PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study
Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARγ), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARγ ligands could inhibit colorectal can...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2010/257835 |
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| author | Hirokazu Takahashi Kunihiro Hosono Takashi Uchiyama Michiko Sugiyama Eiji Sakai Hiroki Endo Shin Maeda Katherine L. Schaefer Hitoshi Nakagama Atsushi Nakajima |
| author_facet | Hirokazu Takahashi Kunihiro Hosono Takashi Uchiyama Michiko Sugiyama Eiji Sakai Hiroki Endo Shin Maeda Katherine L. Schaefer Hitoshi Nakagama Atsushi Nakajima |
| author_sort | Hirokazu Takahashi |
| collection | DOAJ |
| description | Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARγ), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARγ 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 PPARγ ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis. |
| format | Article |
| id | doaj-art-42575decfc4b40928803cf670d5444cc |
| institution | OA Journals |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-42575decfc4b40928803cf670d5444cc2025-08-20T02:37:46ZengWileyPPAR Research1687-47571687-47652010-01-01201010.1155/2010/257835257835PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot StudyHirokazu Takahashi0Kunihiro Hosono1Takashi Uchiyama2Michiko Sugiyama3Eiji Sakai4Hiroki Endo5Shin Maeda6Katherine L. Schaefer7Hitoshi Nakagama8Atsushi Nakajima9Gastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanGastroenterology and Hepatology Division, University of Rochester, Rochester, NY 14627, USABiochemistry Division, National Cancer Center Research Institute, Chuo-Ku, Tokyo 104-0045, JapanGastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, JapanActivating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARγ), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARγ 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 PPARγ ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis.http://dx.doi.org/10.1155/2010/257835 |
| spellingShingle | Hirokazu Takahashi Kunihiro Hosono Takashi Uchiyama Michiko Sugiyama Eiji Sakai Hiroki Endo Shin Maeda Katherine L. Schaefer Hitoshi Nakagama Atsushi Nakajima PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study PPAR Research |
| title | PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study |
| title_full | PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study |
| title_fullStr | PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study |
| title_full_unstemmed | PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study |
| title_short | PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study |
| title_sort | pparγ ligand as a promising candidate for colorectal cancer chemoprevention a pilot study |
| url | http://dx.doi.org/10.1155/2010/257835 |
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