title: A Possible Role for TNF-α in Coordinating Inflammation and Angiogenesis in Chronic Liver Disease and Hepatocellular Carcinoma.
abstract: BACKGROUND
  Increasing evidence supports the hypothesis that chronic and persistent inflammation contributes to cancer development. However, the molecular mechanisms that lead to cancer in chronic inflammation and the role of angiogenesis in inflammation-associated cancer remain poorly understood.
  
  
  METHODS
  NINETY PATIENTS WERE ENROLLED: 30 cases of CHC without cirrhosis, 28 cases of CHC with liver cirrhosis, and 32 cases of HCC and hepatitis C virus infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, served as normal controls. Serum TNF-α levels were measured using the ELISA technique; in situ hybridization and immunohistochemical studies were used to detect hepatic levels of messenger RNA (mRNA) transcripts and mature protein, respectively, for both TNF-α and VEGF.
  
  
  RESULTS
  The highest hepatic expression of TNF-α was noticed in liver cirrhosis specimens compared to noncirrhotic CHC and HCC. Hepatic expression of VEGF and serum level of TNF-α revealed significant increases in the progression of the disease. Moreover, cases with higher grades of inflammation or stages of fibrosis showed significant increases in serum TNF-α and expression of TNF-α and VEGF. Expression of mRNA of both TNF-α and VEGF shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positivity in cases developed HCC.
  
  
  CONCLUSIONS
  VEGF signaling could be one of the molecular signaling pathways involved in TNF-α induced angiogenesis which might pose an important link between inflammation and fibrosis in CHC and HCC development and progression. Moreover, serum inflammatory biomarkers can be used to monitor the disease progression.
authors.affiliation: Department of Pathology.
authors.forename: Olfat
authors.initials: O
authors.lastname: Hammam
authors.forename: Ola
authors.initials: O
authors.lastname: Mahmoud
authors.forename: Manal
authors.initials: M
authors.lastname: Zahran
authors.forename: Azza
authors.initials: A
authors.lastname: Sayed
authors.forename: Rabab
authors.initials: R
authors.lastname: Salama
authors.forename: Karim
authors.initials: K
authors.lastname: Hosny
authors.forename: Ahmed
authors.initials: A
authors.lastname: Farghly