Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gemcitabine is a novel antimetabolite drug that acts by multiple mechanisms, including inhibition of ribonucleoside diphosphate reductase, of dCMP deaminase and of dCTP incorporation into DNA and RNA. Here, we report that gemcitabine induces cytotoxic and clonogenic death of 12 human malignant glioma cell lines at clinically relevant concentrations around 1 microM. Gemcitabine is thus approximately 100-fold more active than the congener drug, cytarabine. Gemcitabine cytotoxicity of glioma cells does not require wild-type p53 activity: (i) there was no difference in the susceptibility to gemcitabine between cell lines with wild-type p53 and cell lines with mutant or deleted p53; (ii) ectopic expression of a temperature-sensitive p53 protein either at wild-type (32.5 degrees C) or at mutant (38.5 degrees C) conformation had no significant influence on gemcitabine-induced cell death. Gemcitabine cytotoxicity was unaffected by the antioxidants, N-acetylcysteine and phenyl-N-tert-butyl-alpha-phenylnitrone. There was no correlation between the susceptibility to gemcitabine and the endogenous expression of the B cell lymphoma-2 (BCL-2)-family proteins BCL-2, BCL-XL, myeloid cell leukemia-1 (MCL-1), BCL-2-associated X protein (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-XS. Ectopic expression of BCL-2 moderately attenuated gemcitabine-induced cell death. Similarly, preexposure to the synthetic steroid, dexamethasone, which is commonly used to control cerebral edema in brain tumor patients, reduced gemcitabine cytotoxicity. We conclude that the clinical evaluation of gemcitabine for the adjuvant chemotherapy of malignant glioma is warranted.
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PMID:Gemcitabine cytotoxicity of human malignant glioma cells: modulation by antioxidants, BCL-2 and dexamethasone. 998 15

Malignant glioma is the most common brain cancer with dismal outcomes. Individual variation of the patients' survival times is remarkable. Here, we investigated the transcriptome and promoter methylation differences between patients of malignant glioma with short (less than one year) and the patients with long (more than three years) survival in CGGA (Chinese Glioma Genome Atlas), and validated the differences in TCGA (The Cancer Genome Atlas) to identify the genes whose expression levels showed high concordance with prognosis of glioma patients, as well as played an important role in malignant progression. The gene coding a key enzyme in genetic material synthesis, dCMP deaminase (DCTD), was found to be significantly correlated with overall survival and high level of DCTD mRNA indicated shorter survival of the patients with malignant glioma in different databases. Our finding revealed DCTD as an efficient prognostic factor for malignant glioma. As DCTD inhibitor gemcitabine has been proposed as an adjuvant therapy for malignant glioma, our finding also suggests a therapeutic value of gemcitabine for the patients with high expression level of DCTD.
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PMID:Gene Expression and Methylation Analyses Suggest DCTD as a Prognostic Factor in Malignant Glioma. 2891 88