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Cancer and IDO

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https://www.readbyqxmd.com/read/28530082/-cervical-cancer-in-israel-2016-facts-insights-and-thoughts-for-the-future
#1
REVIEW
Menahem Fisher, Eduardo Schejter, Ido Solt, Gad Renart
The natural history of precancerous lesions and cervical cancer in Israeli women differs from that reported in the world. In 2011, 244 women were diagnosed in Israel with invasive cervical cancer, with the mortality of 79 women. The incidence of cervical cancer in Israel is about 5 new cases per year per 100,000 women (5.4 Jewish, 3.2 Arab). This figure is very low compared with statistics presented in other countries and has not changed over the last decades. The vast majority of Israeli women were diagnosed due to symptoms and not following Pap smear screening...
September 2016: Harefuah
https://www.readbyqxmd.com/read/28529635/synthesis-of-5-18-f-fluoro-%C3%AE-methyl-tryptophan-new-trp-based-pet-agents
#2
Benjamin C Giglio, Haiyang Fei, Mengzhe Wang, Hui Wang, Liu He, Huijuan Feng, Zhanhong Wu, Hongjian Lu, Zibo Li
Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of (18)F into the tryptophan aromatic ring...
2017: Theranostics
https://www.readbyqxmd.com/read/28515923/expression-of-cxcr-4-and-ido-in-human-colorectal-cancer-an-immunohistochemical-approach
#3
Masaichi Ogawa, Michiaki Watanabe, Takuo Hasegawa, Kohei Ichihara, Kazuhiko Yoshida, Katsuhiko Yanaga
C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is involved in lymphocyte trafficking. Recent studies have demonstrated that, during pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a key role in suppressing the maternal T-cell response against the fetus. In the present study, the significance of CXCR4 and IDO expression in human colorectal cancer (CRC) has been investigated by immunohistochemical assay, and their association with survival was analyzed...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28500847/p53-prevent-tumor-invasion-and-metastasis-by-down-regulating-ido-in-lung-cancer
#4
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...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488695/blockade-of-ido-kynurenine-ahr-metabolic-circuitry-abrogates-ifn-%C3%AE-induced-immunologic-dormancy-of-tumor-repopulating-cells
#5
Yuying Liu, Xiaoyu Liang, Xiaonan Yin, Jiadi Lv, Ke Tang, Jingwei Ma, Tiantian Ji, Huafeng Zhang, Wenqian Dong, Xun Jin, Degao Chen, Yanchun Li, Songyan Zhang, Heidi Q Xie, Bin Zhao, Tong Zhao, Jinzhi Lu, Zhuo-Wei Hu, Xuetao Cao, F Xiao-Feng Qin, Bo Huang
Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28472907/ifn-%C3%AE-based-treatment-of-patients-with-chronic-hcv-show-increased-levels-of-cells-with-myeloid-derived-suppressor-cell-phenotype-and-of-ido-and-nos
#6
Mohamed Labib Salem, Abdel-Aziz A Zidan, Mohamed Attia, Randa E El-Naggar, Mohamed Nassef, Abdel Raouf Abou El-Azm, Hasan El-Bate, Mohamed Yussif, Sohaila Galal, Mohamed Abo Senna, Maha El Demellawy
INTRODUCTION: Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. AIM: The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules...
May 4, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28470686/tumor-cell-expression-of-immune-inhibitory-molecules-and-tumor-infiltrating-lymphocyte-count-predict-cancer-specific-survival-in-pancreatic-and-ampullary-cancer
#7
Kostandinos Sideras, Katharina Biermann, Kevin Yap, Shanta Mancham, Patrick P C Boor, Bettina E Hansen, Hans J A Stoop, Maikel P Peppelenbosch, Casper H van Eijck, Stefan Sleijfer, Jaap Kwekkeboom, Marco J Bruno
Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Tumor tissue from 224 patients with resected pancreatic (n=148) and ampullary (n=76) cancer was used to construct tissue-microarrays...
May 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28470572/tumor-associated-fibroblasts-and-microvessels-contribute-to-the-expression-of-immunosuppressive-factor-indoleamine-2-3-dioxygenase-in-human-esophageal-cancers
#8
Guanglin Cui, Can Li, Gang Xu, Zhenglu Sun, Li Zhu, Zhengfen Li, Wei Zheng, Junling Li, Aping Yuan
Recent studies have provided considerable evidence to support the hypothesis that tumor stroma plays a crucial role in the induction of immune tolerance to human cancers. Here, we investigated the contribution of reactive stromal tumor-associated fibroblasts (TAFs) and microvessels to the immunosuppressive factor indoleamine 2,3-dioxygenase (IDO) expression in the ESCC microenvironment. The immunohistochemical (IHC) analyses demonstrated a significant increased densities of TAFs and microvessels in the ESCC stroma, double IHCs showed that these increased TAFs and microvessels were with a high proliferation activity...
May 3, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28469468/kynurenine-pathway-of-tryptophan-metabolism-regulatory-and-functional-aspects
#9
REVIEW
Abdulla A-B Badawy
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate)...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#10
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#11
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#12
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28336214/indoleamine-2-3-dioxygenase-1-ido1-inhibitors-activate-the-aryl-hydrocarbon-receptor
#13
COMPARATIVE STUDY
Benjamin J Moyer, Itzel Y Rojas, Iain A Murray, Seokwon Lee, Haley F Hazlett, Gary H Perdew, Craig R Tomlinson
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands...
May 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#14
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#15
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/28314306/expression-of-indoleamine-2-3-dioxygenase-gene-is-a-feature-of-poorly-differentiated-non-muscle-invasive-urothelial-cell-bladder-carcinomas
#16
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
#17
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/28299150/awareness-and-practice-of-self-breast-examination-among-female-nurses-at-the-federal-teaching-hospital-ido-ekiti-nigeria
#18
Olusegun Emmanuel Gabriel, Oluwaserimi Adewumi Ajetunmobi, Olabode Muftau Shabi, Olaide Toyin Elegbede, Raymond Akujuobi Okere, Olusegun Adesola Busari, Ayokunle Samuel Dada
Breast cancer is the most common female malignancy linked with high levels of morbidity and mortality in developing countries due to delayed diagnosis. This research assessed the knowledge of signs and risk factors of breast cancer and practice of self breast examination (SBE) among female nurses in a rural tertiary Hospital. Eighty-five nurses ages 20 to 60 years were sampled by simple randomization over a period of eight weeks through a self-administered semi-structured questionnaire. The analysis was done using statistical package for social science version 17...
August 17, 2016: Journal of Public Health in Africa
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
#19
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/28216884/chemical-components-from-aloe-and-their-inhibition-of-indoleamine-2-3-dioxygenase
#20
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
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