Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell death in the core of human brain tumors is triggered by hypoxia and lack of nutrients, but the mode of cell death whether necrosis or apoptosis is not clearly defined. To identify the role of apoptosis in brain tumor cell death, we investigated macromolecular (RNA and protein) synthesis and activity in the central to peripheral region of benign [desmoplastic infantile ganglioglioma (DIG) and transitional meningioma (TMG)] and malignant [ependymoma (END), anaplastic astrocytoma (APA), and glioblastoma multiforme (GBM)] brain tumors derived from five patients who had not received previously radiotherapy or chemotherapy. Normal brain tissue (NBT) served as control. RT-PCR analysis of tumor tissues covering central to peripheral regions detected mRNA overexpression of pro-apoptotic gene bax in malignant tumors, indicating a commitment to apoptosis. The mRNA expression of calpain (a Ca(2+)-dependent cysteine protease) and calpastatin (endogenous calpain inhibitor) was altered resulting in an elevated calpain/calpastatin ratio. Calpain content and activity were increased, suggesting a role for calpain in cell death. In the mitochondria-dependent death pathway, caspase-9 and caspase-3 were also overexpressed in tumors. The increased caspase-3 activity cleaved poly(ADP-ribose) polymerase (PARP). Agarose gel electrophoresis detected a mixture of random and internucleosomal DNA fragmentation in malignant brain tumors. Overexpression of pro-apoptotic bax, upregulation of calpain and caspase-3, and occurrence of internucleosomal DNA fragmentation are now presented indicating that one mechanism of cell death in malignant brain tumors is apoptosis, and that enhancement of this process therapeutically may promote decreased tumor growth.
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PMID:Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: upregulation of calpain and caspase-3. 1211 1

The cancer stem cell hypothesis proposes that tumors contain a small subset of cancer cells, the cancer stem cells, which constitute a reservoir of self-sustaining cells with the exclusive ability to self-renew and maintain the tumor. Markers that define cancer stem cells that are capable of recapitulating brain tumors as xenografts in mice has not been described. We investigated the relationship between expression of nestin and that of PCNA, VCAM-1 and caspase-3 in the xenografts developed from human anaplastic astrocytoma and glioblastoma tumor-derived spheres in the brain of nude mouse. Xenografts obtained from astrocytoma tumor stem cells (ATSC) and glioblastoma tumor stem cells (GTSC) have showed a large number of cells positive for both PCNA and the nestin, demonstrating that nestin expressing cells have a high rate of proliferation. Xenografts from GTSC showed heterogeneous staining pattern with cells that express both nestin and VCAM-1, whereas others cells remained complete negative. In this case it was noticed that most tumor cells with large or multinucleated nuclei coexpress nestin and VCAM-1. In xenografts from ATSC most cells positive for nestin express VCAM-1 and in this case the two proteins appear to occupy the same cytoplasmic region. Both GTSC and ATSC derived xenografts showed cells positive for both caspase-3 and for nestin detected mainly as single cells and as cell clusters located near or around a blood vessel.
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PMID:Co-localization of PCNA, VCAM-1 and caspase-3 with nestin in xenografts derived from human anaplastic astrocytoma and glioblastoma multiforme tumor spheres. 2161 73