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)

The biological aggressiveness of lymph node-positive prostate cancer is closely linked to cancer volume in nodal metastases. We evaluated MIB-1 (Ki-67) labeling index and bcl-2 expression in primary cancer and matched nodal metastases from 138 node-positive patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1992 at the Mayo Clinic. One hundred twenty-eight patients (93%) received androgen deprivation therapy within 90 days after radical prostatectomy. Mean patient age was 66 years (range, 51-78). The median follow-up was 6.7 years (range, 0.03-11). MIB-1 (Ki-67) labeling index was determined by digital image analysis, and nodal cancer volume was determined by the grid method. Systemic progression, defined as the presence of distant metastasis documented by biopsy or radiographic examination, was used as an outcome end point in the Cox proportional hazard models. MIB-1 labeling index in nodal metastases was predictive of systemic progression-free survival (P = 0.001). The 8-year systemic progression-free survival was 100% for those with MIB-1 labeling index <3.5% compared with 78% for those with MIB-1 labeling index > or =7.8%. MIB-1 labeling index correlated with Gleason score, DNA ploidy, and nodal cancer volume (P<0.001, 0.04, and <0.001, respectively). After controlling for nodal cancer volume, MIB-1 labeling index remained significant in predicting systemic progression-free survival (P = 0.047). bcl-2 expression in the primary cancer and lymph node metastasis was associated with systemic progression-free survival in univariate analysis (P = 0.027 and 0.048, respectively) but was not significant after adjusting for nodal cancer volume (P = 0.52 and 0.17, respectively). Our data indicate that assessment of cell proliferation in nodal metastasis is predictive of clinical outcome in prostate cancer patients with regional lymph node metastasis.
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PMID:Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. 1053 47

The newly described apoptosis inhibitor survivin is expressed in many human cancers and appears to play a critical part in both apoptosis regulation and cell cycle progression. Its potential role in malignant melanoma is unknown. In a panel of 30 malignant melanomas, survivin was strongly expressed in all cases (15 of 15) of metastatic malignant melanomas and 13 of 15 cases of invasive malignant melanomas by immunohistochemistry. In invasive malignant melanomas, survivin was also expressed in the in-situ component of the lesion. Survivin expression was found in all cases (11 of 11) of nevi, but not in melanocytes in sections of normal skin. The apoptosis inhibitor bcl-2 was expressed in 26 of 30 cases, but generally at lower levels than that of infiltrating lymphocytes. The mitotic index, as assessed by MIB-1 staining, was consistently higher in metastatic than invasive malignant melanomas. Assessment of apoptotic index by in situ end-labeling revealed extremely low rates of apoptosis in most malignant melanomas. Survivin expression by western blotting was detected in four human metastatic malignant melanoma cell lines but not in cultured normal human melanocytes. Transfection of both YUSAC-2 and LOX malignant melanoma cells with green fluorescence protein-conjugated survivin anti-sense or green fluorescence protein-conjugated survivin dominant negative mutant (Cys84Ala) [corrected] resulted in increased apoptosis in the absence of other genotoxic stimuli. Two-color flow cytometry confirmed that YUSAC-2 cells transfected with survivin anti-sense expressed less endogenous survivin and exhibited an increased fraction of cells with sub-G1 DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of malignant melanomas, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or metastatic disease.
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PMID:Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. 1059 55

Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.
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PMID:Bio-morphological events in the development of the human female mammary gland from fetal age to puberty. 1088 36

We retrospectively evaluated 90 meningiomas for bcl-2 expression, apoptosis counts (per 10 high-power fields [HPF]), MIB-1 labeling indices (LI), and mitosis counts (per 10 HPF). Characteristics were as follows: 37 low-grade (benign) meningiomas: mean apoptosis count, 1.2; MIB-1 LI, 1.0; mitosis count, 0.1; and bcl-2 positivity, 40%; 29 atypical meningiomas: apoptosis count, 3.3; MIB-1 LI, 5.5; mitosis count, 2.2; and bcl-2 positivity, 62%; 24 malignant meningiomas: apoptosis count, 6.5; MIB-1 LI, 12.0; mitosis count, 6.0; and bcl-2 positivity, 67%. By univariate analysis, MIB-1 LI, apoptosis and mitosis counts, and tumor grade were associated significantly with death due to tumor; by multivariate analysis, only mitosis count was independently associated with death due to tumor. We compared similar data for 27 patients with nonrecurrent tumors and 32 patients with recurrent meningiomas. Histologic sections from the initially resected tumor and from the most recent recurrence were reviewed. Only the apoptosis count was significantly higher by univariate analysis in the initial resection specimens from tumors that ultimately recurred vs nonrecurrent tumors. Expression of bcl-2, MIB-1 LI, and mitosis count did not correlate with recurrence. By multivariate analysis, only extent of surgical resection was associated significantly with tumor recurrence. Although bcl-2 immunostaining was not associated statistically with outcome, bcl-2 positivity was more common in atypical and malignant meningiomas than in low-grade tumors.
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PMID:Apoptotic activity and bcl-2 immunoreactivity in meningiomas. Association with grade and outcome. 1088 3

Fifty-three neuroendocrine lung tumors (24 carcinoids, one atypical carcinoid, five large-cell neuroendocrine carcinomas, and 23 small-cell lung carcinomas) were investigated for immunocytochemical expression of several gene products, i.e., p53, Rb, bcl-2, c-kit, mdm-2, cdk-4, p21 proteins, and proliferation index as assessed by MIB-1. The goal of the study was to explore the relationships between histotypes in light of their own gene product-based immunophenotypical profiles. To this aim we applied the multiple correspondence analysis, which is an exploratory statistical multivariate technique that converts a data matrix into a particular type of graphic display in which the rows and columns are depicted as points. Such statistical analysis displayed that some categories of the gene product-based immunophenotyping variables are grouped in the plot identifying three groups: the first group related to carcinoids, the second to small-cell carcinomas, and the third to large-cell neuroendocrine carcinomas. These data support the evidence that carcinoids and small-cell carcinomas are two distinct, apparently immunogenotypically unrelated entities among neuroendocrine lung tumors and that atypical carcinoids and large-cell neuroendocrine carcinomas seem not to represent intermediate steps between them.
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PMID:Gene product immunophenotyping of neuroendocrine lung tumors. No linking evidence between carcinoids and small-cell lung carcinomas suggested by multivariate statistical analysis. 1093 49

The bcl-2 oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18) and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly evaluated by MIB 1, a monoclonal antibody to Ki67 proliferation antigen. Mutation of the p53 gene is considered the most common genetic aberration in colorectal cancer. Immunohistochemical (IHC) staining expression of bcl-2, Ki67, and p53 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas. The aim of the study was twofold: (i) to investigate any correlation between MIB 1, p53, and bcl-2 immunostaining expression in colonic adenomas and carcinomas and (ii) to identify any relation between these markers and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angiolymphatic invasion, tumor grade, and differentiation in colon carcinomas. bcl-2 was consistently higher in adenomas than in carcinomas. There were 44 of 56 (78.6%) adenomas and 27 of 52 (51.9%) carcinomas positive for bcl-2 (P = 0.004). The mean Ki67 labeling index (LI) was 30.05 +/- 7.6 and 38.12 +/- 11.01 in adenomas and carcinomas, respectively (P = 0.0001). p53 was significantly higher in carcinomas (35 of 52 [67.3%]) than in adenomas (18 of 56 [32.1%]) (P = 0.0004). Expression of bcl-2 in carcinoma was associated with a lower p53 levels and lower mean Ki67 LI and with favorable histopathologic parameters. Higher p53 and Ki67 values were associated with prognostically poor histopathologic features (differentiation and Duke's stage). We conclude that, in contrast to p53 and Ki67, bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with favorable pathologic parameters. Furthermore, an inverse relation exists between p53 and Ki67, and bcl-2 IHC expression in colonic neoplasia. Evaluation of bcl-2, p53, and Ki67 IHC expression in colonic carcinoma may be of value in predicting the clinical course in these patients.
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PMID:Immunohistochemical expression of bcl-2 and p53 oncoproteins: correlation with Ki67 proliferation index and prognostic histopathologic parameters in colorectal neoplasia. 1098 68

Apoptosis and proliferation of myocytes were studied in human heart failure (HF). Endomyocardial samples from the right ventricle of 38 patients with terminal HF were compared with 10 traffic accident victims without a history of cardiovascular disease. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of p53, bcl-2, proliferation cell nuclear antigen (PCNA), and proliferation marker MIB-1. Apoptosis of cardiomyocytes, which was not p53-dependent, was present in 0.07 % of myocytes in HF, whereas no apoptotic myocytes were found in the control group (p < 0.01). An increased expression of bcl-2 was found in HF compared to controls (p < 0.01), yet bcl-2 failed to protect myocytes from apoptosis. Increased expression of proliferation markers was found in myocytes in HF compared to controls (PCNA labeling: 3.7% vs. 1.2%, p < 0.01; MIB-1 labeling: 0.1% vs. 0%, p< 0.01). Nevertheless, no mitotic figures in cardiomyocytes were found in our specimens. The volume density of interstitium was 22% in HF vs. 10% in the control group (p < 0.01). In conclusion, apoptosis of cardiomyocytes and fibrosis play an important role in HF, whereas clinical importance and the rate of myocyte proliferation remain to be determined.
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PMID:Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies. 1098 14

To investigate the prognostic value of nuclear morphometry in male breast carcinoma (MBC), histological samples from 50 patients (mean age 62.2 years) were retrospectively analyzed by computerized nuclear morphometry. All patients received surgery; 35 had multiple combinations of adjuvant therapies. Mean follow-up was 67 months (range 1-230). In each case, 100 tumor cells were measured, and the mean nuclear area (MNA), standard deviation of the nuclear area (SDNA), mean nuclear perimeter (MNP), standard deviation of the nuclear perimeter (SDNP) and shape factor (SHF) were calculated. Morphometric features were compared with tumor histological grade, size, nodal status, DNA ploidy evaluated by flow-cytometry and cell proliferative activity assessed by the quantity of argyrophilic nucleolar organizer region-associated proteins (AgNORs), monoclonal antibody (MAb) PC10 against proliferating cell nuclear antigen and MAb MIB-1. Comparison was also made with the immunohistochemical detection of p53, bcl-2, c-erbB-2 and c-myc proteins. Significant association was found between nuclear morphometric parameters and tumor grade, DNA content and cell proliferation indices. SDNA was greater in p53-positive and bcl-2-negative cases; SDNP was greater in p53-positive cases; SHF was lower in p53- and c-myc-positive cases. Overall survival was shorter in carcinomas with high MNA, SDNA, MNP and SDNP and low SHF. In multivariate analysis, performed by testing nuclear morphometric parameters, histological grade, tumor size, nodal status and p53 immunostaining in the Cox model, p53 over-expression and histological grade retained independent prognostic significance. When p53 was excluded, only SDNP appeared as an independent prognostic variable. Our results indicate that nuclear morphometric parameters can identify an aggressive tumor phenotype and provide additional prognostic information for patients with MBC.
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PMID:Nuclear morphometry in male breast carcinoma: association with cell proliferative activity, oncogene expression, DNA content and prognosis. 1110 93

We report the histopathologic findings in endometrial curettings from a 31-year-old woman with dysfunctional uterine bleeding who had received paclitaxel therapy for breast carcinoma. Paclitaxel, a member of the taxane family of antineoplastic agents that is used in the treatment of breast carcinoma, ovarian carcinoma, and non-small cell lung carcinoma, acts by the simultaneous promotion of tubulin assembly into microtubules and inhibition of microtubule disassembly. The curettings in this case showed fragmented menstrual phase endometrium with striking numbers of mitotic figures. Cell divisions were arrested in metaphase. Glandular epithelial cells showed strong immunoreactivity for bcl-2 and MIB-1. We attribute this marked morphologic effect to paclitaxel-induced mitotic arrest of the endometrium.
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PMID:Mitotic arrest of endometrial epithelium after paclitaxel therapy for breast cancer. 1110 73

Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (> or = 5% of cells positive) and cyclin D1 positive (> or = 10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21WAF1/CIP1 (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.
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PMID:Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer. Finbladder Group. 1112 4


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