title: Advances in Hypoxia-Mediated Mechanisms in Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC development and its therapies. However, direct and accurate measurement of oxygen concentration and evaluation of hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions shown by measuring partial pressure of oxygen (pO2), the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC. For the mechanisms, we focus mainly on the roles of oxygen-sensing proteins (i.e., hypoxia-inducible factor and neuroglobin) and hypoxia-induced signaling proteins (e.g., matrix metalloproteinases, high mobility group box 1, Beclin 1, glucose metabolism enzymes, and vascular endothelial growth factor). With respect to therapies, we discuss mainly YQ23, sorafenib, 2-methoxyestradiol, and celastrol. This review focuses primarily on the results of clinical and animal studies.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin Xin
authors.initials: XX
authors.lastname: Xiong
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin Yao
authors.initials: XY
authors.lastname: Qiu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dian Xing
authors.initials: DX
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China chenxq@mails.tjmu.edu.cn.
authors.forename: Xiao Qian
authors.initials: XQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D000071186:Beclin-1 / Q000502:physiology; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D015687:Cell Hypoxia; D005914:Globins / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D024243:HMGB1 Protein / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045726:Metalloproteases / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D000078787:Neuroglobin; D010100:Oxygen / Q000032:analysis; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000071186:Beclin-1; D015415:Biomarkers; D005914:Globins; D005947:Glucose; D024243:HMGB1 Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D045726:Metalloproteases; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human