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)

We examined 28 cases of primary bone lymphomas (PBL; stage IE) and 26 cases of systemic lymphomas involving the bone (SBL; stage IIE to IV). Two histologic types were prevalent: Diffuse large B-cell lymphomas (DLBCL; 26 PBL and 21 SBL) and CD30+ anaplastic large cell lymphomas (ALCL; 1 PBL and 4 SBL). A mature B phenotype (CD45+, CD20+, CD79a+, CDw75+/-, CD10-/+) was established in the DLBCL group. Bcl-2 immunoreactivity was demonstrated in 13/37 cases (35%), and bcl-6 immunostaining was observed in 22/32 cases (69%). ALCL showed null/T phenotype (CD3-/+; CD43+/-; CD30+), with ALK-1 expression in 3/3 cases. With use of a FR3A primer, a monoclonal pattern was demonstrated by PCR analysis in 22/41 lymphomas (54%). Bcl-2 translocation was identified in 2/41 cases (5%). This study details the clinical and pathological characteristics of bone lymphomas. Our immunohistochemical and molecular data suggest that most of them are "de novo" DLBCL and support their follicle center origin.
 ...
PMID:Lymphomas of the bone: a pathological and clinical study of 54 cases. 1249 Sep 75

In the last decades, considerable changes in the classification of lymphomas have been made. In addition to morphology and immunohistochemistry, the last WHO (2001) classification also utilizes cytogenetics and molecular biology. In many cases classification notices oncogenic mechanisms. The authors describe some differences in immunophenotype in certain entities: chronic lymphocytic leukaemia/small lymphocytic lymphoma--CLL/SLL, follicular lymphoma--FL, mantle cell lymphoma--MCL, diffuse large B-cell lymphoma--DLBCL, and anaplastic large cell lymphoma--ALCL, mainly with respect to prognosis. The authors point out to heterogeneity within the individual types of lymphomas from the point of view of morphology, immunohistochemistry and molecular biology. Recently it has been shown, that differences in prognosis are not limited to individual nosologic entities, but also may be found within the particular category of lymphoma. For example, CLL/SLL is divided in two different subunits according to mutational status of variable segment (VH) of the immunoglobulin heavy chain gene. The cases with unmutated VH segment display progressive disease which is in contrast to cases with the same morphology but with mutated VH segment. Similar differences were found in MCL. Attention is drawn to oncogenic and apoptosis-regulating mechanisms, such as gene p53 and the Bcl-2 family.
 ...
PMID:[Non-Hodgkin's lymphomas (from Rappaport to WHO 2001 and nowadays). Review]. 1762 75

DLBCL (diffuse large B-cell lymphoma) is the most common subtype of non-Hodgkin's lymphoma. Current therapy for patients includes chemotherapy and monoclonal antibodies. Although oncogene-targeted therapy is dramatically successful for patients with certain kinds of leukaemias, there are no such agents yet for DLBCL. One reason for this is that several key oncogenes involved in DLBCL pathogenesis are transcription factors, which are difficult to therapeutically target with small molecules. Recent advances in the structural and functional characterization of DLBCL oncogenes have facilitated design of CPPs (cellpenetrating peptides) with potent inhibitory effects on DLBCL and other aggressive lymphomas. CPPs targeting the Bcl (B-cell lymphoma)-6, Bcl-2, Myc and NF-kappaB (nuclear factor kappaB) oncogenic pathways, among others, could improve efficacy and reduce toxicity of anti-lymphoma therapy. Another barrier towards effective therapy in DLBCL is its profound molecular heterogeneity. Combinatorial administration of oncogene-targeted CPPs based on the molecular profiles of individual patient tumours could allow individualized targeted therapy regimens to be developed.
 ...
PMID:Targeting aggressive B-cell lymphomas with cell-penetrating peptides. 1763 52

Diffuse large B-cell lymphomas can be considered primary bone tumors if they are monostotic or polyostotic, affecting multiple skeletal sites without visceral or lymph node involvement. They are rarely considered as extranodal lymphomas or as bone tumors, respectively. To elucidate the prognostic relevance of clinicopathologic characteristics in such disease, we collected a cohort of primary diffuse large B-cell lymphomas of the bone and retrospectively investigated 33 patients. The cohort encompassed the years 1975 to 2004. Protein expression patterns were identified by immunohistochemistry applied to a tissue microarray. The patients included 23 males (mean age, 37 years) and 10 females (mean age, 54 years). Disease stage was I and II in 30 and IV in 3 patients. Within the mean follow-up of 28 months, 6 patients died. Median overall survival was reached after 78 months. Clinical factors favoring a good prognosis were age younger than 53 and administration of chemotherapy. Of the phenotypic markers analyzed (CD10, CD44s, CD138, Bcl-2, Bcl-6, MUM1, and Ki-67), MUM1 expression in more than 10% of the tumor cells and CD10 expression in less than 55% as well as a nongerminal center signature substantiated adverse outcome in a univariate model. In summary, poor survival in PB-DLBCL was clearly predicted in patients older than 53, who had not received chemotherapy, and who demonstrated MUM1 expression and nongerminal center phenotype.
 ...
PMID:Primary diffuse large B-cell lymphomas of the bone: prognostic relevance of protein expression and clinical factors. 1861 98

Mechanisms underlying interactions between the proteasome inhibitor bortezomib and small molecule Bcl-2 antagonists were examined in GC- and ABC-type human DLBCL (diffuse lymphocytic B-cell lymphoma) cells. Concomitant or sequential exposure to non- or minimally toxic concentrations of bortezomib or other proteasome inhibitors and either HA14-1 or gossypol resulted in a striking increase in Bax/Bak conformational change/translocation, cytochrome c release, caspase activation and synergistic induction of apoptosis in both GC- and ABC-type cells. These events were associated with a sharp increase in activation of the stress kinase JNK and evidence of ER stress induction (e.g., eIF2alpha phosphorylation, activation of caspases-2 and -4, and Grp78 upregulation). Pharmacologic or genetic (e.g., shRNA knockdown) interruption of JNK signaling attenuated HA14-1/bortezomib lethality and ER stress induction. Genetic disruption of the ER stress pathway (e.g., in cells expressing caspase-4 shRNA or DN-eIF2alpha) significantly attenuated lethality. The toxicity of this regimen was independent of ROS generation. Finally, HA14-1 significantly increased bortezomib-mediated JNK activation, ER stress induction, and lethality in bortezomib-resistant cells. Collectively these findings indicate that small molecule Bcl-2 antagonists promote bortezomib-mediated mitochondrial injury and lethality in DLBCL cells in association with enhanced JNK activation and ER stress induction. They also raise the possibility that such a strategy may be effective in different DLBCL sub-types (e.g., GC- or ABC), and in bortezomib-resistant disease.
 ...
PMID:Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress. 3111 86

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low-intermediate in 86% of CNS DLBCL patients and high or high-intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.
 ...
PMID:Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma. 1956 5

A 67-year-old man suffered from a left cervical lymph node swelling and tenderness. Biopsy of the cervical lymph node showed pleomorphic large cells containing large atypical nuclei. Immunohistochemical stains of these cells were positive for CD30, but negative for CD3 and CD20. After the biopsy, his left cervical skin was ulcerated. Biopsy of the left cervical skin was performed. Large pleomorphic cells with constricted nuclei and Reed-Sternberg-like cells existed in the dermis and epidermis. Immunohistochemical stains of the former cells were positive for CD30, CD45 and PAX5, but negative for CD3, CD10, CD20, CD15, Bcl-2, EBER ISH, EMA and ALK. He was diagnosed with diffuse large B cell lymphoma, anaplastic variant. He achieved complete remission with CHOP chemotherapy. CD30-positive DLBCL, anaplastic variant is a rare B cell lymphoma. Most of the patients presented with primary nodal disease, and skin involvement of lymphoma is very rare. This is the report of a rare case of CD30-positive DLBCL, anaplastic variant, with both nodal and skin lesions.
 ...
PMID:CD30-positive anaplastic variant diffuse large B cell lymphoma: a rare case presented with cutaneous involvement. 2083 60

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.
 ...
PMID:Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. 2232 54

Diffuse large B-cell lymphoma represents approximately 30%-40% of all diagnoses of non-Hodgkin's Lymphoma and may represent up to 80% of all lymphomas that arise in the palatine tonsils. Several studies have attempted to correlate clinical, laboratorial, and tissue factors with the prognosis of the lymphomas, such as the International Prognostic Index, the tissue expression of some proteins, and the lymphocyte count at the time of diagnosis, as well as to correlate Epstein-Barr virus (EBV) infection with worse prognoses. Patients with palatine tonsil DLBCL, from Salvador, Bahia, Brazil, were studied in order to identify prognostic factors. Twenty-four patients with DLBCL were studied. The factors that negatively influenced the patients' survival rates were the lymphocyte count at the time of diagnosis <1.000/mm(3) and the Bcl-2 protein expression. There was no CD5 expression in these lymphomas, and neither was there an association with EBV infection.
 ...
PMID:Prognostic Biomarkers and EBV Infection Research in Diffuse Large B-Cell Lymphoma of the Palatine Tonsils. 2251 31

Diffuse large B cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) represent aggressive non-Hodgkin lymphomas, particularly in the setting of HIV infection. Since the introduction of highly active antiretroviral therapy (HAART), recent studies have documented improved survival outcome in patients with AIDS-related lymphomas. This study contributes a South African perspective by correlating the HIV status and prognosis of DLBCL and PBL with differentiation profiles assessed by immunophenotyping. Analysis of the morphologic, immunophenotypic and clinicopathologic features of 52 cases of DLBCL and 9 cases of de novo PBL was performed. The overall survival of patients with PBL was poorer than that of DLBCL (logrank p value 0.002). Despite HAART, the overall survival with DLBCL and HIV infection was significantly poorer than HIV negative patients with DLBCL (p value <0.001). Profound immunosuppression was evident in the HIV positive group as the mean CD4 count was 151 cells/mm(3) in DLBCL and 61 cells/mm(3) in PBL. HIV positive patients were significantly younger at presentation with greater likelihood of extranodal lymphoma. When Hans' and Muris' algorithmic stratification of DLBCL were applied, no statistical significance was demonstrated (p values 0.188 and 0.399 respectively). However, when Bcl-2 expression occurred in germinal center-type DLBCL (Hans' defined), improved survival was conferred by the germinal center immunophenotype (p value 0.007). The study demonstrates that DLBCL and PBL have significant potential for aggressive behaviour and poor outcome in the setting of profound immunosuppression due to HIV infection. Further studies are required to assess the effect of targeted-immunotherapy (Rituximab) in combination with recent amendment of the South African national antiretroviral treatment guidelines which has created tremendous potential for improved survival in patients with AIDS-related non-Hodgkin B-cell lymphomas.
...
PMID:Large cell lymphoma: correlation of HIV status and prognosis with differentiation profiles assessed by immunophenotyping. 2367 Feb 12


1 2 Next >>