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)

We analyzed our treatment results of 71 operated patients with cerebral glioblastoma treated by conventional external radiation therapy (mean dose 60.2 Gy) combined with radiosensitizing agents. More than 50% reduction of tumor volume was obtained in 20 patients (28.2%). A response rate of at least 40% was obtained in patients treated with combined ACNU-vincristine-nicardipine, ACNU-5FU-hydroxyurea, or cisplatin alone. The combination of ACNU and vincristine with or without nicardipine resulted in significantly longer survival. The median survival in this group was 101.1 weeks and the two-year survival rate was 45.9%; these results were significantly better than those achieved with other ACNU combinations or other combinations without ACNU. In the analysis of survival, factors correlated to longer survival were a patient age of younger than 45 years, wide resection of the tumor, a good postoperative performance status (KS > or = 70%), a radiation dose of 68-72 Gy, small postoperative tumor remnants (< 20 cm3), no visible tumor after radiation therapy, and the administration of adjuvant chemotherapy. Maximum resection of the tumor and localized irradiation with a dose of 70 Gy combined with ACNU and vincristine appears to be the most effective treatment at present.
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PMID:Radiation therapy combined with radiosensitizing agents for cerebral glioblastoma in adults. 780 73

We analysed long-term follow-up results of 175 patients with malignant glioma (110 glioblastoma and 65 anaplastic astrocytoma) treated under five different regimes during the past two decades. The factors of age (less than 40), histology (anaplastic astrocytoma) and type of adjuvant therapy (radiation and chemotherapy) contributed to long survival. The other important factor was the response to adjuvant therapy. Cases of gross total removal or complete response (CR) of a residual tumour to an adjuvant therapy showed a better prognosis. The three and five year survival rate was 42% and 24%, respectively. The highest CR ratio (23%) was seen in patients treated by intravenous injection of interferon and ACNU in addition to radiotherapy (IAR therapy).
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PMID:Long-term follow-up results of 175 patients with malignant glioma: importance of radical tumour resection and postoperative adjuvant therapy with interferon, ACNU and radiation. 753 70

We have characterized two human glioblastoma cell lines, which were designated as YH cells and AM cells. The two cell lines maintained morphological appearance observed in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture. Inoculation of AM cells into athymic nude mice formed large tumors at a high incidence. As with chemosensitivity to chloroethylnitrosourea, O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in in vitro cultured cells as well as tumor specimens obtained at surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301 fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the both patients, an MGMT activity of original tumors related with responsiveness to ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the respective tumor specimens comes from selection of ACNU-sensitive cells or alteration in biological characteristics during long term culture. These results suggest that cell lines derived human brain tumors are useful targets for understanding the chemosensitivity of human malignant gliomas and for establishing a pertinent chemosensitivity test.
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PMID:Characterization and chemosensitivity of two cell lines derived from human glioblastomas. 814 54

As the prognosis of astrocytic tumors depends on various factors, identifying prognostic factors should be useful for developing strategies to cope with them. Between 1975 and 1994, more than 200 patients with astrocytic tumors were treated in Kagoshima University. Of these patients, 149 (grade I: 17, grade II: 42, grade III: 41, grade IV: 42, unproven: 7) have been followed up. Records of these patients were retrospectively reviewed for age at the time of initial symptoms, gender, histological grade (WHO), extent of tumor resection, radiation therapy, and administration of anticancer agents. We used the Kaplan-Meier method and the Weibull log-linear model to analyze the relation between survival time and these prognostic factors. Survival time was counted from onset of symptoms, and age of initial treatment was used as a covariant. The mean age of males at the initial diagnosis was 40.8 years (n = 77), and that of females was 39 years (n = 72). Using the Kaplan-Meier method, the mean survival time of the 149 patients was 101 months (males; 72.7 months, females; 134.5 months). Mean survival time of grade II was 144.3 months, that of grade III was 95.2 months, and grade IV (glioblastoma) was 15.9 months. Histological grades and mean ages of the groups showed a positive correlation. Among grades II, III and IV, the Kaplan-Meier survival curves were significantly different (p < 0.0001) according to the log-rank test. By the extent of surgical resection (subtotal or greater resection, partial resection, and less than partial resection), the mean survival time showed a significant difference (p < 0.05) on the log-rank test. However, we could not detect a significant difference in survival time between the group that received chemotherapy and the group which did not. The Weibull log-linear analysis indicated that gender, age, histological grade (WHO), extent of surgery, and dose of radiation therapy were prognostic factors. Covariants of grades II, III, and IV made survival time 0.314, 0.179, and 0.069 times as long as that of grade I. The survival time after "partial resection" became 1.415 times as long as the survival time after "less than partial resection". The covariant of "greater than subtotal resection" showed a prolonged survival time of 2.916 compared with that of "less than partial resection". As for age at treatment, the older the patient was, the shorter the survival time. The rate was 0.986 for each year of age. Irradiation of one Gy increased survival time by 1.015 times. Chemoimmunotherapy (dose of ACNU and interferon beta) could not be confirmed as an effective covariant.
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PMID:[The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model]. 882 30

104 N2-frozen samples from 33 astrocytic tumors previously untreated with cytotoxic drugs have been analyzed for the expression of p-glycoprotein transcripts (mdrl) by RT-PCR using beta2-microglobulin as an internal control. A remarkable variation was observed even within a single tumor in 50% of the cases. Nevertheless, a difference became visible between the groups of anaplastic astrocytomas and glioblastomas. While 78% of the grade 3 astrocytomas contained at least a minimum of 1 sample with a very low mdr1 expression, this was the case only in 23% of the glioblastomas. This supports an earlier observation revealing a positive correlation between tumor grading and the tumor cell fraction stained with the monoclonal antibody JSB1. On the other hand, no major differences were found between the histological groups when the samples with the highest mdr1 expression were selected to represent the individual tumors. Those samples are less informative. They might be derived from tumor regions in which capillaries deliver a larger fraction of the total mRNA pool. No induction of mdr1 was observed in some early astrocytoma or glioblastoma cell cultures even after administration of high concentrations of the drugs ACNU and VM26, often used in glioma therapy.
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PMID:Mdr1 mRNA expression differs between grade III astrocytomas and glioblastomas. 902 Mar 93

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.
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PMID:Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma. 907 Mar 38

The author reviewed treatment results of chemoradiation therapy for malignant brain tumors. For astrocytic tumors, radiation therapy combined with radiosensitizing chemotherapeutic agents, mainly nitrosourea compounds (BCNU or ACNU), has been a standard treatment modality for a long time. The therapy is more effective for anaplastic astrocytoma than glioblastoma. The chemoradiation therapy is now applied for medulloblastoma; it prolonged 5-year survival up to 70%. Metastatic brain tumors are frequently treated by radiation therapy alone. When combined with cisplatin, radiation therapy shows a more excellent antitumor effect.
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PMID:[Chemoradiation for malignant brain tumors]. 938 12

The induction of WAF1 gene expression after the treatment with the anticancer agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU; nimustine hydrochloride) was studied in two human glioblastoma cell lines: U-87MG, which bears the wild-type p53 gene, and T98G, which bears the mutant p53 gene. A marked accumulation of WAF1 was observed 3 h after ACNU treatment in both cell lines. The induction of WAF1 mRNA by ACNU was detected by northern blot analysis in these cells. Binding activity of p53 to a p53 consensus sequence increased after treatment in U-87MG cells but not in T98G cells. The existence of a p53-independent WAF1 induction pathway was supported by the apparent accumulation of WAF1 after ACNU treatment in the p53-null human osteosarcoma cell line Saos-2. These findings suggest that there are two possible pathways for WAF1 induction: the p53-dependent pathway through the p53-responsive element and the p53-independent pathway through other elements.
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PMID:p53-independent WAF1 induction by ACNU in human glioblastoma cells. 953 48

We compared the detectability of 99mTc-MIBI and 201Tl-chloride for brain tumor in relationship with histopathology. We also evaluated correlation between therapeutic effect using ACNU, Cisplatine and the degree of MIBI tumor uptake. The subjects were 31 brain tumor histologically confirmed by operation or biopsy. Dual-isotope SPECT technique was performed at both 20 min and 180 min after tracer injection. A tumor to normal lung ratio on both early (ER) and delayed image (DR) and retention index (RI) were calculated. The positive rates of 99mTc-MIBI (90.3% and 77.4%) were comparable to that of 201Tl (90.3% and 80.6%). In the relationship with histopathology, both MIBI and Tl accumulated in 100% of glioblastoma (GBM), metastasis (meta), anaplastic astrocytoma and 25% of low grade astrocytoma on both early and delayed images. On semiquantitative analysis, there were no statistical significance among GBM, meta and anaplastic astrocytoma of ER, DR, RI in the both radiopharmaceuticals. However, both ER and DR in GBM tended to be higher than those of anaplastic astrocytoma. In spite of intense MIBI uptake, GBM patients died within six months except one patient. We concluded that MIBI can be helpful in detecting brain tumor as Tl. MIBI also might be useful in estimating the degree of malignancy in glioma. However, intense MIBI uptake did not mean favorable therapeutic effect in patients with GBM treated with ACNU and Cisplatine.
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PMID:[Evaluation of brain tumor by 99mTc-MIBI: comparison study with 201Tl and predictivity of therapeutic effect]. 959 87

The toxicity and therapeutic effect of the ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convulsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.
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PMID:Ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl-1-nitrosou rea hydrochloride for subarachnoid dissemination of gliomas. 969 73


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