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Publication : Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model.

First Author  Wei C Year  2009
Journal  Cancer Lett Volume  277
Issue  2 Pages  149-54
PubMed ID  19147279 Mgi Jnum  J:147306
Mgi Id  MGI:3840046 Doi  10.1016/j.canlet.2008.11.036
Citation  Wei C, et al. (2009) Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model. Cancer Lett 277(2):149-54
abstractText  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.
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