title: Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis.
  
  
  METHODS
  The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer). Rats were injected DEN at a dose of 30 mg/kg body weight twice a week for 11 weeks and the animals were observed until week 20. Time series sera and organ samples from the DEN animal model were collected to evaluate the dynamic changes.
  
  
  RESULTS
  It was found that serum biochemical indicators (AST, ALT, ALP, TP, T-BIL, IL-6, TNF-α) from DEN-treated group were higher than that from control group. Fibrosis-related index in serum and live tissue were increased, respectively, from week 4 after DEN treatment. The expression of TGF-β1 and α-SMA in DEN-treated group was higher than that in control group. JAK2/STAT3 signaling was significantly up-regulated in DEN-treated group compared to that in control group. The histological examination confirmed that the hepatocarcinogenesis model was successfully established, and 100% of the animals in the DEN-exposed group developed liver tumors at 20 weeks. According to the pathological changes, the model characterized resulted in three stages: the inflammation stage (week 2-6), the fibrosis stage (week 8-12), and the HCC stage (week 14-20).
  
  
  CONCLUSIONS
  The results suggested that the HCC development was associated with IFC axis. The serial progression of hepatocarcinogenesis was according to the sequence of hepatic inflammation, fibrosis and then hepatic tumor.
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.|Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Ding
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
authors.forename: Zhen-Hui
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.|Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wei
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.|Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China.
authors.forename: Luan
authors.initials: L
authors.lastname: Shu
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China. pengyunru@126.com.|Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China. pengyunru@126.com.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Peng
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D004052:Diethylnitrosamine; D018450:Disease Progression; D006505:Hepatitis / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004052:Diethylnitrosamine
keywords: Hepatocellular carcinoma; Inflammation-fibrosis-cancer (IFC) axis; Liver fibrosis; Liver inflammation