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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine BCL-1 B-cell leukemia provides a model of disseminated human B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkins lymphoma (NHL). This model was used to evaluate and compare the anti-leukemic efficacy of recombinant cytokines rIL-1 beta, rIL-2, rIL-6, rTNF alpha, rG-CSF, rGM-CSF and their combinations. Of these 6 cytokines tested, rG-CSF, rIL-1 beta, rIL-2, and rTNF alpha exerted a marked anti-leukemia/lymphoma activity, as reflected by significantly improved survival of treated mice after inoculation of BCL-1 cells. Notably, no additive or synergistic effects were observed when 2-4 cytokines were used in combination. To our knowledge, this report represents the first comparative analysis of recombinant cytokine treatment regimens in an animal model of disseminated B-lineage ALL/NHL.
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PMID:Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination. 128 65

Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.
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PMID:[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma]. 128 51

Cytokines are potent modulators of the physiological immune response. A number of reactive processes are associated with a deregulation of this cytokine expression. Animal models with transgenic mice or transfection experiments have shown that an autocrine or paracrine pathway might be involved in tumor progression and/or tumorigenesis. The study of cytokine expression in malignant lymphomas showed a heterogeneous expression pattern with a number of cases which quantitatively show indications for a marked deregulation of the cytokine expression. The expression od IL-7 and IL-9 seem to be special features of Hodgkin's disease and large cell anaplastic lymphomas. Transfection experiment with IL-9 into mouse T cells results in an autocrine loop and tumorigenesis of the transfected cells. These tumors share a number of similarities to Hodgkin's disease and large cell anaplastic lymphomas in human.
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PMID:[Cytokines and malignant lymphomas]. 128 79

In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane-derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL-1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD.
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PMID:The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease. 128 46

The histopathologic pattern of tissues involved by Hodgkin's disease (HD) suggests excessive activation of environmental cells by cytokines released by Hodgkin-Reed-Sternberg (HRS) cells, which are considered as the neoplastic component of HD lesions. This hypothesis has been supported by many studies performed in vitro using HD cell lines. In this study, we have tried to demonstrate the cytokine-producing cells in an environment as close as possible to the in vivo conditions, using in situ hybridization onto frozen sections of HD samples. [35S]-labelled single-stranded RNA probes were prepared by transcribing human cDNA fragments of the TNF-alpha and IL-1 alpha genes subcloned into appropriate vectors. A total of 19 specimens of HD lesions, including 7 cases of nodular sclerosing (NS) type and 12 cases of mixed cellularity (MC), were tested with both types of probes. Clinical stages included stage I (6 cases), stage II (4 cases), stage III (6 cases) and stage IV (3 cases). TNF-alpha and/or IL-1 alpha expression was observed in 12 among 19 HD cases. However, neither the histological type nor the clinical status of the patients was correlated with the profile of cytokine secretion. Most of the cytokine-producing cells could be identified as HRS cells due to their morphological appearance. In 3 cases, simultaneous analysis by immunohistochemistry and in situ hybridization showed that IL-1 alpha/TNF-alpha mRNA-producing cells simultaneously expressed the CD30 antigen, thereby confirming the HRS nature of these cells.
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PMID:In situ expression of the IL-1-alpha and TNF-alpha genes by Reed-Sternberg cells in Hodgkin's disease. 131 61

The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large-cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.
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PMID:Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients. 132 Sep 56

The most recent sophisticated investigations have provided new and revealing, but also contradictory and controversial information on the biological nature and the cellular origin of Hodgkin and Reed-Sternberg cells (H-RS). Immunophenotypic analyses have shown variable phenotypic antigen expression; but, on balance the data suggest a lymphoid cell expressing T- and/or B-cell-associated markers and certain activation antigens while lacking immunological features of monocytes-macrophages or other lineages. Molecular genetic studies have demonstrated heterogenous findings with respect to rearrangements of T-cell receptor and immunoglobulin genes. Only a small percentage of the cases has rearrangements; this might be due to the threshold of sensitivity of the method combined with the scarcity of the malignant cells. Epstein-Barr virus (EBV) genomes are clonally integrated in the H-RS cells of about half the cases. The significance of these findings--whether EBV is a causative agent or an epiphenomenon--remains to be elucidated. H-RS cells express mRNA and proteins of various cytokines and cytokine receptors implying a predominant role for cytokines in the pathophysiology of HD. The mononuclear and polynuclear H-RS cells are capable of DNA synthesis and nuclear division; the lack of cellular division leads to multinuclearity through the process of endomitosis. Mutations and expression of only a limited number of oncogenes have been tested thus far. Whether the bcl-2 oncogene is involved in HD remains a matter of debate. Aneuploidy and non-random chromosomal abnormalities are the results of cytogenetic analyses of H-RS cells. However, no chromosomal marker specific for HD has yet been found. Thus, while studies of EBV involvement, growth factor production, oncogene expression and chromosomal abnormalities contributed a fair amount of new data on the nature of H-RS cells, only immunophenotyping and genotyping provided some indication of the cellular derivation: an activated lymphoid cell that possibly expresses oncogenes, that probably is infected with EBV, that most likely produces cytokines, that certainly has multiple karyotypic abnormalities.
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PMID:Recent results on the biology of Hodgkin and Reed-Sternberg cells. I. Biopsy material. 133 48

A patient is presented who was treated with ablative therapy for Hodgkin's disease and rescued by reinfusion of peripheral blood stem cells (PBSC). The PBSC were used because previous therapy (chemotherapy and radiation to the pelvis) had resulted in fatty hypocellular marrow which was inadequate for marrow transplantation. The PBSC were collected by leukapheresis before and after recovery of the marrow from suppression with cyclophosphamide to bring the stem cells into cohort cycle and to increase the proportion of stem cells in the peripheral blood for collection. The patient showed a successful recovery on a time scale somewhat longer cells administered, the absence of stimulation by granulocyte macrophage-colony stimulating factor or other cytokine, or potential damage done to stromal elements during previous radiation and chemotherapy. The patient remains in clinical complete remission, fully engrafted, more than one year since his autologous transplant.
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PMID:Peripheral blood stem cell transfusion for marrow replacement. 138 Feb 24

Cerebrospinal fluid (CSF) and serum samples of 20 patients with central nervous system manifestations of hematological malignancies including primary cerebral lymphoma (n = 5) and disseminated non-Hodgkin lymphoma (n = 7) were examined for albumin, IgG, IgM, fibronectin, beta 2-microglobulin, interleukin-6, soluble interleukin-2 receptor, tumor necrosis factor alpha, and oligoclonal immunoglobulin bands. Although a broad range of abnormalities were detected, no reliable CSF parameter for the diagnosis of leptomeningeal spread from hematological neoplasias could be identified. An analysis of 61 repeat lumbar punctures added little to the findings of the first CSF examinations. Currently, immunochemical studies of CSF cell surface markers and early biopsy have probably more clinical value than the determination of the humoral CSF parameters included in this study. However, analysis of cytokine synthesis by single CSF cells using molecular biology techniques may improve the differential diagnosis of hematological neoplasia of the brain and spinal cord in the future.
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PMID:Humoral CSF parameters in the differential diagnosis of hematologic CNS neoplasia. 141 21

Colony-stimulating factor 1 (CSF-1) is a cytokine involved in hematopoiesis and perhaps more importantly in the early stages of immunological defense mechanisms. Although numerous studies of in vitro CSF-1-producing cells have been published, in vivo data is totally lacking. According, we performed immunohistochemical detection of CSF-1-positive cells on frozen sections of reactive lymphadenitis (three cases) and Hodgkin's disease (13 cases) lymph node biopsies, using as antibody a highly specific polyclonal rabbit antiserum prepared in our laboratory. Endothelial cells from high endothelial venules and most fibroblasts were positive in all cases (reactive lymphadenitis and Hodgkin's samples), and most lymphocytes in interfollicular T cell areas showed faint granular positivity in reactive lymphadenitis lymph nodes. Hodgkin and Reed-Sternberg cells were positive in all cases tested, although staining intensity was highly variable and the percentage of positive cells differed from case to case. These data from in vivo biopsies confirm previous results for in vitro CSF-1 production by endothelial cells, fibroblasts, T lymphocytes, and Hodgkin cell lines. They are consistent with the role of this cytokine in immune response and raise the question of its significance in Hodgkin's disease.
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PMID:Immunohistochemical detection of cells positive for colony-stimulating factor 1 in lymph nodes from reactive lymphadenitis, and Hodgkin's disease. 155 43


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