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https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#1
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#2
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28903363/p53-prevent-tumor-invasion-and-metastasis-by-down-regulating-ido-in-lung-cancer
#3
Dongfang Tang, Lu Yue, Ruyong Yao, Lin Zhou, Yuqin Yang, Liming Lu, Wen Gao
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo. As results, we reported that IDO1 expression increased by more than 3...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899580/the-interplay-between-cytokines-and-the-kynurenine-pathway-in-inflammation-and-atherosclerosis
#4
Roland Baumgartner, Maria J Forteza, Daniel F J Ketelhuth
The kynurenine pathway (KP) is the major metabolic route of tryptophan (Trp) metabolism. Indoleamine 2,3-dioxygenase (IDO1), the enzyme responsible for the first and rate-limiting step in the pathway, as well as other enzymes in the pathway, have been shown to be highly regulated by cytokines. Hence, the KP has been implicated in several pathologic conditions, including infectious diseases, psychiatric disorders, malignancies, and autoimmune and chronic inflammatory diseases. Additionally, recent studies have linked the KP with atherosclerosis, suggesting that Trp metabolism could play an essential role in the maintenance of immune homeostasis in the vascular wall...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28864263/mechanism-of-chimeric-vaccine-stimulation-of-indoleamine-2-3-dioxygenase-biosynthesis-in-human-dendritic-cells-is-independent-of-tgf-%C3%AE-signaling
#5
Grace E Esebanmen, William H R Langridge
Cholera toxin B subunit fusion to autoantigens such as proinsulin (CTB-INS) down regulate dendritic cell (DC) activation and stimulate synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased biosynthesis of indoleamine 2,3-dioxygenase (IDO1) may play an important role in CTB-INS vaccine suppression of DC activation. Studies in murine models suggest a role for transforming growth factor beta (TGF-β) in the stimulation of IDO1 biosynthesis, for the induction of tolerance in DCs...
August 21, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28852164/genome-wide-dna-methylation-and-transcriptome-analyses-reveal-genes-involved-in-immune-responses-of-pig-peripheral-blood-mononuclear-cells-to-poly-i-c
#6
Haifei Wang, Jiying Wang, Chao Ning, Xianrui Zheng, Jinlian Fu, Aiguo Wang, Qin Zhang, Jian-Feng Liu
DNA methylation changes play essential roles in regulating the activities of genes involved in immune responses. Understanding of variable DNA methylation linked to immune responses may contribute to identifying biologically promising epigenetic markers for pathogenesis of diseases. Here, we generated genome-wide DNA methylation and transcriptomic profiles of six pairs of polyinosinic-polycytidylic acid-treated pig peripheral blood mononuclear cell (PBMC) samples and corresponding controls using methylated DNA immunoprecipitation sequencing and RNA sequencing...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844802/recent-developments-in-small-molecule-therapies-for-renal-cell-carcinoma
#7
REVIEW
Minsoo Song
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28827067/increased-tryptophan-metabolism-is-associated-with-activity-of-inflammatory-bowel-diseases
#8
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan, and some of its metabolites, reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome can increase susceptibility of mice to colitis. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features. METHODS: We studied 535 consecutive patients with IBD (211 with ulcerative colitis [UC], 234 with Crohn's disease [CD]; 236 male), enrolled in Germany from August 2013 through April 2014 and followed until July 2016...
August 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#9
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#10
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28771034/in-silico-discovery-and-therapeutic-potential-of-ido1-and-tdo2-inhibitors
#11
Finith E Jernigan, Lijun Sun
No abstract text is available yet for this article.
August 3, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28771024/binding-properties-of-different-categories-of-ido1-inhibitors-a-microscale-thermophoresis-study
#12
Francesco Antonio Greco, Alice Coletti, Chiara Custodi, Daniela Dolciami, Alessandro Di Michele, Andrea Carotti, Maura Marinozzi, Nina Schlinck, Antonio Macchiarulo
AIM: Inhibition of IDO1 is a strategy pursued in the immune-oncology pipeline for the development of novel anticancer therapies. At odds with an ever-increasing number of inhibitors being disclosed in the literature and patent applications, only very few compounds have hitherto advanced in clinical settings. MATERIALS & METHODS: We have used MicroScale Thermophoresis analysis and docking calculations to assess on a quantitative basis the binding properties of distinct categories of inhibitors to IDO1...
August 3, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28768924/a-novel-high-throughput-virtual-screening-protocol-to-discover-new-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#13
Haojie Xu, Yunlong Song, Qing Yang
Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the immune escape of tumors and has emerged as a promising target for cancer immunotherapy. Despite its potential in immuno-oncology, very few chemotypes have been reported to date. Here, we disigned a novel high throughput virtual screening (HTVS) cascade protocol, combining both pharmacophore modeling and molecular docking and it was employed to query commercially available compounds to identify novel inhibitors. Among the 23 compounds selected for the in vitro IDO1 inhibitory activity assay, five compounds exhibit greater than 20% inhibition at a test concentration of 10 µM, with two compounds having an IC50 value of 23...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28765120/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#14
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28760910/epacadostat-shows-value-in-two-scchn-trials
#15
(no author information available yet)
In the ECHO-202/KEYNOTE-037 and ECHO-204 trials reported at the 2017 Annual Meeting of the American Society of Clinical Oncology, patients with squamous cell carcinoma of the head and neck responded well to the combinations of epacadostat plus pembrolizumab and epacadostat plus nivolumab. An IDO1 inhibitor, epacadostat also demonstrated promising activity in combination with the PD-1 checkpoint inhibitors in other solid tumors, including melanoma, urothelial carcinoma, renal cell carcinoma, and non-small cell lung cancer...
July 31, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28751450/infiltrating-t-cells-increase-ido1-expression-in-glioblastoma-and-contribute-to-decreased-patient-survival
#16
Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Meijing Wu, Matthew Genet, Galina Gritsina, Balázs Győrffy, Priscilla K Brastianos, David Binder, Jeffrey A Sosman, Francis J Giles, C David James, Craig Horbinski, Roger Stupp, Derek A Wainwright
Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression in human cancer, including the most common primary malignant brain tumor in adults, glioblastoma (GBM), is poorly understood. The major objective of this study is to address this gap in our understanding of how IDO1 expression contributes to the biology of GBM, and whether its level of expression is a determinant of GBM patient outcome. Experimental Design: Patient-resected GBM, the cancer genome atlas, human T cell:GBM co-cultures, as well as nu/nu, NOD-scid and humanized (NSG-SGM3-BLT) mice engrafted human GBM, form the basis of our investigation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#17
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28731684/the-binding-mode-of-n-hydroxyamidines-to-indoleamine-2-3-dioxygenase-1-ido1
#18
Ute F Röhrig, Vincent Zoete, Olivier Michielin
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important target in cancer immunotherapy. The most advanced clinical compound, epacadostat (INCB024360), binds to the heme cofactor of IDO1 through an N-hydroxyamidine function. Conflicting binding modes have recently been proposed, reporting iron binding either through the hydroxyamidine oxygen or through the hydroxyamidine nitrogen atom. Here, we use quantum chemical calculations, docking, and quantum mechanics/molecular mechanics calculations based on available X-ray data to resolve this issue and to propose a physically meaningful binding mode...
August 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28726189/changing-the-properties-of-multipotent-mesenchymal-stromal-cells-by-ifn%C3%AE-administration
#19
N A Petinati, N M Kapranov, A E Bigil'deev, M D Popova, Yu O Davydova, I V Gal'tseva, N I Drize, L A Kuz'mina, E N Parovichnikova, V G Savchenko
We studied changes in the population of human multipotent mesenchymal stromal cells activated by IFNγ. The cells were cultured under standard conditions; IFNγ was added in various concentrations for 4 h or over 2 passages. It was shown that the total cell production significantly decreased after long-term culturing with IFNγ, but 4-h exposure did not affect this parameter. After 4-h culturing, the expression levels of IDO1, CSF1, and IL-6 increased by 300, 7, and 2.4 times, respectively, and this increase persisted 1 and 2 days after removal of IFNγ from the culture medium...
June 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28701757/oncolytic-measles-virus-enhances-antitumour-responses-of-adoptive-cd8-nkg2d-cells-in-hepatocellular-carcinoma-treatment
#20
Aiping Chen, Yonghui Zhang, Gang Meng, Dengxu Jiang, Hailin Zhang, Meihong Zheng, Mao Xia, Aiqin Jiang, Junhua Wu, Christian Beltinger, Jiwu Wei
There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8(+)NKG2D(+) cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8(+)NKG2D(+) cells, mediated by at least three distinct mechanisms...
July 12, 2017: Scientific Reports
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