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Cancer Prevention Research
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Cell, Molecular, and Tumor Biology

Abstract A43: PPARδ promotes colonic inflammation and inflammation-associated tumorigenesis

Dingzhi Wang, Lixia Guo, Wei Ning and Raymond N. DuBois
Dingzhi Wang
1University of Texas MD Anderson Cancer Center, Houston, TX
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Lixia Guo
1University of Texas MD Anderson Cancer Center, Houston, TX
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Wei Ning
2Vanderbilt Medical School, Nashville, TN.
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Raymond N. DuBois
1University of Texas MD Anderson Cancer Center, Houston, TX
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DOI: 10.1158/1940-6207.PREV-11-A43 Published October 2011
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Abstracts: AACR International Conference on Frontiers in Cancer Prevention Research‐‐ Oct 22-25, 2011; Boston, MA

Abstract

Although epidemiologic and experimental evidence strongly indicates chronic inflammation as a risk factor for cancer, it remains unclear how chronic inflammation contributes carcinogenesis. Here we show that deletion of PPARδ diminishes colonic inflammation by reducing infiltration of immune cells via downregulation of pro-inflammatory chemokines and cytokine in a mouse model of colon inflammation. These chemokines are responsible for recruitment of leukocytes from the circulation to local inflammatory sites. Our results further reveal that COX-2 is a downstream target of PPARδ and COX-2-derived PGE2 stimulates macrophages to produce pro-inflammatory chemokines and cytokine. PGE2 is a crucial mediator of colorectal carcinogenesis. More importantly, loss of PPARδ attenuated colonic inflammation-associated adenoma growth in two mouse models of inflammation-associated colorectal cancer. Our results demonstrate that PPARδ promotes chronic colonic inflammation and colitis-associated tumorigenesis. Collectively, these findings indicate that PPARδ plays a pivotal role in connecting colonic inflammation to cancer progression and may represent a potential therapeutic target for prevention or treatment of colorectal cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A43.

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Cancer Prevention Research: 4 (10 Supplement)
October 2011
Volume 4, Issue 10 Supplement
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Abstract A43: PPARδ promotes colonic inflammation and inflammation-associated tumorigenesis
Dingzhi Wang, Lixia Guo, Wei Ning and Raymond N. DuBois
Cancer Prev Res October 1 2011 (4) (10 Supplement) A43; DOI: 10.1158/1940-6207.PREV-11-A43

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Abstract A43: PPARδ promotes colonic inflammation and inflammation-associated tumorigenesis
Dingzhi Wang, Lixia Guo, Wei Ning and Raymond N. DuBois
Cancer Prev Res October 1 2011 (4) (10 Supplement) A43; DOI: 10.1158/1940-6207.PREV-11-A43
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Cancer Prevention Research
eISSN: 1940-6215
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