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

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.
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PMID:CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues. 870 86

We examined paraffin sections for the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha, in 40 cases of Hodgkin's disease. Our purpose was to study the role of these cytokines in the "inflammatory" histological features and "B" symptoms in this disease. Immunohistochemistry with the avidin-biotin-peroxidase complex method was used. The findings were compared with those of 20 cases of non-Hodgkin's lymphomas and of 20 non-neoplastic lymphadenopathies. Evidence for EBV infection and myc and ras oncoproteins expression was also studied in these patients, but no correlation between any of these features and cytokine expression was found. We found a significant correlation between the expression of interleukin-1 beta and several "inflammatory" histological features, as well as between the expression of tumor necrosis factor-alpha and B symptoms and tumor bulk. The differential correlations between these major pro-inflammatory cytokines expression and the "inflammatory" manifestations in Hodgkin's disease are remarkable, considering the complexity of the cytokines composing the cytokine network involved in this disease.
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PMID:Interleukin-1 and tumor necrosis factor-alpha in the Reed-Sternberg cells of Hodgkin's disease. Correlation with clinical and morphological "inflammatory" features. 870 95

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.
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PMID:Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease. 877 39

CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily. CD30 is expressed on normal activated lymphocytes, on several virally transformed T- or B-cell lines and on neoplastic cells of Hodgkin's lymphoma. The interaction of CD30 with its ligand induces pleiotropic effects on cells resulting in proliferation, differentiation, or death. The CD30 cytoplasmic tail interacts with TNF receptor-associated factors (TRAFs), which have been shown to transduce signals mediated by TNF-R2 and CD40. We demonstrate here that TRAF2 also plays an important role in CD30-induced NF-kappa B activation. We also show that TRAF2-mediated activation of NF-kappa B plays a role in the activation of HIV transcription induced by CD30 cross-linking. Detailed site-directed mutagenesis of the CD30 cytoplasmic tail reveals that there are two independent binding sites for TRAF, each interacting with a different domain of TRAF. Furthermore, we localized the TRAF-C binding site in CD30 to a 5-7 amino acid stretch.
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PMID:CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity. 879 Mar 94

Hodgkin disease (HD) is characterized by the presence of a small number (usually <1% of total tumor mass) of the typical Hodgkin and Reed-Sternberg (H-RS) cells in a hyperplastic background of normal reactive lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils, and stromal cells. HRS cells produce various cytokines, growth factors, and express cytokine receptors and activation antigens, implying a predominant role for these molecules in the pathophysiology of Hodgkin disease. HD may therefore be regarded as a tumor of cytokine producing cells. The CD30 antigen has been characterized as a marker for cultured and primary Hodgkin and Reed-Sternberg cells, and was found to be overexpressed in Hodgkin disease and a subgroup of non-Hodgkin lymphomas including large cell anaplastic lymphomas and Burkitt lymphomas. The molecular cloning of the CD30 antigen revealed that CD30 is a member of the tumor necrosis factor/nerve growth factor receptor superfamily. The cloning of the cognate for CD30, currently termed CD30 ligand, confirmed that the CD30 antigen functions as a cytokine receptor. Recombinant CD30 ligand is a membrane-bound protein with pleiotropic biological activities for different CD30+ lymphoma types, but also for the immune system, mainly T cells. CD30L belongs to the emerging tumor necrosis factor ligand superfamily. The CD30-CD30 ligand interaction could have a critical pathophysiological role in malignant lymphomas, particularly Hodgkin disease, large cell anaplastic lymphomas and Burkitt lymphomas, and is also involved in activation and functioning of the T cell-dependent immune system.
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PMID:CD30 ligand, a member of the TNF ligand superfamily, with growth and activation control CD30+ lymphoid and lymphoma cells. 883 95

Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus (EBV). These simian EBV share considerable genetic, biologic, and epidemiologic features with human EBV, including virus-induced tumorigenesis. However, latent, transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions. We have cloned the latent membrane protein 1 (LMP1) homologs from the simian EBV naturally infecting baboons (cercopithicine herpesvirus 12, herpesvirus papio) and rhesus monkeys (cercopithicine herpesvirus 15) for a comparative study with the human EBV oncogene. The transmembrane domains are well conserved, but there is striking sequence divergence of the carboxy-terminal cytoplasmic domain essential for B-cell immortalization and interaction with the tumor necrosis factor receptor signaling pathway. Nevertheless, the simian EBV LMP1s retain most functions in common with EBV LMP1, including the ability to induce NF-(kappa)B activity in human cells, to bind the tumor necrosis factor-associated factor 3 (TRAF3) in vitro, and to induce expression of tumor necrosis factor-responsive genes, such as ICAM1, in human B lymphocytes. Multiple TRAF3 binding sites containing a PXQXT/S core sequence can be identified in the simian EBV LMP1s by an in vitro binding assay. A PXQXT/S-containing sequence is also present in the cytoplasmic domain of the Hodgkin's disease marker, CD30, and binds TRAF3 in vitro. The last 13 amino acids containing a PXQXT/S sequence are highly conserved in human and simian EBV LMP1 but do not bind TRAF3, suggesting a distinct role for this conserved region of LMP1. The conserved TRAF3 binding sites in LMP1 and the CD30 Hodgkin's disease marker provides further evidence that a TRAF3-mediated signal transduction pathway may be important in malignant transformation.
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PMID:Comparative analysis identifies conserved tumor necrosis factor receptor-associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1. 889 3

We investigated the in vitro antitumor activity of monocytes derived from autologous bone marrow transplanted (ABMT) patients treated in vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-four patients (17 female, 17 male), median age 42 (range 3-57) years, were enrolled in the study. Fourteen patients were diagnosed with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD), nine with breast cancer and three with neuroblastoma. Six patients who did not receive GM-CSF post-ABMT served as controls. We assessed cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), expression of the activation antigen CD16, and cytokine production by an enriched population of monocytes (> 90% CD+14) pre-, during and post-GM-CSF administration. Within the group of patients receiving treatment, ADCC was significantly higher during in vivo GM-CSF administration than post-therapy (P < 0.05) and in 50% of these patients, ADCC increased during in vivo GM-CSF administration over pretreatment values. In addition, in vivo GM-CSF administration caused the monocytes to secrete elevated levels of tumor necrosis factor-alpha (TNF-alpha) and GM-CSF (P < 0.05). We conclude that GM-CSF augments monocyte-mediated cytotoxicity post-ABMT, and therefore may have a role in controlling minimal residual disease post-transplant.
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PMID:Granulocyte-macrophage colony-stimulating factor dependent monocyte-mediated cytotoxicity post-autologous bone marrow transplantation. 891 16

The in vivo production of interleukin (IL)-10, IL-6, IL-2, and tumor necrosis factor (TNF)-alpha in tumor samples was investigated by immunohistochemistry in 54 non-Hodgkin's lymphomas (NHLs). Respectively, 55, 89, 23, and 29% of tumor samples were found positive for IL-10, IL-6, IL-2, and TNF-alpha expression by immunohistochemistry. Using reverse transcription-PCR, the mRNA of IL-10 and IL-6 were detectable in all samples tested and in 90 and 34% of the samples for TNF-alpha and IL-2, respectively. In 13 patients, fresh tumor tissue was available for B NHL cell purification with Dynabeads. IL-10, IL-6, IL-2, and TNF-alpha were detectable in the supernatant of 38, 100, 0, and 23% of purified tumor cell preparations (PTCPs), respectively. All patients with detectable IL-10 in culture had increased serum IL-10. IL-6 production by tumor cells and serum IL-6 levels were also found to be highly correlated (P < 0.0001). This suggests that tumor cells are a major source of serum IL-1O and IL-6 in these patients. Exogenous IL-10, IL-6, IL-2, and TNF-alpha significantly enhanced the [3H]thymidine uptake in 13 of 13 (100%), 5 of 13 (38%), 9 of 13 (69%), and 2 of 10 (20%) PTCPs costimulated with anti-CD40, respectively. IL-2, IL-6, and TNF-alpha synergized with IL-10 in 54, 23, and 30% of PTCPs. The combination of IL-10, IL-2, and IL-6 induced the maximal level of proliferation in 12 (92%) of 13 PTCPs. CD40 ligand mRNA expression was also detectable in vivo using reverse transcription-PCR in 28 of the 29 (97%) tumor samples tested, including 11 of those tested for [3H]thymidine incorporation. These results show that IL-1O, IL-6, IL-2, and TNF-alpha are produced in NHL tumors and may cooperate in vivo to increase NHL cell proliferation.
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PMID:Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin's lymphoma cells and act as cooperative growth factors. 896 7

CD40 is a 48 Kd integral membrane protein expressed by cells of B cells, origin, dentritic cells, monocytes, epithelial cells, endothelial cells and tumor cells including carcinomas, B cell lymphomas/leukemias and Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD). CD40 has been clustered as a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily with the corresponding counterstructure, the CD40 ligand (L) being mainly expressed by activated CD4+ T cells, but also some activated CD8+ T cells, basophils, eosinophils, mast cells and stromal cells. CD40L shares significant amino acid homology with TNF particularly in its extracellular domain ("TNF homology region") and is therefore viewed as a member of the TNF ligand superfamily. Binding of CD40L+ T cells to CD40+ B cells is thought to play a major role in T cell-dependent B cell activation, B cell proliferation, Ig isotype switching, memory B cell formation and rescue of B cells from apoptotic death in germinal centers. Mutations of the CD40L gene have been associated with the X-linked hyper-IgM immunodeficiency syndrome, pointing to the critical role of the CD40/CD40L interaction in the T cell-B cell interplay. Accordingly, expression of CD40 by human lympho-hematopoietic tumors has been shown in most of the B cell neoplasias, H-RS cells and HD and some carcinomas. In contrast, CD40L+ tumor cells are almost invariably restricted to CD4+/CD8- T cell lymphomas. Overall, functional CD40/CD40L interactions appear to be critical for cellular activation signals during immune responses and neoplastic tumor cell growth. The understanding of the biology of CD40L has improved our diagnostic and therapeutic repertoire in the management of several human diseases, including CD40+ tumors.
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PMID:CD40/CD40 ligand interactions in normal, reactive and malignant lympho-hematopoietic tissues. 908 33

CD30 is a member of the tumor necrosis factor (TNF) receptor family, originally described as a marker for Hodgkin and Reed-Sternberg cells in Hodgkin's disease, which has been found to be preferentially expressed by T cells producing Th2-type cytokines. The presence of CD30 expression was assessed by both immunohistochemistry and reverse transcriptase-polymerase chain reaction in the target organs of patients with Th1- or Th2-dominated disorders. CD30 expression was found in neither the gut of patients with Crohn's disease nor in the gastric antrum of Helicobacter pylori-infected patients, where there was high interferon-gamma (IFN-gamma) expression. In contrast, high CD30 expression in the apparent absence of IFN-gamma expression was observed in the skin of patients with systemic sclerosis or chronic graft versus host disease (GVHD), which can be considered Th2-dominated disorders. Moreover, high levels of soluble CD30 were found in the serum of both systemic sclerosis and GVHD patients but not in the serum of patients suffering from multiple sclerosis, a Th1-dominated disorder. Thus, CD30 expression appears to be preferentially associated with Th2-type responses not only in vitro but also in vivo.
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PMID:In vivo CD30 expression in human diseases with predominant activation of Th2-like T cells. 912 1


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