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)

Cells of two human glioma lines (UC-35AG, UC-58EG), a human medulloblastoma line (UC-51MB), two rat glioma lines C6, RG2), and a rat schwannoma line (Lew-MS) were injected i.v. into male nude mice (BALB/c nu/nu). Each animal was injected with 10(6) viable cells of a particular line; for each line there was a group of eight to nine animals. The mice developed disseminated (metastatic) tumors from all lines. The incidence of mice developing metastatic tumors was different for the various lines: 2/8 for the UC-34AG, 7/9 for the UC-58EG, 1/8 for the UC-51MB, 7/8 for the C6 line, 8/8 for the RG2 and 1/9 for the Lew-MS line. The shortest survival of the mice with tumors was observed with C6 (all died on days 10-14 post injection), and with RG2 (all died from day 32 to day 39 following injection). With the remaining lines, all mice survived until they were killed on day 40 after injection. Most frequently the tumors developed in the lung. Other organs, e.g., kidney or liver, were sometimes also involved, but usually to a considerably lesser degree than the lung. Metastases never developed in the CNS. It was observed that tumors of certain glioma lines tended to grow in the lung in characteristic patterns and involved or spared other organs.
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PMID:Disseminated (metastatic) tumors in nude mice produced by intravenous injection of cells of human and nonhuman neurogenic tumor lines. 646 77

Seventy-three patients under 18 years of age with a recurrent central nervous system tumor were randomized to receive combination chemotherapy with MOPP or OPP. Patients were stratified according to the tumor type into four major disease categories: (1) medulloblastoma, (2) astrocytoma and other glioma, (3) ependymoma, and (4) miscellaneous tumors to provide equal distribution of patients for each treatment within each disease category. Evaluation of response was based on computerized brain scan findings. Thirty-five patients received MOPP and 38 received OPP treatment. There were three complete and six partial remissions among patients receiving MOPP and one complete and five partial remissions among patients receiving OPP. In addition, six patients on MOPP had stable disease for seven to 21 months. Only two patients on OPP had stable disease(6 and 36 months). Most of responses in both treatment regimens occurred in patients with medulloblastoma and astrocytoma. Median duration of remission was nine months for the MOPP and 11 months for the OPP. Two patients on MOPP regimen had fatal myelosuppression. Although the more toxic MOPP regimen produced more responses than OPP in children, differences in the duration of response or survival were not statistically significant (P = .79 and P = .84, respectively).
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PMID:Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with or without nitrogen mustard (NSC-762)(MOPP vs OPP) in children with recurrent brain tumors. 654 2

Four cases of medulloblastoma in children are reported in which a marked degree of differentiation towards neoplastic adult glioma cells was observed. The original immature and highly malignant tissue had largely disappeared in three and completely disappeared in the fourth. The mature tissues which replaced them included astrocytoma tissues in all four, but ependymoma tissues predominated in two. These cases illustrate a general principle applicable to embryonic tumors, defined as those originating in cells that are still immature. Such maturation and differentiation are presumably associated with a decrease in growth rate and an improved prognosis. A continuation of the process of maturation may account for the unexpectedly favorable course sometimes noted with gliomas in children. The processes of differentiation, dedifferentiation, and anaplasia are discussed, particularly the semantic implications of the terms, and it is suggested that the term "dedifferention" is unfortunate since it may have two different meanings. It may be used as a synonym of anaplasia, or it may imply a progression of change backward on the embryologic pathways along which primitive cells normally mature. The latter may not occur, but the assumption that it does leads to views concerning the glioma group as a whole and the phenomena described in this paper, which we hold to be untentable.
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PMID:Extensive advanced maturation of medulloblastoma to astrocytoma and ependymoma. 667 67

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

We investigated the effects of local administration of interferon (IFN) on 13 patients with recurrent brain tumors. Histologic diagnoses were glioblastoma (eight patients), medulloblastoma (one), ependymoma (one), ependymoblastoma (one), pontine glioma (one), and astrocytoma (one). When tumor recurrence was evident local administration of IFN was started through an Ommaya reservoir, which was placed during repeat craniotomy. No tumor regressions were seen in the patients given weekly injections of IFN; however, in two of six patients given daily injections, a decrease of tumor volume and augmentation of natural killer activity were seen.
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PMID:Local administration of interferon for malignant brain tumors. 668 76

We used diaziquone (NSC 182986) alone and in combination with other antineoplastic drugs to treat six human glioma and one human medulloblastoma tumor lines growing s.c. in athymic mice. Pharmacokinetic studies of diaziquone in the plasma of athymic mice indicated rapid clearance with a half-life of approximately 11.5 min. Diaziquone produced significant growth delays in at least one experiment using each of seven different tumor lines, and it produced consistent and significant delays in five of the seven. There was no obvious difference between a single dose and a dose administered once daily for 5 days, and tumor regressions to a volume smaller than that at treatment were uncommon in any of the single-drug experiments. Using our most extensively characterized human glioma line, D-54 MG, we found striking enhancement of the therapeutic effect by using nontoxic combinations of either diaziquone and carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, NSC 409962) or diaziquone and procarbazine (NSC 77213). These combinations produced significant increases in the median growth delay, significant increases in the number of tumor regressions, and some instances in which no palpable tumors were present 100 days after treatment. In contrast, in experiments using diaziquone -based chemotherapy combinations with either cyclophosphamide, cis-platinum, or vincristine, there was only slight enhancement of the therapeutic effect. These results, using human glioma and medulloblastoma tumor lines in athymic mice, suggest a broad range of activity of diaziquone against primary nervous system tumors and enhancement of its therapeutic effect with either 1,3-bis(2-chloroethyl)-1-nitrosourea or procarbazine. If Phase II and Phase III clinical trials corroborate these findings, the value of the nude mouse system for the evaluation of new therapeutic approaches to brain neoplasms would be further confirmed.
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PMID:Treatment of human glioma and medulloblastoma tumor lines in athymic mice with diaziquone and diaziquone-based drug combinations. 672 74

Antineoplaston (Ap), a new antitumor agent, was clinically tested for effects on malignant brain tumors. The materials were 3 cases of glioblastoma (G,B), 2 cases of anaplastic astrocytoma, 1 case of pontine glioma, 2 cases of metastatic brain tumor and 1 case of medulloblastoma. All patients underwent radiochemotherapy and surgical resection of the tumors except the cases of pontine glioma, metastatic brain tumor and anaplastic astrocytoma. For gliomas, radiochemotherapy was used with Hu-IFN-beta. Ap was administered at a dose of 7-10 g/day in combination with remission maintenance therapy of gliomas. Complete response was obtained in one anaplastic astrocytoma. Partial response was obtained in 2 cases, a pontine glioma and a metastatic brain tumor. No change was observed in 2 cases, an anaplastic astrocytoma and a multiple brain metastasis. Progression of the disease was observed in 4 cases, 3 glioblastomas and 1 medulloblastoma, which showed continuous increase in tumor size. The effects of Ap on malignant brain tumors were considered due to synergy, since it was administered with other drugs and acceleration of tumor cellular differentiation. Ap is useful as an approach to remission maintenance therapy for brain tumors.
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PMID:The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. 747 50

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been implicated in resistance of human brain tumors to alkylating agents. We observed that 14 human medulloblastoma- and glioma-derived cell lines differ in sensitivity to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), as shown by their 28-fold range in 10% survival dose (LD10). By using the substrate analogue inhibitor O6-benzylguanine (O6-BG), we showed that the contribution of MGMT to resistance varies widely, as evidenced by 3- to 30-fold reductions in LD10 among the lines, and varies up to 20-fold among subpopulations of individual lines. Importantly, variability in resistance, manifested as a 20-fold range in LD10, persists after measurable MGMT is eliminated, disclosing differential contributions of other resistance mechanisms to survival. Cells exposed to MNNG while suspended in growth medium are more resistant than cells alkylated as subconfluent monolayers, and MGMT accounts for a smaller proportion of their resistance. Notably, the MGMT content of the lines is not statistically correlated with MNNG resistance or with potentiation of killing by O6-BG, even though MGMT is a biochemically demonstrated determinant of resistance. In contrast, the same lines vary less in resistance to the ethylating agent N-ethylnitrosourea (ENU), and MGMT makes only a small contribution to resistance. Our results strongly indicate that resistance to both MNNG and ENU is multifactorial.
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PMID:Contribution of O6-methylguanine-DNA methyltransferase to monofunctional alkylating-agent resistance in human brain tumor-derived cell lines. 760 82

To assess the possible role of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in resistance of brain neoplasms to the clinically important chloroethylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), we quantitated MGMT activity, BCNU survival, and the effect of ablating MGMT activity on the sensitivity of 14 human medulloblastoma- and glioma-derived cell lines. BCNU resistance, measured as 10% survival dose (LD10), differed eightfold among the lines. Elimination of measurable MGMT activity with the substrate analogue inhibitor O6-benzylguanine (O6-BG) revealed a variable but limited contribution of MGMT to survival. In no case did O6-BG reduce LD10 by more than 3.4-fold. In contrast, O6-BG reduced the LD10 for N-methyl-N'-nitro-N-nitrosoguanidine up to 31-fold in the same cell lines (Bobola MS, Blank A, Berger MS, Silber JR, Mol Carcinog 13:70-80, 1995). Variability in BCNU survival, manifested as a sevenfold range of LD10, persists after measurable MGMT was eliminated, indicating that another mechanism or mechanisms is operating to limit cytotoxicity. Cells alkylated while suspended in growth medium are more resistant to BCNU and display less dependence on MGMT than cells treated while proliferating on a plastic substratum. When alkylated in suspension, most of the lines are either unresponsive to O6-BG or contain a subpopulation that did not respond to O6-BG. Our results demonstrate that BCNU resistance is multifactorial and that MGMT makes a modest contribution to resistance in our lines.
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PMID:Contribution of O6-methylguanine-DNA methyltransferase to resistance to 1,3-(2-chloroethyl)-1-nitrosourea in human brain tumor-derived cell lines. 760 83

The authors investigated the effects of a nontoxic differentiation inducer, phenylacetate (PA), on neuroectodermal tumor-derived cell lines. Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G0/G1 phase of the cell cycle. Phenylacetate decreased transforming growth factor (TGF)-beta 2 production by medulloblastoma Daoy cells. Neutralizing antibodies against either TGF beta 2 or TGF beta 1 failed to block the growth arrest observed. This suggests that, unlike other differentiation agents, such as retinoic acid, the effect of PA on medulloblastoma proliferation is not mediated by a TGF beta pathway. In addition to cytostasis, PA induced marked morphological changes in U-251MG and C6 glioma cells associated with increased abundance of glial fibrillary acidic protein-positive processes. Although the morphology of PA-treated medulloblastoma cells was not significantly altered, the D283 MED cells exhibited increased expression of neurofilament proteins and Hu antigen, indicative of differentiation along a neuronal pathway. The effects of PA on the medulloblastoma cell lines were compared to its effects on the human neuroblastoma cell line BE(2)C, which is capable of a bidirectional differentiation toward a neuronal or a glial/schwann cell pathway. In BE(2)C cells, PA induced differentiation toward a schwann/glial cell-like phenotype, suggesting that the choice of differentiation pathway is cell type and agent specific. These in vitro antiproliferative and differentiation inducing effects of PA suggest that this agent warrants further evaluation as a potential therapeutic modality for the treatment of medulloblastoma and malignant glioma in humans.
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PMID:Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate. 767 18


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