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)

Apoptosis is an active process regulated by a variety of genes. Recently, the molecular cloning, physical mapping and expression analysis of a novel gene of the Bcl-2 family, BCL2L12, was reported. Expression analysis of the BCL2L12 gene in breast cancer confirmed an association of BCL2L12 with favorable prognosis of patients. In the present study, the expression of the BCL2L12 gene was analyzed in colon cancer by RT-PCR. Two transcripts, BCL2L12 and BCL2L12-A, were overexpressed in the cancer tissues as compared to their paired normal mucosa. An association was found between BCL2L12-A transcript expression and nodal status, as well as Dukes' stage. The BCL2L12-A transcript appears to be of importance for colon cancer since its expression is associated with disease progression.
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PMID:Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer. 1549 71

We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive lymphoma cells were used to determine the status of the caspase 8-mediated pathway. Expression levels of Bcl-2 and X-linked inhibitor of apoptosis (XIAP) were used to determine the status of the caspase 9-mediated pathway. Expression of c-Flip, XIAP, Bcl-2, and caspase 3 activity all provided prognostic information. According to these immunohistochemical parameters, inhibition of either or both caspase signaling pathways was detected in all patients. Three groups of patients were identified, one with a caspase 8 inhibition profile, one with caspase 8 and 9 inhibition profiles, and one with a caspase 9 inhibition profile. Caspase 9 inhibition was strongly associated with poor response to chemotherapy and usually with fatal outcome, whereas caspase 8 inhibition was associated with excellent clinical outcome. Thus, our data strongly suggest that inhibition of the caspase 9-mediated pathway, but not the caspase 8-mediated pathway, is a major cause for therapy resistance in patients with nodal DLBCL.
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PMID:Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. 1557 77

Although primary cutaneous follicular lymphoma (FL) is considered a distinct variant of FL in the World Health Organization classification ("cutaneous follicle center lymphoma"), its biologic relationship to nodal FL remains controversial. The clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 17 patients with primary cutaneous FL were studied and compared with 16 patients with secondary cutaneous FL. The head and neck region was the most frequent site at initial skin presentation in both the primary and secondary cases. Among the primary cases, 29% of the 31 biopsies were grade 1, 48% grade 2, 13% grade 3, and 10% grade 3 with diffuse large B-cell (DLBCL) areas. Among the secondary cases, 38% of the 29 skin biopsies were grade 1, 45% grade 2, 3% grade 3, and 7% grade 3 with DLBCL areas with two not evaluable. A floral-like pattern was observed in 32% of primary FL but only 5% of secondary cases. Histologic progression was found in 21% of patients. CD10 expression was demonstrated in 90% (27 of 30) of primary cases and 96% (22 of 23) of secondary cases. Bcl-6 was expressed in all cases tested. Bcl-2 expression was detected in 57% (17 of 30) of the primary cases (100% of grade 1, 43% of grade 2, 40% of grade 3), whereas all secondary cases were bcl-2 positive (P=0.0002). The t(14;18) translocation was identified by interphase fluorescence in situ hybridization (FISH) in biopsies from 31% (4 of 13) of the patients with primary FL compared with 77% (10 of 13) of those with secondary lymphoma (P <0.05). Seven of the 17 (41%) patients with primary disease had cutaneous relapse, including 1 who also developed nodal disease. Bcl-2 positivity was seen in 4 of these 7 patients. Eight of the 16 (50%) patients with secondary FL had cutaneous relapse. Primary and secondary cutaneous FL share many clinical and phenotypic features, but primary cases may have some distinctive morphologic features, more frequently lack bcl-2 protein, and often lack the t(14;18) translocation. These findings suggest that primary cutaneous FL are distinctive and often but not always have a pathogenesis different from most of nodal and secondary cutaneous FL.
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PMID:Clinicopathologic, immunophenotypic, and molecular cytogenetic fluorescence in situ hybridization analysis of primary and secondary cutaneous follicular lymphomas. 1561 57

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.
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PMID:Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases. 1573 58

In contrast to nodal large B-cell lymphomas, recurrent chromosomal aberrations have been studied only in a small number of cases of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). We investigated 25 PCDLBCLs (classified according to the WHO-EORTC classification into PCDLBCL, leg-type, 8; and PCDLBCL, other, 17), using an interphase fluorescence in situ hybridization technique. All cases were analyzed for chromosomal aberrations commonly observed in nodal large B-cell lymphomas, including structural aberrations of the genes BCL2, BCL6, and c-MYC, and numerical aberrations of the chromosomes/genes 3, 7, 8, 11, 12, 13, 17, 18q, RB1, and p53. We observed genetic aberrations in 19 (76%) of 25 patients. The most frequent numerical aberrations were gains of chromosome 12 (7 of 25, 28%), 7 (5 of 25, 20%), 3 (5 of 25, 20%), 18q (3 of 25, 12%), 11 (3 of 25, 12%), X (3 of 25, 12%), and losses of chromosome/gene 17/p53 (3 of 25, 12%). BCL2, c-MYC, and BCL6 were rearranged with the IGH gene in 4 (16%), 1 (4%), and none (0%) of 25 cases, respectively. Most aberrations were homogeneously distributed among cases of PCDLBCL, leg-type and of PCDLBCL, other, cases located on the leg or at other body sites, cases with round and cleaved cell morphology, and Bcl-2+ and Bcl-2- cases. These results suggest that PCDLBCLs show similar chromosomal aberrations irrespective of classification, anatomic site, cell morphology, and Bcl-2 expression, and that many similarities between primary cutaneous and nodal diffuse large B-cell lymphomas can be observed.
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PMID:Genetic aberrations in primary cutaneous large B-cell lymphoma: a fluorescence in situ hybridization study of 25 cases. 1583 92

Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein overexpression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis.
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PMID:Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype". 1600 2

Tissue microarrays (TMAs) are potentially suited to find associations between molecular features and clinical outcome. Enhanced cell proliferation, as measured by Ki67 immunohistochemistry, is related to poor patient prognosis in many different tumor types. Ki67 expression shows considerable intratumoral heterogeneity. It is unclear if the TMA format is suitable for the analysis of potentially heterogeneous markers because of the small size of TMA spots. We have analyzed a breast cancer TMA containing 2,517 breast tissues, including 2,222 neoplastic and 295 normal or premalignant samples, for Ki67 labeling index (Ki67 LI) and additional markers with a known relationship to Ki67 LI by immunohistochemistry (ER, PR, Bcl-2, Egfr, p16, p53) and Fluorescence in situ hybridization (HER2, MDM2, CCND1, MYC). A high Ki67 LI was linked to tumor phenotype including grade (p < 0.0001), stage (p < 0.0001), nodal stage (p = 0.0018), and patient prognosis (p < 0.0001), elevated protein levels of p53, p16 and Egfr, reduced levels of Bcl2, ER, and PR (p < 0.0001 each), as well as amplifications of HER2, MYC, CCND1 and MDM2 (p < 0.0001 each). In summary, all expected associations between Ki67 and the analyzed molecular markers could be reproduced with high statistical significance using a TMA containing only one tissue sample per tumor, measuring 0.6 mm in diameter. We conclude that associations with cell proliferation can be reliably analyzed in a TMA format.
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PMID:Tissue microarrays for comparing molecular features with proliferation activity in breast cancer. 1633 4

Clinical outcome in patients with diffuse large B cell lymphomas (DLBCL) is poorly predictable. Expression of proteins related to germinal centre B (GCB) cell or activated B cells (ABC) and expression of apoptosis-regulating proteins Bcl-2 and XIAP have been found previously to be strongly associated with clinical outcome. In this study we aimed to develop an algorithm based on expression of GCB/ABC-related proteins CD10, Bcl-6 and MUM1 and apoptosis-inhibiting proteins Bcl-2, XIAP and cFLIP for optimal stratification of DLBCL patients into prognostically favourable and unfavourable groups. Expression of CD10 and cFLIP was associated with better overall survival (both p = 0.03), whereas expression of MUM1, Bcl-2 and XIAP was associated with poor clinical outcome (p = 0.01, p = 0.0007 and p = 0.03, respectively). Multivariate analysis revealed that Bcl-2 was the strongest prognostic marker followed by CD10 and MUM1. Stratification of patients according to a new algorithm based on expression of these three markers improved patient risk stratification into low and particularly high clinical risk groups (p = 0.04 and p < 0.0001, respectively). We conclude that, in our group of primary nodal DLBCLs, a new algorithm, based on expression of the apoptosis-inhibiting protein Bcl-2 and the GCB/ABC-related proteins CD10 and MUM1, strongly predicts outcome in International Prognostic Index (IPI)-low and -high patients. Its predictive power is stronger than previously published algorithms based on only GCB/ABC- or apoptosis-regulating proteins.
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PMID:Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. 1640 Jun 25

Bcl-2 and clusterin genes have been related to the inhibition of apoptosis, an event that plays a key role in malignant transformation and in invasive disease. In this work, we determine the significance of clusterin and bcl-2 expression in a large series of laryngeal carcinomas. We used immunohistochemical methods and in situ hybridization to examine the expression of these proteins. Nontumoral epithelial laryngeal tissues did not express clusterin and bcl-2 proteins. However, 9% (14 out of 154) and 25% of these tumors (39 of 154) had positive clusterin and bcl-2 staining, respectively. Clusterin expression was significantly related to the degree of local invasion and higher bcl-2 expression was found in these clusterin-positive tumors (p < 0.05). Bcl-2 expression was significantly correlated with supraglottic localization, nodal metastases, invasion in depth, and poorly differentiated tumors. However, by multivariate analysis, bcl-2 was shown to be an independent predictor of good prognosis in these tumors (OR = 0.12, 95% CI = 0.02-0.91). These findings indicate that clusterin and bcl-2 are upregulated in laryngeal carcinomas and their expression is related to the invasiveness of these tumors.
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PMID:Expression of the antiapoptotic proteins clusterin and bcl-2 in laryngeal squamous cell carcinomas. 1667 13

Resistance to chemotherapy in therapy-refractory diffuse large B-cell lymphomas (DLBCL) is related to inhibition of the intrinsic apoptosis pathway. Human soluble tumour necrosis factor (TNF)-related apoptosis-inducing ligand (hsTRAIL/Apo2L) induces apoptosis via the alternative, death-receptor mediated apoptosis pathway and might be an effective alternative form of therapy for these lymphomas. This study investigated whether hsTRAIL/Apo2L could actually induce apoptosis in isolated lymphoma cells of DLBCL biopsies of patients with chemotherapy-refractory DLBCL. Twelve out of a total of 22 DLBCL samples were sensitive to hsTRAIL/Apo2L. These sensitive lymphomas included seven clinically chemotherapy-refractory lymphomas. Furthermore, hsTRAIL/Apo2L induced apoptosis in DLBCL cells and in B-cell lines that showed high expression levels of inhibitors of the intrinsic apoptosis pathway: Bcl-2 and/or X-linked inhibitor of apoptosis (XIAP). hsTRAIL/Apo2L-sensitive lymphoma cells showed expression of the TRAIL receptors R1 and/or R2 and absence of R3 and R4. We conclude that hsTRAIL/Apo2L induced apoptosis in a subpopulation of chemotherapy-refractory nodal DLBCL and that disruption of the intrinsic apoptosis-mediated pathway and expression of Bcl-2 and XIAP did not confer resistance to hsTRAIL/Apo2L-induced apoptosis in DLBCL. Thus, based on our results, further exploration of hsTRAIL/Apo2L as an alternative treatment for patients with chemotherapy-refractory DLBCL should be considered.
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PMID:Human soluble TRAIL/Apo2L induces apoptosis in a subpopulation of chemotherapy refractory nodal diffuse large B-cell lymphomas, determined by a highly sensitive in vitro apoptosis assay. 1684 71


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