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 production of cytokines was analysed in Hodgkin's disease (HD) derived cell lines by enzyme linked immunosorbent tests (ELISA) and Northern blot experiments. Our results demonstrate that HD derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, TNF alpha, TNF beta and GM-CSF but not IL1 beta, IL2, IL3 and G-CSF. In cell lines with a high expression of CD25 (the light chain of the IL2 receptor), we found soluble IL2 receptors in the supernatants. In addition, receptors for IL6 could be detected in most of the HD derived cell lines. However the growth of HD derived cell lines, which produce IL6 and IL6 receptors could not be inhibited by anti-IL6 antibodies. From our data we conclude, that IL6 and additional cytokines may be involved in the biology of HD.
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PMID:Production of multiple cytokines by Hodgkin's disease derived cell lines. 129 32

We have examined the Hodgkin's disease derived cell line Co in terms of its capacity to differentiate in vitro. Co cells show the characteristics of immature T cells and express CD3 molecules in the cytoplasm. On activation with 12-O-tetradecanoylphorbol-13-acetate (TPA) these cells express the CD3 antigen and the T cell receptor alpha beta (TCR alpha beta) on the cell surface. Surface expression of the activation marker CD25 (IL2 receptor) was also greatly increased, whereas CD4 and CD8 levels were not altered. Supernatants of TPA-stimulated Co cells contained the cytokines IL2, IL3, IL4 and IL8, whereas these cytokines were not detected in the supernatants of untreated cells. Different subclones of the Co cell line differed in their response to TPA with respect to the induced CD3 and TCR expression. Our data demonstrate that a Hodgkin's disease derived cell line can be induced to differentiate in vitro from a pre-T cell phenotype towards a more mature T cell. It is possible that similar processes may occur in Hodgkin's disease in vivo.
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PMID:In vitro differentiation of a Hodgkin's disease derived cell line. 139 15

The complex histological pattern in Hodgkin's disease and in part in large cell anaplastic lymphomas (ALCL) suggests that close interactions exist between the tumor cells and reactive bystander cells. These interactions are most likely mediated by short ranged cytokines. The production of cytokines was analyzed in primary tissues and cell lines from Hodgkin's disease and ALCL by enzyme linked immunosorbent tests (ELISA), Northern blotting, immunohistological staining and in situ hybridization experiments. Our results indicate that Hodgkin's disease derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, IL9, TNF alpha and TNF beta but not IL1 beta, IL2, IL3 and G-CSF. In addition, the receptors for IL6 were detected in some of the cell lines. The expression of IL6 and IL6 receptors and IL9 has been confirmed for some primary tissues of Hodgkin's disease. From our data, we conclude that IL6, IL9 and additional cytokines are involved in the biology of Hodgkin's disease and ALCL.
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PMID:Activation of cytokines in Hodgkin's disease. 145 74

Studies of peripheral blood lymphocytes (PBL) and plasma from patients with malignant lymphoma [Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL)] show that plasma soluble interleukin 2 receptor (sIL2R) levels are closely linked with disease status [normal volunteers (n = 15) 402 +/- 158 u/ml; patients with Hodgkin's disease in remission (n = 4) 525 +/- 195 u/ml or with active disease (n = 11) 3026 +/- 1602 u/ml (p < 0.001); patients with non Hodgkin's lymphoma in remission (n = 6) 462 +/- 202 u/ml, active disease (n = 15) 2713 +/- 1755 u/ml, (p < 0.001)] but no correlation between sIL2R and the inhibition of interleukin 2 (IL2) generated cytotoxicity for the cell line K562. In only 1 of 15 patient plasma samples studied was there a dose dependent inhibition of IL2 generated cell killing. In a further patient, IL2 generated K562 killing was inhibited at all doses (500-3000 brmp units/ml); treatment of this plasma with anti-Interleukin 4 (alpha IL4) had no effect on the potent inhibitory activity of the plasma. Plasma sIL2R levels were markedly elevated in patients receiving IL2 in vivo (pre treatment 520 +/- 170 IU/ml, during treatment 5578 +/- 2564 IU/ml, p = 0.05). The aetiology of immunosuppression in patients with lymphoma appears to be multi-factorial; although sIL2R correlates with disease activity it does not appear to directly mediate immunosuppression in most patients with malignant lymphoma.
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PMID:Plasma soluble interleukin 2 receptor levels in patients with malignant lymphoma are correlated with disease activity but not cellular immunosuppression. 837 18

We investigated the potential of ten cytokines (IL2, IL3, IL4, IL6, IL10, IL13, G-CSF, GM-CSF, interferon alpha, interferon gamma) and all-trans-retinoic acid to modulate the spontaneous proliferative response in vitro of purified B-non Hodgkin's lymphoma cells of various histological subtypes. 19 malignant lymph nodes were studied. In each case the growth could be influenced by several of these modulators. Cytokines most often implicated were interferon gamma (14/19 cases, 73.7%), IL4 (13/19 cases, 68.4%), interferon alpha (12/19 cases, 63.1%). IL2 (9/19 cases, 47.3%), IL6, IL10, IL13 and ATRA were less frequently involved (6/19 cases, 31.6%) and hematopoietic growth factors (IL3, GM-CSF, G-CSF) were rarely implicated (2/19 cases, 10.5%). The values of growth stimulation ranged from a 1.1-fold to a 6.1-fold increase, and the values of growth inhibition ranged from 15% to 98%. Each cytokine could be either inhibitory or stimulatory depending on the sample analyzed, and no relationship could be found with the histological subtype. Two notable exceptions were IL2, displaying exclusively a positive effect, and ATRA displaying exclusively a negative effect. Overall, these results may have strong implications for future clinical studies using cytokines in the treatment of lymphomas. Ideally, the pattern of in vitro growth response to cytokines or ATRA should be determined individually before undertaking any cytokine treatment.
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PMID:Growth modulation of freshly isolated non-Hodgkin's B-lymphoma cells induced by various cytokines and all-trans-retinoic-acid. 913 Jun 25

In this study, we have investigated whether a pattern of cytokine gene expression can be found in non-Hodgkin's peripheral T-cell lymphoma (PTCL). By using RNase protection assays and RT-PCR, we have systematically studied IL1alpha, IL1beta, IL1-Ra, IL2, IL4, IL5, IL6, IL9, IL10, IL12p35, IL12p40, IL13, IL14, IL15, IFNgamma, IFNbeta, TNFalpha, TNFbeta, LTbeta, and TGFbeta1, TGFbeta2 and TGFbeta3. Twenty-two cases of PTCL inclusive of three nasal NK-cell lymphomas were selected for the study; three cases of reactive lymphoproliferation were included for comparison. Results show that IFNgamma gene expression (key Type 1 cytokine) was frequently detected [18/22 (82 per cent)]. In contrast, IL4 (key Type 2 cytokine) was only detected in 4/22 (18 per cent) of cases (weaker than IFNgamma in three cases). This distinction was also found at the protein level by immunohistochemistry. In addition, TNFbeta and TNFalpha (strongly expressed by Type 1 cells) were almost complimentarily detected [4/19 (21 per cent)] and 12/19 (63 per cent), respectively). In contrast, neither IL5 nor IL13 (strongly expressed by Type 2 cells) were detected at all. However, 14/22 cases expressed IL10, another Type 2 cytokine, which suggests that the autoregulatory feedback loop is stimulated. Compared to the tumour types, the cytokine profiles in the reactive lymphoproliferative types also resembled a Type 1-like pattern but was less striking. The overall result suggested a preferential expression of certain cytokines, and these cytokines may play an important role in pathophysiologic progression in these T-cell disorders.
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PMID:Preferential type 1-1 cytokine gene expressions in peripheral T-cell lymphomas. 1064 Oct 32

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.
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PMID:Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification. 1275 25

The intracellular profiles of T helper type 1 (Th1) and T helper type 2 (Th2) T-cell cytokines by peripheral blood (PB) CD3+ T-cells in patients with classical Hodgkin lymphoma (HL) has not been investigated before. The present study examines the cytoplasmic production of interleukin (IL) 2, 4, 10, tumour necrosis factor alpha (TNFalpha), and interferon gamma (IFNgamma) by activated PB CD3+ T-cells and compares them with the profiles observed with normal individuals. We report a significantly lower mean level of intracellular IL2, TNFalpha and IFNgamma at any time post-cell activation in cells isolated from patients with HL compared with the normal control group. In contrast, the mean level of cytoplasmic IL4 was significantly higher in the HL compared with the control group. No significant difference between the two groups was observed with IL10. In the HL patient group, there was a significantly higher percentage of CD3+CD8+ T-cells that synthesised IL4 compared with the CD3+CD4+ subpopulation, no such difference was observed in normal controls. The intensity of IL4 (expressed as relative median fluorescence) was significantly higher in the CD3+CD8+ cells of the patients with HL compared with the CD3+CD4+ sub-population, or with normal CD3+CD8+ cells. In conclusion, there is reduced intracellular IL2, TNFalpha and IFNgamma and increased cytoplasmic IL4 production by activated PB T-cells in patients with HL. The CD3+CD8+ sub-population is responsible for the increased levels of IL4.
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PMID:Intracellular cytokine profiles by peripheral blood CD3+ T-cells in patients with classical Hodgkin lymphoma. 1295 25

Although the production of interleukin (IL) 2 and interferon (IFN) gamma by peripheral blood lymphocytes in patients with Hodgkin lymphoma (HL) is well documented, the synthesis of IL4 has not been investigated before. The present study examines the production of IL4 by 2-day phytohaemaglutinin (PHA)-stimulated peripheral blood (PB) cells in HL and correlates the cytokine levels with the proportion of the different T-cell sub-populations. We observed a significant increase in the mean level of production of IL4 in patients with HL when compared with normal controls. The increased amount of IL4 in patients with HL correlated significantly with the proportion of the CD3(+)CD8(+) cells but not with CD3(+)CD4(+). The intensity of cytoplasmic IL4 (expressed as relative median fluorescence (RMF)) was significantly higher in the CD3(+)CD8(+) cells of the patients with HL compared with the CD3(+)CD4(+) sub-population, or with the normal CD3(+)CD8(+) cells and correlated with the levels of IL4 release in culture supernatants. In conclusion, there is increased production of IL4 by PHA-activated PB lymphocytes in HL. The CD3(+)CD8(+) T-cell population appears to be responsible for this increased synthesis.
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PMID:Interleukin 4 production by peripheral blood lymphocytes in patients with classical Hodgkin lymphoma. 1465 80

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T cells (CTL) is effective for the prophylaxis and treatment of EBV-induced lymphoma in hematopoietic stem cell recipients. However, in EBV-positive Hodgkin's disease (HD) the efficacy of adoptively transferred EBV-specific CTL may be limited by tumor-derived immunosuppressive factors, such as T-cell growth factor (TGF) beta, interleukin (IL)13 and the chemokine TARC. Local delivery of IL12 to tumor sites by tumor-specific CTL could provide direct antitumor effects and overcome the CTL-inhibitory effects of the Th2 tumor environment while avoiding the systemic toxicity of recombinant IL12. EBV-specific CTL transduced with a retrovirus vector expressing the p40 and p35 subunits of IL12 as a single molecule (Flexi-IL12), produced IL12 following antigenic stimulation. This resulted in an elevated production of Th1 cytokines, including interferon gamma and tumor necrosis factor alpha, and a reduction in the Th2 cytokines IL4 and IL5. Flexi-IL12-transduced CTL resisted the antiproliferative and anticytotoxic effects of exogenous TGFbeta, likely by antagonizing the TGFbeta-induced downregulation of the Th1 transcriptional factor T-bet. In addition, Flexi-IL12-transduced CTL demonstrated a proliferative advantage in the presence of inhibitory supernatants from HD-derived cell lines. Tumor-specific, Flexi-IL12-transduced EBV-specific CTL should have a functional advantage over unmodified CTL, particularly in the presence of the adverse Th2 cytokine environment produced by Hodgkin tumor cells.
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PMID:A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells. 1468 54


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