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)

Recent evidence indicates that Reed-Sternberg (RS) cells from many cases of Hodgkin's disease have features of activated lymphocytes and that lymphokines from activated lymphocytes induce proliferation of L-428 RS cells. It is shown here that a lymphokine similar to a lymphokine secreted by activated lymphocytes is secreted by L-428 cells. This lymphokine has a molecular weight approximately equal to 68,000 daltons, identical to glycosylated recombinant interleukin-4 (rIL-4), and cross-reacts with monoclonal anti-IL-4 in Western immunoblotting. This Hodgkin's cell growth factor (HCGF) is 100% neutralized by polyclonal anti-IL-4 antibodies and competes for the IL-4 receptor. After acid-elution, the L-428 RS cell has been shown to have 3,396 +/- 120 high-affinity receptor sites/cell. HCGF competes with rIL-4 for this receptor and L-428 cells contain mRNA for IL-4. Although all evidence indicates that IL-4 is an important secreted autocrine growth factor for L-428 RS cells, anti-IL-4 has no effect on the sustained serum-free growth of these Hodgkin's cells, suggesting that either the IL-4 receptor and the IL-4 receptor-growth factor complex are protected from antibody inhibition or other mechanisms are responsible for the sustained proliferation of L-428 RS cells.
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PMID:Interleukin-4 is an autocrine growth factor secreted by the L-428 Reed-Sternberg cell. 172 8

The leucocyte antigen CD23 is upregulated in the early stages of B-cell activation by Interleukin-4 (IL-4), and functions as an IgE receptor and lymphocyte growth factor. We have studied the expression of CD23 in 68 cases of non-Hodgkin lymphoma (NHL) using the antibody BU38. This new antibody has the great advantage of being applicable to routinely-processed paraffin sections. CD23 was expressed in tumour cells in 27 out of 36 cases of low grade NHL and 3 out of 32 cases of high grade NHL. Follicular dendritic cells were strongly positive and were seen in follicular lymphomas. Macrophages were also positive and were numerous in high grade lesions.
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PMID:CD23 expression in non-Hodgkin lymphoma: immunohistochemical demonstration using the antibody BU38 on paraffin sections. 174 98

The detection of an increasing number of cytokines and the demonstration of autocrine and paracrine mechanisms perpetuating tumor growth prompted the investigation of the expression of the cytokines IL-2, IL-3, IL-4, IL-5, IL-6, IFN gamma, Tac, and GMCSF in primary lymph-node biopsies of patients with peripheral T-cell lymphoma (n = 11), Hodgkin's disease (n = 13), and large-cell anaplastic lymphoma (n = 6) by means of Northern blot analysis and in situ hybridization (ISH); 15 of 28 cases had IL-6 message, predominantly in cases of Hodgkin's disease (HD) and large-cell anaplastic lymphomas (LCAL). Interferon gamma was found in about 50% of the cases among all entities. Other cytokine expression was rare except two cases of HD with high amounts of IL-4 mRNA. These results indicate that large amounts of growth factor transcripts are present in a variety of malignant lymphomas. The meaning of this expression is still unclear. It may be a loss of physiologic regulation within the cytokine network which may thus influence neoplastic cell growth as some cases have a quantity of cytokine expression which is similar or even above that of stimulated T cells. ISH demonstrates in individual cases that the expression is at least in part due to malignant cells.
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PMID:Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth. 195 32

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

Interleukin-4 (IL-4), originally identified as a B-cell growth factor, has been shown to inhibit certain stages of hematopoietic stem cells. Recently, IL-4 has been recognized as a negative regulatory factor in the growth of hematologic malignancy. In myeloid leukemias, IL-4 can suppress the growth of growth factor-dependent leukemic blast cells derived from acute myelogenous leukemia (AML). IL-4 also suppresses the growth of chronic myelomonocytic leukemia cells through inhibiting the "autocrine" production of IL-6 or granulocyte/macrophage colony-stimulating factor. In lymphoid malignancies, IL-4 can inhibit the proliferation of neoplastic cells from Ph1-positive acute lymphoblastic leukemia, non-Hodgkin's B-cell lymphoma, and multiple myeloma. Thus, IL-4 is expected to be useful as a therapeutic agent for these hematologic malignancies.
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PMID:The role of interleukin-4 in the negative regulation of leukemia cell growth. 768 64

Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germinal centers. B lymphocytes from normal germinal centers and lymph nodes infiltrated by follicular lymphoma were isolated by immunomagnetic depletion of cells bearing CD4, CD8, or slgD for study in vitro. Follicular lymphoma cells expressing Bcl-2 protein were shown to resist apoptosis after isolation, and could be induced to proliferate in a culture system previously described for the growth of normal B lymphocytes. By the use of a mouse fibroblast monolayer transfected with the CDw32 Fc receptor to present CD40 monoclonal antibody in the presence of interleukin-4, prolonged culture was possible. Karyotypic analysis of cultured lymphoma cells showed the t(14;18) translocation, with clonal identity confirmed by polymerase chain reaction amplification of the breakpoints and direct sequence analysis. These findings support the hypothesis that resistance to apoptosis is an influence on the initiation of follicular lymphoma, and provide a novel means of studying in vitro the intercellular reactions that may be important in progression of the disease.
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PMID:Isolated follicular lymphoma cells are resistant to apoptosis and can be grown in vitro in the CD40/stromal cell system. 769 Dec 40

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymphoma cells by either membrane IgM cross-linking or phorbolester stimulation. The ability of phorbolesters to substitute for anti-IgM antibodies in the activation of normal and malignant human B cells has been taken as evidence for the involvement of protein kinase C (PKC) in signals transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells show a distinct regulation of HLA-class II expression. In certain lymphoma cases phorbol-myristate-acetate (PMA) not only fails to up-regulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 induced class II expression. This negative signal induced by PMA seems to operate specifically in HLA-class II regulation because PMA can induce other anti-IgM mediated events like blast transformation and induction of IL-4 responsiveness at the same time. Therefore these cells support the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM antibodies and phorbolesters influence the regulation of HLA-class II expression in a contrary direction.
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PMID:Differential signal requirement for upregulation of HLA-class II molecules in human lymphoma B cells. 834 Feb 86

19 patients with advanced cancer were entered into a phase I study of recombinant human interleukin-4 (rhu IL-4). The predominant clinical side-effects included flu-like symptoms, gastrointestinal upset, lethargy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occurred; this was life threatening in 1 patient. The maximum tolerated dose (MTD) was 400 micrograms/m2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes suggesting IL-4 induced liver damage. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) showed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.
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PMID:Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis. 839 97

Dendritic cells (DC) are potent antigen-presenting cells that are integral to the initiation of T cell immunity. The ability to culture these cells in vitro has allowed DC immunotherapy to be investigated as a mechanism of enhancing immune responses against various malignancies. We examined the optimal time for generating DC and compared DC generated from normal donors for allogeneic blood stem cell transplantation, or patient's with non-Hodgkin's lymphoma or breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. Experiments were conducted to compare DC cultured prior to and post mobilization chemotherapy. Blood was obtained from consenting patients prior to granulocyte colony-stimulating factor (G-CSF) administration with (non-Hodgkin lymphoma and breast cancer) or without (normal donors) chemotherapy. A sample of apheresis product (AP) was obtained at the time of apheresis. DC were generated from peripheral blood mononuclear cells by culturing the adherent cells in the presence of interleukin-4 and granulocyte-macrophage colony-stimulating factor. Resultant DC were harvested and examined for yield, morphology, phenotype, and function. All cell populations yielded highly pure DC, as assessed by light microscopy and flow cytometry. The average cellular yield was significantly greater from AP than steady-state blood in paired and unpaired samples. Yield did not correlate with the percentage of CD14(+) cells, and it negatively correlated with CD34 counts. DC from breast cancer patients functioned significantly better than DC from lymphoma patients in a mixed lymphocyte reaction. These data suggest that the optimal timing of culturing DC is after mobilization, and that differences may exist in the functional capabilities of DC derived from different patient populations.
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PMID:Generation of dendritic cells ex vivo: differences in steady state versus mobilized blood from patients with breast cancer, with lymphoma, and from normal donors. 1167 8

Little is known about the distribution in normal cells of CLIP-170, a linkage mediator between endocytic vesicles and microtubules, and restin, a splice variant encoded by the same gene and marker for Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin disease. Although only trace amounts of CLIP-170/restin are present in peripheral blood mononuclear cell subpopulations, monocyte-derived dendritic cells (DCs) and interleukin-4 (IL-4) + CD40L-activated B cells express high levels of CLIP-170/restin. CLIP-170/restin colocalizes preferentially with membranes of intermediate macropinocytic vesicles, suggesting a new function of CLIP-170/restin in the trafficking of macropinosomes to the cytoskeleton, which is a crucial step in antigen presentation. The strong expression of CLIP-170/restin in HRS cells, DCs, and activated B cells underscores their functional similarities supporting a function-based concept of HRS cells as professional antigen-presenting cells.
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PMID:Hodgkin and Reed-Sternberg cell-associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells. 1243 98


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