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)

We have correlated the serum levels of TNF alpha and soluble TNF receptor superfamily members with clinico-pathologic parameters in patients of Hodgkin's disease (HD, N = 26) and non-Hodgkin's lymphoma (NHLs, N = 35). HD patients had significantly higher levels of TNF alpha, sTNFRI, and sTNFRII in serum while NHL patients had significantly higher levels of sTNFRI, sTNFRII, sCD27, and sFas as compared to controls. In NHL patients the levels of sCD27 correlated directly and significantly with the high-stage disease, bone marrow involvement, lymph nodal presentation, and serum LDH levels. Similarly in NHL patients, levels of sFas also correlated directly and significantly with the presence of high stage disease. HD patients with B symptoms had significantly higher levels of sTNFRII.
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PMID:Circulating levels of TNF alpha and TNF receptor superfamily members in lymphoid neoplasia. 1099 26

The malignant Reed-Sternberg cell of Hodgkin disease is an aberrant B cell that persists in an immunolgically mediated inflammatory infiltrate. Despite its nonproductive immunoglobulin genes, the Reed-Sternberg cell avoids the usual apoptotic fate of defective immune cells through an unknown mechanism. A likely candidate is the surface receptor, CD40, consistently expressed by Reed-Sternberg cells, and the first link in the pathway to NF-kappa B activation, the central regulator of cytokine production and apoptosis. CD40 signaling in B lymphocytes coordinates the immune response, including immunoglobulin isotype switch and Fas-mediated apoptosis. CD40-induced NF-kappa B activation is mediated by adapter proteins, the TNF receptor (TNFR)-associated factors (TRAFs), especially TRAFs 2, 3, and 5. Using a Hodgkin cell line, this study demonstrates that CD40 activation of NF-kappa B is mediated by proteolysis of TRAF3. Results further demonstrate that the pathway can be blocked by treatment with pharmacologic doses of a specific protease inhibitor, pepstatin-A, even in the presence of a mutated NF-kappa B inhibitor, I-kappa B alpha. The stability of TRAF3 regulates CD40/NF-kappa B-mediated control of the immune response, which is central to the biologic activity of the Reed-Sternberg cell. Prevention of TRAF3 proteolysis may be an entry point for design of novel pharmaceuticals to treat Hodgkin disease and immune system disorders. (Blood. 2000;96:2841-2848)
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PMID:Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor. 1102 20

The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express several members of the tumor necrosis factor (TNF) receptor family, including CD30 and CD40, and secrete several cytokines and chemokines. However, little is known about what regulates cytokine and chemokine secretion in H/RS cells. Although H/RS cells are predominantly of B-cell origin, they frequently share phenotypic and functional features with dendritic cells (DCs). Previous studies reported that receptor activator of nuclear factor kappaB (NF-kappaB) (RANK), a member of the TNF receptor family, is expressed on DCs, and that RANK ligand (RANKL) enhances DC survival and induces them to secrete cytokines. This study reports that, similar to DCs, cultured H/RS cells expressed RANK. However, unlike DCs, H/RS cells also expressed RANKL. Soluble RANKL activated NF-kappaB and induced messenger RNA expression of interferon-gamma, interleukin-8 (IL-8), IL-13, IL-9, IL-15, and RANTES, in addition to the receptors for IL-9, IL-13, IL-15, and CCR4. RANKL increased IL-8 and IL-13 levels in the supernatants of H/RS cell lines, an effect that was blocked by soluble RANK. Furthermore, soluble RANK decreased the basal level of IL-8 in one cell line, suggesting that IL-8 was induced by an autocrine RANKL/RANK loop. RANKL had no effect on H/RS cell survival in culture, and it did not modulate the expression of bcl-2, bcl-xL, bax, or inhibitors of apoptosis proteins. These data provide evidence of further functional similarities between DCs and H/RS cells. The coexpression of RANK and RANKL in H/RS cells suggests that they may regulate cytokine and chemokine secretion in H/RS cells by an autocrine mechanism.
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PMID:Functional expression of receptor activator of nuclear factor kappaB in Hodgkin disease cell lines. 1200 8

Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in MLBCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-kappa B (NF- kappa B), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-kappa B pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway.
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PMID:The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. 1293 71

We studied whether signaling through CD30, a member of the TNF receptor family, affected acute infection with HIV-1, encompassing its entire replicative cycle. Several non-Hodgkin cell lines, targets of CXCR4-dependent (X4) HIV-1 infection, were positive for CD30 expression. CD30 ligation induced up-regulation of viral replication only in certain CD30+ cell lines. Enhancement of X4 virus replication by CD30 engagement inversely correlated with both CD30 surface density and constitutive NF-kappaB activation. Conversely, expression of CD30, but not of other members of the TNF receptor family, was proportional to constitutive NF-kappaB binding. Concomitantly, secretion of soluble (s) CD30 increased in all cell lines by CD30 ligation. sCD30 release was enhanced by engagement of CD30 alone and, to a greater extent, by co-engagement of CD3 also in primary gamma delta T lymphocytes, along with complementary modulations of their surface CD30 expression. sCD30-containing supernatant specifically inhibited HIV-1 expression induced by CD30 engagement in chronically infected ACH-2 T cells; thus sCD30 may act as a negative feed-back molecule. In conclusion, we have delineated novel features of CD30 biology and underline the peculiar link of CD30 expression to constitutive NF-kappaB activation which is pivotal to both HIV replication and cell survival.
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PMID:CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes. 1457 82

Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.
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PMID:Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. 1696 9

CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over-expression provides a diagnostic marker for a subset of non-Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti-CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one-hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over-expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL.
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PMID:The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma. 1797 41

The soluble decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. It is regarded as a decoy receptor released from tumor cells to escape host immune response by neutralizing the cytotoxic and immunomodulatory effects of FasL, LIGHT and TL1A. Overexpression of DcR3 has been observed in several human malignancies; however, only limited information exists on the role of DcR3 in non-Hodgkin lymphoma especially for B-cell origin. In the current study, the expression profile of DcR3 was analyzed by RT-PCR and immunohistochemistry (IHC) in a set of lymphoma cell lines including T-cell and B-cell lymphomas. The result demonstrated that overexpression of DcR3 was detected in most T-cell lymphoma cells, which was consistent with previous reports. Interestingly, overexpression of DcR3 was also detected both in the B-cell lymphoma cell lines and diffuse large B cell lymphoma (DLBCL) patients. DcR3 overexpression was associated with a worse prognosis in DLBCL patients (p=0.05). An in vitro study showed that neutralization of DcR3 increased the percentage of doxorubicin-mediated apoptosis in two B-cell lymphoma cell lines, which indicated the possibility of DcR3 mediated chemo-resistance in B-cell lymphomas. We suggest that overexpression of DcR3 is associated with a worse prognosis in DLBCL and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells.
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PMID:Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome. 1869 85

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is unique among the members of the TRAF family, as it lacks the N-terminal RING/zinc-finger domain. Also the function of TRAF1 is not clearly established, with many papers reporting contradictory results. Here we show that TRAF1 interacts with BAFF receptor, a member of the TNF receptor family, and positively regulates activation of the alternative NF-kappaB pathway. Ectopic expression of TRAF1 causes degradation of TRAF3, stabilization of NIK, and processing of p100 to produce the mature form p52. In addition, we show that knocking-down expression of TRAF1 in the Hodgkin's disease derived cell line L1236, interfere with p100 processing and with p52 mediate gene transcription. Collectively these results support a role for TRAF1 as a positive regulator of the NF-kappaB alternative pathway.
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PMID:TNF receptor-associated factor 1 is a positive regulator of the NF-kappaB alternative pathway. 1969 91

It has become clear that cancer is not merely a growth of autonomously proliferating cells, but that other non-malignant cell types are a functional part of the disease. Immune cells, fibroblasts, specialized mesenchymal cells and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. Classical Hodgkin's lymphoma (cHL) is characterized by only a few malignant cells and an abundance of inflammatory cells. Hodgkin and Reed-Sternberg (HRS) cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils and mast cells. A constitutive activity of NF-kappaB and an altered JAK-STAT signalling pathway are part of the biological background associated with the increased expression of cytokines and cytokine receptors seen in HRS cells. Over-expression of the members of the TNF receptor family, especially CD30 and CD40, is a hallmark of HRS cells. cHL is a tumour where aberrant cytokine production contributes not only to the proliferation of HRS cells but also to the maintenance of an appropriate environment for the tumour cells. In addition, several chemokines contribute to the composition of the inflammatory background in cHL. This review summarizes updated information on the complex interactions between the HRS cells and their tissue microenvironment and highlights the development of newer therapeutic strategies aimed at targeting the non-malignant inflammatory/immune cellular components of HL that are involved in cancer cell growth and/or immune escape.
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PMID:The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape. 2052 19


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