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

Hodgkin/Reed-Sternberg (H-RS) cells express lymphoid activation markers like CD25 and CD30 which are present only on a small minority of normal cells. Currently, most experimental approaches in Hodgkin's lymphoma are aimed at targeting H-RS cells via monoclonal antibodies against CD25 and CD30: immunotoxins constructed by linking the antibody moiety chemically to deglycosylated ricin A-chain destroy up to 60% of small H-RS tumors in mice. The most potent immunotoxin is currently being scaled up for clinical trials. Other experimental strategies use bispecific constructs that, after binding to the cell surface of H-RS cells, convert prodrugs into their toxic counterparts, or employ monoclonal antibodies for active immunotherapy.
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PMID:Experimental therapy in Hodgkin's disease. 133 74

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

In the present paper, the authors describe the production and testing of immunotoxins for clinical application in Hodgkin's disease. The immunotoxins were constructed by chemical coupling of deglycolysated ricin-A to monoclonal antibodies against antigens on Hodgkin's and Reed-Sternberg cells (CD25, CD30, IRac). The cytotoxic effect of the immunotoxins was investigated in vitro against Hodgkin's and Reed-Sternberg cells (H-RS) and in vivo against solid Hodgkin's tumors in nude mice and disseminated Hodgkin's tumors in SCID mice. Cross-reactivity with normal tissue and the staining behaviour observed in sections of Hodgkin's tissue of various subtypes proved important parameters for the assessment of clinical applicability. Of more than 30 evaluated MoAb's, eight immunotoxins were produced, of which six showed both, cytotoxic effects of considerable potency against Hodgkin's tumor cells and low cross-reactivity with vital human organs. The most effective immunotoxin, RFT5 gamma 1.dgA, (CD25) inhibits the growth of H-RS cells at concentrations of 7 pMol and destroys about 60% of solid Hodgkin's tumors of 0.5 cm in diameter in nude mice. This immunotoxin binds to virtually all tumor cells in more than 90% of patients with Hodgkin's disease. Sufficient quantities of RFT5 gamma 1.dgA were produced for the treatment of patients with refractory Hodgkin's disease. These patients are currently being treated in a phase I clinical trial.
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PMID:[New perspectives in oncology: is selective destruction of tumor cells with immunotoxins in Hodgkin's disease an additional therapeutic alternative?]. 146 Dec 15

Non-Hodgkin's lymphomas (NHL) are part of the spectrum of disease associated with HIV infection. However, there are only occasional reports of NHL of T-cell origin in HIV-infected patients. A previously asymptomatic HIV-infected man, who was seronegative for human T-lymphotropic virus type I antibodies, developed a high-grade peripheral T-cell lymphoma of anaplastic large-cell type which was Ki-1 + (CD30 +), HLA-DR+, epithelial membrane antigen +, CD25 +, CD71 +, CD2 + and CD5 +. Pan-B markers CD19 and CD22 and histiocytic marker CD68 were negative. At diagnosis the patient had 0.3 x 10(9)/l T-helper lymphocytes. The response to chemotherapy was dramatic and the patient is alive and disease-free 18 months after treatment. A review of previously described peripheral T-cell lymphomas in HIV-positive individuals is performed, and we conclude that the spectrum of neoplasms in such cases is probably broader than originally thought.
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PMID:Ki-1+ anaplastic large-cell lymphoma of T-cell origin in an HIV-infected patient. 165 81

Lymph node cells from a patient with Hodgkin's disease (HD) were cultured without Epstein-Barr virus (EBV) or leukine adjuvant. A cell line (719-AB) emerged from the culture after four weeks. The cell line express CD20 (79%), CD 21 (30%), CD30 (63%), CD 35 (61%) antigens and weakly CD25 (19%). using Southern Blot technique, the existence of specific EBV DNA and polyclonal immunoglobulin genes rearrangement were observed in the cell line. In order to obtain a monoclonal antibodies (MoAb), mice Balb/C were immunized with this cell line. The splenic cells suspension of immunized animals were fused with the mouse myeloma NS1. Antibody IgM kappa from secreting clones 2B44 was studied using both indirect immunofluorescence with labeled anti-mouse immunoglobulin and immunohistochemistry based on alkaline phosphatase/antiphosphatase complex (APAAP) and ModAMeX technique on a panel of normal or pathological cells. Normal peripheral lymphocytes, monocytes, polymorphonuclear cells, and erythrocytes, did not react. The MoAb 2B44 recognized the dendritic reticulum cells and the smooth muscle cells of vessels on frozen section and paraffin section from HD or reactive lymph nodes. On specially processed paraffin sections (ModAMeX) Reed-Sternberg cells (RSC) were reactive with 2B44 MoAb (in 2 cases out of 5 tested). The molecular weight of the antigen recognized by 2B44 MoAb is of 37 kd. The description of a new epitope shared by different histological components might be of interest for defining a new cluster and better understanding the nature of RSC.
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PMID:Production of a monoclonal antibody (2B44) reactive on a shared epitope on dendritic reticulum cells, smooth muscle cells of vessels and Reed-Sternberg cells. 172 34

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.
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PMID:Increased levels of circulating interleukin-6 in patients with Hodgkin's disease. 174 97

Activated tumor-infiltrating T lymphocytes (TIL-T) were quantitated prospectively in excisional biopsy specimens of 49 B-cell non-Hodgkin's lymphomas (NHL) of various grades and compared with eight benign lymphoid hyperplasias (BLH) to identify any potential difference in host T-cell response. Immunotyping of tissue-cell suspensions was done by three-color flow cytometry, which was complemented by immunocytology by using cytocentrifuged preparations. Two activated T-cell subsets were studied: acutely activated TIL-T (CD3+ CD25+ HLADr-) and chronically activated TIL-T (CD3+ CD25- HLADr+). Results showed an association of the more aggressive intermediate/high-grade B-cell NHL with a higher percentage of late-phase activated TIL-T and a progressive increase with the grade of malignancy: 10.29%, 23.25%, 33.87%, and 47.78% (means) for BLH and for low-, intermediate- and high-grade B-cell NHL, respectively. Differences for this subset were significant (P less than 0.050) for the following comparisons: hyperplasia versus intermediate-grade NHL (P less than 0.0012), hyperplasia versus high-grade NHL (P less than 0.0002), and low versus high-grade NHL (P less than 0.0080). The percentage of acutely activated TIL-T cells did not show a statistically significant difference between the groups. The results suggest a host T-cell response to proliferating neoplastic cells in B-cell NHL. Paradoxically, the response does not appear to be protective for the host since the intensity is directly proportional to the grade of malignancy. However, the recognition of this response may have clinical applications since its amplification with biological response modifiers may result in effective adoptive immunotherapy of B-cell NHL. Further clarification of the specificity and biologic significance of host T-cell activation in B-cell NHL will require functional studies of isolated lymphocytic subpopulations from neoplastic tissue.
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PMID:Activated T-cell subsets in benign lymphoid hyperplasias and B-cell non-Hodgkin's lymphomas. 188 60

Twenty-three monoclonal antibodies (MAbs) against the IL-2 receptor alpha-chain (CD25) were evaluated as ricin A-chain immunotoxins for the treatment of Hodgkin's disease. Primary screening used an indirect assay in which the cells were treated with the test antibody followed by a Fab' immunotoxin against mouse immunoglobulin. This screening identified 5 MAbs which inhibited protein synthesis in L540 Hodgkin cells by 50% at a concentration (IC50) of 6 x 10(-11) M or less: RFT5 gamma 1, RFT5 gamma 2a, B-B10, B-F2 and B-G3. These MAbs were then linked directly to deglycosylated ricin A-chain (dgA) and were confirmed to have potent and specific toxicity for L540 cells. The immunotoxins had the following potency order: RFT5 gamma 1 greater than RFT5 gamma 2a greater than B-B10 greater than B-F2 greater than B-G3. The most effective immunotoxin, RFT5 gamma 1.dgA, had an IC50 value of 7 x 10(-12) M, which is the same as that of whole ricin. In vivo, a single intravenous injection of 48 micrograms of RFT5 gamma 1.dgA, RFT5 gamma 2a.dgA, B-B10.dgA or B-F2 induced lasting complete remissions in 78, 66, 50 and 44%, respectively, of nude mice bearing subcutaneous solid L540 tumours of 0.7 cm diameter. Two tumours which regrew after B-B10.dgA treatment were re-established in tissue culture. Both had reduced sensitivity to B-B10.dgA in vitro but not to immunotoxins recognizing different antigens on Hodgkin cells. The MAbs that produced the most potent immunotoxins, RFT5 gamma 1, RFT5 gamma 2a and B-B10, had no significant cross-reactivity with normal human tissues outside the lymphoid system as judged from indirect immunoperoxidase staining of frozen sections. By contrast, B-F2 strongly stained normal human renal tubules.
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PMID:Immunotoxins constructed with anti-CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent anti-tumour effects against human Hodgkin cells in vitro and solid Hodgkin tumours in mice. 191 43

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.
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PMID:Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes. 193 92


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