Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growth factor receptor family that signals apoptotic cell death in sensitive cells. Expression of Fas and its agonistic ligand (FasL/TNFSF6) was investigated in ex vivo pediatric brain tumor specimens of various histologic types. Fas expression was identified in all of the 18 tumors analyzed by flow cytometry and immunohistochemistry. FasL expression was identified in most of the 13 tumors analyzed by both Western analysis and immunohistochemistry. Nine of these tumor specimens were treated with either the agonistic anti-Fas antibody (APO-1) in combination with protein A or FasL in short-term cytotoxicity assays. Sensitivity to apoptosis induced by the topoisomerase II inhibitor, etoposide, was also assessed. Despite the presence of Fas, all the specimens analyzed demonstrated a high degree of resistance to Fas-mediated apoptosis. These 9 specimens also showed a high degree of resistance to etoposide. Only 2 of the 9 specimens were susceptible to etoposide-induced cell death, whereas only 3 were sensitive to Fas-mediated apoptosis. One brain tumor was sensitive to both Fas ligation and etoposide treatment. This contrasted with the high degree of susceptibility to both etoposide- and Fas-induced apoptosis observed in the reference Jurkat cell line. The results suggest that Fas expression may be a general feature of tumors of the CNS and that a significant degree of resistance to Fas-mediated apoptosis may exist in ex vivo pediatric brain tumor specimens.
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PMID:Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are resistant to apoptosis induction. 1158 92

Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TIIalpha expression was found to extend over a wide range in the study cohort (3.9-69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TIIalpha <12 vs. >or=12) with profoundly different 5-year progression-free survival (60% vs. 8%; p = 0.0108, log-rank test) and overall survival (100% vs. 8%; p = 0.0038) rates. TIIalpha expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R = 0.919, p < 0.001). A high TIIalpha labeling index remained associated with short progression-free survival (p = 0.022) and overall survival (p = 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.
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PMID:DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas. 1211 82