IL-4 and IL-17A Cooperatively Promote Hydrogen Peroxide Production, Oxidative DNA Damage, and Upregulation of Dual Oxidase 2 in Human Colon and Pancreatic Cancer Cells.

IL-4 and IL-17A Cooperatively Promote Hydrogen Peroxide Production, Oxidative DNA Damage, and Upregulation of Dual Oxidase 2 in Human Colon and Pancreatic Cancer Cells. J Immunol. 2019 Sep 23;: Authors: Wu Y, Konaté MM, Lu J, Makhlouf H, Chuaqui R, Antony S, Meitzler JL, Difilippantonio MJ, Liu H, Juhasz A, Jiang G, Dahan I, Roy K, Doroshow JH Abstract Dual oxidase 2 (DUOX2) generates H2O2 that plays a critical role in both host defense and chronic inflammation. Previously, we demonstrated that the proinflammatory mediators IFN-γ and LPS enhance expression of DUOX2 and its maturation factor DUOXA2 through STAT1- and NF-κB‒mediated signaling in human pancreatic cancer cells. Using a panel of colon and pancreatic cancer cell lines, we now report the induction of DUOX2/DUOXA2 mRNA and protein expression by the TH2 cytokine IL-4. IL-4 activated STAT6 signaling that, when silenced, significantly decreased induction of DUOX2. Furthermore, the TH17 cytokine IL-17A combined synergistically with IL-4 to increase DUOX2 expression in both colon and pancreatic cancer cells mediated, at least in part, by signaling through NF-κB. The upregulation of DUOX2 was associated with a significant increase in the production of extracellular H2O2 and DNA damage-as indicated by the accumulation of 8-oxo-dG and γH2AX-which was suppressed by the NADPH oxidase inhibitor diphenylene iodonium and a DUOX2-specific small interfering RNA. The clinical re...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research

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Source: Life Sciences - Category: Biology Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Small cell lung cancer (SCLC) is an aggressive lung cancer subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this disease has remained nearly unchanged for over 30 years. Here, we have taken a CRISPR-based screening approach to identify genetic vulnerabilities in SCLC that may serve as potential therapeutic targets. We used a single-guide RNA (sgRNA) library targeting ~5000 genes deemed to encode "druggable" proteins to perform loss-of-function genetic screens in a panel of cell lines derived from autochthonous genetically engineered m...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Authors: Zeng X, Liu Q, Yang Y, Jia W, Li S, He D, Ma R Abstract Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Surgical Endoscopy - Category: Surgery Source Type: research
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Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
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Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
AbstractThe application of robotic technology allows for the performance of multi-organ liver resections by multidisciplinary teams in a minimally invasive manner. Their technique and outcomes are not established. Herein we describe our technique with robotic liver surgery combined with colon, pancreas and urologic resections. Our patients are an 84-year-old (yo) female (Body Mass Index, BMI: 25) with a recently diagnosed right colon adenocarcinoma and two synchronous liver metastases at segments 5 and 6, a 75-year-old female (BMI: 50.4) with a history of right renal cell cancer status post (s/p) right robotic radical neph...
Source: Journal of Robotic Surgery - Category: Surgery Source Type: research
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