Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology. Histological features currently define it. Persistent painless lymphadenopathy due to expansion of sinuses infiltrated with benign histiocytes and plasma cells and emperipolesis are the characteristic features of SHML. Our study includes seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides and blocks were reviewed. IHC was performed on the main lesion, from a panel of S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane antigen. In our series we have work up available in 7 cases out of which a detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a stable disease, while one developed histiocytic sarcoma after a gap of four years.
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PMID:Sinus histiocytosis with massive lymphadenopathy--a review of seven cases. 1718 39

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous entity. The pattern of CD15, CD30 and Bcl-2 expression is not well documented, especially in local population. We investigated 67 consecutive cases of DLBCL by immunohistochemistry on paraffin-embedded tissue. The male to female ratio was 1.2:1 with median age of 55 years, and more common nodal than extranodal in presentation. Only 3 of 67 cases expressed CD15. In addition, three cases showed weak membrane staining for CD30. Only one of these three cases was noted to have co-expression of CD15 and with occasional tumour cells showing weak CD30 expression. Bcl-2 protein was expressed in 43 of 67 (64%), more frequently in nodal than in extranodal tumours. In conclusion, CD15 and CD30 expressions are infrequent in DLBCL, and co-expression is rare. Bcl-2 protein expression is common in DLBCL.
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PMID:The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma. 1724 18

Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage 1E disease, a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphomas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults.
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PMID:Primary follicular lymphoma of the testis and epididymis in adults. 1759 72

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.
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PMID:Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells. 1791 49

BCL-2 was the first antideath gene discovered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.
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PMID:Bcl-2-family proteins and hematologic malignancies: history and future prospects. 1836 12

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.
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PMID:Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes. 1838 58

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL have been proposed as a practical method to validate and surrogate results obtained by gene expression profiling. We studied 71 patients with primary nodal DLBCL at diagnosis, who received anthracycline-based therapy with or without rituximab. Immunohistochemistry was performed using anti-CD10, Bcl-6, MUM1 and Bcl-2 antibodies in order to assess the ontogenic profile of neoplastic cells and to verify its relation with clinical outcome. Survival data were analysed using an explorative Cox model. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL were not associated with prognosis. By contrast, Bcl-6 expression was associated with a longer lymphoma-free survival while immunoreactivities for MUM1 or Bcl-2 were not significantly related to patient outcome. Bcl-6 expression alone proved to be a prognostic marker in primary nodal DLBCL and seemed to be more reliable to predict clinical outcome in these disorders than the immunohistochemical algorithms for the detection of the germinal centre/non-germinal centre immunophenotype.
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PMID:Bcl-6 protein expression, and not the germinal centre immunophenotype, predicts favourable prognosis in a series of primary nodal diffuse large B-cell lymphomas: a single centre experience. 1860 21

We sought to determine the clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with post-transplant lymphoproliferative disorders (PTLDs). Eighty-four patients diagnosed with PTLDs between 1980 and 2004 at the University of Pittsburgh Medical Center were identified. Immunohistochemical staining was performed on tumor tissue at the time of diagnosis for the following proteins: Bcl-2, Bcl-6, c-myc and p53. The median survival for all patients was 20.8 months, 95% CI: (7.4-77.6). On univariate analysis for OS, the following poor prognostic factors were identified: age at transplant >60 years (p = 0.024), multiorgan transplant (p = 0.019), ECOG > 2 (p < 0.0001), grafted organ involvement (p < 0.0001), extranodal disease (p = 0.011), early (<1 year) PTLDs (p < 0.0001), stage IV (p = 0.0017), EBV positive (p = 0.012) and elevated white blood count (p = 0.010). Good prognostic factors included ECOG<2 (p < 0.0001), late (>1 year) PTLDs (p = 0.002), early stage at diagnosis (stages I and II, p = 0.005), nodal disease (p = 0.0053), monomorphic disease (0.0034), initial immunosuppression reduction (p = 0.0015) and use of rituximab (p = 0.045). Bcl-2 but not Bcl-6, c-myc, or p53 correlated with poor survival, p = 0.0036. This study identifies new clinical and pathological markers for poor survival in PTLDs.
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PMID:Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant. 1879 8

BCL-2 was the first anti-death gene discovered, a milestone with far reaching implications for tumor biology. Multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including six antiapoptotic, three structurally similar proapoptotic proteins and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. These proteins, in turn, are regulated through myriad post-translational modifications and interactions with other proteins. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis and autophagy, thus operating as nodal points at the convergence of multiple pathways with broad relevance to oncology. Experimental therapies targeting Bcl-2-family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may soon be available.
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PMID:Bcl-2 family proteins and cancer. 1895 68

The aims of this study were to define the initial pathological and clinical characteristics, and prognostic factors of patients with primary breast malignant lymphoma (PBL). All patients treated at the Institut Curie for lymphoma with breast involvement were reviewed. A pathological review of all cases was performed. Forty-five cases were selected in whom 38 cases were of diffuse large B-cell lymphoma. A complete analysis was then performed on these 38 patients. Twenty out of 28 cases (71%) of cases were Bcl-2 positive and four out of 28 (14%) had a CD10 positive staining. Peculiar initial characteristics showed nodal involvement in 58% of the cases and two or more extra-nodal sites in 31% of the cases. Among the 37 patients for whom all data were available, and according to the International Prognostic Index, 19 patients (51%) were classified in the low-risk group, 5 cases (14%) in the low- to intermediate-risk group, 6 patients (16%) in the intermediate- to high-risk group, and 7 (19%) case in the high-risk group. At the end of initial therapy, 34 patients (89%) achieved CR. With a median follow-up of 96 months, 18 patients (47%) relapsed of whom 3 had a relapse in central nervous system site. The 5-year disease-free (DFS) and overall survivals (OS) were 54% and 61%, respectively. In multivariate analysis, the presence of 2 or more extranodal sites was prognostic for lower DFS (P = 0.0008) and OS (P = 0.09), and a performance status > or = 1 was prognostic for lower OS (P = 0.005). Finally, when our series was compared with a historical series of 111 patients with aggressive nodal lymphomas, we observed significant lower survival rates in localized PBL (P < 0.03). Initial breast localization has a pejorative impact on the outcome of patients with Non-Hodgkin's Lymphoma (NHL), with an impressive adverse influence of additional extranodal sites. These results suggest a specific management of NHL with breast involvement.
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PMID:Primary breast non-Hodgkin's lymphoma: a large single center study of initial characteristics, natural history, and prognostic factors. 1919 67


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