Abstract:
:Several promising chemopreventive agents have for lung cancer emerged in preclinical models and in retrospective trials. These agents have been shown to modulate pathways altered in carcinogenesis and reduce markers of carcinogenesis in animal and cell culture models. Cancer-prone transgenic mice with oncogenic Kras expressed in the airway epithelium (CcspCre/+ ; KrasLSL-G12D/+ ) were raised on diets compounded with myo-inositol. These animals form lung premalignant lesions in a stereotypical fashion over the ten weeks following weaning. Mice raised on myo-inositol containing diets showed potent reduction in the number, size, and stage of lesions as compared to those raised on control diets. myo-inositol has previously been reported to inhibit phosphoinositide 3-kinase (PI3K) signaling. However, in mice raised on myo-inositol, total PI3K signaling was largely unaffected. Proteomic and cytokine analyses revealed large reduction in IL-6 related pathways, including STAT3 phosphorylation. This effect was not due to direct inhibition of IL-6 production and autocrine signaling within the tumor cell, but rather through alteration in macrophage recruitment and in phenotype switching, with an increase in antitumoral M1 macrophages.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Unver N,Delgado O,Zeleke K,Cumpian A,Tang X,Caetano MS,Wang H,Katayama H,Yu H,Szabo E,Wistuba II,Moghaddam SJ,Hanash SM,Ostrin EJdoi
10.1002/ijc.31152subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1405-1417issue
7eissn
0020-7136issn
1097-0215journal_volume
142pub_type
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