Effect of surgical treatment on the cellular immune response of gastric cancer patients

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 ± 8.9) was not different after tumor resection (43.6 ± 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 ± 5.8%, N = 20) or not (27.3 ± 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 ± 7.5%) or to healthy individuals (33.2 ± 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF-ß) since the patients with cancer had reduced production of TGF-ß1 (269 ± 239 pg/ml, N = 20) in comparison to the normal individuals (884 ± 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF-ß1 production by peripheral leukocytes.33934

IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in jak2v617f-positive myeloproliferative neoplasms

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The recurrent V617F mutation in JAK2 (JAK2(V617F)) has emerged as the primary contributor to the pathogenesis of myeloproliferative neoplasms (MPN). However, the lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indicates the need for identifying pathways that cooperate with JAK2. Activated JAK2 was found to be associated with the insulin receptor substrate 2 (IRS2) in non-hematological cells. We identified JAK2/IRS2 binding in JAK2(V617F) HEL cells, but not in the JAK2(WT) U937 cell line. In HEL cells, IRS2 silencing decreased STAT5 phosphorylation, reduced cell viability and increased apoptosis; these effects were enhanced when IRS2 silencing was combined with ruxolitinib. In U937 cells, IRS2 silencing neither reduced cell viability nor induced apoptosis. IRS1/2 pharmacological inhibition in primary MPN samples reduced cell viability in JAK2(V617F)-positive but not JAK2(WT) specimens; combination with ruxolitinib had additive effects. IRS2 expression was significantly higher in CD34(+) cells from essential thrombocythemia patients compared to healthy donors, and in JAK2(V617F) MPN patients when compared to JAK2(WT). Our data indicate that IRS2 is a binding partner of JAK2(V617F) in MPN. IRS2 contributes to increased cell viability and reduced apoptosis in JAK2-mutated cells. Combined pharmacological inhibition of IRS2 and JAK2 may have a potential clinical application in MPN.The recurrent V617F mutation in JAK2 (JAK2V617F) has emerged as the primary contributor to the pathogenesis of myeloproliferative neoplasms (MPN). However, the lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indi7669486959sem informaçãoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)sem informaçã

Surgical Treatment Of Fungal Bolus In Acute Lymphoid Leukemia [tratamento Cirúrgico De "bola Fúngica" Em Leucemia Linfóide Aguda (lla).]

Case report of a 24 year old female patient with ALL that developed pulmonary invasive aspergillosis during aplastic phase of induction chemotherapy. She was treated with antibiotics and amphotericin B. After recovering from neutropenia, she developed a mycetoma in the inferior lobe of the right lung, which required lobectomy. Nine months after surgery the patient is well, in complete remission of ALL and with no evidence of infection. One month after lobectomy, chemotherapy had been reintroduced. Attention should be called to this form of therapy of Aspergillosis, as a successful way to eradicate this fungal infection that responds poorly to antifungal drugs currently used.38317417

Parvovirus B19 Pure Red Cell Aplasia In A Renal Transplant Recipient [aplasia Pura De Série Vermelha Secundária A Parvovirose Em Transplantado Renal]

[No abstract available]30170Handgretinger, P.F.R., Schaefer, H.E., (2000) Pure red cell aplasia. Brit J Haematol, 111, pp. 1010-1022Wong, T.Y., Chan, P.K., Leung, C.B., Szeto, C.C., Tam, J.S., Li, P.K., Parvovirus B19 infection causing red cell aplasia in renal transplantation on tacrolimus (1999) Am J Kidney Dis, 34, pp. 1132-1136Ahsan, N., Holman, M.J., Gocke, C.D., Groff, J.A., Yang, H.C., Pure red cell aplasia due to parvovirus B19 infection in solid organ transplantation (1997) Clin Transplant, 11, pp. 265-270Flores, A.V., Ionescu, D.N., Melhem, M.F., Parvovirus B19 infection in immunocompromised host (2007) Arch Pathol Lab Med, 131, pp. 799-80

Hairy Cell Leukemia And Multipe Autoimmune Manifestations In A Human Immunodeficiency Virus-infected Patient

Aggressive B-cell lymphomas are clearly related to HIV infection. However, the relationship of HIV infection to low-grade B- or T-cell lymphomas and Hodgkin's disease is not well established. The authors describe a case in which hairy cell leukemia was associated with lupus anticoagulant and direct Coombs' test in an HIV-positive patient.66632532

Effect of surgical treatment on the cellular immune response of gastric cancer patients

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 ± 8.9) was not different after tumor resection (43.6 ± 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 ± 5.8%, N = 20) or not (27.3 ± 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 ± 7.5%) or to healthy individuals (33.2 ± 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF-ß) since the patients with cancer had reduced production of TGF-ß1 (269 ± 239 pg/ml, N = 20) in comparison to the normal individuals (884 ± 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF-ß1 production by peripheral leukocytes

Stathmin 1 is involved in the highly proliferative phenotype of high-risk myelodysplastic syndromes and acute leukemia cells

Stathmin 1 is an important cytoplasmic microtubule-destabilizing protein that plays critical roles in proliferation and accurate chromosome segregation through regulation of microtubule dynamics. High levels of Stathmin 1 expression have been reported in leukemia and solid tumors. However, Stathmin 1 has not been studied in myelodysplastic syndrome cells. We, herein, report that significantly higher Stathmin 1 levels were observed in proliferating hematopoietic cells, in high-risk MDS and acute leukemia cells. In addition, Stathmin 1 silencing in U937 and Namalwa leukemia cells reduced cell proliferation and clonogenicity. Our data suggest that Stathmin 1 expression may be related to the highly proliferative phenotype of hematopoietic cells and add new insights into the participation of Stathmin 1 in hematological malignancies.Stathmin 1 is an important cytoplasmic microtubule-destabilizing protein that plays critical roles in proliferation and accurate chromosome segregation through regulation of microtubule dynamics. High levels of Stathmin 1 expression have been reported in382251257sem informaçãosem informaçã

Costimulatory Molecule Expression On Leukocytes From Mice With Experimental Autoimmune Encephalomyelitis Treated With Ifn-β

Interferon-β (IFN-β) is of benefit in the treatment of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), but the mechanisms by which it exerts this beneficial effect remain uncertain. The present data demonstrate that IFN-β therapy impairs the proliferative response to concanavalin A (ConA) and myelin basic protein (MBP), decreases expression of the CD80 molecule on leukocytes of treated mice, and may thereby impede the Th1 cell activation-promoting anergy in EAE. Moreover, IFN-β therapy increases expression of the CTLA4 molecule, which induces a counterregulatory Th2 response. The reduction of CD80 expression with concomitant increase of CTLA4 expression alters the course of EAE and may be useful as a monitor in therapy with IFN-β.236293298Rudick, R.A., Goodkin, D.E., Jacobs, L.D., Herndon, R.M., Richert, J.R., Salazar, A.M., Fischer, J.S., Witham, R.H., Impact of interferon beta 1a on neurologic disability in relapsing multiple sclerosis (1997) Neurology, 49, pp. 358-363. , The Multiple Sclerosis Collaborative Research Group (MSCRG)Zhao, G.J., Koopmans, R.A., Li, D.K., Bedell, L., Paty, D.W., Effect of interferon beta 1-β in MS: Assessment of annual accumulation of PD/T2 activity on MRA (2000) Neurology, 54, pp. 200-206. , UBC MS/MRI Analysis Group and the MS Study GroupYasuda, C.L., Al-Sabbagh, A., Oliveira, E.C., Diaz-Bardales, B.M., Garcia, C.A.A.C., Santos, L.M.B., Interferon beta modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion (1999) Immunol. Invest., 28, pp. 115-126Ruuls, S.R., Labie, M.C.D.C., Weber, K.S., Botman, C.A.D., Groenestein, R.J., Dijkstra, C.D., Olsson, T., Van Der Meide, P.H., The length of treatment determines whether IFN-β prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats (1996) J. Immunol., 157, pp. 5721-5731Weiner, H.L., Friedman, A., Miller, A., Khoury, S.J., Al-Sabbagh, A., Santos, L.M.B., Sayeg, M., Hafler, D.A., Oral tolerance: Immunologic mechanisms and treatment of murine and human organ-specific autoimmune diseases by oral administration of autoantigens (1994) Annu. Rev. Immunol., 12, pp. 809-837Ozenci, V., Kouwenhoven, M., Huang, Y.M., Kivisakk, P., Link, H., Multiple sclerosis is associated with an imbalance between tumor necrosis factor-α (TNF-α) and IL-10-secreting blood cells is corrected by interferon-beta (IFN-beta) treatment (2000) Clin. Exp. Immunol., 120, pp. 147-153Petereit, H.F., Bamborschke, S., Esse, A.D., Heiss, W.D., Interferon gamma producing blood lymphocytes are decreased by interferon beta therapy in patients with multiple sclerosis (1997) Mult. Scler., 3, pp. 180-183Brod, S.A., Marshall, G.D., Henninger, E.M., Sriram, S., Khan, M., Wolinsky, J.S., Interferon beta 1b treatment decreases tumor necrosis factor α and increases interleukin 6 production in multiple sclerosis (1996) Neurology, 46, pp. 1633-1638Byskosh, P.V., Reder, A.T., Interferon beta 1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis (1996) Multiple Sclerosis, 1, pp. 262-269Gayo, A., Mozo, L., Suarez, A., Tunon, A., Lahoz, C., Gutierrez, C., Long-term effect of IFN-β1b treatment on the spontaneous and induced expression of IL-10 and TGF-β1 in MS patients (2000) J. Neurol. Sci., 179, pp. 43-49Chabot, S., Yong, V.W., Interferon beta 1b increases interleukin 10 in a model of T cell-microglia interaction. Relevance to MS (2000) Neurology, 55, pp. 1497-1505Nicoletti, F., Di Marco, R., Patti, F., Reggio, E., Nicoletti, A., Zaccone, P., Stivala, F., Reggio, A., Blood levels of transforming growth factor beta 1 (TGF-β1) are elevated in both relapsing remitting and chronic progressive multiple sclerosis (MS) patients and are further augmented by treatment with interferon beta (IFN-β1b) (1998) Clin. Exp. Immunol., 113, pp. 96-99Lenschow, D.J., Walunas, T.L., Bluestone, J.A., CD28-B7 system of T cell costimulation (1996) Annu. Rev. Immunol., 14, pp. 233-258Kuchroo, V.K., Das, M.P., Brown, J.A., Ranger, A.M., Zamvil, S.S., Sobel, R.A., Weiner, H.L., Glimcher, L.H., B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy (1995) Cell, 80, pp. 707-718Perrin, P.J., Scott, D., Quigley, L., Albert, P.S., Feder, O., Gray, G.S., Abe, R., Racke, M.K., Role of B7:CD28/CTLA4 in the induction of chronic relapsing experimental allergic encephalomyelitis (1995) J. Immunol., 154, pp. 1481-1490Miller, S.D., Vanderlugt, C.L., Lenchow, D.J., Pope, J.G., Karandikar, N.J., Dal Canto, M.C., Bluestone, J.A., Blockade of CD80/B71 interaction prevents epitope spreading and clinical relapses of murine EAE (1995) Immunity, 3, pp. 739-745Deibler, G.E., Martenson, R.E., Kies, M.W., Large-scale preparation of myelin basic protein from central nervous tissue of several mammalian species (1972) Prep. Biochem., 2, pp. 139-165Racke, M.K., Bonomo, A., Scott, D.E., Cannella, B., Levine, A., Raine, C.S., Shevach, E.M., Rocken, M., Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease (1994) J. Exp. Med., 180, pp. 1961-1966Noronha, A., Toscas, A., Jensen, M.A., Interferon beta decreases T cell activation and interferon γ production in multiple sclerosis (1993) J. Neuroimmunol., 46, pp. 145-153Rudick, R.A., Carpenter, C.S., Cookfair, D.L., Tuohy, V.K., Ransohoff, R.M., In vitro and in vivo inhibition of mitogen-driven T-cell activation by recombinant interferon beta (1993) Neurology, 43, pp. 2080-2087Chambers, C.A., Kuhns, M.S., Egen, J.G., Allison, J.P., CTLA4 mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy (2001) Annu. Rev. Immunol., 19, pp. 565-694Perez, V.L., Van Parijs, L., Biuckians, A., Zheng, X.X., Strom, T.B., Abbas, A.K., Induction of peripheral T cell tolerance in vivo requires CTLA4 engagement (1997) Immunity, 6, pp. 411-417De Simone, R., Giampaolo, A., Giometto, B., Gallo, P., Levi, G., Peschle, C., Aloisi, F., The costimulatory molecule B7 is expressed on human microglia in culture and in multiple sclerosis acute lesions (1995) J. Neuropathol. Exp. Neurol., 54, pp. 175-187William, K., Ulvestad, E., Antel, J.P., B7/BB-1 antigen expression on adult human microglia studied in vitro and in situ (1994) Eur. J. Immunol., 24, pp. 3031-3037Ding, L., Linsley, P.S., Huang, L.-Y., Germain, R.N., Shevach, E.M., IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression (1993) J. Immunol., 151, pp. 1224-1234Genç, K., Dona, D.L., Reder, A.T., Increased CD80 + B cells in active multiple sclerosis and reversal by interferon-β1b therapy (1997) J. Clin. Invest., 99, pp. 2664-2671Liu, Z., Pelfrey, C.M., Cotleur, A., Lee, J.-C., Rudick, R.A., Immunomodulatory effects of interferon beta-1a in multiple sclerosis (2001) J. Neuroimmunol., 112, pp. 153-162Huang, Y.-M., Hussien, Y., Jin, Y.-P., Soderstrom, M., Link, H., Multiple sclerosis: Deficient in vitro responses of blood mononuclear cells to IFN-β (2001) Acta Neurol. Scand., 104, pp. 249-256Huang, Y.-M., Stoyanova, N., Jin, Y.-P., Teleshova, Y., Hussien, Y., Xiao, B.-G., Fredrikson, S., Link, H., Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-β and IL-10 (2001) Clin. Exp. Immunol., 124, pp. 306-314Carrero, B.M., Bennett, F., Chau, T.A., Ling, V., Luxenberg, D., Jussif, J., Baroja, M.L., Madrenas, J., CTLA4 (CD152) can inhibit T cell activation by two different mechanisms depending on it level of cell surface expression (2000) J. Immunol., 165, pp. 1352-135