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 clinical, pathologic, and immunologic features unique to Hodgkin's disease can be explained by the following hypothesis. A viral transformation of a lymph node cell leads to proliferation of tumor cells and the generation of an immune response consisting of lymphokine production, B cell activation and concomitant suppression of further T cell activation, but ineffective cellular cytotoxicity against the tumor cells. The result of this interaction would be chronic infiltration around the transformed cells, increased immunoglobulin synthesis, and anergy. Failure to destroy the target cells would result in chronicity of these features and progressive disease.
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PMID:Hodgkin's disease and anergy. 36 74

Interleukin 6 (IL-6) is a pleiotropic lymphokine which can stimulate a variety of cells including B and T lymphocytes. It has been suggested that IL-6 plays a crucial role in several diseases such as human plasmacytoma, cardiac myxoma or Castleman's Disease by autocrine or paracrine stimulation. To analyse whether IL-6 is involved in the biology of Hodgkin's Disease (HD), we investigated the expression of IL-6 and IL-6 receptor (IL-6R) in cell lines and primary specimens from patients with HD. IL-6 specific transcripts were detected in three out of six HD derived cell lines by Northern blot analysis and in the culture supernatants of four HD derived cell lines by ELISA. Its biological activity was confirmed by proliferation of an IL-6 dependent cell line. By in-situ hybridization experiments IL-6 specific transcripts were detected in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues in two out of three patients. mRNAs specific for the IL-6 receptor were detected in five HD derived cell lines. Staining of HD derived cell lines revealed expression of the receptor molecules in five cell lines; Western blot experiments confirmed the 80kDa receptor protein in the cells. Immunohistology in primary specimens revealed expression of the receptor molecules on H and RS cells in 8 out of 16 cases with HD. Expression was mostly detected in the mixed cellularity subtype of HD. Elevated levels of IL-6 were detected in the sera of more than 50% of patients with HD. Taken together our data suggest that IL-6 might be involved in the biology of HD.
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PMID:Hodgkin and Reed-Sternberg cells express interleukin 6 and interleukin 6 receptors. 149 29

Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute-phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL-6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.
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PMID:Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease. 171 Jan 52

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 prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations.
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PMID:Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study. 186 30

Interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cell therapy has antineoplastic activity in renal cancer and malignant melanoma. In order to explore the activity of this therapy in Hodgkin's disease and non-Hodgkin's lymphoma, the Extramural IL-2/LAK Working Group (ILWG) treated 27 patients on two protocols using high-dose IL-2 and autologous LAK cells. Two of 12 patients with Hodgkin's disease experienced partial responses lasting 6 and 12 weeks. No patient with non-Hodgkin's lymphoma responded (p = NS). The toxicities of therapy were similar to those reported by the ILWG from trials of IL-2/LAK in solid tumors, consisting of transient hemodynamic, cardiopulmonary, renal and hepatic dysfunction, skin rash, fever, and flu-like symptoms. In view of the low response rate and the brief duration of these responses, we do not recommend the regimens reported here for further investigation in Hodgkin's disease or non-Hodgkin's lymphomas.
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PMID:Phase II trial of high-dose interleukin-2 and lymphokine-activated killer cells in Hodgkin's disease and non-Hodgkin's lymphoma. 186 45

10 lymphoma patients given a total of 26 courses of intravenous continuous infusion of recombinant interleukin-2 (rIL-2) alone without lymphokine-activated killer cells were analysed retrospectively for the frequency and pattern of bacterial infections associated with the immunotherapy. 4 episodes of septicaemia and 7 episodes of soft tissue infections resulted from the 26 courses of rIL-2 infusion. Although there was no death due to infection, all these infections were clinically significant, needing systemic antibiotic therapy and resulting in prolonged hospitalisation. Gram-positive infections occurred significantly (p less than 0.001) more often than gram-negative infections. Patients with non-Hodgkin's lymphoma had a higher incidence of infection than patients treated for Hodgkin's disease, analysed either as infection per patient treated (p less than 0.05) or infection per course of rIL-2 given (p less than 0.02).
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PMID:Bacterial infections in lymphoma patients treated with recombinant interleukin-2. 204 46

We conducted a phase II study utilizing interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-2 was given at a fixed dose of 3 x 10(6) U/m2/day administered as a 24-h continuous intravenous infusion with LAK cells. Nineteen extensively treated patients were entered and 15 were evaluable. In general, this regimen was reasonably well tolerated with mild toxicities that were rapidly reversible. Patients who completed therapy did so without dose attenuations. However, discontinuation of therapy was necessary in four patients due to atypical toxicities that were not clearly dose related. Two patients (one NHL and one HD) had partial remissions of brief duration, four had disease stabilization, and seven had progressive disease. While there were not sufficient numbers to evaluate critically any NHL or HD subtype, this regimen does not appear to have significant activity for either disease.
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PMID:Interleukin-2 lymphokine-activated killer cell therapy of non-Hodgkin's lymphoma and Hodgkin's disease. 204 94

We report the natural killer (NK) and lymphokine activated killer (LAK) cell activities in peripheral blood lymphocytes (PBL) from untreated patients with Hodgkin's disease (HD) and from healthy donors. The frequency of LAK cell precursors was also studied using limiting dilution analysis (LDA). About 75% of the HD patients had normal NK activity. There was a higher percentage of low NK responders (mean percent NK activity of healthy donors--2 SD) in patients with lymphocyte depletion histologic grade of the disease and those who were in clinical stage IV, suggesting a correlation of decrease in NK activity with poor prognosis. We found efficient LAK activity against the NK-sensitive K562 cells and NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumour targets in both low and normal NK responder HD patients, irrespective of the histopathological grade and clinical stage of the disease. In concordance with their good LAK cell activity, HD patients showed a frequency distribution of LAK cell progenitors in the PBL comparable to that of healthy donors.
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PMID:Natural killer and lymphokine activated killer cell functions in Hodgkin's disease. 238 35

A new cell line, SUP-HD1, was established from the pleural effusion of a patient with nodular sclerosing Hodgkin's disease (NSHD). The SUP-HD1 cells had the characteristic morphology of Reed-Sternberg cells and contained acid phosphatase and nonspecific esterase. The cells lacked the Epstein-Barr virus (EBV) genome and reacted with monoclonal antibodies (MoAbs) against CD15 (Leu-M1), CD25 (Tac), CD71 (OKT9), Ki67, and HLA-Dr. However, the SUP-HD1 cells were nonreactive with MoAbs that specifically identify T lymphocytes, B lymphocytes, and macrophage/myeloid cells. Karyotype analysis of the cell line showed clonal abnormalities involving 1p13, 7p15, 8q22, and 11q23, chromosomal locations, at which breakpoints have been reported in HD. Southern blot analysis demonstrated rearrangement of the immunoglobulin heavy chain and kappa light chain genes as well as the gene for the beta chain of the T-cell receptor (TCR). Transcriptional analysis showed expression of RNAs for kappa light chain, interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) but not IL-2. The SUP-HD1 cells lacked cytoplasmic and surface immunoglobulin heavy chain, but a small amount of cytoplasmic kappa light chain was detected. The presence of nuclear factor kappa B (NF kappa B), a B-lymphocyte-associated transcription factor, was demonstrated in stimulated and unstimulated cells. In addition, the SUP-HD1 cell line, produced IFN-gamma, a T-lymphocyte-associated lymphokine. Based on these data, the SUP-HD1 cells appear to be aberrant lymphocytes with characteristics of both activated B and T lymphocytes. Elaboration of lymphokines such as IFN-gamma by the malignant cells may represent one explanation for the unique clinical and pathologic features of HD.
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PMID:SUP-HD1: a new Hodgkin's disease-derived cell line with lymphoid features produces interferon-gamma. 232 24


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