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)

Telomerase activity has a close relationship with malignancies in many cell types and it is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). Utilizing the hTERT promoter, the authors developed a gene delivery system of Fas associated protein with death domain (FADD) (hTERT/FADD). FADD is a protein which plays an important role in the apoptotic pathway of Fas. Over-expression of FADD induces apoptosis in the cells regardless of Fas expression on the cell surface. We hypothesized that we might be able to restrict the expression of FADD in malignant glioma cells if we use the gene transfer system under the control of hTERT promoter. This study was designed to investigate whether the hTERT/FADD construct induces apoptosis effectively in malignant glioma cells while keeping normal cells intact. First, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we confirmed that hTERT mRNA was expressed in human malignant glioma cells (U373-MG, A172 and GB-1), but not in cultured astrocytes (TEN) or fibroblasts (MRC5). After transient transfection with the hTERT/FADD construct, a significant number of FADD-positive cells and apoptotic cells were detected in hTERT-positive malignant glioma cells. In contrast, hTERT-negative astrocytes and fibroblasts remained intact. Furthermore, subcutaneously implanted U373-MG tumors treated with the hTERT/FADD construct reduced in volume significantly compared to the conrol treatment (p=0.0001). Gene transfer of FADD under the control of the hTERT promoter may be a novel and promising therapy to kill hTERT-positive malignant glioma cells while sparing normal brain cells lacking hTERT.
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PMID:A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter. 1160 3

Serious dermatologic adverse events such as erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported in patients receiving antiepileptic drugs (AEDs) and cranial radiotherapy (RT). Given the frequency of AED-associated rashes and the infrequency of serious dermatologic adverse events after cranial RT, we sought to further assess the prevalence of cutaneous eruptions in patients receiving an AED before and after cranial RT. We reviewed medical records of patients taking AEDs while undergoing RT for a high-grade glioma and recorded demographic, disease, and treatment parameters, as well as the development of rashes. Rashes were found in 19 % of patients taking AEDs. Phenytoin was most commonly implicated (93 %) in rash formation compared with other AEDs (P < 0.0001), both before and during RT. Most rashes (76 %) occurred before starting RT (P < 0.0001). However, of those during RT, most were associated with phenytoin compared with other AEDs (P = 0.002). One case of SJS was noted in a patient receiving phenytoin prior to RT. While rashes were slightly less prevalent in patients receiving temozolomide compared with those not receiving temozolomide (3.4 vs 4.8 %), this difference was not statistically significant (P = 0.65). Rashes are relatively common in patients receiving AEDs, with the highest incidence associated with phenytoin. However, the risk of serious dermatologic events is low. There did not appear to be an association between the receipt of cranial radiotherapy and the development of AED-associated rash with phenytoin or other AEDs.
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PMID:EMPACT syndrome: limited evidence despite a high-risk cohort. 2479 90