Document Detail

Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model.
MedLine Citation:
PMID:  19147279     Owner:  NLM     Status:  MEDLINE    
Germline mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder with a predisposition to gastrointestinal polyposis and cancer. Hyperactivation of mTOR-signaling has been associated with PJS. We previously reported that rapamycin treatment of Lkb1(+/-) mice after the onset of polyposis reduced the polyp burden. Here we evaluated the preventive efficacy of rapamycin on Peutz-Jeghers polyposis. We found that rapamycin treatment of Lkb1(+/-) mice initiated before the onset of polyposis in Lkb1(+/-) mice led to a dramatic reduction in both polyp burden and polyp size and this reduction was associated with decreased phosphorylation levels of S6 and 4EBP1. Together, these findings support the use of rapamycin as an option for chemoprevention and treatment of PJS.
Chongjuan Wei; Christopher I Amos; Nianxiang Zhang; Jing Zhu; Xiaopei Wang; Marsha L Frazier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-01-14
Journal Detail:
Title:  Cancer letters     Volume:  277     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-03-30     Completed Date:  2009-05-07     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  149-54     Citation Subset:  IM    
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MeSH Terms
Antibiotics, Antineoplastic / therapeutic use*
Carrier Proteins / physiology
Disease Models, Animal
Germ-Line Mutation
Intestinal Polyps / genetics,  pathology,  prevention & control*
Mice, Knockout
Peutz-Jeghers Syndrome / genetics,  pathology,  prevention & control*
Phosphotransferases (Alcohol Group Acceptor) / physiology
Protein-Serine-Threonine Kinases / genetics*
Signal Transduction
Sirolimus / therapeutic use*
TOR Serine-Threonine Kinases
Grant Support
CA 123603/CA/NCI NIH HHS; CA 16672/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; P30 CA016672-34S59033/CA/NCI NIH HHS; P30 ES 007784/ES/NIEHS NIH HHS; P30 ES007784-13/ES/NIEHS NIH HHS; P50 CA 70907/CA/NCI NIH HHS; P50 CA070907/CA/NCI NIH HHS; P50 CA070907-09/CA/NCI NIH HHS; P50 CA070907-10/CA/NCI NIH HHS; R03 CA123603-02/CA/NCI NIH HHS
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Carrier Proteins; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/Stk11 protein, mouse; EC Serine-Threonine Kinases; EC protein, mouse; EC Kinases; W36ZG6FT64/Sirolimus

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