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)

Viral hepatitis is a common and important problem in immunocompromised cancer patients. The present study was conducted to investigate changes in some cellular and humoral immunological parameters as a consequence of HCV infection in non Hodgkin's lymphoma patients (NHL). The study included 40 NHL patients: 20 anti-HCV antibody positive (Gr. I ), and 20 anti-HCV antibody negative (Gr.II ). In addition, forty non-cancer controls (NCCs) were included: 20 of them were anti-HCV antibody positive (Gr. III) and 20 anti-HCV antibody negative (Gr. IV). The studied immunological parameters included serum levels of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors (s-TNFr) measured by ELISA, as well as assessment of T and B lymphocyte subsets by PAP immunostaining method. Mean IL-1 level (pg/ml) was significantly higher in Gr. 1 (14 +/- 6) and Gr. III (20 +/- 12) as compared to those in Gr. II (7 +/- 5) and Gr. IV (9 +/- 6). Mean IL-2 level (pg/ml) was also significantly higher in Gr. I (132 +/- 101) and Gr. III (135 +/- 59) compared to those in Gr. II (36 +/- 29) and Gr. IV (31 +/- 48). On the other hand, level of IL-6 showed no significant difference between groups. The mean level of sTNF-r, (ng/ml) was only significantly higher in Gr. I (2.9 +/- 1.7) when compared to that in Gr. IV (1.9 +/- 2.2). In group IV, the average percentage of CD3 (70 +/- 4%) and CD4 (44 +/- 5%) were significantly higher than in those of Gr. I (CD3 = 51 +/- 11%, CD4 = 30 +/- 12%), Gr. II (CD3 = 52 +/- 7%, CD4 = 30 +/- 8%), and Gr. III (CD3 = 52 +/- 9%, CD4 = 26 +/- 8%). From all the above immunological and virological features two main tips could be inferred: (1) HCV leads a mild course of infection in NCCs evidenced by normal ALT level in all but 20% of subjects, normal IL-6, sTNF-r, lower counts of CD4+ T cells and hence a mild hepatocellular injury, and (2) In the immunocompromised NHL patients the virus leads potentially more aggressive course as evidenced by higher viremia, as well as significant elevation in sTNF-r, and CD8+ depression.
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PMID:Hepatitis C Virus and related changes in immunological parameters in non Hodgkin's lymphoma patients. 1572 87

Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma.
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PMID:Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes. 1605 35

Classical Hodgkin lymphoma (HL) is characterized by the presence of Reed-Sternberg (RS) cells, which are transformed post-germinal center B cells destined for apoptosis since they have not undergone successful immunoglobulin gene rearrangement. Several mechanisms, including latent infection by Epstein-Barr virus (EBV), allow these cells to survive. It is remarkable that many of the signaling pathways that promote survival are shared between the EBV-induced proteins, such as EBNA1, LMP1, and LMP2, and other molecules that are upregulated in RS cells. A key role is played by the presence of constitutive nuclear factor (NF)-kappaB, which is induced by LMP1, as well as by CD30, CD40, tumor necrosis factor (TNF)-alpha, and Notch1 interactions, and results in the upregulation of at least 45 genes including chemokines, cytokines, receptors, apoptotic regulators, intracellular signaling molecules, and transcription factors. The other characteristic of classical HL is the presence of an extensive inflammatory infiltrate. Key features of this infiltrate are that it comprises Th2 and T regulatory cells and generally lacks Th1 cells, CD8 cytotoxic T cells, and natural killer (NK) cells. The RS cells appear to induce this infiltrate by the secretion of Th2 type chemokines such as TARC and MDC. The RS cells also produce cytokines that inhibit Th1 responses, as interleukin (IL)-10 and transforming growth factor (TGF)-beta express CD95 ligand, which induces apoptosis of activated Th1 and CD8 T cells. Other important mechanisms that allow the RS cells to escape an effective anti-EBV immune response include the downregulation of HLA class I in EBV-negative cases or the presence of a polymorphism in HLA class I in EBV-positive cases that allow escape from CD8-mediated cytotoxicity. On the other hand, expression of HLA-G allows the escape from NK cells that would normally recognize the HLA class I-negative RS cells. Overall, the cellular infiltrate in HL appears to play a decisive role in allowing the RS cells to survive by providing an environment that suppresses cytotoxic immune responses and providing cellular interactions and cytokines that support the growth and survival of RS cells. Future therapeutic strategies could focus directly on the NF-kappaB activation, on various receptors to ligand interactions, on the chemokine and cytokine network, or on the induction of effective anti-EBV latent protein immune responses.
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PMID:Immunobiology and pathophysiology of Hodgkin lymphomas. 1630 86

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

Increased angiogenic activity has been demonstrated in lymphoproliferative diseases including Hodgkin's disease. In the current study, the levels of circulating angiogenic molecules in 60 Hodgkin's patients were determined prior to and after treatment and correlated to disease stage and prognostic score. Hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were increased in Hodgkin's patients in comparison to healthy controls (p<0.001). Angiogenin and angiopoietin-2 levels did not differ from controls. HGF, VEGF, TNF-alpha and angiogenin decreased significantly in Hodgkin's patients after standard treatment (p<0.001 for HGF, p<0.05 for VEGF, TNF-alpha and angiogenin). Furthermore, HGF and TNF-alpha increased with advancing stage of disease (p<0.05). HGF and VEGF correlated significantly with IL-6 (r=0.56, p<0.0005 and r=0.57, p<0.001 respectively). In conclusion, Hodgkin's disease displays an angiogenic activity as depicted by the increased serum levels of a number of angiogenic cytokines. HGF seems to be the prominent molecule in Hodgkin's disease, which may be used to monitor the disease status and the response to treatment.
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PMID:Angiogenic molecules in Hodgkin's disease: results from sequential serum analysis. 1656 54

A patient with rheumatoid arthritis (RA) developed an atypical lymphoproliferative disorder (LPD) after methotrexate and cyclosporine A, which regressed after suspension of both drugs. After subsequent treatment with rituximab, the LPD was still undetectable. Anti-tumor necrosis factor a therapy was used when the arthritis relapsed, but an aggressive B-cell non Hodgkin's lymphoma developed. Molecular analyses showed an oligoclonal B-cell expansion at the LPD step. A minor clone with significant sequence homology to B-cell lymphomas arising in Sjogren's syndrome and mixed cryoglobulinemia syndrome, given rise to the non-Hodgkin's lymphoma. Treatment of rheumatoid arthritis associated with lymphoproliferation represents a clinical challenge, and common pathogenetic pathways to lymphoma may occur in different autoimmune diseases.
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PMID:Atypical lymphoproliferation progressing into B-cell lymphoma in rheumatoid arthritis treated with different biological agents: clinical course and molecular characterization. 1667 74

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.
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PMID:Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma. 1701 37

We report herein a rare case of IgAN associated with Hodgkin's disease in a 14-year-old boy. Clinical manifestations and laboratory parameters were improved after treatment with CHOP chemotherapy and enalapril. Urinary proteins were isolated and examined using state-of-the-art proteomic technology, before and during the treatment course. Two-dimensional gel electrophoresis showed obvious alterations in the urinary proteome profile in response to such therapy. Quantitative intensity analysis and gel mapping revealed 14 altered proteins with reduced excretion levels during the treatment course, including albumin, albumin complexed with decanoic acid, alpha-1 antitrypsin, cadherin-11 precursor, collagen alpha 1 (VI) chain precursor, complement C1q tumor necrosis factor-related protein, Ig heavy chain, Ig light chain, kininogen, inter-alpha-trypsin inhibitor (alpha-1 microglobulin), inter-alpha-trypsin inhibitor heavy chain, leucine-rich alpha-2 glycoprotein, beta-2 microglobulin, and transferrin precursor. Their potential roles in the pathogenesis and pathophysiology of IgAN are discussed.
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PMID:IgA nephropathy associated with Hodgkin's disease in children: a case report, literature review and urinary proteome analysis. 1714 26

Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non-Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically investigated the effects of other established NHL risk factors in relation to the tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172 cases and 982 population-based controls in a U.S. multicenter study. We investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both an autoimmune condition and the TNF G308A GA/AA (OR(NHL), 2.1; 95% CI, 1.0-4.2) or the IL10 T3575A TA/AA genotype (OR(NHL), 1.6; 95% CI, 0.9-2.6) compared with individuals without an autoimmune condition and with the common TNF G308A GG or IL10 T3575A TT genotype, respectively; results were similar for DLBCL and follicular lymphoma. We found that elevated DLBCL risk associated with last-born status was more pronounced among those with TNF G308A GA/AA (OR(DLBCL), 2.7; 95% CI, 1.1-6.4) or IL10 T3575A TA/AA (OR(DLBCL), 2.9; 95% CI, 1.6-5.2). Similarly, elevated DLBCL risk associated with obesity (body mass index, > or = 35 versus <25 kg/m(2)) was observed only among those with TNF G308A GA/AA (OR(DLBCL), 2.5; 95% CI, 1.1-5.7) or IL10 T3575A TA/AA genotypes (OR(DLBCL), 2.0; 95% CI, 1.1-3.5). These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles.
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PMID:Immune mechanisms in non-Hodgkin lymphoma: joint effects of the TNF G308A and IL10 T3575A polymorphisms with non-Hodgkin lymphoma risk factors. 1751 Apr 37

The aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20-based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell-specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.
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PMID:Antibody therapy in aggressive lymphomas. 1802 38


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