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 Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis, pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI. pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.
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PMID:Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas. 1129 23

Bcl-2 expression was studied by immunohistochemistry on laryngectomy specimens from 176 patients. Of the 176 tumours, 11% had positive bcl-2 staining. Bcl-2 expression was significantly correlated with tumour grade: 5% of well-differentiated tumours, 12% of moderately-differentiated tumours and 23% of poorly-differentiated tumours had positive expression of bcl-2. Nodal metastases were also found to be significantly related to bcl-2 expression: 36% of nodal metastases for negative bcl-2 expression compared with 70% for positive expression. The risk of nodal metastases increased significantly with the presence of bcl-2 expression, moderate or poor differentiation and supraglottic involvement. The risk of nodal metastases increased significantly with the presence of increasing numbers of risk factors: 11% without risk factor, 21% with one risk factor, 49% with two risk factors and 77% with three risk factors. Bcl-2 expression in laryngeal carcinoma is significantly correlated with tumour grade and nodal metastases. It has added prognostic value for nodal metastases together with tumour grade and site of tumour involvement.
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PMID:The clinicopathological significance of bcl-2 expression in the surgical treatment of laryngeal carcinoma. 1130 54

Cutaneous follicle center lymphoma (FCL) is reported to have a unique immunophenotype and clinical course as compared with nodal FCL. We studied 19 cases of FCL of the skin using paraffin embedded tissue. An immunohistochemistry panel included CD45, CD3, CD20, CD43, CD21, bcl-2, bcl-6, CD5, and CD10. Molecular studies were performed by polymerase chain reaction for immunoglobulin heavy chain (IgH) and t(14;18). Trisomy 3 was performed by fluorescent in situ hybridization (FISH) in 13 cases. Follow up was obtained in 17 cases (range 3 to 137 months). Patients included 10 females and 9 males ranging in age from 33 to 88 years at first presentation (mean, 64). Twelve of 19 presented in the head and neck and 6 in the trunk and 1 on the arm. All had no known lymph node disease at presentation. Seventeen patients had no nodal disease with a minimum 3 month follow-up; 2/19 had unknown lymph node status with no follow-up. All cases were immunoreactive with CD20 and negative with CD3. Bcl-2 was immunoreactive in 11/18 cases, bcl-6 in 15/15, CD10 in 14/17, CD43 in 2/16 (both were CD10 immunoreactive) and CD5 in 1/15 (it was also bcl-6 immunoreactive). Eight of 18 cases were monoclonal for IgH. Three of 17 showed the presence of t(14;18). FISH was positive in 4 cases for trisomy 3 ranging from 16 to 22% (12% threshold). Follow-up showed no evidence of disease in 14/17 patients (4 to 137 mos). 3/17 patients are alive with disease (17 to 100 mo), and no patients died of disease.
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PMID:Cutaneous follicle center lymphoma: a clinicopathologic study of 19 cases. 1155 77

The description of primary cutaneous follicular lymphoma has raised interest in the differential diagnosis of this versus disseminated follicular lymphoma involving the skin. We report here on four cases of Stage IV follicular lymphoma, diagnosed in skin biopsy, in which cutaneous lesion was the most noticeable feature of clinical presentation. In all cases, the morphological features were superimposed over typical nodal follicular lymphoma. Apart from classic B-cell markers, they were characterized by CD10 and bcl6 positivity, markers of follicle germinal center cells; and bcl2 expression, with a corresponding t(14;18) translocation in three of three cases examined. In all four cases, bone marrow study and clinical staging revealed disease that had disseminated since diagnosis. Follow-up showed relapsing cutaneous and nodal disease in two cases. The only difference observed with a control group of 10 cases of primary cutaneous follicular lymphoma was the absence in this group of t(14; 18). Disseminated classical follicular lymphoma has to be considered in the differential diagnosis of follicular lymphoma presenting in the skin. This series of cases suggests that the presence of t(14;18) could imply the existence of disease that has disseminated beyond the skin and that cases harboring this translocation could be candidates for systemic polychemotherapy.
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PMID:Cutaneous presentation of follicular lymphomas. 1155 89

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.
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PMID:Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma. 1156 25

Peripheral T-cell lymphomas (PTCL) are usually characterized by aggressive clinical behaviour and poor clinical outcome, but their biological background has not been extensively investigated to date, due to their low incidence, about 10% of all non-Hodgkin's lymphoma cases in Western countries, and also to the paucity of specific molecular-genetic abnormalities. Neverthless, there is increasing biological and clinical evidence that primary nodal PTCL should be considered separately from extra-nodal cases, but little is known about biological factors of possible clinical and prognostic impact. This immunohistochemical study has analysed the expression of p53, Mdm2, p21(WAF1), BCL-2 and p-glycoprotein (MDR-1 gene product) in a series of 45 cases of nodal peripheral T-cell lymphomas (PTCL) with 'high-grade' histology. The immunohistochemical findings were then correlated with proliferative activity and clinical outcome. p53 was over-expressed in 13 cases (28.9%). p53 positive cases showed significantly higher proliferative activity (p<0.01), more frequent expression of Bcl-2 (p<0.01) and less frequent expression of p21(WAF1) than p53 negative cases. Mdm2 and p-glycoprotein were expressed in 4/13 (30.8%) and 8/13 (61.5%) p53 positive cases respectively, and in none (0%) of the p53 negative cases (p<0.01). Analysis of the survival curves showed that p53 positive cases were associated with a significantly poorer clinical outcome than p53 negative cases, in terms of both overall survival (p=0.0032) and event-free survival (p=0.0004). Furthermore, multivariate analysis showed that p53 expression was the most important independent prognostic variable. These findings indicate that p53 over-expression identifies a subset of nodal PTCL cases with a distinctive biological profile (higher proliferative activity, less frequent expression of p21(WAF1) and more frequent expression of Bcl-2, Mdm2 and p-glycoprotein than p53 negative cases) and poor clinical outcome. The immunohistochemical analysis of p53 expression is a simple, rapid and low-cost method which may provide information of potential clinical and prognostic value in nodal peripheral T-cell lymphomas.
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PMID:p53 over-expression identifies a subset of nodal peripheral T-cell lymphomas with a distinctive biological profile and poor clinical outcome. 1167 35

The exact classification of primary cutaneous follicle center cell lymphomas (FCCLs) has been the subject of ongoing debate. In the classification of cutaneous lymphomas proposed by the European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphoma Project Group, cutaneous follicle center cell lymphoma (FCCL) is defined as a proliferation of centrocytes and centroblasts showing a diffuse pattern of growth in the great majority of cases, and presenting only rarely a true follicular pattern. CD10 and Bcl-2 are usually not expressed by neoplastic cells, and the t(14:18) is absent. By contrast, nodal follicular lymphoma is a tumor with a follicular pattern, characterized by the proliferation of CD10+, Bcl-2+ follicular cells, and by the presence of the t(14;18) in most cases. In this review we outline the clinicopathologic, phenotypic, and molecular features of primary cutaneous FCCL, reviewing criteria for diagnosis and differential diagnosis of this peculiar variant of cutaneous B-cell lymphoma.
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PMID:Primary cutaneous follicle center cell lymphoma. 1169 44

The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that "molecular staging" be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53(nac)) and phenotypic expression of Bcl-2, MUC-1 and p27(kip-1) may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers.
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PMID:Molecular staging of colorectal cancer in African-American and Caucasian patients using phenotypic expression of p53, Bcl-2, MUC-1 AND p27(kip-1). 1180 99

Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta 1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin beta 1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin beta 1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.
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PMID:Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. 1187 May 34

The main objectives of this study were to determine the feasibility of administering high doses of cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) every 14-21 days to patients with follicular small cleaved cell lymphoma. For each patient, the treatment was not considered feasible if fewer than four cycles of cyclophosphamide chemotherapy could be administered on schedule (i.e. at least every 29 days) or (1) hospitalization of the patient for longer than three days was necessary for neutropenic fever (38 degrees C) or bacteriologically documented infection in > 50% of the cycles, or (2) grade > or = 2 hemorrhage in association with thrombocytopenia of grade > or = 3 severity occurred in > 50% of the cycles or (3) non-hematologic toxicity (excluding nausea/vomiting and alopecia) of grade > or = 3 occurred in > 50% of cycles. The goal was to have a treatment program feasible in 75% or more of the treated patients. The secondary objectives were to determine the toxicities, the complete and partial response rates, and the time to treatment failure (TTF). The trial also attempted to assess the effectiveness of this treatment program in eradicating Bcl-2 rearrangements by PCR, and to assess complete remission duration in relationship to PCR results in patients who respond to this chemotherapy program. Patients were required to have histologically documented non-Hodgkin's lymphoma of the subtypes follicular, predominantly small cleaved cell (IWF-B) or follicular mixed, (IWF-C). Patients were required to have Stage IV disease including histologic evidence of bone marrow involvement. Measurable disease was required and patients were also required to have one of the following risk factors: > or = 2 extranodal sites, node or nodal group > or = 5 cm. Submission of fresh bone marrow for molecular genetic studies for the presence of Bcl-2-Ig fusion DNA was mandatory in previously untreated patients. Patients had to be between 18 and physiologic age 55 years (carefully selected patients over age 55 years were also eligible), expected survival > 2 years, performance status 0-1, and have adequate renal, hepatic and bone marrow function, and a cardiac ejection fraction > or = 50%. Cyclophosphamide 4.5 g/m2 i.v. was given with mesna every 14 days with rhG-CSF support. Twenty-nine patients were accrued to this trial. The median follow-up time is 5.0 years, with a range of 2.5-6.7 years. The overall response rate was 75% (9 CRs 37.5%, 9PRs 37.5%). The median duration of survival is 5.53 years. The 1-year estimated probability of freedom from treatment failure was 50% and of survival at 1 year was 92%. No strong association was observed between TTF and age, symptomatic stage, histology performance status, number of extranodal sites or baseline Bcl-2 status. At 3 years the survival of all patients was 78% and failure free survival was 17%. 15 (62%) of the 24 eligible previously untreated patients met the criteria for feasibility specified in the protocol. The 95% CI for the feasibility rate is (44 and 82%). Twenty-two of the 24 (92%) previously untreated patients had specimens submitted for testing for Bcl-2 rearrangements. Thirteen of the 22 (59%) were found to have rearrangements at baseline. Post-treatment specimens were submitted for seven of the 13 patients. Four of the seven converted to Bcl-2 negative following treatment. Eight of 13 Bcl-2 positive patients (62%) had a clinical response to treatment. The 95% exact binomial CI for the total response rate in this subgroup is (28 and 88%). This study demonstrates that repetitive doses of cyclophosphamide at 4.5 g/m2 every two weeks with rhG-CSF support can be administered to selected younger patients with advanced follicular lymphoma with morphologic involvement of the bone marrow with acceptable non-hematologic toxicity.
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PMID:High dose cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) in the treatment of follicular, low grade non-Hodgkin's lymphoma: CALGB 9150. 1191 6


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