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)

In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain.
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PMID:Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. 131 Aug 94

Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkin's disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.
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PMID:Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations. 132 11

CD40 is a transmembrane protein that belongs to a superfamily of proteins related to nerve growth factor receptor. CD40 is expressed on B cells and some B cell malignancies. It appears to be involved in B cell proliferation and the prevention of apoptosis in germinal center cells, which is accompanied by expression of bcl-2. Its expression is up-regulated by the EBV protein latent membrane protein-1 and cytokines interleukin-4 and interferon-gamma. The expression of CD40 in 37 cases of Hodgkin's disease and 23 cases of non-Hodgkin's lymphoma (11 T cell lymphomas and 12 B cell lymphomas) was examined by paraffin section immunohistochemistry using the BB-20 monoclonal antibody. In 26 of 37 cases of Hodgkin's disease the Reed-Sternberg cells showed strong membrane or cytoplasmic expression of CD40. Only 3 of 23 non-Hodgkin's lymphomas showed any expression of CD40 and then only weakly. There was no correlation between expression of bcl-2 or latent membrane protein-1 with CD40 expression. These results show that there is probable hyperexpression of CD40 in Hodgkin's disease and suggest that dysregulation of CD40 expression may play a role in the pathogenesis of Hodgkin's disease.
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PMID:CD40 expression in Hodgkin's disease. 753 45

The CD30 antigen was originally described as a specific surface marker for Hodgkin's lymphoma. Recent work established CD30 as a member of the tumor necrosis factor/nerve growth factor receptor superfamily whose ligand (CD30L) has also been cloned and expressed; CD30L is active as membrane-bound type II glycoprotein. Here, CD30L mRNA expression was studied in a panel of 102 continuous human leukemia-lymphoma cell lines and was found only in four Burkitt lymphoma, one Burkit-type acute lymphoblastic leukemia and one non-Hodgkin's lymphoma (NHL) cell line. The product of CD30L mRNA is expressed as a membrane protein on the surface of these malignant B-cell lines. Treatment of these cell lines with soluble CD27L, phorbol ester or staphylococcus aureus Cowan antigen resulted in the enhancement of cell surface CD30L protein expression. CD30L mRNA was not detected in normal unstimulated peripheral blood (PB) monocytes, monocyte-derived macrophages, or T-cells, but was detected in primary granulocytes; exposure to activating reagents induced and upregulated CD30L transcription in these different PB populations. While CD40 and CD30L surface protein expression on PB monocytes could be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level. Similarly, PB monocyte-derived macrophages and granulocytes remained negative for CD30 mRNA and protein expression, regardless of stimulation. Only activated T-cells expressed CD30 mRNA and surface protein. CD30L-transfected cells and cells constitutively expressing CD30L delivered a similar stimulus for proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line KARPAS-299. These data provide strong evidence for the involvement in growth regulation of recombinant and natural CD30L through its interaction with the CD30 receptor. Collectively, these data suggest that the CD30L-CD30 interaction has potent biological activity and might play a critical role in the immune response and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.
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PMID:Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. 752 56

CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed-Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes.
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PMID:Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines. 753 May 8

CD30 is a recently described member of the tumor necrosis factor/nerve growth factor receptor superfamily. In this report, we show that following incubation of L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts, as determined in gel retardation assays. The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h. By comparison, an isotype-matched antibody had no effect on NF-kappa B activation. Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30-mediated NF-kappa B activation correlated with the proportion of CD30+ cells. In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and possibly other transcription factors. Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation.
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PMID:CD30 ligation induces nuclear factor-kappa B activation in human T cell lines. 758 85

The role of Epstein-Barr virus (EBV) in the pathogenesis of Hodgkin's disease (HD) has not yet been clarified. Using RNA in situ hybridization (ISH) and immunohistochemistry (IHC), the occurrence of small Epstein-Barr virus encoded RNA (EBER) and latent membrane protein-1 (LMP-1) was studied in 22 tissue samples from 21 patients between 4 and 17 years of age with Hodgkin's disease. EBER was detected in eight of 21 patients (38%) in Hodgkin and Reed-Sternberg cells and reactive lymphocytes irrespective of initial clinical stage and histological subtype, whereas LMP-1, positive in ten of 21 patients (48%), was restricted to neoplastic cells. All cases positive for EBER expressed LMP-1 as well. Additionally, oncoprotein Bcl-2 was identified in nine of 21 patients (43%), indicating, besides immortalization of HD cells by EBV, a further growth advantage due to apoptosis prevention by overexpression of this protein. Proliferation-associated antigens Ki-S1 and Ki-S5 were highly expressed in Hodgkin and Reed-Sternberg cells. CD 30 antigen was found in most cases, using two different antibodies (90% and 80%). The presence of this protein, which belongs to the family of nerve growth factor receptor (NGFR), is related to high expression of Ki-67 protein, detected by Ki-S5. CD 20 antigen was detectable in only three of 21 patients (14%). If we compare results of ISH and IHC with clinical data, the occurrence of EBV genome in children with HD seems to have no adverse effect on the final outcome of these patients.
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PMID:The impact of EBV, proliferation rate, and Bcl-2 expression in Hodgkin's disease in childhood. 814 17

FAS/APO-1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis factor/nerve growth factor receptor family, and which can trigger apoptosis in some lymphoid cell lines. Immunohistochemistry combined with Northern blotting allowed determination of the pattern of FAS/APO-1 expression in a series of Ki-1 [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight anaplastic large cell lymphomas. CD30 negative tumours used as controls included 27 B-cell non-Hodgkin's lymphomas. 14 T-cell non-Hodgkin's lymphomas, four reactive lymphadenitis, and non-lymphoid tissues. Immunohistochemistry, performed on frozen sections, revealed a strong FAS/APO-1 expression in 25 out of 27 (92%) Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were positive. In contrast, positive FAS/APO-1 immunostaining was observed only in 22 out of 41 (53%) CD30 negative non-Hodgkin's lymphomas. Northern blot analysis detected variable amounts of the FAS/APO-1 transcript in the immunohistochemistry-positive samples. These results suggest possible hyper-expression of FAS/APO-1 (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.
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PMID:Frequent expression of FAS/APO-1 in Hodgkin's disease and anaplastic large cell lymphomas. 852 87

The CD30 surface molecule is a recently identified member of the tumor necrosis factor/nerve growth factor receptor superfamily. Within the cytoplasmic signal transducing domain, CD30 shares no significant homology to other members of this family. Signaling events engaged via CD30 are still unknown. We here identify the NF-kappabeta transcription factor as a target of the CD30-induced signal pathway in Hodgkin's disease (HD) cells. Exposure of HD cells to CD30 ligand induces release of interleukin-6 (IL-6) that can be duplicated by cross-linking HD-cells to an agonistic anti-CD30 specific monoclonal antibody (alphaCD30), but not by cross-linking to an isotype-identical irrelevant monoclonal antibody. Cross-linking of HD cells to alphaCD30 leads to enhanced accumulation of IL-6 mRNA in a time-dependent fashion resulting from transcriptional activation of the IL-6 promoter. Transient transfection assays using a series of deleted IL-6 promoter constructs linked to the human growth hormone gene as a reporter gene furthermore indicate that transcriptional activation of the IL-6 promoter requires the presence of an intact NF-kappabeta binding site. In addition, introduction of an NF-kappabeta binding site appeared to be sufficient to confer inducibility of an heterologous promoter on activation of CD30 in HD cells. Cross-linking of CD30 promotes rapid and transient binding activity of nuclear proteins to the NF-kappabeta recognition site of the IL-6 promoter. Supershift experiments using a series of monoclonal antibodies recognizing distinct members of the NF-kappaBeta transcription factor family furthermore indicate that in CD30 cross-linked HD cells p50, p65/Rel-A, and Rel-B are present, whereas the c-rel protein is not.
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PMID:Activation of Hodgkin cells via the CD30 receptor induces autocrine secretion of interleukin-6 engaging the NF-kappabeta transcription factor. 1101 49

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


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