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)

We investigated ICAM-1/CD54 tissue immunoreactivity and serum levels of its soluble form (sICAM-1) in patients with Hodgkin's disease (HD) at diagnosis. ICAM-1 was strongly expressed in involved tissues, and sICAM-1 serum levels were higher in HD (79 patients) than in controls (P < 0.01), and in patients with more advanced or more active disease (stages III + IV vI + II: P = 0.002; stage 'B' v 'A': P < 0.0001; 'bulky' disease v non-'bulky': P = 0.042). We suggest that tissue ICAM-1 overexpression leading to increase of circulating sICAM-1 may interfere with the lymphocyte adhesion machinery thus contributing to the well-known immune derangement of HD.
 ...
PMID:ICAM-1 tissue overexpression associated with increased serum levels of its soluble form in Hodgkin's disease. 810 21

Intercellular adhesion molecule-3 (ICAM-3), the third receptor for lymphocyte function-associated antigen molecule-1 and a new member of the immunoglobulin superfamily has been recently characterized using specific monoclonal antibodies. In the present study, we show immunocytochemically that ICAM-3 is present on T and B cells in the mantle zones and on a subpopulation of follicular center cells in reactive lymph nodes and only occasionally in endothelium. In 52 cases of Hodgkin's disease, ICAM-3, although present on the majority of the reactive lymphoid cells, was absent from the Reed-Sternberg cells and their variants. However, in 28 cases (54%), there was prominent endothelial staining in small vessels. Similar findings were noted in 16 out of 49 cases (33%) of non-Hodgkin's lymphomas. This finding suggests that analogous to ICAM-1 and ICAM-2, ICAM-3 expression can be induced on endothelial cells in lymphoid neoplasms, probably by an as yet unidentified cytokine-mediated mechanism.
 ...
PMID:ICAM-3 expression on endothelium in lymphoid malignancy. 821

The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.
 ...
PMID:Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker for survival. 853 15

Reed-Sternberg cells, the neoplastic cells of Hodgkin's disease, express all membrane molecules required to function as antigen-presenting cells (APCs), such as major histocompatibility complex (MHC) class II antigens and the recently characterized B7 proteins, which are of critical importance for APC to adequately stimulate CD4+ T cells. As APC do, Reed-Sternberg cells also express the adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58), via which T cells are able to adhere to the cell. MHC antigens, B7 proteins as well as the adhesion molecules are expressed by Reed-Sternberg cells in virtually all cases of Hodgkin's disease, irrespective of the subtype. In vitro studies have shown that Hodgkin's disease-derived cell lines are potent stimulators of mixed lymphocyte cultures and that the MHC antigens, B7 proteins and the adhesion molecules, expressed by Hodgkin's disease-derived cell lines, are essential for such a function. Taken together, these data strongly suggest that Reed-Sternberg cells function as APC in vivo, and that the APC function of the cell is a major common denominator of Hodgkin's disease. The APC function of Reed-Sternberg cells does not support the hypothesis that they derive from dendritic cells, since activated B and T cells may also exert an APC function. Analysis of the antigens that are potentially expressed by Reed-Sternberg cells may greatly advance our knowledge on the pathogenesis of Hodgkin's disease and may allow the development of immunotherapy as an alternative treatment method.
 ...
PMID:The antigen-presenting cell function of Reed-Sternberg cells. 858 Aug 27

The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.
 ...
PMID:Elevated serum levels of soluble ICAM-1 in non-Hodgkin's lymphomas correlate with tumour burden, disease activity and other prognostic markers. 879 Jan 63

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expressed mainly by activated T cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, regarded as the malignant components of Hodgkin's disease (HD), display high levels of the counter-receptors for these ligands, ie CD30, CD40 and 4-1BB. CD30L and CD40L are known to share some biological activities that can be linked to the unbalanced secretion of cytokines seen in HD. In addition, cell contact-dependent molecules such as adhesion or activation antigens are critically involved in T cell/H-RS cell interactions. Primary and cultured H-RS cells frequently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD40L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells on the mRNA and protein level, as a result of transcriptional gene activation. Furthermore, enhanced CD54 surface expression by these cells is accompanied by increased shedding of surface-bound CD54, as evidenced by high levels of the 82 kDa soluble (s) CD54 form detectable in culture supernatants after specific stimulation. Addition of CD30L in combination with CD40L to cultured H-RS cells additively enhanced CD54 surface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.
 ...
PMID:The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. 865 79

The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV) and is expressed in Reed-Sternberg (RS) cells of EBV-associated Hodgkin's disease (HD). We have studied the effect of this oncoprotein on the formation of RS cells in the EBV-negative HD cell lines L-428 and KM-H2 as well as on the formation of multinucleated cells in the mononuclear human embryonic kidney cell line 293. LMP1 prototype (B95-8) and its naturally occurring carboxy terminal 30 base pair deletion variant LMP1-del were transfected into the cell lines and cytocentrifuge preparations were analysed after 24, 48, 72, 144, 216, and 240 h. While no oncoprotein expression was seen in the KM-H2 cell lines, expression of LMP1 and LMP1-del was observed in the L-428 and 293 cell lines. In the HD cell line L-428 oncoprotein expression was infrequent but when observed was very strong and preferentially associated with multinucleated RS cell morphology (71% of LMP1 positive cells). This is in contrast with the untransfected or transfected but not expressing cells where intermediate mononuclear elements predominated over multinucleated RS cells (< 3%). Frequent oncoprotein expression was observed in the 293 cells and again was associated with multinuclearity. These LMP1 expressing 293 giant cells showed strong expression of ICAM-1(CD54), not detectable in the untransfected cells. In the LMP1-del transfectants giant cells with more than four nuclei were frequently observed. However, giant cells were much less frequent in 293 cells transfected with the amino terminal deletion variant of LMP1 or the lytic form of LMP1, known to induce low NF-kappa B activation compared to the LMP1 prototype. Therefore, LMP1 mediated NF-kappa B activation appears to be involved in polycaria formation. The strong association of LMP1 expression with multinuclearity in a genetically unstable condition -the L-428 and 293 cells show multiple chromosomal abnormalities-suggests that this oncoprotein including its naturally occurring carboxy terminal deletion variant promote the formation of multinuclear cells, in particular of RS cells in EBV-associated HD.
 ...
PMID:Expression of the LMP1 oncoprotein in the EBV negative Hodgkin's disease cell line L-428 is associated with Reed-Sternberg cell morphology. 880 84

Hodgkin's disease (HD) is characterized by the presence of the typical, clonal malignant Hodgkin and Reed-Sternberg (H-RS) cells in a hyperplastic background of normal reactive lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils and stromal cells. The neoplastic nature of HD is based on aggressive clinical progression, presence of the proliferating and atypical H-RS cells, aneuploidy and cellular clonality. Immunophenotypical studies have demonstrated frequent expression of lymphoid "activation markers' including CD15, CD25, CD30, CD40, CD54, CD70, CD71, CD80, CD86 and MHC class II and less frequent expression of T- or B-cell-associated antigens by the neoplastic H-RS cells. The clonality of H-RS cells is demonstrated by clonal EBV integration, clonal cytogenetic abnormalities including p53 mutations and clonal immunoglobulin rearrangements in some HD cases. There is involvement of diverse molecules with oncogenic potential, including presence of viruses (Epstein-Barr virus and human herpes virus-6) and/or oncogenes/tumour suppressor genes (bcl-2/bcl-x, p53/MDM-2, c-myc, c-fms, N-ras, lck). The histopathological presentation and characteristic clinical features of HD correlate with an unbalanced production of multiple cytokines and define HD as a tumour of cytokine-producing cells. The proportion of malignant H-RS cells to reactive cellular components and fibrosis is dependent on the production of particular cytokines and allows subtyping of HD cases. The combined use of immunohistochemical, biochemical and molecular techniques has thus allowed recognition that HD represents more than one clinico-pathological entity with different types of H-RS cells. The defined mechanism for the biological nature, origin and oncogenesis of H-RS cells remains not fully understood, but is susceptible to further analysis using modern technology.
 ...
PMID:Pathophysiology of Hodgkin's disease: functional and molecular aspects. 892 38

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.
 ...
PMID:CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. 905 27

Two genes encoding the latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) were isolated from a single case of Hodgkin's disease (HD) and were tested for their biological activities. The LMP1 gene from the Reed-Sternberg cells contained point mutations relative to the prototype LMP1 gene, leading to amino-acid exchanges. The LMP1 gene from passenger lymphocytes showed identical point mutations, but also had an in-frame insertion of 132 base pairs within the 33-bp repeat region. This insert encoding 44 amino acids contained the sequence PSQQS, corresponding to the potential TRAF-binding motif PXQXT/S. When compared to the B95.8 gene, both HD-derived LMP1 genes showed an increase in the transformation of Rat-1 rodent fibroblasts. The transforming ability of the LMP1 gene with the insertion was greater than that of the other HD-derived LMP1, and was comparable with the highly transforming LMP1-Cao gene derived from a nasopharyngeal carcinoma. The HD-derived genes stimulated expression of the cell-surface markers, CD40 and CD54, similarly to the LMP1-B95.8 gene, while the LMP1-Cao gene had a significantly reduced ability to induce these proteins. In contrast, the LMP1-Cao transactivated an NF-kappaB-response element more efficiently than did the HD-derived genes. Transfer of the 132-bp insert alone into the B95.8 gene did not increase its transforming activity to the LMP1-Cao level, indicating that additional mutations in the LMP1 gene are necessary for modulating this function.
 ...
PMID:Isolation and analysis of two strongly transforming isoforms of the Epstein-Barr-Virus(EBV)-encoded latent membrane protein-1 (LMP1) from a single Hodgkin's lymphoma. 953 80


<< Previous 1 2 3 4 5 6 Next >>