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)

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

The distinction between noninvasive and invasive or malignant thymoma has been severely compromised by a lack of objective morphological criteria. A reliable marker of tumor aggressiveness is, therefore, mandatory for predicting the tumor behavior. Forty thymic epithelial tumors, including 5 noninvasive thymomas, 18 invasive thymomas, and 17 thymic carcinomas (Rosai's classification) were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. The thymic epithelial cells showed positive immunostain for bcl-2 in 0, 7, and 16 of these categories, respectively. Thymic carcinomas had a significantly higher proportion of bcl-2 expression than thymomas (P < .0001). A significantly higher expression of bcl-2 protein was also shown in thymoma-associated myasthenia gravis (P < .05). However, p53 showed no correlation with the histological subtypes nor clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoreactivity, but this result was not statistically significant (P = .07). In conclusion, these data indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial neoplasms.
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PMID:Detection of bcl-2 and p53 in thymoma: expression of bcl-2 as a reliable marker of tumor aggressiveness. 889 96

Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.
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PMID:Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. 909 68

In this immunohistochemical study we investigated the expression of Bcl-2 and Bax apoptosis related proteins in node-negative breast carcinomas. The results were correlated with the recurrence rate of the patients. In order to avoid the influence of the most important tumor prognostic parameters we selected two groups of node negative breast ductal carcinomas that were grade II according to Bloom and Richardson classification, had a diameter of 1-3 cm but differed in clinical outcome: 44 of the patients had a 10 year disease-free survival while 46 developed metastatic disease in the same period of time. Bcl-2 and to a lesser degree Bax expression were inversely related with distant metastases (Pbcl-2 = 0.007, Pbax = 0.03). Combined analysis of Bax/Bcl-2 expression in relation to clinical outcome showed that the absence of both factors was more strongly associated with the development of distant metastases (P = 0.006, Ptrend = 0.001). Our findings indicate that Bcl-2 and Bax apoptosis-related proteins are good indicators of prognosis in node-negative breast cancer patients, and their combined absence, suggestive of serious deregulation of the apoptotic process, may contribute to the biologic aggressiveness of the tumors.
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PMID:Prognostic significance of apoptosis related proteins Bcl-2 and Bax in node-negative breast cancer patients. 925 70

Flow cytometry and microscopy analyses have demonstrated that 9-nitrocamptothecin (9NC) induces apoptosis in prostate carcinoma LNCaP, DU-145 and PC-3 cells grown in culture or as xenografts. 9NC induces apoptosis regardless of the ability of the cells to induce tumors following xenografting into nude mice. Detection of apoptosis by flow cytometry was preceded or accompanied by increased cell size, loss of nuclear structure and vacuolization, as the tumor regressed, but no visible chromatin fragmentation. This is the first demonstration that 9NC is curative for human prostate carcinoma xenografts in the nude mouse model in the absence of detectable drug-induced toxicity during and after tumor regression. These findings indicate that 9NC may develop into a chemotherapeutic drug for the effective treatment of prostate cancer patients. Further, there was no apparent correlation of the steady-state level of the apoptosis-regulating proteins, Bcl-2, Bcl-XL, Bax and Ich-1, with tumorigenicity of the prostate cells xenografted in nude mice, aggressiveness of tumors grown in nude mice, and induction of apoptosis by 9NC. However, the TIAR protein was present at markedly high levels in all prostate carcinoma cell lines and this may correlate with their susceptibility to 9NC-induced apoptosis.
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PMID:Establishment of human prostate tumor xenografts in nude mice and response to 9-nitrocamptothecin in vivo and in vitro does not correlate with the expression of various apoptosis-regulating proteins. 941 21

A better knowledge of the biological aggressiveness of individual tumors could facilitate the selection of treatment in prostate cancer patients. This study assesses the influence of histological and molecular features in core needle biopsy specimens of prostate cancer on tumor-specific survival. Formalin-fixed core needle biopsy specimens from 111 consecutive patients (mean follow-up, 5.0 years) were immunohistochemically examined for their proliferative activity (Ki67 labeling index [LI]) and expression of p53 and Bcl-2. Overexpression of p53 was found in 16% of the biopsy specimens and was mainly restricted to poorly differentiated tumors. Bcl-2 positivity was found in 20% of tumors. The median Ki67 LI was 7.5%. There was a strong relationship between Ki67 LI and Gleason grade, with a continuous increase in the proliferative activity from low-grade to high-grade tumors (P = .0006). Univariate tumor-specific survival analysis showed that high Gleason score (P = .0018), high percentage of biopsy tumor involvement (P = .0227), high Ki67 LI (P = .0007), and p53 positivity (P = .0024) were predictors of tumor-related death. A high Ki67 LI emerged as the only independent predictor of tumor-specific survival in multiparametric analysis. These results indicate that core needle biopsy specimens of the prostate not only are useful for diagnosis of malignancy but also can provide valuable prognostic information. Immunohistochemical examinations of molecular features may be a helpful adjunct for a better pretherapeutic assessment of prostate cancer aggressiveness and therefore contribute to an improved initial patient management.
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PMID:Ki67 labeling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer. 974 10

We have reported that bcl-2 is expressed in normal human thyroid epithelium and that its expression is down-regulated in undifferentiated thyroid tumors. Production of IL-6 was concomitantly down-regulated in these forms. Based on these observations, we analyzed whether insertion of bcl-2 would reverse the highly malignant phenotype of a thyroid cell line (ARO) derived from an undifferentiated carcinoma. This cell line fails to produce Bcl-2 and IL-6. By infection with a bcl-2 retroviral vector, ARO cells expressing bcl-2 (ARObcl-2) were obtained. Compared with parental cells, expression of bcl-2 was associated with enhancement of growth potential (DNA synthesis, in vitro proliferation rate, anchorage-independent growth in semi-solid media). Chemotaxis and invasive potential in Boyden chambers were also increased. bcl-2-expressing cells showed a reduced response to apoptotic stimuli (low-serum conditions or anti-neoplastic drugs). Large branched colonies were formed in Matrigel from ARObcl-2 cells but not from parental cells. Finally, ARObcl-2 cells showed a decreased latency of tumor appearance when injected into immunodeficient mice. Potentiation of the malignant phenotype of ARO cells by bcl-2 was not ascribed to altered expression of (i) cytokine/growth factors (IL-4, IL-6, IL-8, IL-10, IL-12, TGF-alpha, TGF-beta), (ii) thyroid-specific transcripts (TG, TPO, TSH-R, PIGF, PAX-8) or (iii) genes influencing tumor aggressiveness [VEGF, HMGI (Y), HMGI-C]. Our data indicate that bcl-2 potentiates the malignant phenotype of ARO cells not only by limiting the response to apoptotic stimuli but also by enhancing proliferation and tumor aggressiveness.
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PMID:Potentiation of the malignant phenotype of the undifferentiated ARO thyroid cell line by insertion of the bcl-2 gene. 1036 45

About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999.
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PMID:Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. 1056 96

Bcl-2 and p53 are the most relevant proteins in apoptosis and tumor development. Telomerase functions in the maintenance of telomeres and is indispensable for immortalization. Bcl-2 was reported as a direct modulator of telomerase activity, and a correlation between p53 and telomerase activity was reported. The aim of this study was to determine the relationships between Bcl-2, p53, and telomerase activity in non-small cell lung cancer. Immunostaining for Bcl-2, p53, and Ki-67 was performed in 64 surgically resected non-small cell lung cancers, and a fluorescence-based telomeric repeat amplification protocol assay for semiquantitative analysis of telomerase activity was done. Twenty-eight (44%) and 33 (52%) cases showed positive staining for Bcl-2 and p53, respectively. Bcl-2 expression was associated with negative lymph node involvement (P = 0.0248). p53 expression was associated with tumor size (P = 0.0244), p stage (P = 0.0391), and proliferative activity (P = 0.0004). Telomerase activity was detected in 89.1% and was closely associated with aggressive clinicopathological features. Telomerase activity was higher in p53-positive tumors (P < 0.0001), but represented no correlation with Bcl-2 expression (P = 0.3239). Interestingly, when the cases were stratified by histological grade and the level of Ki-67 labeling index, Bcl-2 expression was more clearly associated with favorable clinicopathological features and lower telomerase activity only in low-grade tumors. In conclusion, p53 is closely associated with telomerase activity. In low-grade tumors, Bcl-2 is inversely correlated to telomerase activity. Our results suggest that the biological role of the Bcl-2 protein alters according to tumor aggressiveness, thereby cofunctioning with telomerase against genetic instability.
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PMID:Telomerase activity and Bcl-2 expression in non-small cell lung cancer. 1095 74

Desmoid tumors and fibrosarcomas (FS) are part of a wide spectrum of disordered fibroblastic growth that display striking clinical and phenotypic differences. This study was designed to characterize molecular abnormalities that are associated with these differences and to determine their clinical relevance. A cohort of 24 desmoid tumors and 25 low-grade (LG) and 14 high-grade (HG) FS that were clinically and pathologically well characterized was analyzed for alterations in expression of Ki-67, Bcl-2, retinoblastoma gene product (pRB), and p53 by immunohistochemistry. LG-FS and HG-FS showed abnormal expression of Ki-67 (32 versus 86%), Bcl-2 (48 versus 57%), and pRB (56 versus 93%). In contrast, desmoid tumors showed a normal phenotype with these markers. p53 overexpression was identified in 20% of LG-FS and in 29% of HG-FS cases but only in 4% of desmoid tumors. There was an increasing trend in the proportion of abnormal expression of Ki-67, Bcl-2, pRB, and p53 with the increase of tumor aggressiveness from desmoid tumors to LG-FS to HG-FS. The molecular differences between tumor entities were highly statistically significant (P < 0.01). Significant associations between abnormal expression of pRB and recurrence-free survival of LG-FS patients (P = 0.05) and between Ki-67 overexpression and recurrence-free survival for tumors of >5 cm were observed (P = 0.02). The demonstrated differences of molecular alterations in HG-FS, LG-FS, and desmoids appear to be related to biological aggressiveness of such tumors, and they might be useful to differentiate between histologically similar cases of desmoid tumors and LG-FS. pRB and Ki-67 status may be useful to predict recurrence in certain subsets of patients.
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PMID:Characterization of molecular abnormalities in human fibroblastic neoplasms: a model for genotype-phenotype association in soft tissue tumors. 1130 4


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