Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphoma induction in rabbits by an unknown factor derived from an HTLV-II-producing simian (Cynomolgus) leukocyte cell line (Si-IIA) is reported. Thirteen of 17 male Japanese white rabbits (76%) inoculated intravenously with Si-IIA cells developed malignant lymphoma including Hodgkin-like lymphoma between 62 and 167 days after inoculation. Histologically, there was extensive diffuse or nodular infiltration of either large cell type or mixed type lymphoma cells in many organs, frequently involving the spleen, liver, lymph nodes and kidneys, and less frequently the thymus, bone marrow, lungs, heart, skin and gastrointestinal tract. Hodgkin-like lymphoma was also observed in two rabbits. Chromosomal analysis of five cell lines established from tumor-bearing rabbits revealed the male rabbit karyotype. The immunophenotype of these tumor cells was usually T-cell (CD5+ or -, RT1+, RT2+ or -, CD45+, CD4-, RABELA- and MHC class II-DQ+) except for Hodgkin-like lymphoma cells which expressed only CD45. However, integration of the HTLV-II provirus genome could not be demonstrated in the tumor tissues or any of the rabbit cell lines by polymerase chain reaction or Southern blot analysis. Moreover, no lymphoma was induced by inoculation of HTLV-IIC, MOT (other HTLV-II-producing human cell lines) or TALL-1 (control). Two of four rabbits injected with cell-free pellets from Si-IIA cultures died of malignant lymphoma (15-20 days). Five irradiated rabbit cell lines were inoculated but only one (Ra-SLN) induced lymphoma in 1 of 3 rabbits at 27 days. Neither Herpesvirus saimiri nor Herpesvirus ateles (simian oncogenic viruses) was detected in Si-IIA cells by immunofluorescence testing. These data suggest that the high rate of lymphoma induction in rabbits may be caused not by only HTLV-II or well known simian oncogenic viruses, but rather by an unknown passenger agent derived from Si-IIA or HTLV-IIA, with which Si-IIA was established.
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PMID:HTLV-II non-integrated malignant lymphoma induction in Japanese white rabbits following intravenous inoculation of HTLV-II-infected simian leukocyte cell line (Si-IIA). 792 26

BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8 A 7. The reactivity of 8 A 7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8 A 7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8 A 7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.
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PMID:Expression of BAFF-R (BR 3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody. 1602 81

B cell-activating factor receptor (BAFF-R) is one of three known receptors for BAFF, a critical regulator of B- and T-cell function. In mice, BAFF-R is required for B-cell maturation and survival, and in mice and humans, the overproduction of BAFF is associated with autoimmune disease. We sought to determine the normal pattern of BAFF-R expression at specific stages of B- and T-cell development and whether this pattern of expression corresponds with related B- and T-cell neoplasms. Most circulating human B cells and a small subset of T cells are BAFF-R-positive. In reactive lymphoid tissues, BAFF-R is expressed by B cells colonizing the mantle zones, by a subset of cells within germinal centers, and rare cells in the interfollicular T-cell zone. BAFF-R is also expressed by B cells colonizing the splenic marginal zone. Seventy-seven (78%) of 116 cases of B-cell lymphoproliferative disorders were BAFF-R-positive by immunohistochemical and/or flow cytometric immunophenotypic analysis, including most cases of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and diffuse large B-cell lymphoma. In contrast, cases of precursor B lymphoblastic lymphoma, Burkitt lymphoma, and nodular lymphocyte-predominant Hodgkin lymphoma exhibit weak to negative staining for BAFF-R. All cases of classical Hodgkin lymphoma and T-cell lymphomas were BAFF-R-negative, including all cases of anaplastic large cell lymphoma, adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, unspecified. These findings highlight BAFF-R as a marker of both normal and neoplastic B cells and raise the possibility that BAFF-R expression is necessary for the survival of a subset of neoplastic B lymphocytes analogous to its known role in promoting normal B-cell maturation and survival.
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PMID:BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. 1622 12

B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell-survival factor expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. The mechanisms involved in BLYS gene expression and regulation are still incompletely understood. In this study, we examined BLYS gene expression, function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that 2 important transcription factors, NF-kappaB and NFAT, are involved in regulating BLyS expression through at least one NF-kappaB and 2 NFAT binding sites in the BLYS promoter. We also provide evidence suggesting that the constitutive activation of NF-kappaB and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-kappaB and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be therapeutic targets in aggressive NHL-B.
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PMID:Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas. 1649 67

Hodgkin lymphoma (HL) originates from the clonal expansion of malignant Hodgkin and Reed-Sternberg (HRS) cells. These B-cell-derived elements constitute less than 10% of the tumoral mass. The remaining tissue is comprised of an inflammatory infiltrate that includes myeloid cells. Myeloid cells activate B cells by producing BAFF and APRIL, which engage TACI, BCMA, and BAFF-R receptors on the B cells. Here, we studied the role of BAFF and APRIL in HL. Inflammatory and HRS cells from HL tumors expressed BAFF and APRIL. Unlike their putative germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells. BAFF and APRIL enhanced HRS cell survival and proliferation by delivering nonredundant signals via TACI and BCMA receptors through both autocrine and paracrine pathways. These signals caused NF-kappaB activation; Bcl-2, Bcl-xL, and c-Myc up-regulation; and Bax down-regulation, and were amplified by APRIL-binding proteoglycans on HRS cells. Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which binds to and neutralizes BAFF and APRIL, or by small-interfering RNAs targeting BAFF, APRIL, TACI, and BCMA inhibited HRS cell accumulation in vitro and might attenuate HL expansion in vivo.
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PMID:Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. 1696 Jan 54

B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), members of the tumor necrosis family of ligands, are expressed by monocytes, macrophages, and dendritic cells, and increased expression of these ligands is noted in lymphomas and plasma cell malignancies. BLyS and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell maturation, transmembrane activator and calcium-modulating cyclophilin ligand interactor, or BAFF-R have been reported in various B-cell malignancies, including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS (in the tumor and in the serum) increased with the transformation of the tumors to a more aggressive phenotype. A high BLyS level inversely correlated with a poor median overall survival, presence of constitutional symptoms, and increased levels of lactate dehydrogenase in patients with non-Hodgkin's lymphoma. Additionally, patients who responded to therapy had a lower BLyS level than those with progressive disease. Several agents targeting BLyS and APRIL are currently being pursued in phase I clinical studies in patients with B-cell malignancies.
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PMID:Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation-inducing ligand in hematologic malignancies. 1702 20

B-lymphocyte stimulator (BLyS) plays a critical role in the survival of B-lymphocytes. In 50 patients with Hodgkin's lymphoma BLyS levels were higher in newly diagnosed patients (median 2.0 ng/mL, range <0.3-56.0) and relapsed patients (8.7 ng/mL, range 1.5-71.5) than in 93 healthy donors (<0.3 ng/mL, range <0.3-0.5). High serum BLyS levels (> or =2.0 ng/mL) in newly diagnosed patients were associated with resistance to therapy (p=0.01) and shorter progression-free survival (log-rank p=0.029, 2-year rate 64% vs 100%). Serum BLyS levels may have prognostic significance in Hodgkin's lymphoma.
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PMID:Prognostic significance of serum B-lymphocyte stimulator in Hodgkin's lymphoma. 1729 86

B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical-pathological features and outcomes. Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean +/- standard error 4493.9 +/- 264.9 pg/ml vs. 2687.0 +/- 200.9 pg/ml; P < 0.0001). Levels above the median value (4242.0 pg/ml) were associated with age > or = 45 years (P = 0.042), advanced stages of disease (P = 0.005), systemic symptoms (P = 0.014) and extranodal involvement (P = 0.009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88.6% as compared to 65.1% of those with levels above the median (P = 0.009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0.046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target.
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PMID:High serum levels of B-lymphocyte stimulator are associated with clinical-pathological features and outcome in classical Hodgkin lymphoma. 1753 76

Mixed cryoglobulinemia syndrome (MCsn) is a systemic vasculitis prevalently mediated by immune complexes, i.e., mixed cryoglobulins, and characterized by non-neoplastic B-cell lymphoproliferation favouring the progression into frank B-cell non-Hodgkin lymphoma (NHL) in 5-10% of patients. The hepatitis C virus (HCV) infection is the etiologic agent in the large majority of MCsn cases and chronic antigenic stimulation by HCV is considered a key mechanism sustaining the proliferation of the RF-secreting B-cell clones. Besides chronic antigenic stimulation, cytokines and growth factors may also play a key role in sustaining B-cell overactivation. B-lymphocyte stimulator (BlyS) was recently described as a critical survival factor for B cells, promoting their activation and maturation. Abnormal production of BLyS alters immune tolerance by allowing the survival of autoreactive B cells, thus triggering autoimmune disorders. BLyS inhibits B-cell apoptosis, and B-cell apoptosis is implicated in the pathogenesis of MCsn, as well as of other autoimmune diseases. Both antiviral therapy and B- cell depletive therapy in MCsn may influence BlyS expression. Antiviral therapy, monotherapy against biologic targets downstream viral infection, or the combination of the two, should be optimized in the single patient and stage of the disease, based on disease pathobiology, efficacy and safety issues.
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PMID:Hepatitis C virus infection, mixed cryoglobulinemia and BLyS upregulation: targeting the infectious trigger, the autoimmune response, or both? 1858 5

Serum B-lymphocyte stimulator (BLyS) levels are elevated in a subset of non-Hodgkin lymphoma (NHL) patients, particularly those with a family history of B-cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B-cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene.
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PMID:Serum BLyS levels increase after rituximab as initial therapy in patients with follicular Grade 1 non-Hodgkin lymphoma. 1905 Dec 65


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