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cytotoxic t cell therapy

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https://www.readbyqxmd.com/read/27936393/suppression-of-protein-tyrosine-phosphatase-ptpn22-gene-induces-apoptosis-in-t-cell-leukemia-cell-line-jurkat-through-the-akt-and-erk-pathways
#1
Elham Baghbani, Behzad Baradaran, Fatemeh Pak, Leila Mohammadnejad, Daryoush Shanehbandi, Behzad Mansoori, Vahid Khaze, Noushin Montazami, Ali Mohammadi, Parviz Kokhaei
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27931590/cytotoxic-t-lymphocyte-associated-protein-4-acts-on-local-draining-lymph-nodes-in-the-allogeneic-abdominal-skin-flap-of-a-rat-model-to-extend-its-survival
#2
G Ma, J Pei, Y Li, Y Han, D Liu
BACKGROUND: Early acute allograft rejection is the result of immune cells mainly composed of thymocyte (T) cells, which are activated, mature, and differentiate in lymphoid tissue. METHODS: Cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) competitively suppresses the cluster of differentiation 28/CTLA4-B7 costimulatory signaling pathway and alters the ratio of T helper 1 to T helper 2, leading to the inhibition of T cell activation. RESULTS: We used lentivirus-packed CTLA4-Ig to infect the local draining lymph nodes of the allograft skin flap in a rat model, which effectively extended the survival of the allograft...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27930541/cytotoxic-th1-and-th17-cells-infiltrate-the-intestinal-mucosa-of-behcet-patients-and-exhibit-high-levels-of-tnf-%C3%AE-in-early-phases-of-the-disease
#3
Giacomo Emmi, Elena Silvestri, Chiara Della Bella, Alessia Grassi, Marisa Benagiano, Fabio Cianchi, Danilo Squatrito, Luca Cantarini, Lorenzo Emmi, Carlo Selmi, Domenico Prisco, Mario Milco D'Elios
BACKGROUND: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. METHODS: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. RESULTS: We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#4
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27927647/gvhd-prevents-nk-cell-dependent-leukemia-and-virus-specific-innate-immunity
#5
Mark D Bunting, Antiopi Varelias, Fernando Souza-Fonseca-Guimaraes, Iona S Schuster, Katie E Lineburg, Rachel D Kuns, Peter Fleming, Kelly R Locke, Nicholas D Huntington, Bruce R Blazar, Steven W Lane, Siok-Keen Tey, Kelli P A MacDonald, Mark J Smyth, Mariapia A Degli-Esposti, Geoffrey R Hill
Allogeneic bone marrow transplantation (allo-BMT) is a curative therapy for hematological malignancies, but is associated with significant complications, principally graft-versus-host disease (GVHD) and opportunistic infections. Natural killer (NK) cells mediate important innate immunity that provides a temporal bridge until the reconstruction of adaptive immunity. Here we show that the development of GVHD after allo-BMT prevented NK-cell reconstitution, particularly within the maturing M1 and M2 NK-cell subsets in association with exaggerated activation, apoptosis and autophagy...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#6
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
While the emergence of bone marrow-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome positive, acute lymphoblastic leukemia (Ph+ ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and employing them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#7
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#8
REVIEW
Elodie Viry, Muhammad Zaeem Noman, Tsolère Arakelian, Audrey Lequeux, Salem Chouaib, Guy Berchem, Etienne Moussay, Jérôme Paggetti, Bassam Janji
Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916837/chloroquine-an-endocytosis-blocking-agent-inhibits-zika-virus-infection-in-different-cell-models
#9
Rodrigo Delvecchio, Luiza M Higa, Paula Pezzuto, Ana Luiza Valadão, Patrícia P Garcez, Fábio L Monteiro, Erick C Loiola, André A Dias, Fábio J M Silva, Matthew T Aliota, Elizabeth A Caine, Jorge E Osorio, Maria Bellio, David H O'Connor, Stevens Rehen, Renato Santana de Aguiar, Andrea Savarino, Loraine Campanati, Amilcar Tanuri
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres...
November 29, 2016: Viruses
https://www.readbyqxmd.com/read/27916138/alcohol-exposure-differentially-effects-anti-tumor-immunity-in-females-by-altering-dendritic-cell-function
#10
Matthew G Thompson, Flor Navarro, Lennox Chitsike, Luis Ramirez, Elizabeth J Kovacs, Stephanie K Watkins
Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response...
December 2016: Alcohol
https://www.readbyqxmd.com/read/27914462/recombinant-mhc-tetramers-for-isolation-of-virus-specific-cd8-cells-from-healthy-donors-potential-approach-for-cell-therapy-of-posttransplant-cytomegalovirus-infection
#11
A S Vdovin, S Y Filkin, P R Yefimova, S A Sheetikov, N M Kapranov, Y O Davydova, E S Egorov, E G Khamaganova, M Y Drokov, L A Kuzmina, E N Parovichnikova, G A Efimov, V G Savchenko
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#12
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#13
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#14
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27906865/management-of-post-transplant-lymphoproliferative-disorders
#15
Gabriela Llaurador, Lauren McLaughlin, Birte Wistinghausen
PURPOSE OF REVIEW: Post-transplant lymphoproliferative disease (PTLD) is a major complication of hematopoietic stem cell and solid organ transplantation. The incidence of transplantation in childhood has been steadily rising, making PTLD the most common form of lymphoproliferation in childhood. The purpose of this review is to summarize the role of the Epstein-Barr virus (EBV) in the pathophysiology and discuss the management of PTLD. RECENT FINDINGS: More than 90% of pediatric PTLD is EBV-positive...
November 30, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27906831/bos-is-associated-with-increased-cytotoxic-pro-inflammatory-cd8-t-nkt-like-and-nk-cells-in-the-small-airways
#16
Greg Hodge, Sandra Hodge, Aeneas Yeo, Phan Nguyen, Emily Hopkins, Holmes-Liew Cl, Paul N Reynolds, Mark Holmes
BACKGROUND: Immunosuppression therapy following lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and pro-inflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in pro-inflammatory lymphocytes following transplant. It is unknown whether these pro-inflammatory lymphocytes target the small and/or large airways in BOS...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#17
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27902998/autoimmune-cytopenias-diagnosis-management
#18
Christian P Nixon, Joseph D Sweeney
The autoimmune cytopenias are a related group of disorders in which differentiated hematopoietic cells are destroyed by the immune system. Single lineage disease is characterized by the production of autoantibodies against red cells (autoimmune hemolytic anemia [AIHA]), platelets (autoimmune thrombocytopenia [ITP]) and neutrophils (autoimmune neutropenia [AIN]) whereas multilineage disease may include various combinations of these conditions. Central to the genesis of this disease is the breakdown of central and/or peripheral tolerance, and the subsequent production of autoantibodies by both tissue and circulating self-reactive B lymphocytes with support from T helper lymphocytes...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27899977/nahco3-enhances-the-antitumor-activities-of-cytokine-induced-killer-cells-against-hepatocellular-carcinoma-hepg2-cells
#19
Ya Hong Yuan, Chun Fang Zhou, Jiang Yuan, Li Liu, Xing Rong Guo, Xiao Li Wang, Yan Ding, Xiao Nan Wang, Dong Sheng Li, Han Jun Tu
The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytes in vitro and promotes tumor cell invasion. In the present study, both in vitro and in vivo experiments were conducted to investigate how NaHCO3 would affect the antitumor activities of cytokine-induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For the in vitro experiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell-conditioned medium (CMCIK)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896231/prolonged-complete-hematologic-response-in-relapsed-refractory-t-large-granular-lymphocyte-leukemia-after-bendamustine-treatment
#20
R Rosamilio, V Giudice, I Ferrara, S Annunziata, L Pezzullo, G Villani, C Baldi, R Guariglia, M Rocco, C Selleri
T-large granular lymphocyte leukemia (T-LGLL) is a chronic clonal proliferation of effector memory cytotoxic CD3(+)CD57(+)CD56(-) T cells and the current guidelines suggest immunosuppressive therapy as first-line therapy, but the treatment of refractory/relapsed patients is still challenging due to the lack of prospective studies. We describe a series of two refractory/relapsed T-LGLL patients successfully treated with bendamustine, a chemotherapeutic agent largely used for B-cell neoplasms, but poorly investigated for the treatment of T-cell diseases...
November 2016: Translational Medicine @ UniSa
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