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)

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.
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PMID:Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. 788 4

Patients with Hodgkin's disease (HD) frequently show elevated serum titers against human herpersvirus-6 (HHV-6) and their tissues contain significantly increased numbers of cells with HHV-6 DNA. This may coincide with similar data of Epstein-Barr virus (EBV) infections. According to in vitro studies, Hodgkin- and Reed-Sternberg (RS) cells can be infected by HHV-6 and may be coinfected by HHV-6 and EBV. Both viruses are potentially oncogenic and also may interfere with the production of various cytokines. We now demonstrate by using immunohistological methods that HHV-6 antigens are present in 77.3% of the HD lymphomas, 37% of which contain the replication-associated p41 "early-late" antigen and 63% the late membrane antigen complex gp116/64/54. Monocytic cell populations including HD and RS cells are most frequently antigen-positive, while lymphoid cells are less frequently. These cells also express IL-6 and IL-6 receptors as well as the IL-2 receptor a chain (CD25), while only occasionally the IL-2 receptor beta chain (p70). IL-6 receptors are significantly more frequently expressed than IL-6 itself. HD and RS cells constitute a significant pool of proliferating cells as reflected by their 95% positivity for PCNA, yet tumor suppressor genes are found in only 21% and the proto-oncogenes fes and met are expressed in various types of cells. The data may indicate that both viruses possibly contribute to the course of the disease through polyclonal stimulations of cell proliferation and coincident dysregulation of the cytokine network control of cell function and proliferation. A direct oncogenic effect of EBV and HHV-6 in HD appears less probable.
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PMID:Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens as compared to oncogenes met and fes, tumor suppressor gene product p53, and interleukins 2 and 6. 789 77

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
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PMID:CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. 810 64

We determined Fas antigen (CD95) expressions on neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma (ATL/L) by a flow cytometoric method. ATL/L cells generally expressed Fas antigen, while few Fas-positive cells were detected in the other lymphoid malignancies such as non-Hodgkin lymphomas, acute lymphoblastic leukemias, and chronic lymphocytic leukemias. The function of Fas antigen was considered normal, since anti-Fas monoclonal antibody induced apoptosis of ATL/L cells. However, clinical subtypes of ATL/L did not associate with the degrees of Fas antigen expression. When recent observations by others were also considered, the apoptosis of ATL/L cells seemed to be under a complex control mechanism which includes a Fas/Fas-ligand system, HTLV-I Tax protein, bcl-2 protein and interleukin-2 (IL-2)/IL-2 receptor system. In addition, the regulation of apoptosis by Fas/Fas-ligand system and bcl-2 protein might be different between T-and B-lineage lymphoid malignancies.
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PMID:[Fas antigen (CD95) expressions and apoptosis of neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma]. 874

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and possible antitumor activity of a ligand fusion-protein, DAB389IL-2, in a phase I trial. This was a multicenter, open-label, dose-escalation trial. Patients with preserved organ function and histologically confirmed relapsed cutaneous T-cell lymphoma (CTCL), other non-Hodgkin's lymphomas (NHL), or Hodgkin's disease (HD) were eligible if their cancer was shown to express the interleukin (IL)-2 receptor by an immunohistochemical assay for the p55 or the p75 subunit. Patients received up to eight courses of DAB389IL-2 given as a short intravenous infusion daily for 5 days with subsequent courses every 21 days. The maximum tolerated dose (MTD) and tumor response was determined according to standard criteria. Seventy-three patients (44 men/29 women), aged 16 to 81 years (mean, 50.7) with CTCL (n = 35), NHL (n = 17), and HD (n = 21) were enrolled. The patients were extensively treated, failing 0 to 15 previous therapies (median, 4). Patients received one to six courses (mean, 3.3) of DAB389IL-2 over a range of 3 to 31 micrograms/kg/day. The dose-limiting toxicity was asthenia, establishing the maximum tolerated dose of 27 micrograms/kg/day. Approximately half of all patients had significant titers of antibody to diphtheria toxin or to DAB389IL-2 at the time of enrollment compared with 92% with titers at the end of treatment. The presence of antibody did not preclude clinical response. There were five complete (CR) and eight partial (PR) remissions in patients with CTCL with one CR and two PR occurring in NHL. The median time to response was 2 months and the duration of response was 2 to 39+ months. No responses were documented in patients with HD. DAB389IL-2 is well tolerated with an MTD of 27 micrograms/kg/day. This ligand fusion-protein showed antitumor effects in patients with IL-2 receptor expressing CTCL and NHL. Additional trials in these diseases are warranted.
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PMID:Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. 942 92

We measured the soluble IL-2 receptor alpha (sIL-2R alpha) in sera and in bone marrow of 20 patients with minimal residual hematological malignances, 6 of them with multiple myeloma (MM), 8 with Hodgkin's disease (HD) and 6 with non-Hodgkin's lymphoma (NHL), low grade. Compared to 10 normal individuals, HD and NHL group of patients had in sera significantly increased levels of sIL-2R alpha (252.8 +/- 42.9 versus 1437.2 +/- 1639 and 761.8 +/- 431 U/ml, respectively). After low-dose IL-2 given subcutaneously once daily at a dose of 1.8 x 10(6) U/patient for 3 weeks, additional significant increase in levels of IL-2R alpha was observed in sera and in bone marrow of patients with NHL (761.8 +/- 431 versus 2633 +/- 788 U/ml and 785 +/- 448 versus 2475 +/- 431 U/ml, respectively). The increase of sIL-2R alpha level after IL-2 therapy was also seen in sera and in bone marrow of HD and MM group; however, because of high standard deviation this increase was not statistically significant. We conclude that 1) in comparison to healthy subjects the levels of sIL-2R alpha remained elevated in HD and NHL patients, even at the stage of minimal residual disease (MRD) after intensive chemotherapy or radiotherapy, 2) the levels of sIL-2R alpha which appeared in sera and bone marrow of patients after IL-2 therapy seemed to be dependent on the type of hematological disorders.
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PMID:Detection of soluble IL-2 receptor in the serum and bone marrow of patients with minimal residual hematological malignancies: induction under therapy with IL-2. 943

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. Although IL-9 was initially described as a T cell growth factor, its role in T cell responses is still unclear. While freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro, and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9 mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Various observations indicate that IL-9 is actively involved in mast cells responses by inducing the proliferation and differentiation of these cells. Other potential biological targets for IL-9 include B lymphocytes, and hematopoietic progenitors, for which higher responses were observed with foetal or transformed cells as compared to normal adult progenitors. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signaling. Signal transduction studies have stressed the role of the Jak-STAT pathway in various IL-9 bioactivities, whereas the 4PS/IRS2 adaptor protein might also play a significant role in IL-9 signaling.
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PMID:Interleukin 9 and its receptor: an overview of structure and function. 950 95

The data of a closed phase I/II trial in patients with resistant Hodgkin's lymphoma indicate promising results using a chemically linked anti-CD25 ricin-A immunotoxin (IT) (RFT5-SMPT-dgA). This IT is based on the high-affinity moab RFT5. Since recombinant DNA technology permits the readier production of large amounts of ITs, we constructed a new RFT5-based fusion toxin [RFT5(scFv)-ETA']. We isolated mRNA from the hybridoma cell line RFT5, synthesized first strand cDNA and performed RT-PCR. Amplified coding regions of the light and heavy chain variable domains were joined together with a synthetic (Gly4-Ser)3 linker. The resulting single chain variable fragment (scFv) was fused to a modified Pseudomonas aeruginosa exotoxin A (ETA') lacking its cell-binding domain I. After IPTG-induced expression in Escherichia coli, the 70 kDa His-tagged fusion protein [RFT5(scFv)-ETA'] was isolated by osmotic shock and sonication under denaturing conditions. The recombinant toxin was purified on a Ni2+-NTA chelating sepharose and eluted with 250 mM imidazole. Pooled protein was renatured, dialyzed and concentrated by precipitation. Binding properties of RFT5(scFv)-ETA' were assessed on the CD25-expressing cell line L540cy by ELISA, immunohistochemistry and FACS analysis. CD25-specific binding was confirmed by immunoprecipitation experiments with recombinant human IL-2 receptor alpha. The in vitro toxicity of the chimeric protein was tested on the Hodgkin-derived cell lines L540cy, L428, L1236, a monocyte cell line U937 and a Burkitt lymphoma cell line BL38. RFT5(scFv)-ETA' inhibited protein biosynthesis of L540cy and L428 cells by 50% at concentrations (IC50) of 18 and 12 ng/ml, respectively. CD25-specific toxicity was confirmed by competitive toxicity assays. These data confirm for the first time binding specificity and toxicity of a recombinant anti-CD25 immunotoxin, against Hodgkin-derived cell lines; its applicability on Hodgkin's lymphoma needs yet to be evaluated in vivo.
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PMID:Construction and in vitro evaluation of RFT5(scFv)-ETA', a new recombinant single-chain immunotoxin with specific cytotoxicity toward CD25+ Hodgkin-derived cell lines. 985 27

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.
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PMID:Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428. 988 70

Clinical impact of s.c. administration of IL-2 and/or IFN alpha was studied in 23 pediatric patients with Hodgkin lymphoma (IFN alpha group) and sarcoma, non-Hodgkin lymphoma, peripheral neuroepitelioma, neuroblastoma, and embryonic carcinoma (IL-2 + IFN alpha group) after autologous PBSC transplantation. Expression of CD3, CD4, CD8, CD25, CD38, CD56, CD71, CD122, and HLA-DR antigens, serum level of the soluble IL-2R alpha, and NK activity against K562 cell line were evaluated in 11 patients representative for both types of immunotherapy. T and, more markedly, NK cell proliferation, induction of activation markers on the surface of T and NK subsets, and elevation of sIL-2R alpha concentrations were seen in the IL-2 + IFN alpha subgroup. In the IFN alpha subgroup, the total number of lymphocytes and expression of activation markers remained unchanged, but the number of CD8+ T cells increased at the expense of CD4+ T and NK cells during the therapy. Cytotoxic activity against K562 cells was not influenced by the immunotherapy in either subgroup. No significant clinical benefit of the immunotherapy was seen in these patients compared to 27 control patients with relevant diagnoses who did not receive immunotherapy.
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PMID:Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients. 1068 13


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