Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The late asthmatic reaction is characterised by elevated numbers of interleukin-4/interleukin-5/CD4-positive T-helper cells type 2 in bronchoalveolar lavage fluid (BALF). Cyclosporin A (CsA) is known to inhibit T-cell proliferation, induce apoptosis of CD4-positive T-cells and downregulate cytokine gene expression. It was assessed whether CsA-induced inhibition of the late asthmatic reaction was associated with apoptosis of BALF T-lymphocytes and other cell types, as well as expression of the antiapoptotic protein B-cell leukaemia/lymphoma 2 gene product (Bcl-2). BALF cells were obtained from asthmatics at baseline and 24 h after allergen-inhalation challenge following prior administration of CsA (n=13) or placebo (n=11). The number of apoptotic CD3-positive T-lymphocytes increased in the CsA but not the placebo group. The numbers of Bcl-2-positive cells were significantly reduced in the CsA but not the placebo group. The majority of Bcl-2-positive cells were CD3-positive T-lymphocytes. The beneficial effect of cyclosporin A in asthma may be related to its inhibitory effect on the late asthmatic reaction via induction of T-cell apoptosis and decreased B-cell leukaemia/lymphoma 2 gene product levels.
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PMID:Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 in asthmatics. 1295 49

Black cohosh (Cimicifuga racemosa) has been used as therapeutics for pain and inflammation in Korean folk medicine. The potential effects of black cohosh extract (BCE) on mast cell-dependent allergy reaction, however, have not been well elucidated yet. In the present study, we investigated the effect of BCE on the allergy reaction using mast cell-dependent in vivo and in vitro models. BCE showed no potential of skin sensitization in local lymph node assay (LLNA). The oral administration of BCE significantly inhibited the anti-IgE-induced passive cutaneous anaphylaxis (PCA) reaction. BCE also showed inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells. In addition, BCE inhibited the IL-4, IL-5 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. These results demonstrated that BCE has an anti-allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.
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PMID:Inhibition of mast cell-dependent allergy reaction by extract of black cohosh (Cimicifuga racemosa). 1520 65

B-cell chronic lymphocytic leukemia (B-CLL), a clonal expansion of B CD5+ cells, is the most frequent type of adult leukemia in western countries. Accumulation of neoplastic B-cells is caused not by their higher proliferation rate, but by their prolonged life-span due to dysregulation of apoptosis. Many proteins act as inducers or inhibitors in controlling apoptosis. A high level of antiapoptotic BCL-2 protein is detected in B cells of B-CLL. Other factors, such as NF-kappaB, PI-3K and PKC, are also involved in the inhibition of malignant cell apoptosis. A high level of p27kip1, an inhibitor of cyclin-dependent kinase that correlates with the degree of in vitro apoptosis, is found in B-CLL cells. The autologous interaction between BAFF, APRIL, and their ligands may also be involved in apoptosis inhibition in B-CLL. Some external factors e.g. cytokines, may suppress apoptosis of malignant cells. IL-4, IL-2, IFN-gamma, and TNF are proven inhibitors, while IL-5 and IL-10 are inducers of apoptosis of these cells. Even though there are reports characterizing some mechanisms of B-CLL cell apoptosis, relatively less is still known about the complex regulation of this process. This requires more precise research, as new anti-leukemic drugs influence the regulation of apoptosis of neoplastic B lymphocytes.
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PMID:[Apoptosis in pathogenesis of B-cell chronic lymphocytic leukemia]. 1522 9

Human T cell leukemia virus type-I (HTLV-I) infection is associated with spontaneous T cell activation and uncontrolled lymphocyte proliferation. An exacerbated type-1 immune response with production of pro-inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is associated with a type-2 immune response with high levels of interleukin (IL-4, IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and immunological consequences of the HTLV-I and S. mansoni infection were evaluated. The immune response in patients with schistosomiasis co-infected with HTLV-I showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific IgE levels when compared with patients with only schistosomiasis (p < 0.05). Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological response was also compared in individuals who had only HTLV-I infection with those who were co-infected with HTLV-I and helminths (S. mansoni and Strongyloides stercoralis). In patients HTLV-I positive co-infected with helminths the IFN-gamma levels were lower than in individuals who had only HTLV-I. Moreover, there were fewer cells expressing IFN-gamma and more cells expressing IL-10 in individuals co-infected with HTLV-I and helminths. These dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis and are inversely associated with the development of liver fibrosis. Moreover, helminths may protect HTLV-I infected patients to produce large quantities of pro-inflammatory cytokines such as IFN-gamma.
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PMID:Clinical and immunological consequences of human T cell leukemia virus type-I and Schistosoma mansoni co-infection. 1548 48

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.
Leukemia 2005 May
PMID:Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. 1577 98

Nude rats bearing the LC-6-JCK human lung cancer xenograft displayed cancer-associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL-6, leukemia-inducing factor, IL-8, IL-5 and IL-11, were secreted to the bloodstream. Proinflammatory cytokines induce acute-phase reactions, as evidenced by a decrease of serum albumin and an increase in alpha1-acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute-phase reactions, whereas anti-PTHrP antibody affected neither proinflammatory cytokine production nor acute-phase reactions. Nevertheless, tumor resection and administration of anti-PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti-PTHrP antibody was associated with increased food consumption; increased body weight from anti-PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC-6-JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti-PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP-induced wasting syndrome.
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PMID:Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. 1580 Sep 41

CD40L generates immune responses in leukemia-bearing mice, an effect that is potentiated by IL-2. We studied the feasibility, safety, and immunologic efficacy of an IL-2- and CD40L-expressing recipient-derived tumor vaccine consisting of leukemic blasts admixed with skin fibroblasts transduced with adenoviral vectors encoding human IL-2 (hIL-2) and hCD40L. Ten patients (including 7 children) with high-risk acute myeloid (n = 4) or lymphoblastic (n = 6) leukemia in cytologic remission (after allogeneic stem cell transplantation [n = 9] or chemotherapy alone [n = 1]) received up to 6 subcutaneous injections of the IL-2/CD40L vaccine. None of the patients were receiving immunosuppressive drugs. No severe adverse reactions were noted. Immunization produced a 10- to 890-fold increase in the frequencies of major histocompatibility complex (MHC)-restricted T cells reactive against recipient-derived blasts. These leukemia-reactive T cells included both T-cytotoxic/T-helper 1 (Th1) and Th2 subclasses, as determined from their production of granzyme B, interferon-gamma, and interleukin-5. Two patients produced systemic IgG antibodies that bound to their blasts. Eight patients remained disease free for 27 to 62 months after treatment (5-year overall survival, 90%). Thus, even in heavily treated patients, including recipients of allogeneic stem cell transplants, recipient-derived antileukemia vaccines can induce immune responses reactive against leukemic blasts. This approach may be worthy of further study, particularly in patients with a high risk of relapse.
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PMID:Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. 1624 92

The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.
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PMID:Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia. 1640 Aug 78

Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined as persistent, marked hypereosinophilia of unknown origin complicated by end-organ damage. Recent research in cellular and molecular biology has led to the characterization of distinct underlying hematological disorders, primitively involving cells of the myeloid or lymphoid lineage. The ability to classify many hypereosinophilic syndrome patients on the basis of pathogenesis of hypereosinophilia has radically changed therapeutic perspectives. Indeed, imatinib mesylate has become first-line therapy for patients in whom the FIP1L1-PDGFRalpha fusion gene is detected, whereas corticosteroids remain the mainstay for management of patients in whom hypereosinophilia is secondary to the overproduction of interleukin 5 by abnormal T-cells. Use of monoclonal anti-interleukin-5 antibodies in the latter group of patients has a strong rationale and could decrease cumulative corticosteroid doses and toxicity. As far as prognosis of these disease variants is concerned, hypereosinophilic syndrome patients with the FIP1L1-PDGFRalpha fusion gene may develop acute myelogenous (eosinophilic) leukemia, whereas those with clonal interleukin-5-producing T-cells have an increased risk of developing T-cell lymphoma. It is currently unclear whether timely therapeutic intervention in such patients could interfere with long-term progression toward malignant hematological disorders.
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PMID:Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants. 1661 67

Adoptive T-cell immunotherapy may provide complementary therapy for childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In this study, we have analyzed the functional characteristics of anti-BCP-ALL effector T cells generated by co-culturing T lymphocytes and dendritic cells (DC) from allogeneic human stem cell transplantation (HSCT) donors. After 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10. Anti-BCP-ALL T cells expressed CD49d and CXCR4 (implicated in the recruitment to bone marrow), and CD62L and CCR7 (involved in the migration to lymphoid organs). In accordance with this profile, T cells significantly migrated in response to the chemokines CXCL12 and CCL19. In conclusion, stimulation of T cells with CD40L+BCP-ALL cells-loaded DC not only elicited the generation of potent and specific anti-leukemic cytotoxic effectors, but also the differentiation of specific and functional Th-1 CD4 lymphocytes. These effectors are fully equipped to reach leukemia-infiltrated tissues and have characteristics to support and orchestrate the anti-tumor immune-response.
Leukemia 2006 Nov
PMID:T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy. 1699 Jul 69


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