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)

The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.
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PMID:Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4). 753 Feb 38

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

Recent nucleic acid hybridization studies have implied that Reed-Sternberg/Hodgkin (RS/H) cells are infected with Epstein-Barr virus (EBV) before malignant transformation, and hence, that Hodgkin's disease could develop as a consequence of malignant transformation of an EBV-infected cell. This study is a detailed immunohistochemical and in situ hybridization characterization of the various lymphoid cells in nine cases of infectious mononucleosis (IM), the acute manifestation of EBV infection. The RS/H-like cells of IM were similar in most respects to their morphologically identical counterparts in Hodgkin's disease; they expressed the EBV-encoded protein LMP1, EBV EBER1 transcripts, and CD30 and rarely, if ever, expressed CD45/LCA or T cell markers. Dissimilarities were limited to CD15 negativity and the absence of a collarette of T cells around the RS/H-like cells of IM compared with their Hodgkin's counterparts. Expression of the immortalizing bcl-2 oncoprotein was variable in the RS/H-like cells of IM, as has been demonstrated in the RS/H cells of Hodgkin's disease by other investigators. An apoptosis assay suggested that many apoptotic cells in IM were EBV-infected T cells, in keeping with the previous in vitro observation that IM-derived T cells succumb to apoptosis. Additionally, the apoptosis assay suggested that RS/H-like cells of IM can succumb to programmed cell death, reminiscent of the mummified RS/H cells seen in Hodgkin's disease. The accumulation of evidence suggests that RS/H-like cells of IM are more similar to true RS/H cells than previously recognized.
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PMID:New characterization of infectious mononucleosis and a phenotypic comparison with Hodgkin's disease. 753 53

The origin of the Reed-Sternberg cell, the neoplastic cell of Hodgkin's disease, has not been defined. We evaluated a case of Hodgkin's disease, mixed cellularity type, which presented in the retroperitoneum of a 45-year-old woman. Reed-Sternberg cells and Hodgkin's cells expressed the characteristic markers CD15 and CD30. In addition, they expressed the B-cell antigens CD19 and CD20, as well as CD45/leukocyte common antigen. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. These results suggest that some cases of Hodgkin's disease are derived from an activated cell of lymphoid origin. This case documents a close relationship between Hodgkin's disease and non-Hodgkin's lymphoma, and it demonstrates that even when newer ancillary techniques are employed these two entities can have overlapping features.
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PMID:Hodgkin's disease, mixed cellularity type, with a B-cell immunophenotype. Report of a case and literature review. 753 89

We report on the immunophenotype, clinical findings and response to aggressive chemotherapy of 18 patients with mediastinal large B-cell lymphoma (MLCL). Cases were collected from a series of 286 high-grade non-Hodgkin's lymphomas (HG-NHL) which, in the period September 1988 to August 1991, were enrolled in a prospective multicentre trial designed to compare the MACOP-B and F-MACHOP regimens. Immunostaining on frozen sections revealed a previously unrecognized phenotype, i.e. co-expression of B-cell (CD19, CD20, CD22, Ig-associated dimer) and activation-associated antigens (CD30 and CDw70) in about 60% of MLCL cases; in contrast, the activation-associated antigens CD25 and Ki-27 (unclustered) were consistently negative. This peculiar phenotype may reflect a derivation of the tumour from a subset of thymic activated B cells. Clinically, the patients (median age 31 years; F/M ratio 2.6) presented with bulky mediastinal mass (72%) associated with mediastinal syndrome in > 50% cases; disease was stage IIA in most cases. All 18 patients received aggressive chemotherapy (F-MACHOP 11; MACOP-B 7). Complete response (CR) was achieved in 57.1% of cases treated with MACOP-B. In contrast, the response of the 11 MLCL treated with F-MACHOP was poor (CR 18.2%) as compared to that of the 135 HG-NHL treated with the same regimen during the trial (CR 69.6%). This difference was still statistically significant after adjusting for negative prognostic factors (mediastinal mass > 10 cm plus increased LDH) and suggests that F-MACHOP might not be the most appropriate regimen for this kind of lymphoma.
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PMID:Mediastinal large B-cell lymphoma: clinical and immunohistological findings in 18 patients treated with different third-generation regimens. 753 25

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.
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PMID:De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct. 754 11

CD30 is a transmembrane receptor of the nerve growth factor/tumor necrosis factor receptor superfamily. Its expression associated with Hodgkin's lymphoma and a subset of non-Hodgkin's lymphoma. Recently, its ligand (CD30L) has been cloned. CD30L enhances the proliferation of peripheral T cells and the Hodgkin's cell line HDLM-2 but seems to exert antiproliferative effects on large cell anaplastic lymphoma cell lines. Since tyrosine kinases are critical regulators of cell growth, we investigated whether CD30L induced changes in cellular tyrosine phosphorylation in CD30-positive lymphoma cell lines. Stimulation with CD30L or with an agonistic mAb against CD30, M44, induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of a cytosolic protein of M(r) 42,000 (p42) in the Hodgkin's lymphomas cell line HDLM-2 but not in other CD30-positive lymphomas. In HDLM-2 cells, the phrobol ester phorbol 12-myristate 13-acetate also stimulated tyrosine phosphorylation of p42, and this effect was enhanced by M44. In marked contrast, agents stimulating the protein kinase A pathway, like forskolin or dibutyryl cAMP, did not affect tyrosine phosphorylation of P42. By immunoprecipitation with mAbs against mitogen-activated protein kinase (MAPK; p42ERKII), a M(r) 42,000 protein was identified which comigrated with p42 on SDS gels and which was phosphorylated on tyrosine residues in response to stimulation of CD30. Immune complex kinase assays showed that M44 mAb induced the activation of MAPK (p42ERKII) and the phosphorylation of a MAPK substrate, myelin basic protein. Taken together, the results suggest that CD30L induces the tyrosine phosphorylation and activation of the MAPK p42ERKII isoform in HDLM-2 cells. These findings may have implications for the understanding of the pathogenesis of Hodgkin's disease.
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PMID:CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin's lymphoma cell line. 754 87

CD30 expression is found on Hodgkin and Reed-Sternberg cells, anaplastic large cell lymphoma cells and on activated B or T lymphocytes. Recently CD30 was shown to be a transmembrane receptor that is significantly homologous to the tumor necrosis factor receptor (TNFR) family. Ligands for most members of this family, including CD30, have now been identified. This review summarizes the role of the different TNFR family members in lymphocyte proliferation and differentiation in an attempt to understand more clearly the role of CD30 expression in the pathogenesis and clinical behavior of non-Hodgkin's lymphomas. We state that CD30 expression is of prognostic relevance in primary cutaneous and nodal T cell lymphomas in contrast to the absence of clinical relevance of CD30 expression in B cell lymphomas.
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PMID:CD30 expression in normal and neoplastic lymphoid tissue: biological aspects and clinical implications. 756 99

High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic features as well as some overlap between established histologic subtypes thus highlighting the difficulties in defining them precisely by making use of the classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25 Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a period of nine years. The International Working Formulation (WF) for NHL, the updated Kiel Classification and, later, morphologic variants of high grade B-cell NHL have been adopted in order to obtain a more detailed and specific histopathologic description of HIV-associated lymphomas. As a consequence of morphologic data, and considering also pathogenetic aspects as derived from literature, we have attempted a pathological categorization of HIV-associated systemic lymphomas based on the recognition of two main groups: the "blastic" cell group and the "anaplastic" one, both including specific cytomorphologic subtypes with, possibly, aggressive HD subtypes within one of them. This categorization uses the WF, the updated Kiel system, and the morphologic variants of high-grade lymphomas, and provides a provisional category for cases with intermediate morphologic features. Thus other histologic subtypes, such as small noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas, immunoblastic ones in particular.
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PMID:Can a specifically-aimed pathologic classification overcome the difficulties in defining HIV-associated lymphomas? 756 63

Lymphomatoid papulosis is a distinct entity in which recurring crops of haemorragic and necrotic papules display a cytologically malignant infiltrate. The aberrent cell is now generally accepted to be an active T helper phenotype. The expression of Ki-1 (CD30) on a significant portion of the infiltrating cells characterizes lymphomatoid papulosis and relates this disorder with Hodgkin's disease, mycosis fungoides and anaplasic T cell lymphoma which may be associated in 10 to 20% of lymphomatoid papulosis. The categorization of this disease as a benign disorder versus lymphoma remains controversial. Studies of T cell receptor gene rearrangement demonstrate clonality in many cases. So, this monoclonal population could have a malignant transformation induced by a triggering stimulus such as genetic translocation, or viral infection. Finally, recent opinions consider that lymphomatoid papulosis and Ki-1 (CD30) lymphomas are different parts of a clinical and histological spectrum constituted by cutaneous Ki-1 lymphoid infiltrates.
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PMID:[Lymphomatoid papulosis]. 756 10


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