Promotion of Liver and Lung Tumorigenesis in DEN-Treated Cytoglobin-Deficient Mice
Le Thi Thanh Thuy,Takashi Morita,Kayo Yoshida,Kenichi Wakasa,Masashi Iizuka,Tomohiro Ogawa,Mami Mori,Yumiko Sekiya,Shinobu Momen,Hiroyuki Motoyama,Kazuo Ikeda,Katsutoshi Yoshizato,Norifumi Kawada +12 more
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TLDR
It is suggested that Cygb deficiency induces susceptibility to cancer development in the liver and lungs of mice exposed to DEN, and globins such as Cygb will shed new light on the biological features of organ carcinogenesis.Abstract:
Cytoglobin (Cygb) is a recently discovered vertebrate globin with molecular characteristics that are similar to myoglobin. To study the biological function of Cygb in vivo, we generated Cygb knockout mice and investigated their susceptibility to N,N-diethylnitrosamine (DEN)–induced tumorigenesis. Four-week-old male mice were administered DEN in drinking water at a dose of 25 ppm for 25 weeks or 0.05 ppm for 36 weeks. Cygb deficiency promoted the DEN-induced development of liver and lung tumors. All Cygb+/− and Cygb−/− mice treated with 25-ppm DEN exhibited liver tumors, compared with 44.4% of their wild-type counterparts. Lung tumors were present only in Cygb-deficient mice. More than 40% of Cygb−/− mice developed liver and lung tumors at the nontoxic dose of DEN (0.05 ppm), which did not induce tumors in wild-type mice. Cygb loss was associated with increased cancer cell proliferation, elevated extracellular signal–regulated kinase and Akt activation, overexpression of IL-1β, IL-6, Tnfα, and Tgfβ3 mRNAs, and hepatic collagen accumulation. Cygb-deficient mice also exhibited increased nitrotyrosine formation and dysregulated expression of cancer-related genes (cyclin D2, p53, Pak1, Src, Cdkn2a, and Cebpa). These results suggest that Cygb deficiency induces susceptibility to cancer development in the liver and lungs of mice exposed to DEN. Thus, globins such as Cygb will shed new light on the biological features of organ carcinogenesis.read more
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Journal ArticleDOI
Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice.
TL;DR: The outcome of liver injury after the application of DEN in mice appears to be a suitable animal model for the analysis of some aspects and processes that promote the pathogenesis of hepatocellular carcinoma in humans.
Journal ArticleDOI
Role of the Gut-Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship.
Naoko Ohtani,Norifumi Kawada +1 more
TL;DR: This review introduces and discusses the mechanisms of liver inflammation, fibrosis, and cancer that are influenced by gut microbial components and metabolites and includes recent advances in molecular‐based therapeutics and novel mechanistic findings associated with the gut–liver axis and gut microbiota.
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Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver.
Erika Ramos-Tovar,Pablo Muriel +1 more
TL;DR: In this paper, the authors link the activation of the NF-κB and NLRP3 signaling pathways via reactive oxygen species (ROS) and thioredoxin-interacting protein, respectively, linking the molecular mechanisms of oxidative stress, inflammation and fibrosis.
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Implication of nano-antioxidant therapy for treatment of hepatocellular carcinoma using PLGA nanoparticles of rutin.
Preeti Pandey,Mahfoozur Rahman,Prakash Chandra Bhatt,Sarwar Beg,Basudev Paul,Abdul Hafeez,Fahad A. Al-Abbasi,Muhammad Nadeem,Othman A. S. Baothman,Firoz Anwar,Vikas Kumar +10 more
TL;DR: Histopathological evaluation indicated reduced incidence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessel inflammation and cell swelling with RT-PLGA-NP treatment along with considerable downregulation in the levels of proinflammatory cytokines.
Journal ArticleDOI
Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall.
Xiaoping Liu,Mohamed A. El-Mahdy,James Boslett,Saradhadevi Varadharaj,Craig Hemann,Tamer M. Abdelghany,Raed S. Ismail,Sean C. Little,Danlei Zhou,Le Thi Thanh Thuy,Norifumi Kawada,Jay L. Zweier +11 more
TL;DR: It is demonstrated that knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance, and it is suggested that modulation of the expression and NOD activity ofCygb represents a strategy for the treatment of cardiovascular disease.
References
More filters
Journal ArticleDOI
Immunity, Inflammation, and Cancer
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
Journal ArticleDOI
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
Lisa M. Coussens,Teresa L. Yang-Feng,Yu Cheng Liao,Ellson Y. Chen,Alane M. Gray,John P. McGrath,Peter H. Seeburg,Towia A. Libermann,Joseph Schlessinger,Uta Francke,Arthur D. Levinson,Axel Ullrich +11 more
TL;DR: A novel potential cell surface receptor of the tyrosine kinase gene family has been identified and characterized by molecular cloning and its primary sequence is very similar to that of the human epidermal growth factor receptor and the v-erbB oncogene product.
Journal ArticleDOI
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Christopher J. Sinal,Masahiro Tohkin,Masaaki Miyata,Jerrold M. Ward,Gilles Lambert,Frank J. Gonzalez +5 more
TL;DR: It is demonstrated that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile Acid sensor.
Journal ArticleDOI
The role of signaling pathways in the development and treatment of hepatocellular carcinoma.
TL;DR: The role of the RAF/MEK/ERK pathway, phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, WNT/β-catenin pathway, insulin-like growth factor pathway, hepatocyte growth factor/c-MET pathway and growth factor-regulated angiogenic signaling are explored.
Book ChapterDOI
IL-6 signal transduction and its physiological roles: the signal orchestration model
TL;DR: In this paper, a signal orchestration model was proposed to explain how IL-6 can elicit proinflammatory or anti-inflammatory effects, depending on the in vivo environmental circumstances, which can be seen as a consequence of the orchestration of diverse signaling pathways generated by a given ligand.