***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents . The hypothesis was tested that , in healthy humans , p.o . administration of resveratrol is safe and results in measurable plasma levels of resveratrol . A phase I study of oral resveratrol ( single doses of 0.5 , 1 , 2.5 , or 5 g ) was conducted in 10 healthy volunteers per dose level .  Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-t and em mass spectrometry and quantitated by high-performance liquid chromatography-UV . Consumption of resveratrol did not cause serious adverse events . Resveratrol and six metabolites were recovered from plasma and urine . Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL ( 2.4 μmol/L , mean ± SD ; n = 10 ) , which occurred 1.5 h post-dose . Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher . The area under the plasma concentration curve ( AUC ) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol . Urinary excretion of resveratrol and its metabolites was rapid , with 77 % of all urinary agent-derived species excreted within 4 h after the lowest dose . Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy . However , the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52 Background and Objective Trans-resveratrol is a polyphenol , which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties . The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages . The present study aim ed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food , quercetin and alcohol ( ethanol ) . Methods This was a two-period , open-label , single-arm , within-subject control study in eight healthy subjects . The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a st and ard breakfast , a high-fat breakfast , quercetin 500 mg twice daily and 5 % alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with t and em mass spectrometry . Results The mean ( SD ) area under the plasma concentration-time curve from 0 to 12 hours ( AUC12 ) and maximum plasma concentration ( Cmax ) of trans-resveratrol  were 3558 ( 2195 ) ng •h/mL and 1274 ( 790 ) ng/mL , respectively , after the st and ard breakfast . The high-fat breakfast significantly decreased the AUC12 and Cmax by 45 % and 46 % , respectively , when compared with the st and ard breakfast . Quercetin 500 mg twice daily or 5 % alcohol 100mL did not influence trans-resveratrol pharmacokinetics . Diarrhoea was reported in six of the eight subjects . Significant but not clinical ly relevant changes from baseline were observed in serum potassium and total bilirubin levels . Conclusion Trans-resveratrol 2000 mg twice daily result ed in adequate exposure and was well tolerated by healthy subjects , although diarrhoea was frequently observed . In order to maximize trans-resveratrol exposure , it should be taken with a st and ard breakfast and not with a high-fat meal . Furthermore , combined intake with quercetin or alcohol did not influence trans-resveratrol exposure OBJECTIVE Colon cancer is an exceptionally aggressive disease , and the use of natural or synthetic substances to prevent or decrease cancer risk without adverse effects remains a major challenge . In this study , the mechanistic basis for the chemopreventive effect of resveratrol ( Res ) on 1,2-dimethylhydrazine-induced colon carcinogenesis in an rat model was evaluated . METHODS Rats were r and omized into six groups . Group 1 were control rats , group 2 were control rats that received Res ( 8mg/kg of body weight orally every day ) , and rats in groups 3 - 6 were treated once per week with 1,2-dimethylhydrazine ( 20mg/kg of body weight , subcutaenously , 15 times ) . In addition , groups 4 - 6 received Res ( as in group 2 ) in three dietary regimens : initiation , postinitiation , and entire period . All rats were sacrificed after 30 wk and the degree of inflammation , cell proliferation , apoptosis , and mucosal integrity was evaluated . RESULTS Res supplementation during the entire period significantly amended the expression of inflammatory , cell proliferative , and apoptotic biomarkers such as cyclo-oxygenase-2 , ornithine decarboxylase , caspase-3 , and heat shock proteins 70 and 27 . Moreover , supplementing Res for the entire study period modulated the colonic mucosal protein mucin 1 and 2 expression . CONCLUSION The results clearly indicate that chronic Res supplementation inhibited the colon cancer development through modulating the early and late events of carcinogenesis and helped to maintain the colonic mucosal integrity . Thus our study demonstrates that the chemopreventive efficacy of Res could be attributed to its action on multiple direct targets of carcinogenesis 
    Output:
    
Findings : The major mechanisms of actions through which resveratrol works include proapoptotic , antiproliferation , and anti-inflammation .
Pharmacokinetic human studies suggest good tolerability in healthy subjects , although they have low absorptive characteristics .
Conclusion : Resveratrol appears to have anticancer effects .
Additionally , these studies indicate that resveratrol 's chemoprevention effect is dose and duration dependent .
It has synergistic effect with anticancer drugs in vitro .