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)

A 13-year-old boy with Down syndrome (DS) had a brainstem glioma confirmed at autopsy, 10 years after receiving prophylactic cranial irradiation for acute myeloblastic leukemia. There is no clear association of brain tumors with DS; despite a reported link between leukemia and glioma, a causal association with radiation therapy is more likely.
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PMID:Brainstem glioma after radiation therapy for acute myeloblastic leukemia in a child with Down syndrome. Possible pathogenetic mechanisms. 138 83

Nitrous oxide irreversibly inactivates cob(I)alamin, which serves as a cofactor of the enzyme methionine synthase catalyzing the remethylation of homocysteine to methionine. In patients exposed to nitrous oxide, increase in plasma homocysteine is a responsive indicator of cob(I)alamin inactivation. In the present work, we measured the inactivation of methionine synthase and the concurrent homocysteine export rate of two murine and four human cell lines during nitrous oxide exposure. When cultured in a standard medium with high content (2.3 microM) of folic acid, the methionine synthase of all cell types was inactivated at an initial rate of 0.05 to 0.14 h-1. The inactivation curves leveled off, and a residual activity of 15 to 45% was observed after 48 h of nitrous oxide exposure. The rate and extent of the nitrous oxide-induced inactivation were markedly reduced when the cells were transferred and cultured (greater than 10 days) in a medium containing low concentration (10 nM) of 5-methyltetrahydrofolate. The methionine synthase inactivation increased in a dose-dependent manner when the 5-methyltetrahydrofolate content of the medium was increased from 3 nM to 2.3 microM. The inactivation of methionine synthase was associated with a marked enhancement of homocysteine export rate of murine fibroblasts and a moderate increase in export from two human glioma cell lines. In contrast, in three leukemic cell lines (murine T-lymphoma R 1.1 cells, human promyelocytic leukemia HL-60 cells and human acute myelogenous leukemia KG-1a cells), the homocysteine export rates were not increased during nitrous oxide exposure. In the responsive murine fibroblasts and the glioma cells, the homocysteine export rate varied inversely to the changes in methionine synthase activity induced by nitrous oxide exposure at different concentrations of folate in the medium. The enhancement of homocysteine export rate of some cell types during nitrous oxide exposure probably reflects inhibition of homocysteine remethylation in intact cells, and highlights the utility of extracellular homocysteine as an indicator of metabolic flux through the methionine synthase pathway. No enhancement of homocysteine export despite inactivation of methionine synthase in three leukemic cell lines questions the functional state of the enzyme in these cells.
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PMID:Homocysteine remethylation during nitrous oxide exposure of cells cultured in media containing various concentrations of folates. 160 76

The expression of CD10/CALLA is associated primarily with childhood leukemia of pre-B lymphocyte phenotype. We have compared the hybridization pattern of the CALLA gene from leukemic and normal cells digested with several restriction enzymes. No alterations were noticed with Eco RI, Sac I, Pvu II, Eco RV, Hind III, and Msp I. Since CALLA is also found on other malignancies, we analyzed DNA samples prepared from cell lines derived from leukemia, lymphoma, glioblastoma, retinoblastoma, and neuroblastoma. Normal restriction patterns were observed for all the lines regardless of their CALLA phenotype. Having demonstrated previously that CALLA was structurally identical to neutral endopeptidase 3.4.24.11 (NEP), we have now established a correlation between surface expression of CALLA and NEP activity on leukemia samples and on several cell lines. Malignant cells tested expressed a functionally active enzyme and no gross alteration was present in the CALLA gene. The CD44 gene is expressed on most cells of hemopoietic origin and on greater than 95% of cases of acute lymphoblastic leukemia and acute myeloblastic leukemia studied. It is also expressed on normal astrocytes and on malignant cells of glioma/astrocytoma types. We now report that a similar pattern of hybridization was observed with Sac I, Pvu II, and Eco RI for leukemic samples, normal cells, and malignant cell lines. A polymorphism was recently detected for CD44 using Hind III; leukemic cells and malignant lines also showed this normal polymorphism. Thus no deletion or insertion could be detected in the CD44 gene of leukemic cells and malignant lines, suggesting that no gross DNA alterations were involved. The correlation between surface expression and enzymatic activity of CD10/CALLA and the expression of CD44 on a variety of malignant cells would suggest that the structure and function of these two gene products are probably not altered by the process of transformation.
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PMID:CD10 and CD44 genes of leukemic cells and malignant cell lines show no evidence of transformation-related alterations. 183 12

Two female patients, 42 and 30 years old, respectively, died of acute nonlymphocytic leukemia 43 and 38 months, respectively, after a subsequent treatment: chemotherapy for one and irradiation and chemotherapy for the other, following excision of a malignant glioma. At the time of death, both seemed to be in complete remission of their brain tumor. Both had been treated with procarbazine and nitrosoureas. The latter were responsible for severe myelosuppressive episodes and seem to have played an essential role in the induction of the leukemia. In one case, a myelodysplasia was observed before the onset of the AL and the diagnosis of refractory anemia with excess of blasts seemed warranted. Secondary acute leukemias are rare in the evolution of malignant gliomas and the usefulness of subsequent radiochemotherapy cannot be questioned at the present time. The risks involved in this therapy are minor when compared to the short-term fatal prognosis of this type of tumor.
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PMID:Two cases of acute leukemia following treatment of malignant glioma. 686 Oct 68

We report two patients with acute myeloid leukemia (AML) following therapy for malignant glioma; one was a young women treated heavily with alkylating agents for glioblastoma and the other a young man treated with high doses of procarbazine, lomustine, and vincristine (PCV) for anaplastic astrocytoma. We found 26 other examples of therapy related leukemia in adult and pediatric brain tumor patients. Including our two, there were 12 patients with malignant glioma; median interval from treatment to diagnosis of AML was 31 months. Nine adult malignant glioma patients all received nitrosoureas, some as the sole form of chemotherapy. No definite cases occurred after radiotherapy alone. Based upon analogy with other cancers, the cumulative dose of chemotherapy, especially alkylating agents, is the major risk factor for development of secondary AML. Agents implicated include carmustine (BCNU), lomustine (CCNU), and procarbazine. Conventional radiotherapy appears not to confer additional risk. Progressive macrocytosis, early dose reductions for thrombocytopenia, and refractory anemia may provide early diagnostic clues. Current glioma therapy is leukemogenic but the number of patients who survive the interval required to induce AML is small; nevertheless, the identification of chemosensitive types of glioma, and subgroups of patients who derive the most benefit from chemotherapy, may result in increasing numbers of patients at risk of long term complications. If regimens such as PCV continue to prove valuable in neurooncology the risk of leukemia will require integration into the clinical decision process. A search for more effective therapy with minimal mutagenicity remains critical.
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PMID:Acute leukemia following treatment of malignant glioma. 987 84

Data from the annual survey on transplant activity 1997, collected from 457 transplant teams in 31 European countries by the European Group for Blood and Marrow Transplantation (EBMT) were used to describe current status and to assess relative and absolute changes in indication, donor type and stem cell source compared to 1991. A total of 16950 patients were reported to have a first blood or marrow transplant in 1997, a total of 18 923 procedures, including re- and double transplants were performed. Of the 16950 first transplants, 4751 (28%) were allogeneic, 12199 (72%) autologous transplants. Of the autologous transplants, 829 (7%) were bone marrow derived, 11370 (93%) from peripheral blood stem cells or combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 3311 (70%) were bone marrow, 1440 (30%) were peripheral blood stem cell transplants. In 1991, the respective figures were 2175 allogeneic (44%) and 2786 (56%) autologous transplants, more than 90% of the autologous, all allogeneic transplants bone marrow derived. Main indications in 1997 were leukemias with 5253 transplants (31%), 70% allogeneic; lymphomas with 6773 transplants (40%), 94% autologous; solid tumors with 4154 transplants (24%), 99% autologous; non-malignant disorders with 770 transplants (5 %), 85 % allogeneic. There was an absolute increase of 11971 transplants since 1991. An increase was observed in all disease categories. Marked differences were found, when the relative increase index (RII) for specific disease categories over time was analyzed. In allogeneic transplants, relatively more transplants were performed in 1997 for acute myeloid leukemia beyond 1st complete remission (RII 1.28), myelodysplastic syndromes (RII 1.58), chronic lymphocytic leukemia (RII 1.33) and non-Hodgkin's lymphoma (RII 1.58). For autologous transplant indications, a high relative increase index was observed in myelodysplastic syndromes (RII 3.77), in multiple myeloma (RII 2.12) and carcinoma of the breast (RII 6.37) with a relative decrease in leukemias (RII 0.39) and certain solid tumors such as glioma (RII 0.27) and neuroblastoma (RII 0.46). These data present the current status of blood and marrow transplantation in Europe. They show the change from bone marrow to blood as stem cell source and highlight shifts in indication. They provide a basis for patient counselling and health care planning.
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PMID:Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT). 1045 92

The farnesyltransferase inhibitors (FTIs) were designed to inhibit the post-translational processing of Ras proteins, which are mutated in 30% of all human cancers. Recent studies suggest, however, that the target of FTIs may be a protein other than Ras, and that these agents may be more appropriately used to treat tumors with activated wild-type ras signaling. Preliminary results from several phase II and phase III studies have been reported. The FTIs fail to show significant single-agent activity in non-small cell lung cancer, small cell lung cancer, pancreatic cancer, refractory colorectal cancer, and bladder cancer. Activity has been shown in hematologic malignancies (acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome), breast cancer, and glioma. Several combination studies of FTIs and standard cytotoxic agents are ongoing.
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PMID:Farnesyltransferase inhibitors. 1498 78

Cancers are formed by heterogeneous cell types from immature highly proliferative cells to lineage-committed differentiated cells. Transplantation studies have suggested the existence of "cancer stem cells", individual cells capable of producing an entire tumor. Recent advances in stem cell research have allowed for the demonstration of the existence of cancer stem cells in acute myeloid leukemia, breast cancer, and, most recently, in pediatric brain tumors. Each of these has some similarities with the normal stem cells in the corresponding organs. For example, leukemia stem cells express some, but not all, markers of hematopoietic stem cells. Regarding pediatric brain tumors, putative cancer stem cells were identified from medulloblastoma and also from glioma. These tumor-derived cells self-renew under clonal conditions, and differentiate into neurons and glia as well as into abnormal cells with mixed phenotypes. Interestingly, the tumor stem/progenitors, enriched in culture, maintained proliferation after 4 weeks from transplantation into neonatal rat brain. In this review, we discuss the difference as well as the similarity between tumor and normal stem cells, and also the possible clinical implication of cancer stem cells.
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PMID:[Cancer stem cells in pediatric brain tumors]. 1547 49

This 2002 European Group for Blood and Marrow Transplantation (EBMT) activity survey concentrates on current status, increase and decrease in haematopoietic stem cell transplantation (HSCT) activity in Europe and investigates the association of transplant rates with team density. In 2002, there were 20 207 HSCT, 6915 allogeneic (34%), 13 292 autologous (66%) and 3947 additional re- or multiple transplants collected from 586 centres in 39 European countries. Main indications were leukaemias (6523 (32%; 76% allogeneic)); lymphomas (10 760 (53%; 92% autologous)); solid tumours (1913 (9%; 92% autologous)) and nonmalignant disorders (874 (4%; 92% allogeneic)). Compared to 2001, there were increases (>10%) for AML, ALL 1st CR, CML not 1st cP, MDS, SAA and CLL in allogeneic HSCT and for MDS, Ewing's sarcoma, soft-tissue sarcoma and ovarian cancer in autologous HSCT. Decreases (>10%) were observed in autologous HSCT for acute leukaemias beyond 1st CR, CML cP, glioma, breast cancer and lung cancer. Correlation of transplant rates (number of transplants per 10 million inhabitants) with team density (number of transplant teams per 10 million inhabitants) suggests different diffusion patterns for autologous compared to allogeneic HSCT. These data describe current practice for blood and marrow transplantation in Europe and give some hints about mechanisms involved in HSCT rates.
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PMID:Haematopoietic stem cell transplantation (HSCT) in Europe 2002. Changes in indication and impact of team density. A report of the EBMT activity survey. 1551 6

Activation in transformed cells of normal stem cells' self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene-driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell-resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell-like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1-driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.
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PMID:Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. 1593 83


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