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PPAR Research
Volume 2010, Article ID 257835, 4 pages
Clinical Study

PPAR 𝛾 Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study

1Gastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan
2Gastroenterology and Hepatology Division, University of Rochester, Rochester, NY 14627, USA
3Biochemistry Division, National Cancer Center Research Institute, Chuo-Ku, Tokyo 104-0045, Japan

Received 30 April 2010; Revised 22 June 2010; Accepted 29 June 2010

Academic Editor: Dipak Panigrahy

Copyright © 2010 Hirokazu Takahashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPAR 𝛾 ), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPAR 𝛾 ligands could inhibit colorectal cancer cell growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF) have come to be established as a biomarker of the risk of CRC in azoxymethane-treated mice and rats. In humans, ACF can be detected using magnifying colonoscopy. Previously, CRC and adenoma were used as a target for chemopreventive agents, but it needs a long time to evaluate, however, ACF can be a surrogate marker of CRC even for a brief period. In this clinical study, we investigated the chemopreventive effect of pioglitazone on the development of human ACF as a surrogate marker of CRC. Twenty-nine patients were divided into two groups, 20 were in the endoscopically normal control group and 9 were in the pioglitazone (15 mg/day) group, and ACF and adenoma were examined before and after 1-month treatment. The number of ACF was significantly decreased ( 5 . 8 ± 1 . 1 to 3 . 3 ± 2 . 3 ) after 1 month of pioglitazone treatment, however, there was no significant change in the number of crypts/ACF or in the number and size of adenomas. Pioglitazone may have a clinical application as a cancer-preventive drug. This investigation is just a pilot study, therefore, further clinical studies are needed to show that the PPAR 𝛾 ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis.