Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma. Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine (BCNU), lomustine (CCNU), or semustine (methyl CCCNU) in addition to surgery and radiotherapy. Thirty-three of the 62 patients were involved in a controlled, prospective, randomly allocated study. Quality or quantity of survival was not prolonged in patients who received chemotherapy. Age greater than 64 years, a severe postoperative neurological deficit, or the onset of symptoms less than 12 months prior to surgery were associated with a worse prognosis. The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the regorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis.
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PMID:Adjuvant nitrosourea therapy for glioblastoma. 98 52

Two cultured human glioblastoma cell lines were exposed to graded doses of BCNU, and the sequential cytoxic and cytocidal changes were studied histologically. Changes included cessation of mitotic activity, reduction in population, rounding and clumping of the cells, nuclear pyknosis, and cell death. The intensity of the changes was proportional to the dosage. With 3 daily doses of 18 mug/ml, the population in Tumor A-172 was only 20% of that in the controls, and 75% of the cells present appeared conviable. This dosage is about four times that used in a single course in treating humans. After 3 doses at 60 mug/ml, cell death appeared complete, but transfer without additional treatment brought out 2-min foci of viable cells, with several mitoses. A more anaplastic glioblastoma, T98, was much less sensitive to BCNU, responding only by lowered population density, decreased mitoses and slight-to-moderate cytotoxicity in one experiment.
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PMID:Cytotoxic effects of 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) on cultured human glioblastomas. 125 53

Tumour levels of O6-alkylguanine-DNA-alkyltransferase (O6 AT) and glutathione content (GSH) were correlated with 1, 3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) sensitivity in two human ovarian cancer xenografts (HOC8 and HOC18) and in two human glioblastoma xenografts (HG12 and HG15). HOC8 and HOC18, which were not responsive to BCNU treatment, showed O6 AT levels 14 and 23-fold higher than HG12 that was moderately sensitive to the same BCNU treatment. HG15, which was more sensitive to BCNU than HG12, showed significantly lower O6 AT levels. GSH levels were similar in all tumor xenografts. These data further stress the importance of O6 AT level as a relevant parameter for nitrosourea response in human tumours.
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PMID:Tumour levels of O6-alkylguanine-DNA-alkyltransferase and sensitivity to BCNU of human xenografts. 129 58

The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cisplatin, carboplatin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP + VP-16; (C) CBDCA + BCNU; (D) CBDCA + BCNU + VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
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PMID:Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. 148 54

Little is known about the sensitivity of human glioblastoma cells to hyperthermia alone and in combination with other therapies. We carried out in vitro cell survival studies on the human glioblastoma cell line U-87MG and our model canine glioma canine brain tumor (CBT) cells after multimodality treatment. Ionizing radiation was administered to flasks of cells in logarithmic growth at 500 rads (5 Gy) with consecutive treatment by hyperthermia, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), or cisplatin. Cells were treated with single doses of BCNU at 5 microM with sequentially added radiation or hyperthermia and at 1 to 2 micrograms/ml of cisplatin with hyperthermia. Hyperthermia was administered in a precision controlled water bath at 44 degrees C for 30 minutes in combination with chemotherapy or radiation. In general, the sensitivity of U-87MG and CBT cells was similar for all test regimens. For example, colony formation efficiency decreased by 64% in CBT cells and by 64.4% in U-87MG cells after hyperthermia alone at 44 degrees C for 60 minutes. All combinations of BCNU, hyperthermia, and radiation administered in vitro produced enhanced cell killing, but the effects of multiple modalities were generally additive in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro response of human glioblastoma and canine glioma cells to hyperthermia, radiation, and chemotherapy. 194 32

The production of DNA interstrand crosslinks (ISC) by BCNU and other bifunctional alkylators and the effects of these drugs on the repair of radiation-induced DNA-single strand breaks (SSB) were studied in two human glioblastoma used to assess both DNA-ISCs and DNA-SSBs. BCNU-treated UWR2 and UWR3 cells showed a significant BCNU dose-dependent increase in radiation-induced DNA-SSBs at 6 hrs post-drug treatment, and at 100 microM BCNU DNA-ISC was completely masked in UWR2 cells. There was no enhancement of radiation-induced DNA-SSBs in both cell lines after treatment with cis-DDP, CHZ, or MNU. In the capillary clonogenic cell assay, UWR2 cells were 3.2 times more resistant than UWR3 cells; 0(6)-methylguanine-DNA methyltransferase activity was also 1.8 times higher in UWR2 than in UWR3. Our data suggest caution in the use of the standard alkaline elution technique (with 6 hrs between drug exposure and irradiation) to measure BCNU-induced DNA-ISC induction in highly BCNU-resistant cell lines. We provide evidence that the synergism between BCNU and radiation in the generation of DNA-SSBs is the result of low DNA-SSB repair capacity of the cells, and is further potentiated by the carbamoylating action of BCNU.
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PMID:DNA interstrand crosslinking and strand break repair in human glioma cell lines of varying [1,3-bis(2-chloroethyl)-1-nitrosourea] resistance. 216 50

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.
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PMID:Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma. 254 93

Glioblastomas and previously irradiated recurrent gliomas remain incurable. Chemotherapy is able to palliate patients by shrinking tumors, thereby improving neurological status and quality of life. Chemotherapy may also be capable of prolonging survival in some instances. The effectiveness of chemotherapy against gliomas is comparable to the efficacy of chemotherapy against many other solid tumors. When given in an adjuvant setting along with radiation postoperatively, studies suggest that the nitrosoureas, dibromodulcitol, dianhydrogalactitol, procarbazine, teniposide, dacarbazine, and cisplatin may possibly be useful, although results for many of these drugs are inconclusive. Some chemotherapy combinations also appear to be useful in an adjuvant setting, particularly BCNU plus ifosfamide, BCNU plus cisplatin, CCNU plus dibromodulcitol, and CCNU plus lonidamine. However, there is not yet conclusive evidence that combination chemotherapy is superior to single agent adjuvant chemotherapy in the treatment of gliomas. While the use of chemotherapy prior to postoperative cranial radiation is worthy of further study, it has not to date proven to be more effective than chemotherapy combined with radiation. In patients whose tumors have recurred following radiation, palliation may be achieved with the nitrosoureas, procarbazine, teniposide, and diaziquone. Cisplatin, high dose methotrexate, the interferons, and a variety of other medications also may be of use. As in the case of adjuvant chemotherapy, chemotherapy combinations for recurrent tumor have not been conclusively demonstrated to be superior to single agent treatment, although some CCNU-based combinations are of interest. Many different chemotherapy drugs have been administered by intracarotid infusion. There is a moderately high risk of serious local retinal and neurological toxicity using this approach, and efficacy has not been proven to be improved by this approach. However, further studies of intraarterial administration of chemotherapy are warranted in light of theoretical considerations, pharmacological observations of enhanced local drug concentrations, and the observation that patients who have failed the same drugs intravenously may respond when lower doses of the drug are administered intraarterially. In addition, some patients have had tumor shrinkage in the area infused while tumor has grown in other areas. Thus, while intracarotid chemotherapy must be regarded as still investigational and potentially quite toxic, further studies are indicated. High dose chemotherapy has been administered in combination with autologous bone marrow rescue. High response rates and prolonged survival durations have been reported in some instances, justifying further study despite substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of chemotherapy in the treatment of gliomas in adults. 269 39

Ten congenitally athymic "nude" mice and 10 immunocompetent mice underwent intrathecal inoculation with a human glioblastoma cell line (U87MG) via percutaneous lumbar puncture (5 x 10(5) cells/animal). All of the nude mice developed paraplegia with or without incontinence at 2 weeks and routinely died of inanition 3 weeks postimplantation. Histological examination confirmed extensive proliferation of neoplastic cells within the intrathecal space. A second group of animals was inoculated with 5 x 10(4) cells/animal: 20 nude mice, 10 cyclosporine A-immunosuppressed animals, and 10 immunocompetent control mice. The 20 mice were further divided into four subsets. Subset A did not receive chemotherapy, Subset B received 200 mg of carmustine (BCNU) per m2 by intraperitoneal injection, Subset C received a single dose of 4 mg of methotrexate (MTX) per m2 by intrathecal injection 4 hours after tumor inoculation, and Subset D received 12 mg of intrathecal MTX per m2. Decreasing the concentration of cells per animal by 1 log doubled the time interval required for the development of paralysis and incontinence to 4 weeks. Treatment with intrathecal MTX at a dose of 4 mg/m2 extended the symptom-free period by an additional week (to 5 weeks postinoculation), and a dose of 12 mg/m2 allowed an average of 6 weeks before the onset of neurological impairment. The xenografts did not grow in the immunocompetent control mice, the BCNU-treated group, or the cyclosporine A-immunosuppressed animals. An intrathecal xenograft model of central nervous system malignancies allows a novel approach to the evaluation of experimental chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New xenograft model for assessing experimental therapy of central nervous system tumors: human glioblastoma in the intrathecal compartment of the nude mouse. 283 74

In a series of 22 patients, high dose BCNU (800-1,000mg m-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return. Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.
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PMID:High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma. 285 28


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