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)

The relationship between the growth of tumors and the expression of the protooncogene Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarcoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46%) showed a strong expression of bcl-2 and 13 cases (35%) were moderately positive for bcl-2. Seven cases (19%) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferation rate was determined with the monoclonal antibody MIB 1, directed against the Ki-67 epitope. The data of bcl-2 expression and cellular proliferation rate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.
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PMID:[Osteosarcoma--apoptosis and proliferation. Study of bcl-2 expression]. 785 2

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
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PMID:P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma. 854 51

The proto-oncogene Bcl-2 encodes a protein that protects cells from programmed cell death (apoptosis). The protein is expressed in the proliferative compartment of several normal tissues, including normal colonic crypts. The aim of this study was to test Bcl-2 expression in colorectal neoplasms, assuming that, as a regulator of apoptosis, it might be involved in the progression from adenoma to carcinoma. To this end, Bcl-2 reactivity was tested by immunohistochemistry in hyperplastic polyps, colonic adenomas, and carcinomas and its expression was compared with staining for the proliferation-associated Ki-67 antigen, using the MIB-1 antibody. Bcl-2 expression occurred in 2 out of 10 hyperplastic polyps and in 31 out of 35 (tubular, villous, and tubulovillous) adenomas, irrespective of their degree of dysplasia. Of ten carcinomas, only three were focally Bcl-2-positive, all moderately to well differentiated. In two of four carcinomas in Bcl-2-positive adenomas, no Bcl-2 staining was observed. High numbers of MIB-1-positive cells were found in all hyperplastic and neoplastic lesions, without apparent correlation between proliferation and Bcl-2 expression. These findings suggest that in the pathogenesis of hyperplastic polyps, increased crypt cell proliferation is primarily involved, but in some lesions decreased apoptosis may play a role. Furthermore, the increased Bcl-2 expression in adenomas but not in the majority of the carcinomas suggests either that decreased apoptosis is not usually involved in the pathogenesis of these lesions or that the regulation of apoptosis in colorectal epithelia involves additional regulatory factors.
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PMID:Expression of Bcl-2 protein in hyperplastic polyps, adenomas, and carcinomas of the colon. 869 16

Prognostic factors in oligodendrogliomas are not well defined, even considering the labeling index of proliferation markers. As in other neuroepithelial tumors, the difficulty in calculating cell loss may contribute to this uncertainty. Proliferation markers Ki-67/MIB.1 and PCNA, mitoses, apoptotic nuclei, p53 and bcl-2 expression were investigated in 98 oligodendrogliomas. Apoptosis was assessed by the aspect of nuclei, by in situ end-labeling (ISEL) technique and by c-Jun immunohistochemical demonstration. The Bcl-2 also was immunohistochemically studied for its anti-apoptotic role. Mitotic index (MI), labeling index (LI) for MIB.1 and PCNA and apoptotic index (AI) were calculated and compared among themselves and with histology and survival. It was found that AI correlated with MI (p = 0.001) and was significantly higher in anaplastic than in classic oligodendrogliomas (p = 0.001). Apoptosis occurred only slightly more frequently in cases with high LIs for proliferation markers (MIB.1 and PCNA) (p = non-significant) and it was definitely higher in p53-positive cases (p = 0.008). It did not correlate with bcl-2 which was poorly expressed in oligodendrogliomas, with the exception of cells with astrocytic features. Apoptotic index correlated very weakly with survival (p = 0.05); therefore, it cannot be considered a highly reliable prognostic factor in oligodendrogliomas.
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PMID:Role of apoptosis in the prognosis of oligodendrogliomas. 922 Apr 57

Clinical and histopathological features do not reliably distinguish between benign and malignant pheochromocytomas. Additional markers that might be useful prognostic indicators in the pathological assessment of these tumors are sought. Immunohistochemical expression of MIB-1, Bcl-2, cathepsin B, cathepsin D, basic fibroblast growth factor (bFGF), c-met, and type IV collagenase were studied on formalin-fixed tissue from 33 nonconsecutive cases of pheochromocytoma, selected on the basis of reliable long-term follow-up, to determine associations with malignancy. The study group included 33 patients, 19 men and 14 women, with a mean age of 45 years, including five cases of neurofibromatosis (NF), three familial, and one MEN IIb. Mean follow-up was 63.2 months. Ten patients were determined to have malignant pheochromocytomas by the presence of metastatic disease. Features found to be associated with malignancy included MIB-1 labeling index (5% vs 1%) (P = .0009), male gender (90% vs 43%) (P = .008), extra-adrenal location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and young age (38 years vs 49 years) (P = .05). None of the five cases with NF were malignant (P = .04). S-100 positivity showed a significant (P = .02) but nonlinear association with benign tumors. Absent S-100 correlated with greater tumor weight. Malignancy was not associated with right versus left side or bilaterality, although bilateral tumors were smaller. C-met, bFGF, cathepsin B, cathepsin D, and collagenase were strongly expressed in most tumors and were not predictive of outcome, nor was bcl-2, which was variably expressed. Using multiple logistic regression with malignancy as the dependent variable, MIB-1 continued to show a significant association with malignancy (P = .005) independent of any association with sex, age, or extra-adrenal location. Using a cutoff value of MIB-1 labeling of greater than 3% yielded a specificity of 100% and a sensitivity of 50% in predicting malignancy.
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PMID:Prognostic markers in pheochromocytoma. 1020 74

Graft versus host disease (GVHD) occurs in up to 75% of patients who have had an allogeneic bone marrow transplant (BMT). However, the pathophysiology of this disorder, including the mechanisms responsible for enhanced apoptosis, are poorly understood. Bcl-2 is a cellular protein known to inhibit apoptosis in a variety of human tissues. Therefore, the aim of this study was to evaluate the expression of Bcl-2 in colonic GVHD and to determine its relationship to cell proliferation and apoptosis in this disease. Routinely processed colonic mucosal biopsy specimens from 47 allogeneic BMT patients with diarrhea were evaluated histologically for the grade of GVHD (0-4) and for the degree of apoptosis (apoptosis index). Immunohistochemical staining for Bcl-2 and MIB-1, a cell proliferation marker, was performed, and the results were correlated with the histological findings and with each other. Normal-appearing colonic mucosal biopsy specimens from 10 age-matched patients with noncolonic diarrhea served as controls. Also evaluated were 13 colonic biopsy specimens from 13 patients with chronic ulcerative colitis (three inactive, four mild chronic-active, six moderately severe chronic active) to test the specificity of our findings. When compared with controls, a slight trend toward increased Bcl-2 expression was noted in patients with high-grade GVHD (grade 3 or 4) (P=.09). However, Bcl-2 expression did not correlate with the degree of apoptosis in these patients. In contrast, the degree of Bcl-2 staining correlated positively with the crypt proliferative rate (P=.04). Furthermore, crypt proliferation was significantly higher in the GVHD patients in comparison with controls (MIB-1 index, 27.7+/-17.1 v 15.6+/-11.4, =.02), and increased progressively with each successively higher grade of GVHD, and with the degree of apoptosis. Similar to GVHD, Bcl-2 expression was increased in biopsy specimens of CUC patients with higher grades of active injury and epithelial regeneration. This immunohistochemical study does not provide support for Bcl-2 in the pathogenesis of GVHD-induced apoptosis in the colon, but instead, indicates that this protein may play a nonspecific role in the generalized response to cellular injury in GVHD.
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PMID:Relationship of Bcl-2 expression with apoptosis and proliferation in colonic graft versus host disease. 971 31

We have analysed the expression of bcl-2 protein retrospectively in 34 primary male breast carcinomas (MBC), using the monoclonal antibody bcl-2 in formalin-fixed, paraffin-embedded tissues. Bcl-2 expression was compared with tumour clinicopathological features, sex steroid hormone receptors, DNA content, p53 immunoreactivity and cell proliferative activity assessed by counts of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody PC10 against proliferating cell nuclear antigen and the monoclonal antibody MIB-1. Most (28, or 82.3%) of the 34 cases of MBC were bcl-2 positive. No association was found with clinicopathological features of the tumours, although bcl-2 tended to be more frequently expressed in small tumours (P=0.09) and in cases without necrotic areas (P=0.1). Nor was any association found with hormone receptor status, p53 immunoreactivity, DNA content, cell proliferative activity or patient survival. In multivariate analysis, only proliferative activity (expressed by AgNOR counts) and p53 immunoreactivity had independent prognostic significance. Our results indicate that MBC differs from FBC in that in MBC bcl-2 protein is not related to an oestrogen-dependent transcription pathway and bcl-2 alone is not sufficient to induce increased proliferation. These characteristics, together with the high prognostic value of cell proliferation and the lack of prognostic significance for hormone receptor status, support the hypothesis that MBC is biologically different from FBC.
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PMID:Bcl-2 expression in male breast carcinoma. 976 26

It was previously shown in the PC-295 xenograft that the number of chromogranin A (CgA)-positive neuroendocrine (NE) cells increased after androgen withdrawal. NE cells did not proliferate and differentiated from G0-phase-arrested cells. Here we further characterized NE differentiation, androgen receptor status, and apoptosis-associated Bcl-2 expression in the PC-295 model after androgen withdrawal to assess the origin of NE cells. PC-295 tumor volumes decreased by 50% in 4 days. Intraperitoneal bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%, and the apoptosis was maximal at day 4. Androgen receptor expression and prostate-specific antigen (PSA) serum levels decreased rapidly within 2 days. The number of NE cells increased 6-fold at day 4 and 30-fold at day 7. Five and ten percent of the CgA-positive cells were BrdU positive after continuous BrdU labeling for 2 and 4 days, respectively. However, no MIB-1 expression was observed in CgA-positive cells. NE cells expressed the regulated secretory pathway marker secretogranin III but were negative for androgen receptor and Bcl-2. Bcl-2 expression did increase in the non-NE tumor cells. In conclusion, androgen withdrawal leads to a rapid PC-295 tumor regression and a proliferation-independent induction of NE differentiation. The strictly androgen-independent NE cells that were still present after 21 days differentiated mainly from G0-phase-arrested cells.
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PMID:Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model. 1002 12

Bcl-2 and bcl-xL are proteins known to inhibit cell death (apoptosis). Expression of these proteins in gangliogliomas has not been extensively examined. This study retrospectively evaluates bcl-2 and bcl-x immunostaining in paraffin-embedded materials in gangliogliomas. Twenty-nine gangliogliomas in 17 males and 12 females, age 2.5 to 47 years (mean, 20.7 years), were studied. Nineteen tumors were situated primarily in the temporal lobe. All but three patients presented with seizures ranging from 3 months to 28 years' duration (mean, 11.1 years) before surgery. All tumors histologically were comprised of an atypical neuronal component and a glioma component, which most frequently resembled a low-grade astrocytoma. Cortical dysplasia was observed adjacent to eight tumors. MIB-1 (marker of cell proliferation) labeling indices (percentage of positively staining tumor cell nuclei) ranged from 0 to 7.7 (mean, 0.8). bcl-2 staining was observed in 25 tumors (86%); neuronal staining was present in 24 cases (83%), and glial cell staining in 21 tumors (72%). Bcl-xL staining was only observed in eight gangliogliomas (28%); in all eight tumors (28%), neuronal staining was seen, and focal glial cell staining was present in two cases (7%). Four tumors (14%) did not stain with either bcl-2 or bcl-xL. There appeared to be no relationship between MIB-1 immunostaining and staining with bcl-2 or bcl-xL. bcl-2 expression by immunohistochemistry was observed more frequently than bcl-xL in gangliogliomas. Expression of these proteins may reflect abnormalities of apoptosis, which could play a role in the survival of cells that may be involved in the development of gangliogliomas.
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PMID:Bcl-2 and Bcl-X expression in gangliogliomas. 1037 80

Bcl-2 and Bax have been demonstrated to be associated with apoptosis in breast carcinoma, and the ratio between Bax and Bcl-2 seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2, Bax and the proliferative activity of breast carcinoma. The purpose of this study was to investigate the significance of apoptosis-related genes bcl-2 and Bax and their correlation with expression of p53, tumor proliferation defined by MIB-1 expression and estrogen receptor status. Immunohistochemistry was performed to determine Bcl-2, Bax, p53, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues of 177 invasive breast cancers. Expression of the anti-apoptotic protein Bcl-2 was not correlated with the pro-apoptotic Bax. Bcl-2 immunostaining displayed a negative correlation with increasing histologic grade, p53 and MIB-1 (P < 0.0001, P < 0.05 and P < 0.0001, respectively) and a positive correlation with rising ER immunostaining (r = 0.305, P < 0.0001). Conversely, expression of the apoptosis-promoting protein Bax did not correlate with increasing histologic grade, p53, MIB-1 or ER status. Neither Bcl-2 expression nor Bax expression correlated with age, menopausal status, tumor size, histologic type or axillary lymph node status. These results imply that Bcl-2 is associated with good prognostic markers and the regulation of Bax is complex and does not necessarily correlate with mutant p53 status in breast cancers.
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PMID:Expression of Bcl-2, but not Bax, correlates with estrogen receptor status and tumor proliferation in invasive breast carcinoma. 1050 48


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