Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.
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PMID:Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy. 23 Aug 93

Twenty patients previously treated with surgical resection, radiation therapy, and a nitrosourea for malignant gliomas of the brain were given VM-26 as a second chemotherapeutic agent when evidence of tumor progression occurred. Thirty-five percent achieved an arrest or decrease of neurologic symptoms, with a median length of response (arrest and tumor regression) of 22 weeks.
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PMID:VM-26 as a second drug in the treatment of brain gliomas. 42 30

Between 1981 and 1987, 133 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with surgery and post-operative radiotherapy. 36 AA and 31 GBM patients were treated with adjuvant chemotherapy consisting of CCNU 100 mg/m2 day 1, procarbazine 60 mg/m2 days 1-14, and vincristine 1.4 mg/m2 (max. 2 mg) days 1 and 8, every 6 weeks which we called a "modified PCV" (mPCV) regimen. 37 AA and 29 GBM patients were treated with adjuvant chemotherapy consisting of VM-26 75 mg/m2 days 1 and 2, and CCNU 60 mg/m2 days 3 and 4, every 6 weeks. Prognostic covariates such as patient's age, Karnofsky performance status score and the extent of surgery were balanced between the two treatment groups. The time to tumor progression and survival time for both regimens show that mPCV produces a two-fold increase in these factors at the 50th and 25th percentile for AA patients, but not for GBM patients, although there are more long-term GBM survivors with mPCV than with the VM-26 + CCNU regimen.
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PMID:Advantage of post-radiotherapy chemotherapy with CCNU, procarbazine, and vincristine (mPCV) over chemotherapy with VM-26 and CCNU for malignant gliomas. 132 Dec 39

Verapamil (240 mg daily orally) was tested in a phase II trial to restore vincristine sensitivity in 9 patients with myeloma, chronic lymphatic leukemia and immunocytoma. These tumors were selected because treatment response and tumor progression can easily be ascertained with the help of electrophoresis and marrow studies, blood counts and lymph node examination. All patients were clinically refractory to vincristine-cytoxan-prednisolone combinations, to which adriamycin had been added in 2 patients. One patient was refractory to adriamycin, VM 26, and prednisone. In 2/9 patients a side effect-free second response lasting 5-10 months was observed, with a doubtful response in two additional patients. It is suggested that occasional clinical responses can be seen, despite the fact that in vitro the mean verapamil concentration required to affect vincristine efflux from malignant lymphocytes in 5 mumols/1 and the mean in vivo serum concentration only 1 mumole. Hypothetically, the clinical response can be explained by an overlapping in some patients of an unusually high serum concentration with an unusually low verapamil requirement.
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PMID:Can verapamil induce second response in patients refractory to vincristine? 238 94

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.
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PMID:Combined intraarterial and systemic chemotherapy for intracerebral tumors. 244 73

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.
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PMID:VM-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: preliminary report. 626 37

Second-look operations for glioblastomas, one of the most malignant types of brain tumor, were performed after the administration of chemotherapeutic treatments of general-VM 26 plus ACNU, local-MTX, or interferon-beta in each of ten, two, and three cases, respectively. Patients who had received the treatments were divided into two groups, living and deceased, as of August 1982. Therapeutic evaluation was performed with clinical parameters. Among the cases of CR, one (a 14-year-old female) had undergone surgery four times in the four years following onset, and no trace of tumor shadow appeared on the CT grams that were taken one month after the last surgery. Her performance was evaluated as almost 100% (ECOG). In cases of local administration, one case, which had been treated with IFN-beta, demonstrated an apparent decrease in the growth fraction and a pronounced decrease in tumor progression potency. Cell kinetic analyses were also performed, and cell cycle time and growth fraction were estimated by computer with the aid of flow cytometry. Efficacious chemotherapy yielded a decreased value of the growth fraction and an increase in cell cycle time. The decreased value of the growth fraction demonstrates especially well the effectiveness of a chemotherapeutic regimen. The cell kinetic analyses aided in the rational establishment of a chemotherapeutic regimen. Second-look operations for malignant brain tumors will enable more effective refinements in chemotherapeutic regimens and more successful results.
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PMID:[Second-look operations and chemotherapy for malignant tumors of the brain]. 657 17

Exposure of human and animal cells to inhibitors of topoisomerase I or II has recently been shown to alter gene expression and induce differentiation in a number of experimental systems. We have previously shown that nalidixic acid and novobiocin, inhibitors of topoisomerase II, induce DNA hypomethylation. Since DNA hypomethylation is frequently associated with transcriptional activation, we wished to further explore the relationship between inhibition of DNA topoisomerases and enzymatic DNA methylation. When HT-29 human colonic adenocarcinoma cells were exposed to the specific topoisomerase II inhibitor teniposide (VM-26), a dose-dependent hypomethylation of DNA was observed during the window of drug treatment. Exposure to the topoisomerase I inhibitor camptothecin (CPT) produced a small but not statistically significant trend toward DNA hypomethylation. CPT-treated cells were found to have up to 19 fold increased levels of topoisomerase II protein, which may have compensated for decreased levels of non-drug-bound topoisomerase I. Both VM-26 and CPT were found to increase [H-3]thymidine incorporation into DNA when administered in low dose (0.5 muM VM-26; 8 nM CPT). Combination of VM-26 and CPT (0.5 muM and 8 nM, respectively) produced DNA hypomethyltion, a synergistic increase in [H-3]thymidine incorporation, and an increasing number of cells entering a higher DNA ploidy cycle. Since VM-26 interferes with the DNA strand breakage-reunion reaction by stabilizing a topoisomerase II-relaxed DNA complex, our results suggest that DNA existing in this form may be a poor substrate for DNA methylase. Topoisomerase inhibitor-induced DNA hypomethylation may offer a possible explanation for the induction of differentiation observed upon exposure to this family of drugs. Altered topoisomerase activity occurring during the process of tumor progression may also provide a link between the induction of polyploidy, DNA hypomethylation and aberrant gene expression frequently observed in tumor cells.
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PMID:Effects of inhibitors of topoisomerases-I and topoisomerases-ii on DNA methylation and DNA-synthesis in human colonic adenocarcinoma cells-invitro. 2158 21