title: Cytokines as important playmakers of experimental hepatocarcinogenesis confounded by diabetes.
abstract: OBJECTIVE
  To explore the possible intermediary pathways through which diabetes mellitus (DM) adversely worsens hepatocellular carcinoma (HCC), focusing on cell life controllers as some transcription factors and inflammatory mediators.
  
  
  METHODS
  Forty male albino rats were divided into four groups, control, cancer [given single intra-peritoneal (IP) dose of diethyl nitrosamine, NDEA, 125 mg/kg body weight], diabetic (given single dose of streptozotocin, STZ, 65 mg/kg) and cancer diabetic. HCC was initiated with NDEA, 3 weeks later, DM was induced with STZ. At 14th week, animals were sacrificed. Serum ALT, AST, GGT activities, AFP, IL-6, TNF-α levels and liver tissue Bax and Bcl2 proteins were measured. Liver sections were stained for histological examination. Both histological and AFP variations were chosen to prove cancer development.
  
  
  RESULTS
  NDEA group showed significant increase in liver weight, serum ALT, AST, GGT, AFP, TNF-α, IL-6 and liver Bcl2 protein with decrease in total body weight, liver Bax protein and Bax/Bcl2 ratio. These effects were more pronounced in DENA plus STZ group. IL-6, TNF-α and Bcl2 were positively correlated while Bax and Bax/Bcl2 ratio were negatively correlated to AFP levels reflecting potential diagnostic value.
  
  
  CONCLUSIONS
  Co-induction of DM in the course of hepatocarcinogenesis can dramatically influence disease progression through inflammation and retarded apoptosis. The suggested apoptotic and inflammatory markers seem to be beneficial diagnostic tools for HCC and improve the diagnostic performance of AFP.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Minia University, Egypt. nabilmohie@yahoo.com
authors.forename: Nabil M
authors.initials: NM
authors.lastname: Abdel-Hamid
authors.forename: Maiiada H
authors.initials: MH
authors.lastname: Nazmy
authors.forename: Manal I
authors.initials: MI
authors.lastname: Abdel-Ghany
authors.forename: Walaa H
authors.initials: WH
authors.lastname: Nazmy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism*; D015897:Comorbidity; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D013311:Streptozocin / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D004052:Diethylnitrosamine; D013311:Streptozocin