Chemoprevention of colorectal cancer.
Colorectal cancer is a disease with a high mortality rate and it has been increasing in prevalence worldwide. Chemoprevention, as well as primary and secondary prevention, for colorectal cancer have attracted much attention. Many chemopreventive trials have been performed, and several agents, including nonsteroidal antiinflammatory drugs, such as aspirin and sulindac, cyclooxygenase-2 selective inhibitors, such as celecoxib, vitamin D, folate, and calcium, have been shown to have some effect. In these chemopreventive trials, the targeted lesions used for evaluation were mainly polyps. However, the chemopreventive effects of some agents on polyps may require several years to evaluate. Further, larger polyps may not be susceptible to chemopreventive agents. Aberrant crypt foci (ACF) are tiny lesions at the earliest stage of colorectal carcinogenesis, which consist of large, thick crypts identified by dense, methylene blue staining. We succeeded in identifying human ACF in situ using magnifying endoscopy and found that the number of ACF, particularly dysplastic ACF, increased significantly from normal subjects to adenoma patients and then to cancer patients. We also found that the number, size, and dysplastic features of ACF are significantly correlated with the number of adenomas in adenoma patients. Thus, it was surmised that ACF are precursor lesions of the adenoma-carcinoma sequence in humans and that ACF may be the most appropriate lesions as targets for chemoprevention. We have shown that the number of ACF was significantly reduced in patients treated with sulindac. We are currently proceeding with a randomized, double-blind, chemopreventive trial targeting ACF.
Niitsu
Yoshiro
Y
4th Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, 060-8543 Sapporo, Japan. niitsu@sapmed.ac.jp
Takayama
Tetsuji
T
Miyanishi
Koji
K
Nobuoka
Atsushi
A
Hayashi
Tsuyoshi
T
Kukitsu
Takehiro
T
Takanashi
Kunihiro
K
Ishiwatari
Hirotoshi
H
Abe
Tomoyuki
T
Kogawa
Takahiro
T
Takahashi
Minoru
M
Matsunaga
Takuya
T
Kato
Junji
J
D000818:Animals; D018890:Chemoprevention; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007417:Intestinal Polyps / Q000188:drug therapy; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D011230:Precancerous Conditions / Q000188:drug therapy
D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse