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 pathogenesis of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) involves accumulation of genetic lesions, stimulation and selection by antigen, as well as infection by viruses. Deregulation of cytokine loops has also been proposed to contribute to AIDS-NHL development, although data are available only for a limited number of cytokines. In this study we have utilized a panel of AIDS-NHL cell lines to investigate in detail the pattern of tumour expression and production of a wide spectrum of cytokines. The cytokines investigated included interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, TGF beta2, G-CSF, GM-CSF and SCF. The AIDS-NHL cell lines utilized were representative of both AIDS-related Burkitt lymphoma (AIDS-BL) and AIDS-related body cavity-based lymphoma (AIDS-BCBL). Overall, AIDS-NHL were found to produce IL-6, IL-10 and TNF beta, although with different patterns depending upon the biological features of the tumour. Production of high levels of IL10 preferentially associated with Epstein-Barr virus (EBV) positive AIDS-BL and AIDS-BCBL, although lower levels of the cytokine were also detectable among EBV-negative AIDS-BL. Production of IL-6 was restricted to EBV-positive AIDS-BL and AIDS-BCBL, whereas it was absent among EBV-negative AIDS-BL. Production of TNF beta clustered with AIDS-BL, whereas this was absent among AIDS-BCBL. These results define that the pattern of cytokine expression of AIDS-NHL depends upon the biological features of the tumour and may have implications for the pathogenesis of these disorders.
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PMID:Patterns of cytokine expression in AIDS-related non-Hodgkin's lymphoma. 979 1

PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 (GM-CSF/IL-3) genetically engineered hybrid, has shown greater biological activity in stimulating committed myeloid progenitors than either GM-CSF or IL-3 in vitro, in vivo, and in patients treated with high-dose chemotherapy. However, one concern is that PIXY321 may stimulate the proliferation of malignant cells which have functional GM-CSF or IL-3 receptors. Therefore, using a human tumor cloning assay, we have tested the effects of several concentrations of PIXY321 ranging from 0.1 to 100 ng/ml on tumor cells taken directly from 98 patients with solid tumors and Hodgkin's or non-Hodgkin's lymphomas. Of the 34 evaluable specimens, including 15 breast cancers, 5 ovarian cancers, 5 lung cancers, and 9 lymphomas, none showed stimulation of tumor growth. Interestingly, a significant inhibition of the tumor proliferation was seen in one breast cancer and in one large cell immunoblastic non-Hodgkin's lymphoma after continuous exposure of PIXY321. In conclusion, the use of PIXY321 to reduce myelosuppression after high-dose chemotherapy appears unlikely to result in stimulation of the growth of malignant cells in patients with lymphoma or cancers of the breast, lung, and ovary.
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PMID:Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 fusion protein, on human tumor colony-forming units taken directly from patients. 981 21

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.
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PMID:Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells. 981 88

Immunohistological methods did not elucidate the etiology and pathogenesis of Hodgkin's disease. In "classical" cases the immunophenotype is based on evidence of three markers: CD30+, CD15+, CD20-. Despite the use of more recent methodical approaches a considerable percentage of Hodgkin and RS cells with CD15 antibody is negative. The Epstein-Barr virus (EBV) plays an important part in the development of malignant disease and at the same time a number of nuclear antigens can be detected: EBNA-1, EBNA-2, EBNA-3a,-3b,-3c,LP. Also latent membrane proteins LMP-1, -2a, -2b and two small ribonucleic acids described as EBER-1, EBER-2. Bcl-2 protein was detected in the majority of malignant lymphomas which reduces its value in differential diagnostic reflections. In Hodgkin and RS cells its positivity is not due to translocation or other disorders of the cell genoma. In these cells the expression of mRNA for bcl-2 is much more constant. Most probably there is no cooperation of bcl-2 and p53. Co-expression of the two genes was found only in a small percentage of patients with m.Hodgkin. The varied morphological picture in particular in the mixed type of m. Hodgkin is most probably associated with the formation and release of cytokines, factors which stimulate cell colonies (IL-3, GM-CSF, G-CSF, M-CSF). Non-tumourous cells chemotactically attracted to sites of tumour cells release further cytokines e.g. TGF-beta, IL-1, Il-2, which participate in the overall morphological appearance of the lesion.
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PMID:[Molecular biology aspects of Hodgkin's disease]. 982 63

Bone marrow aspirates are composed of two cellular compartments, an abundant buffy coat suspension and a minor particulate fraction. The particulate fraction is routinely removed by filtration prior to transplantation in order to reduce the risk of embolism. This study shows that the filter-retained fraction includes many multicellular complexes, previously defined as haematons. A haematon is a finely arborized stromal-web which is tightly packed with haemopoietic progenitor cells and differentiated postmitotic cells. Comparison of the pooled buffy coat and the filter-retained materials from healthy donors showed that the haematon fraction contained 8-40 x 10(6) CD34+ cells, 20-115 x 10(3) high proliferative potential colony-forming cells (HPP-CFC) and 0.49-2.67 x 10(6) granulocyte-macrophage colony-forming unit (GM-CFU) which constituted 24+/-8% (10-36; n=8) of the total GM-CFU population harvested. Similar, but more variable recoveries of GM-CFU were obtained from the haematon fractions from patients with breast cancer (21+/-13%; n=10), Hodgkin's disease (33+/-19%; n=4), non-Hodgkin's lymphoma (21+/-18; n=7), but the recovery was lower from patients with acute myelogenous leukaemia (AML) (13+/-13%; n=6). The haematon fraction was enriched in CD34+ cells (2.5-fold), long-term culture initiating cells (LTC-IC/CAFC, week 5) (3.5-fold), HPP-CFC (2.8-fold) and GM-CFU (2.3-fold) over the buffy coat. Purified CD34+ cells expanded exponentially and produced 800 to 4000-fold more nucleated cells, 300 to 3500-fold more GM-CFU and 10 to 80-fold more HPP-CFC in stroma-free suspension culture with interleukin-1 (IL-1beta), IL-3, IL-6, GM-CSF and stem cell factor (SCF), than did the starting cell input. The haematon fraction produced significantly more progenitor cells than the buffy coat in long-term liquid culture (LTC). This was due to the higher frequency of LTC-IC/CAFC and to the presence of the whole spectrum of native, stroma cell-associated CAFC in haematons. Thus, the haematon includes the most productive haematogenous compartment in human BM. This simple enrichment strategy, using filter-retained haematons, provides a rational source of BM cells for large scale experimental and/or clinical studies on haemopoietic stem cells and on critical accessory stromal cells.
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PMID:Large scale recovery and characterization of stromal cell-associated primitive haemopoietic progenitor cells from filter-retained human bone marrow. 1021 40

We report our experience of high-dose cyclophosphamide (HDCY) followed by high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) autografting in patients with diffuse, intermediate and high-grade non-Hodgkin's lymphomas who have failed conventional treatment. From 1991 to 1996, 54 consecutive patients pre-treated with a median of two chemotherapy lines entered the study. Eighteen patients (33%) were still responders to conventional chemotherapy (sensitive relapse), and 20 patients (37%) were in partial response (PR) after chemotherapy (CT). Sixteen patients (30%) were resistant to conventional CT either at presentation (non responder) or in relapse (resistant relapse). Thirty-nine patients had bone marrow involved by disease and fifteen had an hypoplastic marrow following conventional treatment. Patients received HDCY (7gr/m2) and G-CSF or GM-CSF in order to collect PBPC. Median collected CD34+ cells was 12.3 x 10(6)/Kg (range 0.7-197). After HDT (BEAM or Melphalan + TBI) 50 patients underwent PBPC autografting. According to intention to treat, 44 (81%) of 54 patients achieved complete remission (CR) (50% after HDCY and 31% after HDT). Procedure related death occurred in 6 patients (11%), one after HDCY and 5 after autografting. Twenty-nine (66%) of 44 patients are still in CR, 7 to 63 months (median 27 months) after the procedure. Three-year probability of survival, disease-free survival and progression-free survival are 63%, 64% and 52% respectively. In conclusion, HDCY is an effective procedure not only in mobilizing PBPC, but also in reducing tumour burden. HDT with PBPC support may further improve the outcome in this category of high-risk non-Hodgkin's lymphomas.
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PMID:High-dose cyclophosphamide followed by autografting can improve the outcome of relapsed or resistant non-Hodgkin's lymphomas with involved or hypoplastic bone marrow. 1022 12

Women over 65 years are underrepresented in Cancer and Leukemia Group B (CALGB) breast cancer trials of adjuvant chemotherapy. There is greater participation in older patients with metastatic breast cancer except when toxic regimens are involved. Studies of stage III and IV Hodgkin's disease have shown that patients over 60 years achieved lower response rates, more leucopenia and thrombocytopenia, the shortest median time to recurrence, and the shortest median survival time. In acute myeloid leukemia a series of trials confirmed the disparity between young patients and those over 60 years whose complete response rate seldom exceeds 50%. In an effort to reduce toxicity rather than enhance the cure rate, CALGB showed that administration of GM-CSF after intensive induction chemotherapy was of no benefit in patients over 60 years. The use of G-CSF in acute lymphoblastic leukemia reduced hematologic toxicity and improved clinical outcome.
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PMID:Age-Related Clinical Trials of CALGB. 1088 3

As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus.
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PMID:[New immunotherapeutic approaches for the treatment of anaplastic large cell lymphoma in a mouse model]. 1121 40

Co-mobilization of CD34(+) cells and tumor has been documented in patients with different types of cancer undergoing peripheral blood stem cell transplantation (PBSCT). Conflicting reports were published regarding the role of various growth factors in tumor cells mobilization, hence we studied the extent of CD34(+) cells and lymphoma cell mobilization in 35 non-Hodgkin's (NHL) patients primed by cyclophosphamide (Cy) in combination with granulocyte colony-stimulating factor (GCSF) (A, 13 patients), granulocyte-macrophage (GM)-CSF (B, 10 patients), or GM-CSF followed by G-CSF (C, 12 patients). CD34(+) cells were quantitated by flow cytometry and lymphoma cells by the TaqMan Real Time PCR for bcl-2 gene rearrangement. Successful collection in 4 days of > or = 2 x 10(6) CD34(+) cells/kg needed for prompt engraftment was obtained in 76%, 60%, and 58% of patients in arms A, B, and C, respectively. Lymphoma cell mobilization was detected in 35% patients tested, 78% of which had follicular lymphoma. Lymphoma cell mobilization was similar in the three arms of the study, however, presence of lymphoma cells was prevalent in patients who failed to mobilize the amount of 0.4 x 10(6) CD34(+) cells/kg in 2 days ("poor mobilizers") and reached 42%, compared to 17% in the "successful mobilizers" group of patients. Lymphoma cell contamination in PBSCs was detected proportionately in the peripheral blood and in the bone marrow. We conclude that bcl-2 gene rearrangement is prevalent in patients with follicular histology, and, in these patients, an inverse relationship was observed between mobilization of CD34(+) cells and lymphoma cells. Our results explain the high relative risk (1.98) for mobilization in patients with follicular histology.
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PMID:Differential mobilization of CD34+ cells and lymphoma cells in non-Hodgkin's lymphoma patients mobilized with different growth factors. 1127 70

Conflicting results have been reported regarding the effect of various growth factors on the mobilization of natural killer (NK) cells and dendritic cells in patients undergoing stem cell mobilization for autotransplantation. We compared the extent of mobilization of NK cells and dendritic cells in non-Hodgkin's (NHL) patients undergoing mobilization with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, or GM-CSF followed by G-CSF. Overall, 35 patients were studied. NK cells and dendritic were quantitated by flow cytometry. NK cells were defined as the sum of CD56(+) cells and CD56/CD16(+) cells. Dendritic cells were defined as the sum of CD80(+) and CD80(+)/CD14(+) cells. NK activity was determined by by microcytotoxicity assay. NK activity correlated well with the total amount of CD56(+) cells mobilized to the peripheral blood. Patients in the three arms of the study mobilized similar amounts of NK cells and NK activity, and patients who lacked NK activity in the peripheral blood, before mobilization, lacked NK activity in their apheresis collections. In contrast to NK cell mobilization, mobilization of dendritic cells/kg was three- to five-fold higher in patients mobilized with GM-CSF-containing regimens compared to patients mobilized with G-CSF alone. We conclude that GM-CSF-containing mobilization regimens are superior for dendritic cell mobilization but similar in the mobilization of NK cells. Therefore, we recommend using GM-CSF-containing regimens for patients undergoing ex vivo or in vivo manipulation of dendritic cells.
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PMID:Mobilization of dendritic cells and NK cells in non-Hodgkin's lymphoma patients mobilized with different growth factors. 1127 71


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