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Cancer and IDO

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https://www.readbyqxmd.com/read/28641945/surveillance-after-positive-colonoscopy-based-on-adenoma-characteristics
#1
Ido Laish, Ilia Seregeev, Timna Naftali, Fred M Konikoff
BACKGROUND: Patients with adenomatous polyps are at increased risk for developing colorectal cancer based on the characteristics and number of polyps, but less is known about the individual and combined contribution of these factors. This study aimed to better characterize the risk of advanced adenoma and cancer in patients with positive baseline colonoscopy. METHODS: Patients who had polyps at baseline colonoscopy were included in this retrospective cohort study (N=1165) and were categorized into 6 groups: (1) 1-2 non-advanced adenomas (NAA's), (2) ≥3 NAA's, (3) advanced tubular adenoma, (4) small tubulovillous adenoma (TVA), (5) large TVA and (6) multiple advanced adenomas (MAA's)...
May 16, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28640387/dna-mismatch-repair-deficiency-and-hereditary-syndromes-in-latino-patients-with-colorectal-cancer
#2
Charité N Ricker, Diana L Hanna, Cheng Peng, Nathalie T Nguyen, Mariana C Stern, Stephanie L Schmit, Greg E Idos, Ravi Patel, Steven Tsai, Veronica Ramirez, Sonia Lin, Vinay Shamasunadara, Afsaneh Barzi, Heinz-Josef Lenz, Jane C Figueiredo
BACKGROUND: The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. METHODS: A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28637419/pharmacological-inhibitors-of-nad-biosynthesis-as-potential-anticancer-agents
#3
Stephanie Lucas, Claire Soave, Gazal Nabil, Zainab Ahmed, Guohua Chen, Hossny El-Banna, Q Ping Dou, Jian Wang
BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics by targeting through inhibition of cancer metabolism. Nicotinamide adenine dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer...
June 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28604143/combinatorial-antitumor-effects-of-indoleamine-2-3-dioxygenase-inhibitor-nlg919-and-paclitaxel-in-a-murine-b16-f10-melanoma-model
#4
Xiangjing Meng, Guangying Du, Liang Ye, Shanyue Sun, Qiaofeng Liu, Hongbo Wang, Wenyan Wang, Zimei Wu, Jingwei Tian
Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibitor NLG919 in combination with different regimens of paclitaxel in a murine B16-F10 melanoma model. NLG919 increased the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28580171/in-silico-analysis-of-pathways-activation-landscape-in-oral-squamous-cell-carcinoma-and-oral-leukoplakia
#5
Eugene Makarev, Adrian D Schubert, Riya R Kanherkar, Nyall London, Mahder Teka, Ivan Ozerov, Ksenia Lezhnina, Atul Bedi, Rajani Ravi, Rannee Mehra, Mohammad O Hoque, Ido Sloma, Daria A Gaykalova, Antonei B Csoka, David Sidransky, Alex Zhavoronkov, Evgeny Izumchenko
A subset of patients with oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSCC), harbor dysplastic lesions (often visually identified as leukoplakia) prior to cancer diagnosis. Although evidence suggest that leukoplakia represents an initial step in the progression to cancer, signaling networks driving this progression are poorly understood. Here, we applied in silico Pathway Activation Network Decomposition Analysis (iPANDA), a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in OSCC and pre-neoplastic oral lesions...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28554057/the-immune-regulation-in-cancer-by-the-amino-acid-metabolizing-enzymes-arg-and-ido
#6
REVIEW
Giada Mondanelli, Stefano Ugel, Ursula Grohmann, Vincenzo Bronte
Some enzymes degrading amino acids have evolved in mammals to dampen immune responses and maintain peripheral tolerance. The enzymes metabolizing l-arginine and l-tryptophan are particularly powerful, contributing to restrain immunity towards fetal tissues and establish neonatal tolerance. Solid tumors can hijack these formidable pathways to construct a microenvironment highly unfavorable to anti-tumor T lymphocytes able to recognize them, one of mechanisms for their immune evasion. In this review, we analyze emerging concepts in the cross-talk between cells expressing these enzymes, their immune regulatory functions and pharmacological approaches that can target them to enhance cancer immunotherapy...
May 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28551624/immunoregulatory-function-of-lymphatic-endothelial-cells-in-tumor-draining-lymph-nodes-of-human-gastric-cancer
#7
Mao Tokumoto, Hiroaki Tanaka, Yukie Tauchi, Tatsuro Tamura, Takahiro Toyokawa, Kenjiro Kimura, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Lymph node metastasis is the most important prognostic factor for patients with gastric cancer. Increasing evidence suggests that lymphatic endothelial cells (LECs) regulate immune responses. The aim of this study was to examine the effect of LECs on the activation of CD4(+) T cells. MATERIALS AND METHODS: We examined the impact of cancer cells on the phenotype and production of cytokines of LECs derived from tumor-draining lymph nodes. RESULTS: We showed that LECs inhibited CD4(+) T cell production of cytokines, such as IL-2, IL-10, and INF-γ...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28530082/-cervical-cancer-in-israel-2016-facts-insights-and-thoughts-for-the-future
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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