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)

The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin- 4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice bearing s.c. and intracranial tumors. Temozolomide administered daily for a total of five doses demonstrated marked activity against a panel of Mer+ xenografts despite marginal to moderate activity of 1,3-bis(2-chloroethyl)-1-nitrosourea. The growth delays produced by temozolomide in these xenografts were 1.8-7.5-fold greater than those produced by procarbazine. Although temozolomide demonstrated marginal activity against the Mer+ cell line D341 Med when a 5-day schedule was used, a high-dose 1-day schedule resulted in moderate activity. Temozolomide produced increases in median survival of 1285% (adult glioma D-54 MG), 323% (childhood glioma D-456 MG), and 68% (ependymoma D612 EP). Pretreatment of mice with O6-benzylguanine increased temozolomide-induced mortality, requiring reduction of the dosage from 1200 to 750 mg/m2 on the single-day regimen. O6-Benzylguanine pretreatment of mice bearing Mer+ D341 Med increased the growth delay of temozolomide, in duplicate experiments, from -3.1 to 4.8 and 1.1 to 4.9 days. These studies suggest that temozolomide may be active in the treatment of a broad spectrum of central nervous system cancers, including Mer+ tumors resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea.
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PMID:Activity of temozolomide in the treatment of central nervous system tumor xenografts. 779 12

Conventional treatment for medulloblastoma includes surgical resection followed by craniospinal irradiation, with the potential risk of subsequent radiotherapy-induced secondary neoplasms. We report a 23-year-old woman previously irradiated nine years earlier for a cerebellar medulloblastoma who developed a new enhancing lesion in the primary radiation field four weeks following completion of high dose chemotherapy with bone marrow transplantation for recurrent disease. Resection of this lesion revealed a low grade glioma with no evidence of recurrent medulloblastoma.
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PMID:Well differentiated astrocytoma occurring nine years after radiation therapy for medulloblastoma. 780 12

The ability of proton magnetic resonance spectroscopy (1H MRS) to diagnose brain tumors was investigated using in vitro high-resolution spectra. Fifty-eight surgically excised samples of brain tumors (12 glioblastomas, 4 anaplastic astrocytomas, 6 astrocytomas, 12 meningiomas, 6 neurinomas, 4 chordomas, 3 craniopharyngiomas, 2 pituitary adenomas, 2 malignant lymphomas, 1 ependymoma, 1 medulloblastoma, and metastatic brain tumors including 3 pulmonary adenocarcinomas, a hepatocellular carcinoma, and a renal cell carcinoma) and 4 nontumorous lobectomized brains were examined by in vitro 1H MRS. N-Acetyl-aspartate was demonstrated in normal tissues but could not be detected in nonneuroectodermal tumors. Total creatine was decreased in all brain tumors in comparison with normal brain tissues, but was relatively higher in neuroectodermal tumors than in other brain tumors. Choline-containing compounds were present in all tumors except craniopharyngioma, and their concentrations were particularly high in a metastatic brain tumor from hepatocellular carcinoma. The concentration of glycine was high in neuroectodermal tumors, whereas that of taurine was high in medulloblastoma, pituitary adenoma, and renal cell carcinoma. Alanine was increased in meningioma, glioma, and pituitary adenoma. Neurinoma had the largest inositol content among the tumors examined. Thus each type of brain tumor exhibited a characteristic MR spectrum. These data suggested that in vivo 1H MRS might provide clinically useful information about tumor metabolism and aid in the differential diagnosis of tumors. Although excellent anatomical localization of tumors can be readily obtained by MR imaging, MRS may provide additional information in cases in which the differential diagnosis of tumors by MR imaging is difficult.
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PMID:Proton magnetic resonance spectroscopy of brain tumors: an in vitro study. 780 3

We report the findings at follow-up in 67 consecutive children with central nervous system tumors treated over a 5-year-period at a single institution. The diagnoses were supratentorial astrocytoma (n = 12), cerebellar astrocytoma (n = 10), ependymoma (n = 9), medulloblastoma (n = 9), brain stem glioma (n = 6), optic pathway glioma (n = 5), and others (n = 16). The survival rates were 83% for supratentorial astrocytomas at a median of 46.5 months, 90% for cerebellar astrocytomas and 55% for ependymomas at 40 months, respectively, 55% for medulloblastomas at 22 months, 33% for brain stem gliomas at 23 months, and 80% for optic pathway gliomas at 49 months. With regard to neurological sequelae, 13 patients were treated for epilepsy, 13 patients had mild to moderate neurological deficits, and 4 patients were severely disabled. Seventeen of 37 tested patients performed below average on formal neuropsychometric testing, one-fourth attended special education courses, and at least one-fourth suffered from behavioral and adjustment problems.
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PMID:Follow-up and quality of survival of 67 consecutive children with CNS tumors. 784 33

Despite its usefulness in adults with cerebral gliomas, indications for thallium-201 single-photon emission computed tomography (SPECT) in pediatric brain tumor patients are not well defined. We prospectively compared thallium SPECT with gadolinium-enhanced MR (Gd-MR) to determine if thallium SPECT provides clinically useful information that cannot be derived from Gd-MR. We studied 24 pediatric brain tumor patients, 7 at presentation and 17 during therapy. MR imaging included T2 and pre- and postgadolinium T1 images. Thallium SPECT was done within 48 h of MR imaging; thallium indices were calculated for 12 of 14 lesions which showed thallium uptake. Surgery and/or clinical follow-up are available in all patients. The tumors included pilocytic astrocytoma (7), medulloblastoma (5), brainstem glioma or glioblastoma (4), germinoma (3), optic glioma (2), mixed glioma (1), primitive neuroectodermal tumor (1), and choroid plexus carcinoma (1). Among the primary tumors, compared to MR, thallium SPECT was false-negative for tumor in 1 patient and true-positive in 6 patients. Among the patients studied while on therapy, compared to MR, thallium SPECT was true-negative for tumor in 7, true-positive in 5, false-negative in 3, and false-positive in 2. In both groups of patients, thallium SPECT underestimated tumor burden as nonenhancing regions of the tumors were not thallium-avid. Thallium indices did not correlate with histologic grade, biologic aggressiveness, or tumor type. We were unable to establish indications for the use of thallium SPECT in this setting as there was little clinically useful information derived from thallium SPECT that was not provided by Gd-MR.
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PMID:Comparison of gadolinium-enhanced MR and thallium-201 single photon emission computed tomography in pediatric brain tumors. 788 93

We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity against a panel of four medulloblastoma cell lines (D283 Med, Daoy, D341 Med, and D425 Med) and four corresponding sublines with laboratory-generated or clinically acquired resistance to 4-hydroperoxycyclophosphamide [D283 Med (4-HCR), Daoy (4-HCR), D341 Med (4-HCR), and D458 Med] and cross-resistance to melphalan. This is consistent with a nearly total lack of cross-resistance of busulfan to 4-hydroperoxycyclophosphamide. Busulfan was active in the therapy of all but one of the subcutaneous xenografts tested, with growth delays ranging from 14.3 days in D612 EP to 58.4 days in D528 EP. Busulfan produced statistically significant increases in the median survival of mice bearing intracranial D456 MG (66%-90%), D612 EP (18%-33%), and D528 EP (89%) xenografts. These studies suggest that busulfan may be active against medulloblastomas, high-grade gliomas, and ependymomas as well as against cyclophosphamide-resistant neoplasms.
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PMID:Busulfan therapy of central nervous system xenografts in athymic mice. 798 88

Human primary brain tumors differ in their ganglioside composition when compared to adjacent tissues. One ganglioside found in all malignant glioma specimens, but not detected in normal adult brain, is 3'-isoLM1, a ganglioside of the lacto series. This ganglioside was also identified in medulloblastomas with astrocytic differentiation and in brain tissues containing benign proliferating astrocytes. The appearance of 3'-isoLM1 was seen over large regions of brain from glioma but was found mainly in areas either adjacent to the macroscopic tumor or areas corresponding to the tumor in the opposite hemisphere. A high concentration of 3'-isoLM1 was also seen in the corpus callosum, the anatomical structure along which glioma cells may migrate to the opposite brain hemisphere. Ganglioside expressed by cell lines established from primary malignant brain tumors varied widely among cell lines and within a given cell line propagated under different conditions. In in vitro-cultured glioma and medulloblastoma cell lines, gangliosides of the ganglio series dominated and the expression of the lacto series gangliosides, including 3'-isoLM1 was low if at all detectable. However, in vivo growth of solid subcutaneous tumors in nude mice or rats led to a significantly increased expression of the often dominant gangliosides of the lacto series and revealed a decreased expression of ganglio series gangliosides. In conclusion, these findings indicate that environmental factors could strongly influence the expression of gangliosides that may lead to a switch from the ganglio to the lacto series. These results also suggest that ganglioside 3'-isoLM1 is associated with proliferating astrocytes, of both neoplastic and non-neoplastic origin and that this ganglioside may be involved in cell-cell recognition and attachment during development and tumor cell migration.
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PMID:Gangliosides associated with primary brain tumors and their expression in cell lines established from these tumors. 802 53

In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
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PMID:Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. 811 36

Malignant brain tumours (mainly medulloblastoma, glioma, and ependymoma) are the first cause of solid tumours in children, and a major cause of mortality from cancer in paediatrics. The most frequent circumstance of discovery is intracranial hypertension. Early and atypical signs should give the alarm and call for emergency neuroradiological explorations. Major therapeutic advances have been made in the last ten years in the fields of neurosurgery, radiotherapy and chemotherapy of brain tumours in children. Multidisciplinary care is now indispensable usually as part of multicentre cooperative clinical trials. Therapeutic approaches are guided by a concern not only for effectiveness, but also for low toxicity, in order to reduce the long-term sequelae often caused by irradiation of the developing central nervous system.
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PMID:[Malignant cerebral tumors in children]. 814 34

O6-Alkylguanine-DNA alkyltransferase (AT) is a cellular protein that protects cells from the cytotoxic effects of nitrosoureas by repairing alkyl lesions at the O6 position of guanine. We have studied the ability of O6-benzylguanine to deplete AT activity in brain tumor xenografts and thereby increase the sensitivity of these tumors to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In toxicity studies, pretreatment of athymic mice with O6-benzylguanine increased the toxicity of BCNU significantly. After i.p. injection of O6-benzylguanine into athymic mice carrying subcutaneous (s.c.) D341MED, a human medulloblastoma xenograft with a high AT activity, the AT activity of the tumors became undetectable within 1 h and remained depleted until 36 h. In s.c. xenografts to D341MED, treatment with O6-benzylguanine followed 1 h later by BCNU produced a significantly greater growth delay (14.8 days) than was seen with BCNU alone (2.3 days). A lower pretreatment dose of O6-benzylguanine produced a significantly smaller therapeutic effect. Delaying the administration of BCNU until 36 h after O6-benzylguanine resulted in a growth delay (1.2 days) that was not significantly different from that produced by the control or BCNU alone. In athymic mice with intracranial (i.c.) xenografts of D341MED, pretreatment with O6-benzylguanine followed 1 h later by BCNU produced a significantly increased survival as compared with that of the control, BCNU alone, O6-benzylguanine alone, and O6-benzylguanine followed 36 h later by BCNU. In experiments with s.c. xenografts of D245MG, a human glioma xenograft with undetectable AT activity, pretreatment with O6-benzylguanine 1 h prior to BCNU produced a significantly greater effect than was seen with BCNU treatment alone. The combination regimen, however, was not as effective as an equitoxic dose of BCNU alone. These studies suggest that O6-benzylguanine may be a useful adjuvant to nitrosourea therapy in human malignancies that exhibit a range of AT activities and that dose and timing are important variables in achieving therapeutic success. These data also indicate that therapeutic potentiation of BCNU by O6-benzylguanine can be achieved in i.c. tumors. As a result, this approach may be useful in the treatment of neoplasms of the central nervous system.
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PMID:Treatment of subcutaneous and intracranial brain tumor xenografts with O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea. 825 96


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