Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl-2 oncoprotein, a member of a new category of oncogenes associated with the regulation of programmed cell death (apoptosis), has been considered to be involved in biological processes such as tumorigenesis and tumor development. To determine the role of bcl-2 oncoprotein in lung cancer, we preliminarily examined the expression of this protein in various histological types. Immunohistochemical staining using monoclonal bcl-2 oncoprotein antibody was performed in surgically resected frozen specimens. Bcl-2 staining was seen in nine of 13 small cell lung cancers (69%), while only 18 out of 69 non-small cell lung cancers (26%) expressed bcl-2 oncoprotein, showing a significantly increased incidence of bcl-2 oncoprotein expression in the former histological type. Considering the greater aggressiveness of small cell lung cancer compared to non-small cell lung cancer, the possibility exists that the high prevalence of bcl-2 oncoprotein expression in small cell lung cancer is closely associated with tumorigenesis and tumor development.
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PMID:High prevalence of bcl-2 oncoprotein expression in small cell lung cancer. 776 30

We reviewed recent reports on apoptosis and summarized the presentations at the Shirafu Cancer Symposium, 1993. The study of programmed cell death, apoptosis, has become one of the mainstream in cell biology, particularly in immunology, developmental biology and oncology. To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl-2. SBC-3/Bcl-2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl-2. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and Taxol between SBC-3 and SBC-3/Bcl-2 (Ohmori, T. et al. Biochem. Biophys. Res. Commun. 1993). These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis. We speculate that some apoptotic pathways are bcl-2-sensitive and others bcl-2-independent.
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PMID:[Anticancer agents and apoptosis]. 810 88

To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl2. SBC-3/Bcl2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3, with relative resistance values of 3.4, 7.6 and 5.7, respectively. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and taxol between SBC-3 and SBC-3/Bcl2. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC, in a concentration-dependent manner. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl2. Treatment with CDDP resulted in the same degree of DNA fragmentation in SBC-3 and SBC-3/Bcl2. These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis.
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PMID:Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2. 847 31

We reviewed recent investigations on apoptosis related to anticancer chemotherapy. The study of programmed cell death, apoptosis, has become one of the main stream in cellular biology, particularly in immunology, developmental biology and oncology. To determine whether the apoptotic cell death induced by anticancer agents could be inhibited by bcl-2 oncogene, we established a bcl-2 transfected human small cell lung cancer cell line, SBC-3/Bcl-2. SBC-3/Bcl-2 showed higher resistance to ADM, CPT-11 and MMC compared to the parental line SBC-3. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl-2. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and Taxol between SBC-3 and SBC-3/Bcl-2 (Ohmori T, et al: Biochem Biophys Res Commun 1993). These results suggest that bcl-2 can modulate the cytotoxicity of some anticancer agents by inhibiting the process of apoptosis. We speculate that some apoptotic pathways are bcl-2-dependent and others bcl-2-independent.
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PMID:[Anticancer agents and apoptosis]. 858 98

For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas histologically diagnosed. In addition, 3 small cell lung cancer cell lines were studied by Western blotting. Neuroendocrine differentiation in Bcl-2-negative squamous cell carcinomas and adenocarcinomas was examined with chromogranin A and alpha-subunit of Go protein stainings. Bcl-2 protein was detected in 104/111 small cell carcinomas, 8/8 neuroendocrine carcinomas, 0/6 typical (well differentiated) carcinoids, 23/64 squamous cell carcinomas, 4/65 adenocarcinomas, and all 3 small cell lung cancer cell lines. All 8 neuroendocrine carcinomas, 11 of the Bcl-2-positive squamous cell carcinomas, and all 4 Bcl-2 positive adenocarcinomas expressed multiple neuroendocrine markers. The distributions of Bcl-2 and neuroendocrine marker immunoreactivity closely paralleled each other on consecutive sections. In squamous cell carcinomas, Bcl-2-positive cells could be roughly subdivided into those with neuroendocrine differentiation features, usually demonstrating intense Bcl-2 staining, with basaloid tumor cells usually expressing weak to moderate Bcl-2 staining. The present study clearly shows Bcl-2 protein expression to be remarkably differentially regulated according to histological types of lung cancers and to appear to quite likely be closely associated with neuroendocrine differentiation of tumor cells, indicating that bcl-2 is importantly involved in cell development and differentiation, in addition to protecting cells from apoptosis. Bcl-2 might be usable as a neuroendocrine marker in lung cancers and possibly also in neural-crest-derived tumors.
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PMID:Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. 877 38

The expression of the proto-oncogene bcl-2, whose main function appears to be an inhibition of apoptosis, was investigated in 164 cases of primary small cell lung cancer by means of immunohistochemistry in a retrospective analysis. One-hundred twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference in serum LDH levels and proliferative activity between the two groups. An analysis revealed a median survival time of 12 months for patients with bcl-2 positive tumors compared to 9.5 months for patients with bcl-2 negative tumors. Although statistical significance is not achieved, there is a trend towards longer survival in patients whose tumors express bcl-2. This tendency is also reflected by a higher rate of complete remission after chemotherapy: 40% in patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In multivariate analysis, tumor stage followed by Karnofsky index were the most valuable predictors for complete remission. LDH and tumor stage were most predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may reflect a less aggressive mechanism of transformation and a higher susceptibility to cytostatic treatment.
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PMID:Expression of bcl-2--protein in small cell lung cancer. 886 21

Several genetic aberrations have been implicated in the carcinogenesis of small cell lung carcinomas (SCLCs), including tumour suppressor gene p53 deletion and mutation and amplification of the myc family proto-oncogenes. However, their exact ontogeny and carcinogenesis remain unknown. There are no proven aetiological factors for lung carcinoid tumours. Recent evidence suggests that the genetic regulation of apoptosis is of critical importance during tumourigenesis and that oncogene and tumour suppressor genes can regulate the rate, or susceptibility, of cells to undergo apoptosis. In this study, the expression of Bcl-2 protein has been investigated in 77 primary lung neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared with p53 expression. Of the 77 tumours studied, Bcl-2 immunoreactivity was present in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of atypical carcinoid tumours with more than 10 per cent tumour cell positivity. Western and Northern blot analysis revealed that carcinoid tumours expressed the 26 kD protein and bcl-2 transcripts. Whereas 42 per cent of the SCLCs studied displayed p53 protein immunoreactivity in more than 10 per cent of tumour cells, p53 positivity was not found in lung carcinoid tumours. There are statistical differences in Bcl-2 and p53 expression between SCLCs and lung carcinoid tumours. These results suggest that disregulation of the genetic mechanisms controlling apoptosis is a critical step in the progression of SCLC, and the expression of Bcl-2 is involved in the pathogenesis of SCLC and lung carcinoid tumours. The genetic complementation of simultaneously deregulated Bcl-2 and p53 may be implicated in the multistep tumourigenesis of small cell lung cancer.
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PMID:Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. 961 75

The influence of bcl-2 oncogene expression on etoposide-induced apoptosis and clonogenic survival was investigated in five small cell lung cancer (SCLC) cell lines, three of which were bcl-2-expressing and two of which were non-bcl-2-expressing. The bcl-2-expressing lines displayed a lower apoptosis propensity than the non-bcl-2-expressing lines. When bcl-2-expressing cells were incubated in cystine/ methionine-free (CMF) medium, etoposide-induced apoptosis was restored to levels comparable to those seen in non-bcl-2-expressing lines. However, the endpoint of clonogenic survival after drug treatment did not display any consistent pattern that correlated with bcl-2 status. In addition, treatment of the two bcl-2-expressing cell lines with etoposide in CMF medium did not modify their clonogenic survival curves compared to treatment in regular medium. These results are consistent with the idea that bcl-2 expression modulates etoposide-induced apoptosis but not clonogenic survival.
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PMID:Bcl-2 expression correlates with apoptosis induction but not loss of clonogenic survival in small cell lung cancer cell lines treated with etoposide. 984 Jul 19

We investigated the immunohistochemical expression of bcl-2 in 55 non small cell lung cancer patients in order to understand if the altered expression of this gene is involved in the development of this kind of neoplasm. Our results showed bcl-2 immunopositivity to be a frequent event in non small cell lung cancer (54.5%) with a higher expression in squamous carcinomas compared to adenocarcinomas (p = .04). In addition, we found a positive correlation between bcl-2 expression levels and nodal status (p < .003). We suggest that bcl-2 immunostaining could be considered as marker of loco-regional invasivity.
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PMID:Bcl-2 protein expression correlates with nodal status in non small cell lung cancer. 1021 99

Drug resistance is a major problem in patients with small cell lung cancer; in fact, most die of resistant disease, despite an initial response. Several markers of drug resistance have been described in preclinical models, but the mechanism of drug resistance in lung cancer patients remains unknown. The objective of this study was to evaluate the role of the expression of a number of markers of drug resistance, proliferation, and apoptosis in relation to response to chemotherapy and survival in patients with small cell lung cancer. Tumor samples were derived from 93 previously untreated patients who were randomized in a Phase III study to receive cyclophosphamide, epirubicine, and etoposide or cyclophosphamide, epirubicine and vincristine alternating with carboplatin and etoposide. Paraffin-embedded samples, derived from the primary tumor site prior to chemotherapy, were analyzed by immunohistochemistry for expression of markers implicated in drug resistance [topoisomerase (topo) IIalpha, topo IIbeta, and multidrug resistance-associated protein], apoptosis (p53, p21, and bcl-2), or proliferation (Ki67). Response prediction was analyzed by chi2 test and logistic regression analysis; overall and disease-free survival curves were compared by log-rank test and Cox regression analysis. Shorter survival was observed in patients with extensive disease (P = 0.037) and poorer performance status (P = 0.028) and in patients whose tumors expressed high topo IIalpha levels (P = 0.01) and high Ki67 (P = 0.024). By multivariate analysis, the following factors were found to be predictive for worse survival: high expression levels of topo IIalpha, Ki67, and bcl-2; male sex; and extensive disease. High topo IIbeta expression was found to be predictive for lower overall and complete response rate. No relationship between apoptotic pathway markers or MRP and response to chemotherapy was observed. In conclusion, high expression of topo IIalpha was predictive of worse survival, and high expression of topo IIbeta was predictive of lower response rates. Furthermore, lower survival probability was observed in patients with bcl-2-positive tumors. Immunohistochemical assessment of these markers in diagnostic biopsies may give important prognostic information and may help selecting patients in the worse prognostic categories for new therapeutic strategies.
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PMID:Expression of DNA topoisomerase IIalpha and topoisomerase IIbeta genes predicts survival and response to chemotherapy in patients with small cell lung cancer. 1047 85


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