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)

Recent evidence has emphasized the importance of programmed cell death or apoptosis in the maintenance of tissue homeostasis and pathogenesis of tumors. This study, analyzed in breast cancer, investigates the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, hormone receptors and tumor grade. The extent of apoptosis was defined by morphological criteria and the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay. Immunocytochemistry was performed for p53, bcl-2, estrogen receptor, progesterone receptor and Ki-67 expression. Mutant p53 protein was detected using a mutant specific ELISA. Immunoreactivity of p53 significantly correlated with the presence of mutant p53 protein detected by ELISA (r = 0.654, p = 0.00001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). The extent of apoptosis directly correlated with p53 protein accumulation (r = 0.485, p = 0.00041), Ki-67 immunoreactivity (r = 0.435, p = 0.001), histopathological grade (r = 0.492, p = 0.0003), tumor size (r = 0.326, p = 0.023) and lymph node status (r = 0.287, p = 0.047). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). There was no statistically significant association between estrogen and progesterone receptor status and apoptosis. In addition, the TNM stage of the disease correlated with immunoreactivity of p53 (r = 0.572, p = 0.00012) and Ki-67 (r = 0.3744, p = 0.00818). Bcl-2, by inhibiting apoptosis, may cause a shift in tissue kinetics towards the preservation of genetically aberrant cells, thereby facilitating tumor progression. These results imply that rapidly proliferating tumors appear to have a high "cell turnover state" in which there may be an increased chance of apoptosis amongst the proliferating cells. The ability of apoptosis to also occur in the presence of mutant p53 protein suggests the existence of at least two p53-dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it.
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PMID:Spontaneous programmed cell death in infiltrating duct carcinoma: association with p53, BCL-2, hormone receptors and tumor proliferation. 977 89

We have found that the anti-apoptotic Bcl-2 family protein, Bcl-w, was frequently expressed in colorectal adenocarcinomas, with 69/75 showing positive staining with anti-Bcl-w IgG. Adenomas demonstrated a much lower frequency of Bcl-w expression (only 1 of 17), as did adenocarcinomas from other epithelial tissues such as breast (0/8), stomach (1112) and cervix (0/12). Bcl-w status could be related to the histopathological classification of the tumours, with TNM stage III tumours showing significantly higher levels of expression than tumours of better prognostic grade (at P = 0.009). Those patients with node involvement also had tumours with significantly elevated levels of Bcl-w (at P = 0.02), compared to those which were node-negative. The results suggest that Bcl-w could play a general role in the progression from adenoma to adenocarcinoma in the colorectal epithelium. Currently, more data are being collected to allow us to assess the importance of Bcl-w for disease progression and patient survival.
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PMID:Bcl-w expression in colorectal adenocarcinoma. 1063 87

Photodynamic therapy (PDT) in early squamous cell carcinoma of the bronchus has been shown to result in complete response (CR) and cure. However, local recurrence after PDT develops frequently even after complete remission. Because the effect of PDT had been reported to depend on apoptosis, and apoptosis is inhibited by bcl-2 protein, the relationship between the expression of bcl-2 protein and local recurrence after PDT was examined immunohistochemically. From 1983 to 1997, 50 patients with 59 early squamous cell carcinoma of the bronchus received PDT, and a CR was obtained in 43 lesions (72.8%). As there was no recurrence among tumours that were disease-free for more than 2 years, in this study the tumours were defined as cured when recurrence did not occur 2 years subsequent to the receiving of PDT. Of these CR lesions, 31 carcinomas (53.4%) resulted in a cure. Bcl-2 immunoreactivity was detected in 23 tumours (46.9%) and p53 immunoreactivity was detected in 22 tumours (44.9%). When all tumours were divided into either a large tumour with a longitudinal tumour length of 10 mm or more, or a small tumour with a length of less than 10 mm, the large tumour expressed more bcl-2 protein than the small tumour (P = 0.0155). The degree of bcl-2 expression was significantly related with tumour size (P = 0.0155). The expression of bcl-2 and p53 protein was not associated with the cure rate due to PDT. Tumour length and T status in TNM staging were significantly related to the cure by univariate analysis. T status was the only predictor of the cure according to mutivariate analysis. Of 42 CR lesions, the expression of neither bcl-2 nor p53 protein was associated with local recurrence; only T status was significantly associated (P = 0.008). The relationship between the expression of oncoprotein and local recurrence after PDT was not documented in this study. The success of PDT may depend on the exact assessment of tumour size under optimized PDT illumination.
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PMID:Immunohistochemical analysis of Bcl-2 protein in early squamous cell carcinoma of the bronchus treated with photodynamic therapy. 1064 98

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.
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PMID:Predictive survival markers in patients with surgically resected non-small cell lung carcinoma. 2667 25

A prospective study was carried out on ten patients with prostate cancer. The TNM stage, Gleason's grade, general clinical status and, serum PSA level were all registered by the time of diagnosis. Total androgen blockade (TAB) was performed. Serum PSA control and general clinical examination re-biopsy was performed on average 107 days after the start of the therapy. The pre- and post treatment histology included HE and Tunel reaction to show apoptotic cells, as well as p53, bcl2 and Ki67 immunostaining. Clinical improvement of the disease, manifested by regression or by steady state was observed in all ten patients. An increase of apoptotic index, and a decrease of mitotic index was detected in most cases. The serum PSA level decreased in all patients. Ki67, bcl2 and mutant p53 were strongly expressed in tumor cells of patients in whom Gleason's grade was 7 or higher and decreased markedly in all cases upon therapy. Data obtained by repeated biopsy in the course of TAB therapy are indicators of the effectiveness of TAB, like changes in serum PSA, and may be considered as predictive factors.
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PMID:Follow-up of prostate carcinoma patients treated with total androgen blockade by repeated map-biopsy. 1099 42

We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.
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PMID:Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and premalignant lesions: association with clinical characteristics. 1197 95

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.
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PMID:Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens. 1601 58

Increased expression of glucose transporters has been reported in many cancers. It is not known whether Sodium dependent GLucose Transporter 1 (SGLT1) is up-regulated in pancreatic cancer. We studied the expression of SGLT1, Bcl-2 and p53 in primary pancreatic adenocarcinomas related to survival. In primary tumors, mean SGLT1-Hscore (n = 83) was 4.24 (median 3.0, range 0.5-15.0). Patients with positive staining for Bcl-2 had higher mean SGLT1-Hscores than those without Bcl-2 expression: 5.87 vs. 3.07 (P = 0.025). No correlation was found between expression of p53 and SGLT1 (P = 0.881). On multivariate analysis TNM stage (P = 0.015) and SGLT1 (P = 0.030) showed prognostic value for disease free survival (DFS). For overall survival (OS), TNM stage (P<0.001) and chemotherapy (P = 0.048) were prognostic and SGLT1 showed a trend (P = 0.071). In a subgroup of younger patients (age < or = median, 63.9 y) who did not receive chemotherapy, SGLT1 was a very strong predictor of DFS (P = 0.005). We conclude that high SGLT1 expression (H score > median, 3.0) in pancreatic adenocarcinomas was significantly correlated with DFS and a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors was correlated with high Bcl-2 expression, not with p53 expression. This supports our hypothesis that SGLT1 and Bcl-2 expression could serve as prognostic markers in pancreatic cancer.
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PMID:Expression of SGLT1, Bcl-2 and p53 in primary pancreatic cancer related to survival. 1885 13

Beclin-1 is a Bcl-2-interacting protein, and it may delay cell cycle progression and induce autophagy. The function and expression of Beclin-1 and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the lung remain largely unknown. Herein, we investigated the expression of Beclin-1 and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the lung. Tissue samples from 262 cases were used in this study. Immunohistochemical staining for Beclin-1 and Bcl-2 were conducted using a tissue microarray. In squamous cell carcinoma, Beclin-1 expression was strongly positive in 48 (28.6%) of 168 samples, it was moderately positive in 42 (25.0%) of 168 samples, and it was negative or weakly positive in 78 (46.4%) of 168 samples. In adenocarcinoma, Beclin-1 expression was strongly positive in 26 (27.7%) of 94 samples, it was moderately positive in 27 (28.7%) of 94 samples, and it was negative or weakly positive in 41 (43.6%) of 94 samples. Beclin-1 expression was inversely correlated with the tumor size and the primary tumor stage (pT) in both types of tumor. Especially, the TNM stage of adenocarcinoma was inversely correlated with Beclin-1 expression. Our results suggest that a progressively reduced Beclin-1 expression is correlated with the primary tumor growth of squamous cell carcinoma and adenocarcinoma of the lung.
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PMID:Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung. 2177 47

Abnormalities in signal transducer and activator of transcription (STAT) signaling, especially STAT3 and STAT5, are involved in the oncogenesis of several human cancers, including gastric cancer (GC). However, the downstream targets of STAT3 and STAT5 are not fully identified, and the precise roles and the prognostic value of STAT3 and STAT5 in GC have not been fully characterized. In this study, we used ChIP-on-chip to identify STAT3 and STAT5 target genes on a whole genome scale in AGS cells, a human GC cell line. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, which were mainly related to cell growth, metabolism, differentiation, adhesion, immune response, and stress response. Furthermore, we depleted STAT3 and STAT5 with a small interfering RNA, respectively. Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16(ink4a) and p21(waf1/cip1). Moreover, expression of pSTAT3(Tyr705) correlates with TNM stage, differentiation and survival, and is a significant prognostic factor in GC. Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3(Tyr705) expression can predict prognosis in GC.
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PMID:Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. 2232 12


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