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Cancer and IDO

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https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#1
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28790848/the-status-of-immunosuppression-in-patients-with-stage-iiib-or-iv-non-small-cell-lung-cancer-correlates-with-the-clinical-characteristics-and-response-to-chemotherapy
#2
Yuan Wang, Guo-Fang Hu, Zhe-Hai Wang
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28758106/neopterin-as-a-biomarker-of-immune-response-in-cancer-patients
#3
REVIEW
Bohuslav Melichar, Martina Spisarová, Marie Bartoušková, Lenka Kujovská Krčmová, Lenka Javorská, Hana Študentová
With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28735629/dose-dense-carboplatin-paclitaxel-improves-progression-free-survival-in-patients-with-endometrial-cancer
#4
Liron Kogan, Ido Laskov, Zainab Amajoud, Jeremie Abitbol, Amber Yasmeen, David Octeau, Asma Fatnassi, Roy Kessous, Neta Eisenberg, Susie Lau, Walter H Gotlieb, Shannon Salvador
OBJECTIVE: Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer. METHODS: Retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer, undergoing DD protocol (from 2011 to 2015) to a non-overlapping historical cohort with similar characteristics who received treatment every three weeks (2008-2011)...
July 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28735627/inhibition-of-indoleamine-2-3-dioxygenase-activity-by-fatty-acids-and-prostaglandins-a-structure-function-analysis
#5
M Costabile, N K Bassal, J P Gerber, B P Hughes
Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28723862/risk-of-colorectal-cancer-in-chronic-kidney-disease-a-systematic-review-and-meta-analysis
#6
Yuga Komaki, Fukiko Komaki, Dejan Micic, Akio Ido, Atsushi Sakuraba
BACKGROUND: Association between chronic kidney disease and colorectal cancer (CRC) remains unclear. GOALS: To assess the risk of CRC in patients with various chronic kidney diseases before and after kidney transplantation. STUDY: Electronic databases were searched for cohort studies assessing the risk of CRC in patients with chronic kidney diseases. The primary outcome was the risk of CRC among studies that reported the risk as standardized incidence rate (SIR)...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28641945/surveillance-after-positive-colonoscopy-based-on-adenoma-characteristics
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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