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Indoleamine

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https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#1
REVIEW
Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28319781/systematic-study-of-imidazoles-inhibiting-ido1-via-the-integration-of-molecular-mechanics-and-quantum-mechanics-calculations
#2
Yi Zou, Fang Wang, Yan Wang, Wenjie Guo, Yihua Zhang, Qiang Xu, Yisheng Lai
Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations...
March 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#3
REVIEW
Ping Song, Tharmarajan Ramprasath, Huan Wang, Ming-Hui Zou
Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28314306/expression-of-indoleamine-2-3-dioxygenase-gene-is-a-feature-of-poorly-differentiated-non-muscle-invasive-urothelial-cell-bladder-carcinomas
#4
Tvrtko Hudolin, Chantal Mengus, Julie Coulot, Zeljko Kastelan, Ahmad El-Saleh, Giulio C Spagnoli
AIM: To evaluate indoleamine 2,3-dioxygenase (IDO) gene expression in non-muscle-invasive urothelial cell bladder carcinoma (NMIBC). PATIENTS AND METHODS: Seventy-four patients undergoing surgical treatment for NMIBC were enrolled in the study. IDO gene expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: IDO gene expression was detectable significantly more frequently (48/74, 64.86% vs. 5/21, 23...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303855/expression-and-prognostic-value-of-indoleamine-2-3-dioxygenase-in-pancreatic-cancer
#5
Tao Zhang, Xiang-Long Tan, Yong Xu, Zi-Zheng Wang, Chao-Hui Xiao, Rong Liu
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. METHODS: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ)...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28300312/indoleamine-2-3-dioxygenase-in-psoriasis-a-defective-mechanism
#6
S Trabanelli
No abstract text is available yet for this article.
March 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28294066/mechanisms-of-melatonin-in-alleviating-alzheimer-s-disease
#7
Mayuri Shukla, Parichart Boontem, Russel J Reiter, Jutamaad Satayavivad, Piyarat Govitrapong
Alzheimer's disease (AD) is a chronic, progressive and prevalent neurodegenerative disease characterized by the loss of higher cognitive functions and an associated loss of memory. The thus far "incurable" stigma for AD prevails because of variations in the success rates of different treatment protocols in animal and human studies. Among the classical hypotheses explaining AD pathogenesis, the amyloid hypothesis is currently being targeted for drug development. The underlying concept is to prevent the formation of these neurotoxic peptides which play a central role in AD pathology and trigger a multispectral cascade of neurodegenerative processes post-aggregation...
March 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28285566/involvement-of-the-cytokine-ido1-ahr-loop-in-zinc-oxide-nanoparticle-induced-acute-pulmonary-inflammation
#8
Chia-Chi Ho, Hui-Ling Lee, Chao-Yu Chen, Yueh-Hsia Luo, Ming-Hsien Tsai, Hui-Ti Tsai, Pinpin Lin
Zinc oxide nanoparticles (ZnONPs) are widely used in our daily life, such as in sunscreens and electronic nanodevices. However, pulmonary exposure to ZnONPs causes acute pulmonary inflammation, which is considered as an initial event for various respiratory diseases. Thus, elucidation of the underlying cellular mechanisms of ZnONPs can help us in predicting their potential effects in respiratory diseases. In this study, we observed that ZnONPs increased proinflammatory cytokines, accompanied with an increased expression of aryl hydrocarbon receptor (AhR) and its downstream target cytochrome P450 1A1 (CYP1A1) in macrophages in vitro and in mouse lung epithelia in vivo...
March 13, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#9
Sanam Salimi Elizei, Malihe-Sadat Poormasjedi-Meibod, Xia Wang, Maryam Kheirandish, Aziz Ghahary
Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28284339/inhibition-of-indoleamine-2-3-dioxygenase-1-2-prevented-cognitive-impairment-and-energetic-metabolism-changes-in-the-hippocampus-of-adult-rats-subjected-to-polymicrobial-sepsis
#10
Clarissa M Comim, Viviane Freiberger, Letícia Ventura, Francielle Mina, Gabriela K Ferreira, Monique Michels, Jaqueline S Generoso, Emílio L Streck, João Quevedo, Tatiana Barichello, Felipe Dal-Pizzol
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28283500/in-vitro-interactions-of-epacadostat-and-its-major-metabolites-with-human-efflux-and-uptake-transporters-implications-for-pharmacokinetics-and-drug-interactions
#11
Qiang Zhang, Yan Zhang, Jason Boer, Jack G Shi, Peidi Hu, Sharon Diamond, Swamy Yeleswaram
Epacadostat (EPAC) is a first-in-class, orally active inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and has demonstrated promising clinical activity. In humans, three major plasma metabolites were identified: M9 (a glucuronide-conjugate), M11 (a gut microbiota metabolite), and M12 (a secondary metabolite formed from M11). It is proposed that the biliary excretion of M9, the most abundant metabolite, leads to the enterohepatic circulation of EPAC suggested by the human pharmacokinetics of EPAC...
March 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28264810/promoter-methylation-modulates-indoleamine-2-3-dioxygenase-1-induction-by-activated-t-cells-in-human-breast-cancers
#12
Satish K Noonepalle, Franklin Gu, Eun-Joon Lee, Jeong-Hyeon Choi, Qimei Han, Jaejik Kim, Maria Ouzounova, Austin Y Shull, Lirong Pei, Pei-Yin Hsu, Ravindra Kohle, Fang Shi, Jiseok Choi, Katie Chiou, Tim H M Huang, Hasan Korkaya, Libin Deng, Hong-Bo Xin, Shuang Huang, Muthusamy Thangaraju, Arun Sreekumar, Stefan Ambs, Shou-Ching Tang, David H Munn, Huidong Shi
Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells...
March 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28260094/immunosuppressive-macrophages-induced-by-ido1-promote-the-growth-of-endometrial-stromal-cells-in-endometriosis
#13
Jie Mei, Kai-Kai Chang, Hai-Xiang Sun
It was previously demonstrated that anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) stimulated an inflammatory response that subsequently initiated the activation of immunosuppressive macrophages in endometriosis. The aim of the present study was to clarify the effect of IDO1‑induced macrophages on the growth of ESCs in endometriosis. Normal ESCs, ectopic ESCs and normal ESCs treated with plasmid pEGFP‑N1‑IDO1 or SD11‑IDO1 short hairpin RNA were co‑cultured with peripheral blood‑derived monocyte (PBMC)‑driven macrophages directly for 48 h...
February 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28256612/the-role-of-indoleamine-2-3-dioxygenase-aryl-hydrocarbon-receptor-pathway-in-the-tlr4-induced-tolerogenic-phenotype-in-human-dcs
#14
Fabián Salazar, Dennis Awuah, Ola H Negm, Farouk Shakib, Amir M Ghaemmaghami
A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28245795/in-search-of-druggable-targets-for-gbm-amino-acid-metabolism
#15
Eduard H Panosyan, Henry J Lin, Jan Koster, Joseph L Lasky
BACKGROUND: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. METHODS: First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas...
February 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28243244/commentary-indoleamine-2-3-dioxygenase-expressing-aortic-plasmacytoid-dendritic-cells-protect-against-atherosclerosis-by-induction-of-regulatory-t-cells
#16
COMMENT
Pasquale Maffia, Yvonne Döring, Erik A L Biessen, Ziad Mallat
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228105/mesenchymal-stromal-cells-as-vehicles-of-tetravalent-bispecific-tandab-cd3-cd19-for-the-treatment-of-b-cell-lymphoma-combined-with-ido-pathway-inhibitor-d-1-methyl-tryptophan
#17
Xiaolong Zhang, Yuanyuan Yang, Leisheng Zhang, Yang Lu, Qing Zhang, Dongmei Fan, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
BACKGROUND: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration...
February 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28223071/therapeutic-antibody-targeting-of-indoleamine-2-3-dioxygenase-ido2-inhibits-autoimmune-arthritis
#18
Lauren M F Merlo, Samantha Grabler, James B DuHadaway, Elizabeth Pigott, Kaylend Manley, George C Prendergast, Lisa D Laury-Kleintop, Laura Mandik-Nayak
Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2...
February 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28216884/chemical-components-from-aloe-and-their-inhibition-of-indoleamine-2-3-dioxygenase
#19
Ya Nan Sun, Lin Ying Li, Wei Li, Jong Seong Kang, Inkyu Hwang, Young Ho Kim
BACKGROUND: In Korea, Aloe is routinely ingested as a traditional medicine or as a component of health beverages. OBJECTIVE: To research the inhibition of indoleamine 2, 3-dioxygenase (IDO) activities of components from Aloe. MATERIALS AND METHODS: the compounds were isolated by a combination of silica gel and YMC Rp-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-NMR, and MS). All of the isolated compounds were examined for their ability to inhibit IDO, which actively suppresses immune functions by catalyzing the rate limiting reaction in the conversion of tryptophan to kynurenine...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#20
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 21, 2017: Immunity
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