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)

Hodgkin's disease (HD) is considered as a tumor of the lymph nodes histologically characterized by a variety of cell types, resembling a nonspecific inflammatory reaction. The Reed-Sternberg cells present in the granuloma are considered neoplastic due to cytogenetic alterations, tissue culture properties and heterotransplantability. They originate from a macrophage-derived interdigitating reticulum cell. The lymph node is an immunologic organ and its alterations reveal qualitative and/or quantitative defects of the immune system. These are observed in HD at very early stages even with a minimum of lymph node involvement. Considering HD as a neoplasm of the monocyte-macrophage system, our objective was to investigate the functional capability of peripheral blood monocytes transformed into macrophages in vitro. The phagocytic and lytic activities were evaluated by the generation of toxic oxygen metabolites as due to an excessive production of PGE-2. This defect could be corrected by cyclo-oxygenase inhibitors. The defect was present at very early stages of HD and persisted even during prolonged continuous complete remissions. We also found a defect in the ingestion of candida which could not be modified by drug treatment, indicating the existence of a global dysfunction of the phagocyte. Presently, more than 90% of HD patients respond to specific therapy and remain in prolonged remission, being considered "cured". This fact may contribute to the diminished number of reports in relation to the biology of the monocyte-macrophage system in this disease.
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PMID:[The monocyte-macrophage system in Hodgkin's disease]. 264 Apr 76

Expression of class II major histocompatibility (MHC) antigens by peripheral blood monocytes from 12 patients with Hodgkin's disease (HD) were studied employing antiserum and complement-mediated cytotoxicity. Overall, the expression of class II MHC antigens was significantly decreased on HD monocytes (cytotoxicity index [C.I.] = 60.2 +/- 5.8% vs 77.6 +/- 2.8%, P less than .02). This decrease was most marked in patients with more severe disease. In fact, mean alloantigen expression for patients with advanced stages of disease was 58% of that observed in controls. The number of human lymphocyte antigen (HLA)-DR antigenic sites per cell was also reduced as determined by monoclonal anti-DR antibody and FACS analysis. There was 38% more HLA-DR per cell in normal controls than in moderately advanced Hodgkin's patients. Class II MHC antigen expression on HD monocytes were increased partially by an IFN-gamma containing concanavalin A-stimulated human mononuclear cell culture supernatants (Con A sup), although remaining subnormal. When monocytes were cultured with Con A sup and indomethacin, alloantigen expression was increased in HD and control monocytes, but indomethacin failed to normalize class II MHC antigen expression on HD monocytes (C.I. = 72.3 +/- 4.7% vs 90.2 +/- 1.8%, P less than .01). We conclude that PGE accounts only inpart for the decreased alloantigen expression by HD monocytes. Interleukin (IL) 1 production by patients' monocytes was not reduced as compared to normals and therefore does not contribute to the decreased MHC II antigen expression. Decreases in alloantigen expression may be an important determinant of the T cell-mediated immune abnormalities in Hodgkin's disease.
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PMID:Decreased expression of class II major histocompatibility antigens on monocytes from patients with Hodgkin's disease. 348 76

Patients with active Hodgkin's disease demonstrate a significant depression of cellular immunity. The present study, performed with lymphocytes from 16 untreated patients with active Hodgkin's disease and 13 healthy control volunteers, demonstrate an equivalent IL 2 production in vitro in both groups. Our results, however, demonstrate an abnormal regulation of IL 2 production in patients. A negative control of IL 2 production involving monocytes producing PGE 2 able to induce radiosensitive suppressor T lymphocytes, has been identified previously with cells from healthy donors. In the present study we demonstrate that this negative control is hyper functioning with cells from Hodgkin's disease patients.
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PMID:[Abnormal regulation in the production of IL2 in Hodgkin's disease]. 392 5

Many tumors, including Hodgkin's lymphoma, are associated with decreased cellular immunity and elevated levels of prostaglandin E(2) (PGE(2)), a known inhibitor of CD4+ T cell activation, suggested to be involved in immune deviation in cancer. To address the molecular mechanisms tumor-derived PGE(2) might have on primary human CD4+ T cells, we used a whole genome-based transcriptional approach and show that PGE(2) severely limited changes of gene expression induced by signaling through the T cell receptor and CD28. This data suggests an interference of PGE(2) at an early step of T cell receptor signaling: indeed, PGE(2) stimulation of T cells leads to inactivation of lck and reduced phosphorylation of ZAP70. Antiapoptotic genes escaped PGE(2)-induced inhibition resulting in partial protection from apoptosis in response to irradiation or Fas-mediated signaling. As a functional consequence, PGE(2)-treated CD4+ T cells are arrested in the cell cycle associated with up-regulation of the cyclin/cyclin-dependent kinase inhibitor p27(kip1). Most importantly, CD4+ T cells in Hodgkin's lymphoma show similar regulation of genes that were altered in vitro by PGE(2) in T cells from healthy individuals. These data strongly suggest that PGE(2) is an important factor leading to CD4+ T cell impairment observed in Hodgkin's lymphoma.
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PMID:Prostaglandin E2 impairs CD4+ T cell activation by inhibition of lck: implications in Hodgkin's lymphoma. 1642 48

Hodgkin's lymphoma is frequently associated with mast cell infiltration that correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that mast cells promote the growth of Hodgkin's tumor by modifying the tumor microenvironment. A transplantation assay shows that primary murine mast cells accelerate tumor growth by established Hodgkin's cell lines, and promote marked neovascularization and fibrosis. Both mast cells and Hodgkin's cells were sensitive to bortezomib, but mast cells were more resistant to bortezomib. However, bortezomib inhibited degranulation, PGE(2)-induced rapid release of CCL2, and continuous release of vascular endothelial growth factor-A from mast cells even at the concentration that did not induce cell death. Bortezomib-treated mast cells lost the ability to induce neovasculization and fibrosis, and did not promote the growth of Hodgkin tumor in vivo. These results provide further evidence supporting causal relationships between inflammation and tumor growth, and demonstrate that bortezomib can target the tumor microenvironment.
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PMID:Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib. 2243 Jun 34

The overexpression of cyclooxygenase-2 (COX-2) has been documented in many types of cancer occurring in humans and animals. Increasing evidences have shown that the overexpression of COX-2 and increased production of prostaglandin E2 (PGE2) correlate with poor prognosis in human solid tumours and hematological malignancies. Both, in vitro and in vivo studies have demonstrated that increased proliferation of cancer cells as well as an impairment of anti-tumour immunity are influenced by the overexpression of this enzyme. In leukemia and lymphoma, an increased activity of COX-2 and subsequent increase in prostaglandins (PGs) concentration allow cancer cells to evade immune response and contribute to metastases. Cancer stem cells (CSCs) in tumour microenvironment, suppression of innate and adaptive immunity depends on COX-2/PGE22 axis activity which increases in hematological malignancies. Cyclooxygenases inhibitors block the formation of PGs, consequently inhibiting angiogenesis, and in some malignancies they decrease cancer cells proliferation and tumour invasiveness. They also increase apoptosis of CSCs and cancer cells, decrease their drug resistance as well as enhance the host immune response. Therefore COX-2/PGE2 axis suppressors: selective COX-2 inhibitors or PG receptors antagonists have been considered as promising anticancer drugs. In comparative oncology dogs are increasingly used as a large animal model because they share the same environmental conditions with people and are exposed to the same environmental factors and also due to their relatively short life span. In dogs, spontaneously occurring non-Hodgkin lymphomas and leukemias have a large number of genetic and morphological features that are similar to those of humans' corresponding cancers. This, additionally makes the species a useful model for the study of new therapeutic strategies in human oncology. While the influence of COX-2 activity and PGE2 receptors have been evaluated extensively in human cancer, their role in veterinary oncology still needs to be elucidated.
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PMID:The cyclooxygenase-2/prostaglandin E2 pathway and its role in the pathogenesis of human and dog hematological malignancies. 3068 18