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https://www.readbyqxmd.com/read/28719632/viscum-album-neutralizes-tumor-induced-immunosuppression-in-a-human-in-vitro-cell-model
#1
Carmen Steinborn, Amy Marisa Klemd, Ann-Sophie Sanchez-Campillo, Sophie Rieger, Marieke Scheffen, Barbara Sauer, Manuel Garcia-Käufer, Konrad Urech, Marie Follo, Annekathrin Ücker, Gunver Sophia Kienle, Roman Huber, Carsten Gründemann
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays...
2017: PloS One
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#2
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28719596/the-influence-of-fcgr2a-and-fcgr3a-polymorphisms-on-the-survival-of-patients-with-recurrent-or-metastatic-squamous-cell-head-and-neck-cancer-treated-with-cetuximab
#3
T Magnes, T Melchardt, C Hufnagl, L Weiss, C Mittermair, D Neureiter, E Klieser, G Rinnerthaler, S Roesch, A Gaggl, R Greil, A Egle
FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#4
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719513/dihydrofolate-reductase-genetic-polymorphisms-affect-methotrexate-dose-requirements-in-pediatric-patients-with-acute-lymphoblastic-leukemia-on-maintenance-therapy
#5
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
We have aimed to determine the effect of polymorphisms in regulatory regions of the DHFR gene in relation to methotrexate (MTX) dose adjustments and drug-induced toxicity in children on maintenance therapy for acute lymphoblastic leukemia (ALL). In total, 41 children diagnosed with ALL were screened for 3 tag-single nucleotide polymorphisms in the DHFR promoter (C-1610G, C-680G/T, A-317G) and an intronic 19-bp insertion/deletion. Genotypes were analyzed in relation to dose requirements and toxicity. The percentage of MTX dose administered (with respect to protocol-recommended values) was affected by DHFR polymorphisms...
July 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28719344/protective-effect-of-edaravone-against-a%C3%AE-25-35-induced-mitochondrial-oxidative-damage-in-sh-sy5y-cells
#6
G-L Zhang, L Zhang, Y-Y Guo, Z-L Ma, H-Y Wang, T Li, J Liu, Y Du, L Yao, T-T Li, J-M Du
Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28719295/regional-differences-in-the-prevalence-of-major-opportunistic-infections-among-antiretroviral-na%C3%A3-ve-human-immunodeficiency-virus-patients-in-japan-northern-thailand-northern-vietnam-and-the-philippines
#7
Louie Mar A Gangcuangco, Ikumi Sawada, Naho Tsuchiya, Cuong D Do, Thanh Thuy T Pham, Archawin Rojanawiwat, Marissa Alejandria, Katerina Leyritana, Yoshiyuki Yokomaku, Panita Pathipvanich, Koya Ariyoshi
To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#8
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718997/mesenchymal-stem-cell-derived-factors-immuno-modulatory-effects-and-therapeutic-potential
#9
REVIEW
Vladislav Volarevic, Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Valentin Djonov, Nebojsa Arsenijevic
Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28718965/long-term-effects-galectin-1-and-specific-immunotherapy-for-allergic-responses-in-the-intestine
#10
Li-Tao Yang, Qing Shu, Xiang-Qian Luo, Zhi-Qiang Liu, Shu-Qi Qiu, Jiang-Qi Liu, Hai-Jian Guo, Lin-Jing Li, Mao-Gang Li, Da-Bo Liu, Li-Xin Xia, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Mast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells' functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation. METHODS: An intestinal allergy mouse model was developed. The co-administration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine were observed in sensitized mice...
July 18, 2017: Allergy
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#11
REVIEW
Praveen Sridhar, Fabio Petrocca
Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28718424/targeted-therapy-and-immunosuppression-in-the-tumor-microenvironment
#12
REVIEW
Michael J Allegrezza, Jose R Conejo-Garcia
Small-molecule inhibitors offer great promise for targeting pathways that are specifically deregulated in different tumors. However, such 'targeted' therapies also elicit poorly understood effects on protective antitumor immunity. Given the emerging relevance of immunotherapies that boost pre-existing T cell responses, understanding how different immune cells are affected by small-molecule inhibitors could lead to more-effective interventions, alone or combined with immunotherapy. This review discusses the growing array of activities elicited by multiple 'targeted' inhibitors on antitumor immunity, underscoring the complex effects resulting from diverse activities on different immune cell types in vivo, and the need to conduct mechanistic research that identifies drugs performing well not only in immunocompromised mice but also in the presence of spontaneous or therapeutic antitumor immunity...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#13
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28717763/burkitt-s-lymphoma-and-b-cell-lymphoma-unclassifiable-with-features-intermediate-between-diffuse-large-b-cell-lymphoma-and-burkitt-s-lymphoma-in-patients-with-hiv-outcomes-in-a-south-african-public-hospital
#14
Gerhard Sissolak, Matthew Seftel, Thomas S Uldrick, Tonya M Esterhuizen, Nooroudien Mohamed, Danie Kotze
PURPOSE: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. METHODS: We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717358/clinical-response-to-vedolizumab-in-ulcerative-colitis-patients-is-associated-with-changes-in-integrin-expression-profiles
#15
Friederike Fuchs, Daniela Schillinger, Raja Atreya, Simon Hirschmann, Sarah Fischer, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
BACKGROUND: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. METHODS: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28717086/therapy-related-acute-myeloid-leukemia-after-the-long-term-administration-of-low-dose-etoposide-for-chronic-type-adult-t-cell-leukemia-lymphoma-a-case-report-and-literature-review
#16
Naoki Shimada, Nobuhiro Ohno, Ryuji Tanosaki, Shigeo Fuji, Yuhko Suzuki, Koichiro Yuji, Kaoru Uchimaru, Arinobu Tojo
A 61-year-old woman with chronic-type adult T-cell leukemia-lymphoma (ATL) had been taking low-dose oral etoposide for progressive lymphocytosis. After taking this for 3.5 years, she was diagnosed with therapy-related acute myeloid leukemia (t-AML), with a chromosomal translocation of t (6:11) (q27; q23). She thus received remission induction therapy, consolidation therapy, and allogeneic hematopoietic stem cell transplantation. Although both t-AML and ATL were in remissive states, she died of a therapy-related infection within 1 year...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#17
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T-C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell cycle inhibitor CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716862/gene-therapy-for-wiskott-aldrich-syndrome-in-a-severely-affected-adult
#18
Emma C Morris, Thomas Fox, Ronjon Chakraverty, Rita Tendeiro, Katie Snell, Christine Rivat, Sarah Grace, Kimberly Gilmour, Sarita Workman, Karen Buckland, Katie Butler, Ronnie Chee, Alan D Salama, Hazem Ibrahim, Havinder Hara, Cecile Duret, Fulvio Mavilio, Frances Male, Frederick D Bushman, Anne Galy, Siobhan O Burns, H Bobby Gaspar, Adrian J Thrasher
Until recently hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harbouring integrations near oncogenes...
July 17, 2017: Blood
https://www.readbyqxmd.com/read/28716739/phototoxicity-in-a-laryngeal-cancer-cell-line-enhanced-by-a-targeting-amphiphilic-chlorin-photosensitizer
#19
Milene N O Moritz, Carlos Rossa, Kleber T de Oliveira, Marciana P Uliana, Janice R Perussi
BACKGROUND: Photodynamic therapy (PDT) has been established in several countries as an alternative therapy for the treatment of various malignancies. This therapy involves the incorporation of a photosensitizer (PS) that is activated by visible light and form reactive oxygen species leading to target cell death by apoptosis or necrosis. Previously, our group has demonstrated that CHL-T (semi-synthesized from chlorophyll a and containing a linked solubilizing group TRISMA(®)) presented a pronounced potential to induce death in HeLa cell line after PDT...
July 14, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#20
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
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