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)

We assessed the humoral effect of resting and phorbol esters preincubated monocytes from Hodgkin's disease patients (HDMo) and healthy subjects (nMo), on granulocyte progenitors (CFU-dG) growth using a double diffusion chamber technique. The release of colony stimulating activity and indomethacin-dependent inhibitors by resting HDMo and nMo was found to be cell-concentration dependent. However, phorbol myristate acetate preincubated HDMo (PMA-HDMo) in contrast to nMo at low concentrations (2.5 x 10(4] were unable to increase the CFU-dG growth stimulation. On the other hand, at a higher cell number (5 x 10(4], phorbol treated HDMo stimulated the myeloid colony formation, whereas nMo suppressed the CFU-dG proliferation. Further enhancement of HDMo and nMo concentrations induced a pronounced inhibition of CFU-dG-derived colony formation, caused by an increased PGE2 production. After incubation with the cyclooxygenase inhibitor-indomethacin, PMA-HDMo showed considerably more granulocyte colony formation than nMo. Our results suggest that the observed abnormalities in the function of HDMo could be associated with an excessive production of PGE2 and a general dysfunction of these cells in Hodgkin's disease.
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PMID:Impaired release of colony stimulating activity by monocytes from Hodgkin's disease in response to phorbol myristate acetate activation. 196 22

In a previous work, the authors found that the peripheral blood monocytes from patients with Hodgkin's disease (HD) had depressed lytic capability to kill Candida pseudotropicalis and depressed phagocytic function. The aim of this study was to evaluate if cyclooxygenase inhibitors could correct the defective macrophage functions. Fifteen untreated patients with HD and 10 normal subjects were studied. The incubation of the cells from the patients with HD with indomethacin (IM) at 1, 3, and 10 micrograms/ml and with acetylsalicylic acid (ASA) at 20 micrograms/ml increased their previously deficient ability to kill C. pseudotropicalis, reaching values close to those of normal subjects. The oral administration of ASA during 1 week also corrected the monocyte lytic deficiency in the patients' group. Neither the in vitro nor the in vivo treatment with these cyclooxygenase inhibitors had any significant effect on normal subjects' monocytes' lytic function. The drugs did not improve the impaired phagocytic function in patients with HD. These results indicate that the failure of the lytic activity of the monocytes in HD could be associated to an excessive production of PGE2, and the oral administration of inhibitors of the cyclooxygenase activity can correct such abnormality whereas the phagocytic dysfunction is not reverted by them.
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PMID:Normalization of monocyte candidacidal deficiency by cyclooxygenase inhibitors in Hodgkin's disease. 392 13

Patients with active Hodgkin's disease (HD) often demonstrate an impaired T-cell proliferative response to phytohemagglutinin (PHA). The present study examined if interleukin regulation of the PHA response was defective in HD. The Hodgkin's PHA response was impaired at all concentrations of PHA utilized. Indomethacin increased the proliferative response but did not bring it to control levels. Stimulation of the cells with both PHA and irradiated Ia+ B cells normalized proliferation despite identical PGE2 concentrations as in the PHA alone cultures. Hodgkin's monocytes produced normal amounts of interleukin 1 (IL-1). Interleukin 2 (IL-2) production by Hodgkin's T cells was decreased in the PHA stimulated cultures, but was normal in the PHA and Ia+ cell stimulated cultures. In response to PHA stimulation alone, Hodgkin's T cells expressed less IL-2 receptor than control cells. The data suggest the diminished PHA response in HD is due to impaired IL-2 production resulting in diminished IL-2 receptor expression. However, when an Ia+ cell source is added to PHA as an additional stimulator, both TCGF production and proliferation are normalized. Monocytes serve to modulate the magnitude of the PHA response through production of both interleukin 1 and PGE2. However, in the presence of sufficient IL-2 production the influence of monocytes is minimized.
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PMID:Impaired interleukin regulation of the phytohemagglutinin response in Hodgkin's disease. 392 53

Prostaglandin E (PGE) production was evaluated in 18 normal subjects and 29 patients with Hodgkin's and non-Hodgkin's lymphomas. Plasma PGE levels of patients were found to be highly increased. Increased PGE synthesis was demonstrated in conditioned media from peripheral blood and bone marrow mononuclear cells, arising from the adherent cell fraction enriched in monocytes. No relationship with clinical or pathological findings was observed.
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PMID:Increased prostaglandin E production in malignant lymphomas. 393 56

The secretion of PGE2 from monocytes of newly diagnosed patients with Hodgkin's disease (HD) was compared to that of patients in remission, who were not receiving either chemotherapy or radiotherapy, and normal controls. We found that monocyte monolayers of some patients, both newly diagnosed and those in remission, secreted markedly elevated levels of PGE2. The lymphocyte proliferative response to PHA was increased to a similar extent in both newly diagnosed patients and those in remission when cultured in the presence of indomethacin. PGE2 concentrations in the medium of mononuclear cultures correlated with the lymphocyte proliferative response to PHA (P less than 0.05). However, no correlation of monocyte PGE2 production with decreased E rosette forming lymphocytes, anergy or clinical stage could be demonstrated. We suggest that PGE2 secretion by monocytes is indicative of an 'activated' state of these cells. It is, however, unlikely that PGE2 is the only molecular species responsible for the decreased cellular immune function in HD. 'Activated' monocytes may be part of the immune response in this disease and may be responsible for the decreased cellular immunity.
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PMID:Monocyte PGE2 secretion in Hodgkin's disease and its relation to decreased cellular immunity. 657 80

Plasma levels of the circulating metabolite of prostaglandin (PG) E2, 15-keto-13,14-dihydro-PGE2 (KH2PGE2), were determined radioimmunologically after conversion to the stable degradation product 11-deoxy-15-keto-13,14-dihydro-11,16-cyclo-PGE2 (DKH2-cyclo-PGE2). In healthy volunteers a plasma level of 25 +/- 2 pg/ml (mean +/- S.E.M., n = 24) was found. The plasma level of KH2PGE2 was significantly decreased after administration of acetylsalicylic acid (4 x 1 g/24 hours). A significant elevation of the plasma levels of the circulating metabolite of PGE2 was observed in patients with bronchogenic carcinoma as compared to healthy controls, while no elevation was found in patients with chronic myeloid leukemia, lymphatic leukemia and non-Hodgkin lymphoma. The increased plasma levels of KH2PGE2 in the patients with bronchogenic carcinoma were independent of the clinical condition, histological type of tumor, tumor spread and therapeutic regimen. The results indicate that the elevated plasma level of the circulating PGE2 metabolite in patients with bronchogenic carcinoma is not an expression of malignant disease in general. On the other hand, the results do not suggest that the increase in the plasma level of KH2 PGE2 is a biochemical tumor marker closely related to a particular clinical feature of patients with bronchogenic carcinoma.
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PMID:Plasma levels of 15-keto-13,14-dihydro-prostaglandin E2 in patients with bronchogenic carcinoma. 658 45

Prostaglandin synthesis and T lymphocyte colony formation have been examined in previously untreated patients with Hodgkin's disease. Mononuclear cells have been isolated from peripheral blood and spleens of these patients. Significant augmentation in prostaglandin E levels were noted in the mononuclear cell cutures from Hodgkin's disease patients compared with controls (1.64 +/- 0.29 vs. 0.39 +/- 0.09 ng/10(6) cells, P < 0.005). Measured prostaglandin E levels increased with advancing stage of disease. Virtually all of the prostaglandins were synthesized by the adherent monocyte cell population. Prostaglandin E was the major product. Clonal expansion of a T lymphocyte precursor cell, which gives rise to colonies > 50 cells, was determined by a layered soft agar method. T colony formation was significantly reduced in patients with stage II, III, and IV disease. There were progressively reduced colony numbers seen with advancing stage of disease (609 +/- 209, 416 +/- 158, 207 +/- 58 compared with normals 2,274 +/- 360 colonies/10(6) cells plated; P < 0.005). The addition of inhibitors of endogenous prostaglandin synthesis resulted in significant augmentation of T colony number. However, a consistent relative decrease in T colony number was seen even when endogenous prostaglandin E synthesis was blocked. It would appear that both the prostaglandin-dependent and independent T colony precursor cells are lost with progressive stage of disease. A causative role of augmented prostaglandin synthesis in this stage-dependent reduction of T colony formation could not be established.
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PMID:Stage-dependent reduction in T colony formation in Hodgkin's disease. Coincidence with monocyte synthesis of prostaglandins. 696 91

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