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)

Microwave heating of histologic sections in citrate buffer (MAR) is a widely used method of antigen recovery but often results in loss of tissue sections. Low-temperature antigen retrieval (LTAR), incubation at 80 degrees C in citrate buffer for 2 hours with trypsin pretreatment is an alternative method reported to result in better antigen recovery for specific antigens as well as decreased loss of tissue sections. To optimize our immunohistochemical evaluation of breast carcinomas, we compared the efficacy of these methods of antigen recovery for several important antigens. Ten breast carcinomas were immunostained for estrogen and progesterone receptors (ER and PR), Ki-67/ MIB 1, p27/Kip-1, and Bcl-2 after MAR, LTAR with enzymatic pretreatment, or no antigen recovery. The immunohistochemical staining was scored and compared for each antibody and antigen recovery combination. The proportion of tissue lost from each slide after staining also was assessed. More and stronger positive staining was achieved with antibodies to Ki67/MIB 1 and ER when LTAR was used compared with the other two methods; in contrast, optimal staining with antibodies to Bcl-2 was achieved when MAR was used. Staining with anti-p27/Kip- was nearly equal with either LTAR or MAR. Staining with anti-PR was slightly better with MAR than with LTAR. Tissue loss was greatest for MAR compared with LTAR or with no antigen recovery. For selected cases, LTAR caused focal tissue damage, and either the immunostaining with LTAR had to be repeated or only a portion of some tissue sections would be used for examination. LTAR was the most effective for ER and Ki-67/MIB 1. MAR provided the most intense staining for Bcl-2 and PR, but this enhanced staining must be weighed against the greater tissue section loss from MAR. This study demonstrated that AR methods are not equally applicable to all antibodies.
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PMID:Methods of antigen recovery vary in their usefulness in unmasking specific antigens in immunohistochemistry. 1098 77

Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic factor. However, evaluation of the prognostic significance of the expression of proteins involved in regulation of cell proliferation remains controversial. In the present study, expression of Ki-67, PCNA and cyclin D1 was estimated in a group of 89 surgically resected non-small cell lung carcinomas using immunohistochemistry. The results were compared with expression of bcl-2 and p53 and with clinicopathological parameters including patients' survival. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation between Ki67 and PCNA expression. Forty five of 88 tumours (51%) showed overexpression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the cytoplasm and only a small group of tumours (9/88, 10%) showed nuclear staining as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tumours, respectively. All these markers were found to be independent of clinicopathological parameters, except for Ki-67 and bcl-2 expression, which was associated with squamous cell carcinomas. It is concluded that none of the markers that were studied can be used as an independent prognostic factor, whereas the following combinations of markers may have favourable prognostic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and lack of cyclin D1 expression and low Ki-67 expression.
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PMID:Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2. 1099 69

Typical bronchial carcinoids are usually considered fairly benign tumors. Metastases do however occur, and up to 10% of the patients ultimately die from their disease. To identify prognostic markers, we immunostained 43 typical bronchial carcinoids with antibodies against 8 possibly relevant hormones, oncogenes, tumor suppressor genes, adhesion molecules, and proliferation markers. Altogether 12 patients (28%) had metastatic disease, of whom 10 had regional lymph node metastases at diagnosis. Distant metastases have occurred in 5 patients (12%); all of these have died from their disease. Patients with high expression of Ki-67 had shorter survival time (P < 0.01). None of the immunostained hormones correlated to distant metastases or shorter survival time, but gastrin-releasing peptide correlated to metastatic disease (P < 0.05). All patients who died had CD44-negative tumors (P < 0.001). Nuclear nm23 staining correlated to decreased risk for metastatic disease and distant metastases per se (P < 0.01). Bcl-2 and p53 were associated with increased risk for distant metastases (P < 0.05 and P < 0.01, respectively). We conclude that some patients with typical bronchial carcinoids die from their disease and that gastrin-releasing peptide, Bcl-2, and p53 may be of importance for the malignant transformation of the tumor. Moreover, CD44, nm23, and Ki-67 may give valuable prognostic information and help identify the patients at risk of disease-related death.
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PMID:Prognostic markers in patients with typical bronchial carcinoid tumors. 1099 44

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing of messenger RNA. These splice variants have been shown in several cancer cell types and are thought to be involved in tumor progression. The aim of the current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other markers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal antibodies: anti-CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cells were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 variants tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms varied, depending on lung cancer histology. In general, CD44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 cases with metastases, tumor cells had high v6 and Ki-67 expression, but these data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in anaplastic small cell or large cell cancers only v10 expression seems to correlate with proteins associated with tumor growth and progression.
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PMID:Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer. 1105 26

Neuroendocrine lung tumors (NELT) from 50 patients were studied immunohistochemically. Malignant carcinoid and small-cell lung carcinoma (SCC) have a higher level of apoptosis than ordinary carcinoid. An increase of apoptosis index in NELT coincides with an increase in NELT proliferative activity (Ki-67, Bcl-2, c-myc, p-53) as compared to a typical carcinoid. Phagocytosis of apoptotic bodies was absent in SCC. Classic SCC differs from combined SCC by a higher apoptosis index and lower expression of p-53 and Bcl-2. Metastatic SCC differs from SCC without metastases by lower apoptosis level and higher level of proliferative indices (Ki-67, Bcl-2) of tumor cells. Development of unbalance between apoptosis and proliferation may result from mitosis and apoptosis pathology.
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PMID:[Small cell carcinoma and carcinoids of the lung: morphology of apoptosis and expression of biomolecular markers of tumor growth]. 1107 93

Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB- 1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p = 0.013). Irradiation caused the reduction of MIB-1+ (p = 0.0015), DO-7+ (p = 0.0043) and the increase of Bcl-2+ cells (p = 0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p = 0.0186) and no treatment (p = 0.0158), low ISNT scores (p = 0.0018) and high DO-1 scores (p = 0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-I and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.
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PMID:Distinct radiochemotherapy protocols differentially influence cellular proliferation and expression of p53 and Bcl-2 in glioblastoma multiforme relapses in vivo. 1108 75

Bone marrow CD34(+) cell apoptosis (annexin V), proliferation (Ki-67), and Bcl-2-related protein expression was evaluated by flow cytometry in 102 patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia secondary to MDS (MDS-AML) and in 30 normal donors (NBM). Apoptosis was significantly increased in refractory anemia (RA)/RA with ringed sideroblasts (RARS) (56.9% [20.4%-93.6%]) and refractory anemia with excess blasts (RAEB) (51.2% [25.2%-76. 6%]) compared with NBM (16.7% [3.4%-35.3%], P <.0001). In RA/RARS, apoptosis always exceeded proliferation (Ki-67-positivity, 26.1% [9.5%-47.8%]; apoptosis:proliferation ratio 2.08 [1.15-3.63]); whereas in RAEB, this ratio equalized (1.14 [0.93-2.08]) due to increased proliferation (40.4% [22%-69.5%]). Progression to RAEB in transformation (RAEB-t)/MDS-AML was associated with a significant reduction in apoptosis (22.3% [2.1%-53.2%]; P <.0001) and proliferation (16.8% [1.9%-75.8%); P =.04; ratio 1.69 [0.16-12.21]). Pro-apoptotic (Bax/Bad) versus anti-apoptotic (Bcl-2/Bcl-X) Bcl-2-related protein ratios were increased in RA/RARS compared with NBM (2.57 [1.93-9.42] versus 1.89 [0.65-4.1]; P =.06), whereas disease progression was associated with significantly reduced ratios (1.16 [0.06-3.32]; P <.0001) due primarily to increased Bcl-2 expression. Apoptosis and Bax/Bad:Bcl-2/Bcl-X ratio were inversely correlated with both International Prognostic Scoring System score and cytogenetic risk group; highest levels observed in patients with low score and/or good risk cytogenetics. There was a trend toward an association between Bcl-2-related protein expression and apoptosis (P =.07). This study indicates that MDS progression arises through multiple hits that alter levels of CD34(+) cell apoptosis and proliferation. Early disease is associated with excessive apoptosis and elevated ratio of apoptosis to proliferation. Increased proliferative rates are observed in RAEB, whereas leukemic transformation arises through inhibition of apoptosis rather than excessive cell growth. Although disease progression is accompanied by a fall in pro-apoptotic versus anti-apoptotic Bcl-2-related protein ratios, heterogeneity in patterns of protein expression indicates that factors additional to Bcl-2 family members play a role in the deregulated apoptosis in MDS. (Blood. 2000;96:3932-3938)
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PMID:The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. 1109 80

We conducted a retrospective immunohistochemical evaluation of the prognostic significance of the expression of p53 and the related proteins Bax, Bcl-2, growth arrest and DNA damage (Gadd45), murine double minute 2 (Mdm2) and p21(WAF1/CIP1) in chemonaive tumours taken from 66 patients with ovarian cancer. Ki-67 expression (a marker of cell proliferation) was also evaluated immunohistochemically, while apoptosis within malignant cells was determined with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay. The expression of each of the following proteins was significantly associated in the tumours (P < 0.05 unless otherwise stated): Bax with Bcl-2 (P < 0.01); Bax with Mdm2; p21(WAF1/CIP1) with Gadd45 (P < 0.01); p21(WAF1/CIP1) with p53; p53 with Mdm2. Univariate analysis showed that expression of p53, Bax, bulk residual disease and International Federation of Gynecology and Obstetricians (FIGO) stage were all strongly correlated with response to chemotherapy (P < 0.01). Similarly, the FIGO stage and Ki-67 expression (P < 0.01), as well as pathological subtype and bulk residual disease (P < 0.05), were prognostic factors for disease progression. The FIGO stage and Ki-67 expression were significant prognostic factors for overall survival (P < 0.01), with Gadd45 expression and pathological subtype also significant (P < 0.05) in a univariate analysis. Multivariate analysis for response to chemotherapy showed that expression of p53, Bax and FIGO stage were all independent prognostic factors (P < 0.01). The FIGO stage was the most important independent prognostic factor for progression and survival on multivariate analysis (P < 0.01). However, Ki-67 expression was also an independent prognostic factor for disease progression (P < 0.05) and approached significance for survival (P = 0.055). Taken together, these data suggest that determination of Ki-67 expression could supplement established prognostic factors.
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PMID:p53 and related proteins in epithelial ovarian cancer. 1109 5

The fetal and post-natal development of the pig ovary involves both proliferation and apoptotic loss of germ cells, follicle formation and growth, and the initiation of oocyte meiotic maturation. The present study measured the expression of the proto-oncogene Bcl-2 immunohistochemically on paraffin sections of pig ovaries to determine its relationship with folliculogenesis on Days 50 and 80 post coitum (p.c.) and on Days 1, 21, and 56 post partum (p.p.). The expression of the steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase (3betaHSD) was used to determine the lineages of the cells forming the ovarian follicles, and the expression of the cell proliferation-associated nuclear antigen Ki-67 was used to determine germ cell proliferation and the initiation of follicle growth. Expression of Ki-67 showed that many oogonia were proliferating on Days 50 and 80 p.c. Granulosa cells were more proliferative on Day 56 p.p. than at any other stage; Ki-67 was expressed in 70% of growing follicles and granulosa cells had a 3% mean staining index per section. Less than 4% of germ cells and follicles had morphological signs of degeneration during the period of the study. Bcl-2 was most abundant on Days 21 p.p. and 56 p.p.; staining was localized to stromal cells among follicles and in small clusters in the cortical medullary junction (CMJ). 3BetaHSD staining on Day 50 p.c. was seen in cords of stromal cells within the medulla of the ovary, and in the stromal cells investing the oogonial nests. On Days 80 p.c., 1 p.p., 21 p.p., and 56 p.p., 3betaHSD was expressed in the granulosa cells of primary or primordial follicles at the CMJ. Production of Bcl-2 by somatic cells may support germ cell and preantral follicle survival.
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PMID:Expression of bcl-2 and 3-beta hydroxysteroid dehydrogenase protein during oocyte and follicle development in fetal and post-natal pig ovaries. 1110 Dec 84

Fifty-six primary neuroendocrine lung tumors were examined morphologically and histologically and their apoptosis level was determined. Malignant carcinomas were characterized by increased apoptotic index and enhanced expression ofBcl-2, Bak, p53, and Ki-67 compared to typical carcinoid. However, apoptosis in these tumors was not completed. Proteins of the Bcl family play an important role in the regulation of spontaneous apoptosis in neuroendocrine lung tumors. Bcl-2 accumulating in the nucleus is a morphological analogue of phosphorylated inactive form of this protein, which does not inhibit apoptosis. Expression of Bcl-2 and Bax decreases in small-cell lung carcinoma (SCLC) with metastases indicating attenuation of apoptosis and development of metastatic clones resistant to apoptosis induces.
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PMID:Role of Bcl-2, Bax, and Bak in spontaneous apoptosis and proliferation in neuroendocrine lung tumors: immunohistochemical study. 1114 May 90


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