and the time exposure. NADH-diaphorase activity is the first to be affected, then biochemical changes (involving the metabolism of RNA and proteins) and morphological alterations (especially of mitochondria) follow. This suggests that VM-26 may act primarily upon the mechanism of respiration of the cell.
Animals↗
Malignant gliomas treated after surgery by combination chemotherapy and delayed irradiation. Part I: Analysis of results.
Forty-six patients with gliomas were introduced after surgery into a therapeutic programme of six cycles of combination chemotherapy with VM26 and CCNU, followed by delayed irradiation six months after surgery with an average dose of 5,800 rads. After irradiation the same preradiation chemotherapy was readministered for an average of four cycles. The results were compared to those from another group of 28 patients treated only by the same chemotherapy (CRC and C groups sucessively). Twelve patients (26%) died before irradiation in the CRC group, six patients (13%) had recurrences at the time of irradiation, and 28 patients (61%) had no clinical or radiological signs of recurrence at the time of irradiation. For the total of treated patients the median survival after surgery was 17 months, and 46% of the patients were surviving at 18 months. The percentage of survivors at 18 months was significantly more elevated in the group treated by combination chemotherapy and delayed irradiation than in a control group treated by the same combination chemotherapy alone. This result suggests that in approximately 50% of cases combination chemotherapy after surgery, and delayed irradiation six months after surgery, cumulated their effects on survival time.
Adolescent↗