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)

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

Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD.
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PMID:Increased levels of circulating cytokines in patients with untreated Hodgkin's disease. 158 17

Hodgkin's disease (HD) is a neoplastic disease that is characterized by unbalanced and/or unregulated cytokine production. Information accumulated in our own and other laboratories indicates that the cytokines interleukin-1 (IL-1), IL-5, IL-9, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and transforming growth factor-beta (TGF-beta) are secreted by Hodgkin's and Reed-Sternberg (H-RS) cells. These and perhaps additional cytokines are likely to be responsible for the unique histopathologic and clinical alterations seen in patients with HD. In this study, we confirmed that IL-6 is produced by cultured H-RS cells as well as by H-RS cells in tissues. By using an enzyme-linked immunosorbent assay, we found that approximately 2 to 10 ng/ml of IL-6 was secreted by cultured H-RS cells (10(6) cells/ml). In tissues, we were able to immunolocalize IL-6 in the cytoplasm in 10 to 30% of H-RS cells by using rabbit polyclonal and mouse monoclonal anti-IL-6 antibodies. There was no correlation among the IL-6 staining intensity, number of H-RS cells stained, and the degree of plasma cell infiltration. However, in 3 of 17 cases studied, a large number (60%) of H-RS cells were positive for IL-6, and in these patients, abundant plasma cells were present. In one patient, the involved lymph node also showed histologic features similar to those of Castleman's disease. In this patient, we noted abundant IL-6 expression not only in H-RS cells, but also in most reactive histiocytes. The cultured H-RS cells did not express functional receptors for IL-6, and exogenously added IL-6 did not induce proliferation of these cells. We also conducted studies with specific anti-IL-4 antibodies, which did not show IL-4 production by H-RS cells in both cultures and tissues. In tissues, only rare IL-4 positive lymphoid cells or dendritic cells were identified. Thus, the study demonstrated that adequate amounts of IL-6 are required for an abundant plasma cell reaction, and that an additional source of IL-6 from histiocytes is essential for the formation of Castleman's disease-like changes in lymph nodes involved by HD. Furthermore, IL-4 is not likely to be responsible for the T-lymphocyte reaction in tissues, by a mechanism distinct from that in T-cell-rich B-cell lymphomas.
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PMID:Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease. 163 58

Evidence has accumulated which indicates that efficacy of chemotherapy correlates with dose intensity and with total dose. For most cytotoxic agents, the major limiting factor for escalation of dose intensity is myelotoxicity. Attempts have been made to circumvent myelotoxicity by autologous bone marrow transplantation. Recently, it has been demonstrated that progenitors enriched from the peripheral blood can also be used successfully for autografting. The concentration of progenitor cells in peripheral blood is lower than that in bone marrow but myelosuppressive chemotherapy or hematopoietic growth factors, or a combination of both can be exploited to enhance the progenitor cell yield. The studies reported here are sequential. In the first study, eight patients with advanced Hodgkin's disease received myelosuppressive regimen consisting of cytarabine (100 mg/m2/12h SC days 1 to 5) and daunorubicin (45 mg/m2/d, days 3 and 4). Progenitor cell leukapheresis was performed during the rebound phase of hematopoiesis. All eight patients were treated with super-dose chemotherapy with progenitor cell transplantation. One patient died of CNS toxicity 48 days after transplantation but all other seven had sustained engraftment. In the second study, human recombinant GM-CSF (at 250 micrograms/m2/d as continuous infusion) was administered to twelve patients. Leukapheresis was started at a white blood count (WBC) of greater than 10 x 10(9)/L and the dosage of rhGM-CSF adjusted to keep the WBC between 10 x 10(9)/L and 20 x 10(9)/L. The median duration of rhGM-CSF application was 11.5 days and a median number of six leukaphereses performed. The median increase in the number of granulocyte-macrophage colony forming units (CFU-GM)/ml of peripheral blood was 8.5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Utilization of recombinant human GM-CSF to enhance peripheral progenitor cell yield for autologous transplantation. 167 38

Five patients with resistant non-Hodgkin lymphoma (NHL) were given granulocyte-macrophage colony-stimulating factor (GM-CSF, 250 micrograms/m2 daily) after the BEAM pretransplant chemotherapy regimen (carmustine 300 mg/m2, etoposide 1.2 g/m2, cytarabine 800 mg/m2, melphalan 140 mg/m2) because persistent lymphoma cell infiltration of the bone marrow precluded autologous bone-marrow transplantation (BMT). In three patients full haemopoietic reconstitution occurred, with similar kinetics to that seen after autologous BMT. The other two patients died without sustained haemopoietic recovery. GM-CSF may replace autologous BMT in highly selected cases of NHL with progressive disease and bone-marrow involvement.
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PMID:GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen. 167 55

The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days. Elevations of nadirs of absolute neutrophil counts (ANC) and significant shorting of neutropenic periods of ANC below 2,000/mm3 were observed with patients given KRN 8601. KRN 8601 is significantly superior over placebo (p less than 0.0001), while overall safety evaluation showed no significant difference between the two groups. All the above results indicate that KRN 8601 is extremely usefull for the neutropenia induced by chemotherapy.
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PMID:[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study]. 168 88

This manuscript summarizes our experience with recombinant human granulocyte colony-stimulating factor (rhG-CSF) with high-dose Cytoxan, carmustine and etoposide (CBV in Hodgkin's disease). rhG-CSF regularly shortened the neutropenic phase following autologous bone marrow transplantation. However, this effect was more marked on the latter part of neutrophil recovery than the early part of granulocyte recovery to 100 granulocytes/microliters. The frequency of afebrile episodes was not reduced by rhG-CSF administration, but there was a tendency for the duration of fever to be shortened. Increasing doses and continuous infusion did not hasten the early part of neutrophil recovery needed to prevent the onset of infection, but was more effective than bolus infusion in increasing the rate of late neutrophil recovery. If fevers are to be prevented in this patient population, the duration of an absolute granulocyte count of less than 100/microliters will have to last only a few days. Recombinant hematopoietic growth factors alone do not hasten recovery fast enough to prevent the onset of afebrile episodes. Studies are described using both recombinant growth factor and peripheral blood and bone marrow cells to see if the neutropenic trough can be further shortened over that achievable with growth factor and autologous transplant alone.
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PMID:Use of recombinant human hematopoietic growth factors and autologous bone marrow transplantation to attenuate the neutropenic trough of high-dose therapy. 169 Dec 46

We have studied the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF), hG macrophage-CSF (hGM-CSF), and gibbon interleukin-3 (gIL-3) on cell proliferation and differentiation in human long-term bone marrow culture (LTBMC). hG-CSF induced a maximal increase of 2.3-fold in both total nonadherent cells and GM cluster-forming cells, but only an increase of 1.7-fold in GM-colony-forming cell (GM-CFC) numbers, influencing mainly neutrophil differentiation. Cultures treated with hGM-CSF demonstrated a peak of 12.8-, 21- and 3.2-fold elevations in total nonadherent cells, cluster, and GM-CFC, respectively, and influenced differentiation of neutrophils, monocytes, eosinophils, and lymphocytes. Cultures treated with gIL-3 demonstrated the largest expansion in the GM-CFC population, reaching a maximum of 5.3-fold in relation to that of unstimulated controls. IL-3 treatment also increased the numbers of GM clusters and mature cells (including all myeloid cells and lymphocytes) 7.8- and 4.8-fold, respectively. Similar quantitative and qualitative changes were induced by G-CSF, GM-CSF, and IL-3 in LTBMCs of patients in remission after treatment for acute lymphoblastic leukemia or Hodgkin's lymphoma. Overall, the expansion of GM progenitor cells in cultures treated with growth factors was larger in the adherent cell layer than in the nonadherent cell fraction. In addition, hGM-CSF, gIL-3, and hG-CSF to a less extent, increased the cycling rates of GM-CFC progenitors located in the adherent layer. These results indicate that hG-CSF is a much less potent stimulus of hematopoiesis in LTBMC than the other CSFs assayed, and that the increases in cell production after treatment with G-CSF, GM-CSF, or IL-3 may be achieved by primary expansion of different cell populations within the hierarchy of the hematopoietic system. The effects of the growth factors were transient and the longevity of hematopoiesis in the cultures was not altered, suggesting that treatment with IL-3, GM-CSF, or G-CSF had not compromised the ability of primitive cells to give rise to mature cells. This indicates that the stromal microenvironment in LTBMC can override potential differentiation-inducing activities of the CSFs.
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PMID:Effects of recombinant human granulocyte colony-stimulating factor (CSF), human granulocyte macrophage-CSF, and gibbon interleukin-3 on hematopoiesis in human long-term bone marrow culture. 169 95

This paper describes the properties of a continuous cell line derived from the blast cells of a patient with acute myeloblastic leukemia (AML), secondary to the treatment of Hodgkin's disease. The line grows slowly without stimulation but responds to interleukin-3 (IL-3), GM-CSF and mast cell growth factor (MGF), a ligand for the receptor encoded by the c-kit oncogene. When OCI/AML-4 cells are exposed to MGF with IL-3 or GM-CSF, additive or synergistic effects are seen. Combinations of MGF and G-CSF, IL-6 or CSF-1 give less growth than MGF alone. OCI/AML-4 cells are sensitive to retinoic acid; a dose related decrease in clonogenic cells is observed when OCI/AML-4 cells are exposed to retinoic acid in suspension culture. OCI/AML-4 cells are sensitive to cytosine arabinoside (ara-C), but the ara-C dose-response curve can be changed by altering the regulatory milieu in suspension culture. The cells are more ara-C sensitive in MGF or G-CSF than in IL-3 or GM-CSF. Following a 24 h exposure to retinoic acid, the ara-C sensitivity increases; in contrast, after a similar exposure to hydrocortisone, the cells become less ara-C sensitive. These changes in ara-C sensitivity occur in cells that are actively making DNA, as indicated by the reduction in colony formation after exposure to tritiated thymidine. Since OCI/AML-4 cells respond to many of the regulators that affect the growth of freshly obtained AML blast cells, it is proposed that this cell line may be useful for the study of regulation on AML in general and the interaction between different regulators in particular.
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PMID:OCI/AML-4 an acute myeloblastic leukemia cell line: regulation and response to cytosine arabinoside. 171 61

It is widely believed that hemopoietic stem cells have to be mobilized from extravascular sites into the circulation to guarantee a sufficient and safe blood stem cell autograft. The question of using mobilized or non-mobilized stem cells for transplantation purposes addresses the quality of hemopoietic engraftment rather than its feasibility. Two aspects are of clinical relevance: 1. The increment of peripheral cell concentration per time, and 2. shortening the duration of total aplasia following myeloablation and stem cell transplantation. When comparing the various stem cell mobilization techniques the CFU-GM yield per apheresis was highest during rh GM-CSF application (250 micrograms/m2/day continuous i.v. infusion), whereas the MNC yield was not greatly affected. More severe side effects were seen during rh GM-CSF infusion: One patient experienced an axillary phlebothrombosis. In a series of 15 advanced stage Hodgkin's lymphoma patients the reconstitutive ability of the various stem cell autografts, whether chemotherapy-, cytokine-, or non-mobilized, did not vary. Particularly in acute leukemias, mobilization of hemopoietic precursor cells does not necessarily exclude a concomitant mobilization of clonogenic tumor cells, and, therefore, the probability of disease-free survival after ABSCT might be lower when using mobilized stem cells for transplant.
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PMID:[The role of stem cell mobilization in the scope of autologous blood stem cell transplantation]. 172 28


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