Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PCNU, the latest nitrosourea analogue to be subjected to clinical trials, held promise as a superior chemotherapy agent for brain tumors because of more favorable biochemical and cytotoxic characteristics in laboratory studies. Thirty-nine children with a variety of recurrent primary CNS tumors, all of whom had evaluable disease, participated in a phase II PCNU trial. Their mean age was 9.7 (3-20) years. PCNU was administered as a 2 hour intravenous infusion in one of 2 dose schedules at 6-7 week intervals; 100-125 mg/m2 for minimally treated patients and 70-90 mg/m2 for heavily treated patients. Response was assessed after 2 courses of chemotherapy after attempting to taper the steroid dose. The overall objective response rate was 18% (7/39) for a mean of 5.9 months (2+ -12). Only partial responses were observed. Disease-specific responses rates were: brainstem glioma--18% (3/17); cerebral glioma--27% (3/12); ependymoma--1/1; and primitive neuroectodermal tumors--(0/9) including 5 medulloblastomas, 2 pineoblastomas and 3 cerebral primitive neuroectodermal tumors. Toxicity was primarily hematologic and clinically significant thrombocytopenia (less than 50,000 mm3) was encountered in 30/38 (79%) patient trials. Modest activity of PCNU in recurrent childhood gliomas is confirmed. Our response rates, using objective CT criteria, are somewhat lower than those reported for BCNU and CCNU. Because of comparable hematologic toxicity and efficacy, intravenous PCNU does not appear to offer a clinical advantage to existing nitrosoureas for children with recurrent brain tumors using a 2 hour intravenous infusion schedule.
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PMID:PCNU and recurrent childhood brain tumors. 368 86

Three ACNU-resistant subclones were isolated and characterized from a wild-typed 9L rat glioma cell line in culture. At an early stage after cloning, these ACNU-resistant subclones showed a high frequency of chromosomal aberrations compared with nonresistant 9L cells. These ACNU-resistant subclones revealed a cross resistance to BCNU, CCNU, methyl CCNU, nitrogen mustard, cyclophosphamide, and cis-platinum, which are alkylating agents. Further studies are necessary to clarify the mechanisms of ACNU-resistance from the aspect of repair of DNA alkylation damage.
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PMID:ACNU-resistant mutants of 9L rat glioma cell line. Isolation and preliminary characterization of these subclones. 386 92

One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.
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PMID:Assay of anti-cancer drugs in tissue culture: relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma. 397 31

Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF (5800 cGy, 30 fractions, 6 weeks), MDF (6141 cGy, 69 fractions, 4 1/2 weeks, at 89 cGy every 4 hours 3 times daily) and MDF in combination with MISO (1.25 gm/M2 three times weekly for the first 3 weeks). In January 1983, the CF arm was dropped and a high dose MDF arm added (7120 cGy, 80 fractions, 5 1/2 weeks, at 89 cGy per fraction every 4 hours 3 times daily). CCNU chemotherapy was given at the time of tumor progression. One hundred and twenty-eight patients were evaluated (38 CF, 42 MDF, 37 MDF plus MISO, and 11 high dose MDF). Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF (p less than .002). The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.
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PMID:Misonidazole combined with hyperfractionation in the management of malignant glioma. 609 Mar 67

Glioma 26 (G26) is a chemically induced ependymoblastoma of mouse. It was used through sub-cutaneous and/or intracranial injection in 7 experiences which showed that this experimental model was able to select drugs acting on intracranial tumors : nitrosourea (CCNU), VM 26, procarbazine (PCB). Combination chemotherapy (VM 26-CCNU ; VM 26 CCNU-PCB) was more active than monochemotherapy in 2 out of 3 experiences. It seems that the variability of the results is at least partly due to the important tumoral necrosis in tumors treated by combination chemotherapy and to technical problems. The latters can be avoided by the mechanical dispersion of tumor cells and by their injection through a stereotaxic frame. Selection of drugs is easier and cheaper to perform with G 26 than with other in vivo and in vitro experimental models. The main problem for all models remains their lack of specificity.
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PMID:[Interest of glioma 26 in the selected chemotherapy of intracranial tumors (author's transl)]. 625 44

Therapeutic goals cannot be the same for every patient with malignant glioma, as suggested by the study of 106 cases seen from 1975 to 1982. Seventy patients were uniformly treated by surgery, chemotherapy and radiotherapy. Two clinical parameters, i.e. age and postoperative neurological status (NS), were used to divide patients into three groups with a significantly different prognosis. Median survival was 59.5 months for group 1 (age 50 or less, good NS) and 11.5 months for group 2 (age 51 to 65 and good NS, or younger than 51 but poor NS). For group 3 (age 51 to 65 and poor NS, or older than 65), survival was six months. From 1978, two trials were carried out, with therapy being adjusted to each group. Whatever the group, surgical excision was done whenever it was consistent with preservation of the neurological status and followed by combination chemotherapy (Vincristine-VM 26-CCNU). For group 1, radiotherapy was not modified: 60 grays were delivered to the tumor and surrounding safety margin in 30 fractions over 6 weeks. Patients in group 2 received 69 grays in two daily fractions over 6 weeks (1.15 Gy each morning and evening five days a week). With this modified treatment, median survival was brought up to 20.5 months. Patients in group 3 were treated initially by surgery and chemotherapy; radiotherapy was restricted to recurrences. This policy significantly improved patients' comfort by enabling their prompt return to home. The median survival for 14 patients was 10.5 months. Our experience suggests that different therapeutic goals should be set for each group. In group 1, therapy should be aimed at obtaining prolonged survival. In group 3, survival remains short and the main concern is to improve patients' comfort. As patients in group 2 have an intermediate prognosis, they are the best candidates for therapeutic trials designed to improve the response to radiotherapy and chemotherapy.
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PMID:[Supratentorial malignant glioma in adults. Adjustment of the treatment of 3 groups according to a clinical classification]. 630 84

A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.
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PMID:Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors. 654 19

Two human brain tumors which were previously established in nude mice were used to determine antitumor efficacy of various therapeutic agents. These tumors were a medulloblastoma (TE-671) and a glioma (U-251) with mass doubling times of 3.5 and 5.5 days respectively as subcutaneous implants in nude mice. Intracranial (i.c.) tumor challenge was accomplished by inoculating tissue culture-grown cells of either tumor into the right cerebral hemisphere to a depth of 3 mm. Median survival time (MST) in untreated mice with 10(5) i.c. injected TE-671 cells was approximately 30 days and 53 days in the U-251 tumor. With 2 X 10(5) U-251 tumor cells the MST was 27-31 days. Groups of mice which had been inoculated with tumor were treated with various doses and schedules of antineoplastic compounds by the i.p. route. The TE-671 tumor responded to AZQ treatment with an increase in life span (ILS) of 37% compared to untreated controls and an ILS of 30% with CCNU treatment. BCNU and PCNU were ineffective. With the U-251 tumor BCNU produced an ILS of greater than 60%, with 75% cures, greater than 112% ILS with PCNU and 49% ILS with CCNU. Neither tumor responded to procarbazine, PALA, dianhydrogalactitol, D-O-norleucine or dibromodulcitol. The U-251 tumor was treated on various schedules and doses with BCNU and found to respond well on late as well as early treatment. A new drug (rapamycin) being investigated by the NCI was found to be very effective against the U-251 tumor. This model system should prove valuable in assessing the effects of various chemotherapeutic modalities against brain tumors.
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PMID:Human brain tumor xenografts in nude mice as a chemotherapy model. 668 50

Metastatic spread of an optic glioma through a ventriculoperitoneal shunt resulted in the accumulation of malignant ascites in a young boy. Chemotherapy with vincristine, CCNU, and prednisone resulted in regression of the ascites and no further tumor progression. Extracranial metastasis of such a slow growing tumor is a rare occurrence; however, in this case, the spread through the shunt further emphasizes the need for protective filters in the shunts.
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PMID:Metastasis of an optic glioma through a ventriculoperitoneal shunt. 686 Oct 97

Fifty-eight patients harboring recurrent malignant brain tumors were evaluated. CCNU (110 mg/m2) was administered on Day 1, procarbazine (60 mg/m2) was administered daily for 14 days beginning on Day 8, and vincristine (1.4 mg/m2) was administered on Days 8 and 29 of each 6-week cycle of therapy. Therapy was continued until tumor progression was documented. Before each course, a neurologic examination was performed and radionuclide and computerized tomographic scans were obtained. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Of the 46 patients harboring recurrent malignant gliomas, 12 (26%) responded to therapy, 18 (39%) had tumor progression, and 16 (35%) had disease stability. Nineteen of the 46 patients were not previously treated with another form of chemotherapy: eight (42%) responded to therapy, eight (42%) had disease stability, and only three (16%) had early tumor progression. The median time to tumor progression was 26 weeks for patients responding to therapy or having disease stability. Approximately 30% of the patients were alive without evidence of tumor progression at 1 year. Evaluated by time to tumor progression and rate of tumor response or stabilization, this combination was similar to the BCNU-5-fluorouracil combination used for patients harboring recurrent malignant glioma.
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PMID:Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. 740 56


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