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Indoleamine 2,3-dioxygenase

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https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#1
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29141887/apoptosis-in-mesenchymal-stromal-cells-induces-in-vivo-recipient-mediated-immunomodulation
#2
Antonio Galleu, Yanira Riffo-Vasquez, Cristina Trento, Cara Lomas, Luigi Dolcetti, Tik Shing Cheung, Malte von Bonin, Laura Barbieri, Krishma Halai, Sophie Ward, Ling Weng, Ronjon Chakraverty, Giovanna Lombardi, Fiona M Watt, Kim Orchard, David I Marks, Jane Apperley, Martin Bornhauser, Henning Walczak, Clare Bennett, Francesco Dazzi
The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141444/associations-among-obesity-inflammation-and-tryptophan-catabolism-in-pregnancy
#3
Maureen Groer, Dietmar Fuchs, Allyson Duffy, Adetola Louis-Jacques, Amy D'Agata, Teodor T Postolache
OBJECTIVE: To evaluate relationships among obesity in pregnancy and plasma levels of tryptophan (TRP) and kynurenine (KYN), inflammatory markers, and depressed mood. METHODS: Pregnant women ( N = 374) were enrolled, and data were collected at a mean gestation of 20 weeks in this cross-sectional study. Plasma was analyzed for TRP, KYN, neopterin, and nitrite levels. Women completed demographic and mood scales. RESULTS: There was a statistically significant inverse correlation between body mass index (BMI) and TRP and positive correlations between BMI and KYN and the kynurenine/tryptophan (KYN/TRP) ratio...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29136692/-expression-and-prognostic-values-of-pd-1-pd-l1-and-ido-1-in-sinonasal-malignant-mucosal-melanoma
#4
H Q Liu, B Q Zou, S Y Wang
Objective: To investigate the correlation between the expression of programmed death-1(PD-1), PD ligand-1(PD-L1), indoleamine 2, 3-dioxygenase 1(IDO-1) and clinical parameters in sinonasal malignant mucosal melanoma (SNM). Methods: Samples from 86 SNM patients who did not receive immune-targeted therapy and radio-chemotherapy were analyzed for PD-1, PD-L1, and IDO-1 expression by immunohistochemistry. Results: High clinical/pathologic staging, brain metastases and advanced age were independent risk factors of poor prognosis...
November 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29133053/synthesis-and-biological-evaluation-of-new-berberine-derivatives-as-cancer-immunotherapy-agents-through-targeting-ido1
#5
Yan-Xiang Wang, Wei-Qiang Pang, Qing-Xuan Zeng, Zhe-Song Deng, Tian-Yun Fan, Jian-Dong Jiang, Hong-Bin Deng, Dan-Qing Song
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125937/novel-specificity-of-ido-enzyme-involved-in-the-biosynthesis-of-mating-pheromone-in-the-ciliate-blepharisma-stoltei
#6
Mayumi Sugiura, Hajime J Yuasa, Terue Harumoto
Mating pheromones (gamone 1 and gamone 2) in the ciliate Blepharisma are biologically active substances that trigger sexual reproduction (conjugation) under starvation conditions. Gamone 1 is a glycoprotein secreted by type I cells, and gamone 2 is a tryptophan (Trp)-derivative compound secreted by type II cells. Both gamones stimulate complementary mating type cells to promote each gamone production and induce pair formation. To elucidate the biosynthetic pathway of gamone 2, we investigated the enzymes involved in the pathway and the specificity of the enzymes...
September 18, 2017: Protist
https://www.readbyqxmd.com/read/29120388/synthesis-and-molecular-modeling-studies-of-n-hydroxyindazolecarboximidamides-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#7
Dong-Ho Lee, Joo-Youn Lee, Jieun Jeong, Miok Kim, Kyung Won Lee, Eunseo Jang, Sunjoo Ahn, Chang Hoon Lee, Jong Yeon Hwang
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N'-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme...
November 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29118088/ido-immune-status-after-chemoradiation-may-predict-survival-in-lung-cancer-patients
#8
Weili Wang, Lei Huang, Jian-Yue Jin, Shruti Jolly, Yong Zang, Huanmei Wu, Li Yan, Wenhu Pi, Lang Li, Andrew L Mellor, Feng-Ming Spring Kong
Host immunity influences the impact of radiotherapy (RT) in cancer but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during and after RT administration and then correlated to overall survival (OS), progression-free survival and disease progression rate in patients...
November 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#9
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111717/discovery-of-a-novel-and-selective-indoleamine-2-3-dioxygenase-ido-1-inhibitor-3-5-fluoro-1h-indol-3-yl-pyrrolidine-2-5-dione-eos200271-pf-06840003-and-its-characterization-as-a-potential-clinical-candidate
#10
Stefano Crosignani, Patrick Bingham, Pauline Bottemanne, Hélène Cannelle, Sandra Cauwenberghs, Marie Cordonnier, Deepak Dalvie, Frederik Deroose, Jun Li Feng, Bruno Gomes, Samantha Greasley, Stephen E Kaiser, Manfred Kraus, Michel Négrerie, Karen A Maegley, Nichol Miller, Brion W Murray, Manfred Schneider, James Solowiej, Albert E Stewart, Joseph Tumang, Vince R Torti, Benoit Van den Eynde, Martin Wythes
Tumors use tryptophan-catabolizing enzymes such as Indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. SAR around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode...
November 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29104473/the-inhibition-of-indoleamine-2-3-dioxygenase-1-by-connexin-43
#11
Han-Chen Lin, Chih-Jen Yang, Yu-Diao Kuan, Wei-Kuang Wang, Wen-Wei Chang, Che-Hsin Lee
Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29091890/the-effect-of-clinically-relevant-doses-of-immunosuppressive-drugs-on-human-mesenchymal-stem-cells
#12
Eliska Javorkova, Julie Vackova, Michaela Hajkova, Barbora Hermankova, Alena Zajicova, Vladimir Holan, Magdalena Krulova
Immunosuppressive drugs are used to suppress graft rejection after transplantation and for the treatment of various diseases. The main limitations of their use in clinical settings are severe side effects, therefore alternative approaches are desirable. In this respect, mesenchymal stem cells (MSCs) possess a regenerative and immunomodulatory capacity that has generated considerable interest for their use in cell-based therapy. Currently, MSCs are tested in many clinical trials, including the treatment of diseases which require simultaneous immunosuppressive treatment...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29080383/clinical-significance-of-tryptophan-catabolism-in-hodgkin-lymphoma
#13
Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida
Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients' affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88...
October 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/29066694/-clinical-evaluation-of-indoleamine-2-3-dioxygenase-in-the-serum-of-patients-with-locally-advanced-breast-cancer-during-mohs-paste-treatment
#14
Hitomi Kubota, Kenichi Sakurai, Shigeru Fujisaki, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
Locally advanced breast cancer lesions often compromise patients' quality of life(QOL). Mohs paste is a histopathological fixative with zinc chloride as the main ingredient. It is applied when performing chemosurgery for skin tumors. In recent years, this paste has reportedly been very effective for the control of various symptoms of skin metastases in inoperable advanced cancers, such as pungent odor and hemorrhage, in the field of palliative care. We evaluated the clinical significance of indoleamine 2, 3-dioxygenase(IDO)in the serum of patients with locally advanced breast cancer during Mohs paste treatment...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29066687/-indoleamine-2-3-dioxygenase-activity-during-letrozol-therapy-for-an-elderly-breast-cancer-patient
#15
Kenichi Sakurai, Shigeru Fujisaki, Hitomi Kubota, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during letrozol therapy for an elderly patient with locally advanced breast cancer. IDO activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high performance liquid chromatography(HPLC). Serum Trp/Kyn levels of the patient before endocrine therapy were lower than those after endocrine therapy. IDO activity decreased after endocrine therapy and correlat- ed with the number of metastatic lymph node lesions during letrozol therapy...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29066685/-indoleamine-2-3-dioxygenase-activity-during-fulvestrant-therapy-for-aromatase-inhibitor-resistant-metastatic-breast-cancer
#16
Kenichi Sakurai, Shigeru Fujisaki, Hitomi Kubota, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)for breast cancer patients between different clinical stages and patient ages. IDO activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high performance liquid chromatography(HPLC). Serum Trp/Kyn levels in Stage IV breast cancer patients were lower than in patients at other stages. Serum Trp/Kyn levels of breast cancer patients over the age of 70 years were lower than in patients under the age of 69 years...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29057249/indoleamine-2-3-dioxygenase-and-survivin-peptide-vaccine-combined-with-temozolomide-in-metastatic-melanoma
#17
Nikolaj Juul Nitschke, Jon Bjoern, Trine Zeeberg Iversen, Mads Hald Andersen, Inge Marie Svane
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) and survivin have been identified as potential targets for cancer vaccination. In this phase II study a vaccine using the peptides Sur1M2 and IDO5 was combined with the chemotherapy temozolomide (TMZ) for treatment of metastatic melanoma patients. The aim was to simultaneously target several immune inhibiting mechanisms and the highly malignant cells expressing survivin. METHODS: HLA-A2 positive patients with advanced malignant melanoma were treated biweekly with 150 mg/m(2) TMZ daily for 7 days followed by subcutaneous vaccination with 250 µg of each peptide in 500 µL Montanide solution at day 8...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29054599/indoleamine-2-3-dioxygenase-expression-in-primary-cutaneous-melanoma-correlates-with-breslow-thickness-and-is-of-significant-prognostic-value-for-progression-free-survival
#18
Felicia Rubel, Johannes S Kern, Kristin Technau-Hafsi, Sibylle Uhrich, Kaethe Thoma, Georg Häcker, Nikolas von Bubnoff, Frank Meiss, Dagmar von Bubnoff
The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO-inhibitors were added to the regimen. Data on IDO-expression in primary human melanomas are however incomplete and conflicting. Here, we show that the level of IDO-expression in primary human melanoma cells significantly correlates with Breslow thickness (p = 0...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29051706/investigation-of-the-tissue-distribution-and-physiological-roles-of-indoleamine-2-3-dioxygenase-2
#19
Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball
Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/29046648/the-relationships-among-tryptophan-kynurenine-indoleamine-2-3-dioxygenase-depression-and-neuropsychological-performance
#20
Knut A Hestad, Knut Engedal, Jon E Whist, Per G Farup
It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO) is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 10(3) (KT Ratio) in serum and cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established...
2017: Frontiers in Psychology
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