Polyethylene glycol and prevalence of colorectal adenomas

Dorval, Étienne; Jankowski, Jean Marie; Barbieux, Jean-Pierre; Viguier, J.; Bertrand, Philippe; Brondin, Brigitte; Bougnoux, Philippe; Corpet, Denis E.

doi:10.1016/s0399-8320(06)73511-4

Cited by 14 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our group confirmed that this was not model-specific by demonstrating the efficacy of PEG 3350 in the MIN (multiple intestinal neoplasias) mouse model, a genetically driven model of intestinal neoplasia (23). While definitive (randomized placebo-controlled) studies are ongoing, it is heartening to note a 52% neoplasia risk reduction with PEG in a casecontrol study (15). The effect size in this clinical study is at least comparable and probably superior to the efficacy reported with NSAIDs.…”

Section: Discussionsupporting

confidence: 63%

“…Polyethylene glycol (PEG) has recently received attention as a promising chemopreventive agent of a superior capacity with potent anti-proliferative properties in both cell culture and animal models of colon carcinogenesis (12)(13)(14). This promising effect has also been corroborated in a pilot clinical (case-control) study (15). The chemopreventive efficacy of PEG appears to be better than that of widely used NSAIDs (16) and notably, its safety profile appears outstanding given that it is not systemically absorbed.…”

Section: Introductionmentioning

confidence: 74%

See 1 more Smart Citation

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

Roy

Koetsier²,

Tiwari³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Polyethylene glycol (PEG) is a safe and effective chemopreventive agent against colorectal carcinogenesis in cell culture, animal models and human subjects. Although the precise molecular mechanism is unclear, we previously reported that PEG suppresses colonic epithelial proliferation. As cellular proliferation is driven by complex G1-S phase transition, we now characterize the role of PEG on cell cycle regulation. We focused our attention on the effect of PEG on the CDK inhibitor p21 cip1/waf1 , which is implicated in early colon carcinogenesis and is upregulated by non-steroidal anti-inflammatory drugs. These studies were done in the azoxymethane-treated (AOM) rat model as well as in HT-29 colon cancer cells. Immunohistochemical analysis revealed that while AOM decreased the p21 expression (75%, p<0.01) in the premalignant colonic mucosa, PEG induced p21 levels back to normal. These findings paralleled a decreased BrdUrd incorporation (78%, p<0.001) and hypophosphorylated retinoblastoma protein (Rb; by 47%) signifying PEG's antiproliferative activity. Furthermore, in HT-29 cells, PEG decreased proliferation as measured by PCNA (68% reduction), increased p21 expression (2.3-fold), induced cell cycle arrest during G0/G1 phase (45% reduction in S phase cells) and inhibited the phosphorylation of Rb (by 52% compared to untreated). PEG caused greater than a 2-fold induction of protein and mRNA level of p21 cip1/waf1 in HT-29 cells. These results demonstrate for the first time that PEG is involved in p21 regulation concomitant with G1➝S phase cell cycle arrest and it is through these effects that it can exert its anti-proliferative and hence chemopreventive role.

show abstract

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 74%

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

Roy

Koetsier²,

Tiwari³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…The first example is the serendipitous discovery that polyethylene glycol (PEG) is a potent chemopreventive agent in rats (100). Four years later, a population study showed that humans taking PEG-based laxatives have only half the risk of developing colorectal adenoma compared to non-users (101). Another example is beef meat promotion of carcinogenesis in rats.…”

Section: Discussionmentioning

confidence: 99%

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Corpet

Pierre

2005

European Journal of Cancer

Self Cite

201

128

View full text Add to dashboard Cite

To cite this version:Denis E Corpet, Fabrice Pierre. How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men.. European Journal of Cancer, Elsevier, 2005, 41 (13), pp.1911-22. <10.1016/j.ejca.2005.06.006>. D.E. Corpet, F. Pierre / European Journal of Cancer 41 (2005) 1911-1922 AbstractTumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we made a meta-analysis of aspirin, betacarotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention.

show abstract

“…Given the chemoprevention potential demonstrated in rats and mice it was considered worth investigating the role of macrogols as a chemopreventive agent of colorectal cancer in humans. To our knowledge only one study has attempted to evaluate the chemopreventive potential of macrogol laxatives in humans [19]. In this population based cross-sectional study findings suggestive of a protective effect of one macrogol-4000 based laxative were observed, however no consideration was given to the timing of macrogol exposure in relation to disease initiation or to the duration or quantity of macrogol use [19].…”

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Risk Reduction following Macrogol Exposure: A Cohort and Nested Case Control Study in the UK

et al. 2013

View full text Add to dashboard Cite

Background and AimsAnimal studies have demonstrated macrogol laxatives may reduce colorectal cancer (CRC) risk. This study aimed to investigate the association between macrogol prescribing and CRC risk.MethodsA case-control study nested within a cohort of laxative users was conducted using data from the UK General Practice Research Database. Six controls per case were identified and to account for the lead time of CRC, additional control sets were selected on the index date backdated by 1 to 5 years. Exposure to macrogols and covariate status before each of the backdated index dates was established. Conditional logistic regression was used to calculate the risk of CRC following macrogol prescribing adjusted for potential confounders.Results4734 incident CRC cases were identified; 2722, 2195, 1789, 1481 and 1214 had received a laxative prescription before the index dates backdated by 1 to 5 years. A suggestion of a non-significant reduction in CRC risk associated with ‘macrogol after other laxative’ prescribing was observed when the index date was backdated by 1 and 2 years, ORadj = 0.87 (CI950.74–1.03) and ORadj = 0.80 (CI950.65–1.00) compared to non-macrogol laxative exposure. The odds ratios reduced further and were significant when backdated by 3, 4 and 5 years, ORadj = 0.68 (CI950.50–0.92), ORadj = 0.60 (CI950.40–0.90) and ORadj = 0.30 (CI950.14–0.64) respectively. This reduction in risk was not observed, however, for ‘macrogol only’ and ‘macrogol before other laxative’ exposure categories.ConclusionsIn this study we observed a reduced CRC risk associated with macrogol prescribing after accounting for the lead time for CRC. Further studies are required to determine whether the association is causal and whether it can partly be explained by selective prescribing.

show abstract

Polyethylene glycol and prevalence of colorectal adenomas

Cited by 14 publications

References 26 publications

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Colorectal Cancer Risk Reduction following Macrogol Exposure: A Cohort and Nested Case Control Study in the UK

Contact Info

Product

Resources

About