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)

Precise quantitation of apoptotic cells in meningiomas is necessary to determine the role of apoptosis in tumor growth and recurrence. In this study, we investigated the incidence of baseline apoptosis in relation to p53 and bcl-2 protein expression, proliferation status as expressed by Ki-67, PCNA and mitotic counts, standard clinicopathological parameters and patients' outcome, in a series of 59 patients with primary intracranial benign and atypical meningiomas. Seven tumors recurred (11.9%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Tissues consisted of archival formalin-fixed paraffin-embedded meningioma specimens. The apoptotic index (AI) ranged from 0% to 2.90% (mean: 0.50%), increased with proliferative activity (p = 0.014), had lower values in transitional meningiomas (p = 0.001) and was unrelated to grade and p53 expression. Increased AI predominated among bcl-2 negative tumors (p = 0.041) and tended to be accompanied by a shortened recurrence-free survival, in univariate (p = 0.0407) as well as in multivariate analysis (p = 0.0405). These results implicate apoptotic rate in meningioma growth and recurrence and denote that assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valid prognostic information irrespective of other parameters.
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PMID:Apoptosis detected with monoclonal antibody to single-stranded DNA is a predictor of recurrence in intracranial meningiomas. 1180 77

AIM:To determine the extent of apoptosis and its possible relationship with the changes of p53, Waflp21, bcl-2, and c-myc at different stages of esophageal carcinogenesis.METHODS:Two hundred and forty-one esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China were used in this study.Apoptotic cells and apoptotic bodies were identified by well-established morphological criteria. The extent of apoptosis and its possible relationship with the rate of cell proliferation (PCNA) and changes of p53, Waf1p21, bcl-2,and c-myc were analyzed in samples with esophageal precancerous and cancerous lesions.RESULTS:The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelia as the cells immunostaining-positive for p53, bcl-2, c-myc and PCNA.The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm(2) of the tissue section) were low in the normal epithelia,and increased significantly as the lesions progressed from BCH to DYS and to SCC.The extent of apoptosis correlated well with the cell proliferation indices based on PCNA. The total number of positive cells for p53 stain was much higher than that of apoptotic cells. No difference in apoptotic indices was found between p53-positive and p53-negative samples. Waf1p21-positive cells resided in cell layers were higher in number than p53 and PCNA-positive cells. The number of immunostaining positive cells for Waflp21 increased slightly from normal to BCH,but decreased in DYS and SCC. Positive staining samples for bcl-2 and c-myc increased as the lesions progressed from BCH to DYS and to SCC. No apparent correlation between apoptosis and Waf1p21, bcl-2 or c-myc expression was observed.CONCLUSION:The extent of apoptosis was low in normal esophageal epithelium and increased as the lesions progressed. The apoptotic cells were located in the same hyperproliferative cell compartment as cells immunostaining-positive for p53, bcl-2,c-myc and PCNA,but no apparent correlation between apoptosis and these parameters was observed,possibly due to the complexities of molecular changes in esophageal carcinogenesis.
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PMID:Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China. 1181 1

Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G(0/1)-S transition block and a 'sub-G(0/1)' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
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PMID:In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: evaluation of antiproliferative activity and apoptosis induction. 1182 70

Determination of proliferative activity in tumours may be valuable in diagnosis and prognosis. In this study, commonly used proliferation markers were investigated and compared in 12 cases of human glioblastoma. Paraffin sections were incubated with four commercial Ki67-equivalent antibodies, anti-PCNA, and anti-bcl-2. S-phase fraction and mitotic activity were determined as well. The different Ki67 antibodies gave satisfactory immunostainings, though they provided a wide range of proliferation indices (PI) intra- and intertumorally. Correlations between the Ki67 antibodies and the other proliferation markers were, broadly speaking, poor. PCNA immunostaining was hampered by disturbing background staining. Few bcl-2-immunoreactive cells were observed, mainly gemistocytes. Flow cytometric analyses provided reliable S-phase fraction values, and two aneuploid tumours were detected. The mitotic activity was generally high. Thus, mitotic counting remains a convenient method for assessing proliferative activity in astrocytic tumours. Ki67 antibodies are important alternatives, for instance in stereotactic brain biopsies. Under all circumstances, proliferation markers should be used in combination with established histopathological criteria for malignancy in these tumours.
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PMID:Proliferative activity in human glioblastomas assessed by various techniques. 1184 28

Apoptosis is a common pathological feature in acute myocardial infarction (AMI), however, its role in the later phases (>10 days) of AMI and in post-infarction left ventricular remodeling has not been characterized. The aim of the study was to identify signs of ongoing cell apoptosis late post AMI. Sixteen hearts were collected at autopsy from subjects 12 to 62 days after the onset of AMI. In situ end-labeling of DNA fragmentation (TUNEL) and co-staining with caspase-3 were performed. Double-positive cells were defined as apoptotic and the apoptotic rate was calculated. Values are expressed as median and interquartile range. Co-stainings with muscle-actin, splicing factor (SC35), PCNA, bax and bcl-2 were also performed. Apoptotic rates at site of infarction [25.4% (17.0-28.4%)] were significantly higher v those at remote regions [0.7% (0.5-0.8%) P<0.001] and significantly correlated to left ventricular longitudinal and transverse diameters [ r = +0.70 (P=0.016) and r = +0.63 (P=0.004) respectively]. Moreover, in subjects with persistently occluded infarct-related artery (14 cases) there was a significantly higher apoptotic rate at the site of infarction compared to those (2 cases) with patent artery [26.0% (21.9-28.5%) v 4.5% (0.6% and 8,4%);P=0.033]. A significantly greater bax immuno-reactivity close to the infarction v remote areas was found (P<0.001). High grade apoptosis is present at sites of infarction in the later phases post AMI. This is more evident if the infarct-related artery is persistently occluded and signs of ventricular remodeling are present. These data may provide an explanation of progressive late left ventricular dysfunction.
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PMID:Apoptosis and post-infarction left ventricular remodeling. 1185 56

Leiomyosarcoma of the oral cavity is a very rare tumor that is associated with aggressive clinical behavior and low survival. In this paper, we report two new cases of leiomyosarcoma affecting the mandibular gingiva and mandible of a 35-year-old male and the mandible of a 51-year-old female. Given the difficulty in the histopathologic discrimination between benign and malignant smooth muscle tumors and the absence of reliable histologic parameters for prognostication of leiomyosarcomas, we evaluated the diagnostic and prognostic value of various immunohistochemical and molecular markers. By means of immunohistochemistry and quantitative real-time PCR analysis, we detected protein expression of PCNA, bcl-2, CDK4, p53 and MDM2 in both our cases and MDM2 amplification in our second case. The literature, pertinent to oral leiomyosarcoma and to molecular analysis of smooth muscle tumors, is reviewed.
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PMID:Oral leiomyosarcoma: review of the literature and report of two cases with assessment of the prognostic and diagnostic significance of immunohistochemical and molecular markers. 1185 69

Non-small cell lung cancer (NSCLC) is a malignant tumor with poor prognosis. Although the prognostic variables determining short-term survival have been well described, relatively little attention has been paid to factors associated with long-term survival. In search of these factors we studied the expression of several molecular markers in NSCLC. Only tumor samples of patients with squamous cell carcinomas and stage III tumors with a postoperative survival of at least 5 years and those of patients who died within 2 years after resection were selected for this study. The expression of several parameters including oncogene and suppressor gene products, proliferative, apoptotic, angiogenic and resistance-related factors were investigated and the differences in these two extreme populations were determined by the Wilcoxon rank sum test. Factors involved in proliferation (ras, fos, erbB-1, jun, cyclin A) were downregulated whereas factors involved in apoptosis (p53, bcl-2, CD95) were upregulated in the long survival group. Direct measurement of parameters of proliferation (cell cycle analysis by flow cytometry, PCNA index) revealed a lower proliferative activity in tumors of the long survivors compared to short survivors. In conclusion, tumors of the long survival group are characterized by a downregulation of factors involved in proliferation and an upregulation of factors involved in apoptosis. These tumors may grow more slowly and this may influence long-term survival of patients with NSCLC.
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PMID:Characteristics of long-term survivors of untreated lung cancer. 1200 38

It is now recognized that apoptosis plays an important role in the pathogenesis of tumors. This study evaluated the extent of apoptosis in different grades of ovarian tumors and correlated it with the expression of apoptosis regulatory genes, p53 and bcl-2 and with the total proliferative compartment of the tumor defined by the expression of the proliferating cell nuclear antigen (PCNA). Apoptosis was evaluated by the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay. Expressions of p53, bcl-2 and PCNA were analyzed by immunohistochemistry. A negative correlation was observed between the expression of bcl-2 and the extent of apoptosis (r = -0.3336, p = 0.019). P53 accumulation directly correlated with the extent of apoptosis (r = 0.485, p = 0.00041). The labelling index of PCNA also showed correlation with expression of p53 (r = 0.49, p = 0.00000). Apoptosis was significantly higher in poorly differentiated tumors when compared to the well- and moderately-differentiated tumors (r = 0.49152, p = 0.00034). Such poorly-differentiated tumors also showed high p53 overexpression and loss of bcl-2 expression. The present study thus provides evidence that dysregulation of apoptosis and its regulatory genes is associated with increasing malignant potential and may thus contribute to the pathogenesis of ovarian tumors.
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PMID:Apoptosis in epithelial ovarian tumors. 1204 36

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.
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PMID:Biomarkers for breast cancer. 1214 73

The renin angiotensin system plays an important role in growth and development. Exposure of the neonate to an ACE inhibitor increases mortality and results in growth retardation and abnormal development. We have demonstrated that ACE inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. To evaluate the role of endogenous angiotensin in cardiac development, the relationship between ACE inhibition, cell proliferation, apoptosis, several modulators of apoptosis (bcl-2, bcl-xl, and clusterin) was examined in the developing rat heart. Thirty-five newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting of bcl-2, bcl-xl, and clusterin. An additional 10 rat pups were treated with hydralazine (10 mg/kg/d) or a vehicle, to serve as a hypotensive control. Cell proliferation was determined by PCNA immunostaining, and apoptosis was detected using the total TUNEL technique. Enalapril treatment resulted in a 24% mortality, reduced body weight, and decreased heart weight (p < 0.05). Enalapril decreased proliferating myocytes by 23%, and reduced proliferating cardiac interstitial cells by 8.1% (p < 0.05). Enalapril also decreased myocytes apoptosis by 60%, but the proportion of myocytes undergoing apoptosis was 10-fold less than that of proliferating cells. Cardiac bcl-2 mRNA, clusterin mRNA, bcl-2 protein, and bcl-xl protein content were not changed, but clusterin protein expression was decreased by enalapril treatment. Hydralazine did not alter cardiac cell proliferation or apoptosis. We conclude that ACE inhibition decreases cell turnover in the developing rat heart, which may contribute to cardiac growth impairment. The loss of myocytes may lead to greater myocyte hypertrophy and myocardial damage during later life.
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PMID:Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart. 1219 62


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