PMID- 23845075
OWN - NLM
STAT- MEDLINE
DCOM- 20140331
LR  - 20191112
IS  - 1875-6417 (Electronic)
IS  - 1573-3998 (Linking)
VI  - 9
IP  - 5
DP  - 2013 Sep
TI  - The influence of diabetes in the pathogenesis and the clinical course of 
      hepatocellular carcinoma: recent findings and new perspectives.
PG  - 382-6
AB  - Up to 50% of patients with hepatocellular carcinoma (HCC) have the so-called 
      "cryptogenic cirrhosis." Most of them are affected by at least one of the 
      condition characterizing the metabolic syndrome, as obesity or diabetes. Recent 
      observations found that type-2 diabetes mellitus (DM) confers a three-fold risk 
      of HCC. Main molecular feature of the conditions of metabolic syndrome is insulin 
      resistance, i.e. the reduced sensitivity to insulin action and, as consequence, 
      increased secretion of this hormone. Insulin resistance and hyperinsulinemia 
      influence hepatocarcinogenesis via several molecular pathways, such as 
      phosphatase and tensin homolog (PTEN)/P13K/Akt and MAPK kinase (MAPKK). Diabetes 
      also seems to influence negatively the prognosis and the clinical course of HCC 
      patients, independently from the cause of the underlying cirrhosis. It's well 
      known that insulin-sensitizing drugs may reduce the incidence of HCC. Metformin 
      activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has 
      growth inhibition effects on human cancer cell lines via inhibition of its 
      downstream target mammalian target of rapamycin (mTOR), and decreases the 
      expression of Livin, a protein involved in both cell proliferation and 
      survivalexpressed at high level in neoplastic cell. Also thiazolidinediones seem 
      to prevent tumor formation in the liver via the inhibition of peroxisome 
      proliferator-activated receptor gamma-independent regulation of nucleophosmin. 
      More debated is the role of sulfonylureas in decreasing HCC incidence in diabetic 
      patients. Further investigations are needed to define reliable indications to 
      therapy and surveillance in patients with diabetes or insulin resistance.
FAU - Facciorusso, Antonio
AU  - Facciorusso A
AD  - Section of Gastroenterology, Department of Medical Sciences, University of 
      Foggia, AOU Ospedali Riuniti, Viale Pintom, 71100 Foggia, Italy. 
      antonio.facciorusso@virgilio.it
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Diabetes Rev
JT  - Current diabetes reviews
JID - 101253260
RN  - 0 (Hypoglycemic Agents)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/pathology
MH  - Carcinoma, Hepatocellular/diagnosis/epidemiology/*etiology/therapy
MH  - Diabetes Mellitus, Type 2/*complications/diagnosis/epidemiology
MH  - Disease Progression
MH  - Fatty Liver/complications/epidemiology/pathology
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Insulin Resistance/physiology
MH  - Liver Neoplasms/diagnosis/epidemiology/*etiology/therapy
MH  - Non-alcoholic Fatty Liver Disease
EDAT- 2013/07/13 06:00
MHDA- 2014/04/01 06:00
CRDT- 2013/07/13 06:00
PHST- 2013/01/08 00:00 [received]
PHST- 2013/06/25 00:00 [revised]
PHST- 2013/06/25 00:00 [accepted]
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2014/04/01 06:00 [medline]
AID - CDR-EPUB-53510 [pii]
AID - 10.2174/15733998113099990068 [doi]
PST - ppublish
SO  - Curr Diabetes Rev. 2013 Sep;9(5):382-6. doi: 10.2174/15733998113099990068.