Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the mechanism of apoptosis in brain tumors, we analyzed the expression of apoptosis-related gene products in cultured glioma cells and biopsied brain tumor specimens. Fas, Bcl-2 family (Bcl-2, Bcl-x and Bax) and ICE family (ICE, Ich-1) were found to be involved in tumorigenesis of certain brain tumors. It was also clarified that OK-432 activated mononuclear cells could kill T98G glioblastoma cells by apoptotic mechanism through the Fas ligand/Fas system.
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PMID:[Expression of apoptosis-related gene products in human brain tumors and apoptosis-inducing therapy]. 874 89

We characterized three human brain tumor cell lines (D54, HBT-20, and HBT-28) with respect to resistance to etoposide (VP-16), a topoisomerase II-reactive drug. All three cell lines were inherently resistant to VP-16 when compared to other human cell lines, with D54 showing the greatest resistance using colony formation assays. Resistance to VP-16 has been attributed to decreased drug uptake and changes in topoisomerase II; however, drug uptake and topoisomerase II protein levels (immunoblot) were no lower in D54 than in HBT-20 and HBT-28, cell lines relatively more sensitive to VP-16. More to the point, measurement of topoisomerase II-mediated DNA cleavage of cellular DNA after treatment with VP-16 showed that the topoisomerase II in these cells was active. These data indicate mechanisms other than those attributable to decreased drug uptake or altered topoisomerase II exist for clinical resistance to VP-16. VP-16-induced DNA cleavage has been associated with apoptosis in some cell lines; however, neither DNA laddering nor morphological changes characteristic of apoptosis were detected in these cell lines after treatment with VP-16. Bcl-2 and mutant p53 were present in these cells. Either of these conditions can prevent apoptosis and could explain a dissociation between the proximal mediator of VP-16-induced cytotoxicity (topoisomerase II-DNA complex formation) and cellular death.
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PMID:Expression of topoisomerase II, bcl-2, and p53 in three human brain tumor cell lines and their possible relationship to intrinsic resistance to etoposide. 981 36

We examined the expression of the p53 and bcl-2 family in embolized meningiomas and investigated the interaction between them. p53 and its downstream effector p21 accumulated mainly in perinecrotic areas, where apoptosis was also observed. bcl-2 was often expressed in the areas distant from necrosis, whereas Bax was immunostained more intensely in the perinecrotic areas. Double staining for both p53 and Bcl-2 showed a reciprocal pattern. This appeared to be due to the down-regulation of Bcl-2 by p53. However, regulation of Bax by p53 was not distinct. The expression of p21 was not apparent 13 days after embolization, and apoptosis was observed until 6 days after embolization. The effect of embolization was most likely temporary, although growth arrest has been reported to persist for a long time in a limited number of embolized cases.
Brain Tumor Pathol 1998
PMID:Alteration of bcl-2 and bax expression in embolized meningiomas. 987 58

It has been suggested that overexpression of the Bcl-2 oncoprotein in human cancer cells contributes to their resistance to apoptosis induced by chemotherapy. We report here that a novel dipeptidyl proteasome inhibitor, CEP1612, at low concentrations rapidly induces apoptosis in human Jurkat T cells overexpressing Bcl-2 and also in all human prostate, breast, tongue and brain tumor cell lines we have tested to date, without exception. In contrast, etoposide, a standard anticancer drug, fails to kill these cells when employed under the same conditions. The apoptosis-inducing abilities of CEP1612 and its analogous compounds match precisely their order for inhibition of the proteasome chymotrypsin-like activity. CEP1612-induced apoptosis is p53-independent, inhibitable by a tetrapeptide caspase inhibitor, and associated with accumulation of the cyclin-dependent kinase inhibitors p21 and p27. Furthermore, CEP1612 selectively accumulates p27 and induces apoptosis in simian virus 40-transformed, but not the parental normal, human fibroblasts. Proteasome inhibitors such as those investigated herein might therefore have potential use as novel anticancer drugs.
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PMID:Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts. 989 13

We used the rat C6 gliomal cell line to investigate the potential role of ginsenoside Rh2 (G-Rh2) in brain tumor. G-Rh2 induced many apoptotic manifestations in C6 gliomal cells as evidenced by changes in cell morphology, generation of DNA fragmentation, activation of caspase and production of reactive oxygen species (ROS). As a result, cotreatment with antioxidants or a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone effectively attenuated G-Rh2-induced cell death. However, specific cleavage of poly(ADP-ribose)polymerase into 85 kDa protein was not detected as demonstrated in many other apoptotic paradigms. Expression levels of Bcl-2 and Bax remained unchanged following G-Rh2 treatment. Furthermore, G-Rh2-induced cell death in C6 gliomal cells overexpressing antiapoptotic protein, Bcl-X(L), was comparable to that in parental cells. Taken together, our data indicate that G-Rh2-induced cell death is mediated by the generated ROS and the activation of caspase pathway in a Bcl-X(L)-independent manner.
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PMID:Ginsenoside RH-2 induces apoptotic cell death in rat C6 glioma via a reactive oxygen- and caspase-dependent but Bcl-X(L)-independent pathway. 1044 19

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.
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PMID:TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme. 1151 57

The effects of sodium butyrate (SB) and trichostatin A (TSA) on cell proliferation andapoptosis against human glioma T98G, U251MG, and U877MG cells were investigated. Upon exposure to either SB or TSA, cell proliferation was reduced, and apoptosis detected by DNA fragmentation analysis and the cleavage of CPP32 was induced. Previously, we reported that SB increased the expression levels of p21 (WAF-1) and inhibited G1-S transition of the cell cycle. In this study, we showed that TSA also increased p21 expression, suggesting that histone deacetylase (HDAC) inhibitors may up-regulate p21 protein in common and thus arrest proliferation in the G1 phase of the cell cycle. To further determine the underlying molecular mechanisms of apoptosis with either SB or TSA treatment, we studied the expression levels of apoptosis-related proteins in human glioma cells. SB increased the expression of the Bad protein, although the expression of Bcl-2, Bcl-xL, Bax, and Fas was not changed by theaddition of SB. TSA treatment also up-regulated the expression of Bad protein. The results suggest that HDAC inhibitors such as SB and TSA induce apoptosis through an increase in Bad protein in human glioma cells in vitro.
Brain Tumor Pathol 2001
PMID:Histone deacetylase inhibitors such as sodium butyrate and trichostatin A induce apoptosis through an increase of the bcl-2-related protein Bad. 1190 66

The Bcl-2 family is composed of a group of related proteins that either prevent or promote apoptosis. This study was undertaken to assess the prognostic value of Bcl-2, Bcl-x, and Bax in patients with astrocytomas. Tissue samples from 104 astrocytomas (WHO grade 2, 21 cases: grade 3, 49 cases; grade 4, 34 cases), including 68 primary and 36 recurrent tumors, were examined immunohistochemically for Bcl-2, Bcl-x, and Bax expression. Patient charts were reviewed for clinical presentation, and survival was followed. The mean values of the Bcl-2, Bcl-x, and Bax labeling indexes (LI) were 15.9 +/- 13.1%, 53.2 +/- 35.3%, and 25.9 +/- 23.2%, respectively. Statistical analysis showed that the Bcl-x LI of high-grade (grade 3 or 4) astrocytomas was higher than that of low-grade (grade 2) tumors (P = 0.0064). There were no significant differences in patient survival between the high- and low-LI groups of Bcl-2, Bcl-x, and Bax. Since the mechanism and regulation of apoptosis are still unclear, it seems difficult to use the Bcl-2 family as a biological marker in predicting the prognosis of patients with astrocytomas.
Brain Tumor Pathol 2001
PMID:Expression of Bcl-2, Bcl-x, and Bax proteins in astrocytomas in relation to patient survival. 1190 68

In this study the role of cyclooxygenase-2 (COX-2) in primitive neuroectodermal tumor (PNET) the most malignant brain tumors of childhood was investigated. COX-2 expression in human brain tumor biopsy samples (seven/seven) was about 6-8-fold higher than normal brain tissue and several PNET cell lines also express COX-2. The effect of selective COX-2 inhibitors, celecoxib and rofecoxib on the growth of two PNET cell lines (DAOY and PFSK) was determined. Celecoxib was more potent than rofecoxib in suppressing cell growth. Growth inhibition by celecoxib and rofecoxib was independent of Bcl-2 expression. Celecoxib suppressed the expression of Akt and activated the caspase-3 in DAOY and PFSK, whereas rofecoxib did not have such an effect.
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PMID:Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: effect of celecoxib and rofecoxib. 1191 65

Ten pediatric medulloblastoma patients were analyzed for DNA content, cell cycle, expression of drug resistance, apoptosis, cell proliferation, and N-myc genes to determine their prognostic significance. Medulloblastoma patients with progressive disease had fourth ventricle foraminal extension and larger tumors in the imaging studies. Patients with aneuploid tumors responded well to treatment regimens as compared with those with diploid tumors. Cell cycle analysis showed that the patients with progressive disease had a high S-phase fraction in the tumor cell population as compared with patients with favorable response to treatment. The correlation coefficients between Bcl-2 and MRP, Bcl-2 and Bax, p53 and p21, as well as Ki67 and PCNA were positive and significant, indicating their possible coregulated expression. The relationship between these markers indicates their relative and cumulative effect on cellular drug resistance, apoptosis, and/or cell proliferation in pediatric medulloblastomas.
Brain Tumor Pathol 2002
PMID:Molecular studies in pediatric medulloblastomas. 1245 84


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