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)

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.
 ...
PMID:Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. 1714 87

CPT-11, a derivative of camptothecin (CPT) that interacts with type-I DNA topoisomerase, induced apoptosis in HL60 and Daudi cells in vitro. This cytotoxic activity was time and dose dependent, and was prevented by cycloheximide (CHX), a protein synthesis inhibitor, indicating the requirement of new protein synthesis for CPT-11-induced apoptotic cell death. Ac-Tyr-Val-Ala-Asp-aldehyde (YVAD) and Ac-Asp-Glu-Val-Asp-aldehyde (DEVD), synthesized tetrapeptide inhibitors of interleukin(1beta)-converting enzyme (ICE)- and CPP32/Yama-like proteases, were used to examine the CPT-11-induced death signal transduction. These inhibitors blocked CPT-11-induced cytotoxicity in a time- and dose-dependent manner. Cytotoxic activity of SN-38, an active metabolite of CPT-11, was about 1000-fold that of CPT-11 and was also prevented by CHX, YVAD and DEVD. The doses of YVAD, however, were a little too high; the prevention by YVAD is then thought to be non-specific. In addition, lymphocytes obtained from normal and lpr(cg) mutant mice showed similar susceptibility to CPT-11 cytotoxicity. These results indicate the direct involvement of CPP32/Yama-like protease in the CPT-11-induced death signal transduction pathway, and no involvement of Fas antigen in the pathway.
 ...
PMID:Involvement of CPP32/Yama-like protease in CPT-11-induced death signal transduction pathway. 2065 Feb 53


<< Previous 1 2