PMID- 28415598
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20221207
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 22
DP  - 2017 May 30
TI  - Caloric restriction delays early phases of carcinogenesis via effects on the 
      tissue microenvironment.
PG  - 36020-36032
LID - 10.18632/oncotarget.16421 [doi]
AB  - Caloric restriction (CR) is an effective and consistent means to delay aging and 
      the incidence of chronic diseases related to old age, including cancer. However, 
      the precise mechanisms responsible for the beneficial effect of CR on 
      carcinogenic process are yet to be identified.In the present studies the 
      hypothesis was tested that the CR might delay carcinogenesis via modulatory 
      effects exerted on the age-associated, neoplastic-prone tissue microenvironment. 
      Using a well characterized, orthotopic cell transplantation (Tx) system in the 
      rat, preneoplastic hepatocytes isolated from liver nodules were injected into 
      either old syngeneic rats fed ad libitum (AL) or animals of the same age given a 
      CR diet (70% of AL feeding). Analysis of donor-derived cell clusters performed at 
      10 weeks post-Tx revealed a significant shift towards smaller class sizes in the 
      group receiving CR diet. Clusters comprising more than 50 cells, including large 
      hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of 
      spontaneous endogenous nodules was also decreased by CR. Markers of cell 
      senescence were equally expressed in the liver of AL and CR groups. However, 
      higher levels of SIRT1 and FOXO1 proteins were detected in CR-exposed livers, 
      while expression of HDAC1 and C/EBPbeta were decreased. These results are 
      interpreted to indicate that CR delays the emergence of age-associated neoplastic 
      disease through effects exerted, at least in part, on the tissue 
      microenvironment. Nutrient-sensing pathways might mediate such modulatory effect.
FAU - Cadoni, Erika
AU  - Cadoni E
AD  - Department of Biomedical Sciences, Unit of Experimental Medicine University of 
      Cagliari-Italy, Cagliari, Italy.
FAU - Marongiu, Fabio
AU  - Marongiu F
AD  - Department of Biomedical Sciences, Unit of Experimental Medicine University of 
      Cagliari-Italy, Cagliari, Italy.
FAU - Fanti, Maura
AU  - Fanti M
AD  - Department of Biomedical Sciences, Unit of Experimental Medicine University of 
      Cagliari-Italy, Cagliari, Italy.
FAU - Serra, Monica
AU  - Serra M
AD  - Department of Biomedical Sciences, Unit of Experimental Medicine University of 
      Cagliari-Italy, Cagliari, Italy.
FAU - Laconi, Ezio
AU  - Laconi E
AD  - Department of Biomedical Sciences, Unit of Experimental Medicine University of 
      Cagliari-Italy, Cagliari, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Foxo1 protein, rat)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.5.1.98 (Hdac1 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - *Caloric Restriction
MH  - Carcinogenesis
MH  - *Cell Transplantation
MH  - Cells, Cultured
MH  - Cellular Senescence
MH  - Hepatocytes/*pathology/transplantation
MH  - Histone Deacetylase 1/metabolism
MH  - Liver/*pathology
MH  - Liver Neoplasms/*diet therapy
MH  - Male
MH  - Nerve Tissue Proteins/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Sirtuin 1/metabolism
MH  - Tumor Microenvironment
PMC - PMC5482635
OTO - NOTNLM
OT  - aging
OT  - caloric restriction
OT  - carcinogenesis
OT  - microenvironment
OT  - pre-neoplastic hepatocytes
COIS- CONFLICTS OF INTEREST Authors declare no conflicts of interest.
EDAT- 2017/04/19 06:00
MHDA- 2018/03/27 06:00
PMCR- 2017/05/30
CRDT- 2017/04/19 06:00
PHST- 2017/02/07 00:00 [received]
PHST- 2017/03/14 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/05/30 00:00 [pmc-release]
AID - 16421 [pii]
AID - 10.18632/oncotarget.16421 [doi]
PST - ppublish
SO  - Oncotarget. 2017 May 30;8(22):36020-36032. doi: 10.18632/oncotarget.16421.