Shinichiro Yoshitani

Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiber zerumbet

The modifying effects of dietary feeding of zerumbone isolated from Zingiber zerumbet on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed. In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei. To induce ACF rats were given three weekly subcutaneous injections of AOM (15 mg/kg body weight). They were also fed the experimental diet containing 0.01% or 0.05% zerumbone for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 84+/-13 ACF/rat at the end of the study (week 5). Dietary administration of zerumbone caused reduction in the frequency of ACF: 72+/-17 (14% reduction) at a dose of 0.01% and 45+/-18 (46% reduction, p<0.001) at a dose of 0.05%. Feeding of zerumbone significantly reduced expression of COX-2 and prostaglandins in colonic mucosa. Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei. These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF.

Troglitazone, a Ligand for Peroxisome Proliferator-activated Receptor γ Inhibits Chemically-induced Aberrant Crypt Foci in Rats

The biological roles of peroxisome proliferator‐activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARγ ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present tune‐course study was conducted to investigate possible modifying effects of a PPARγ ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg/kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg/kg b.w.)‐induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARγ ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.

Efficacy of Postoperative UFT (Tegafur/Uracil) Plus PSK Therapies in Elderly Patients with Resected Colorectal Cancer

To establish the sufficient therapy for elderly colorectal cancer patients, we retrospectively compared postoperative Tegafur/Uracil (UFT; Taiho Pharmaceutical Co., Ltd., Tokyo, Japan) and UFT plus protein-bound polysaccharide kureha (PSK) therapies in elderly patients with resected colorectal cancer. A total of 63 patients were collected; 39 patients were administered only with UFT (control group) and 24 patients were treated with UFT+PSK (PSK group). There were no differences in patient background, surgical outcomes, and drug compliance between the two groups. The 3-year relapse-free survival rate was 47.8% in the control group and 76.2% in the PSK group (p = 0.041). The 3-year overall survival (OS) rate was 52.8% in the control group and 80.8% in the PSK group (p = 0.0498). By subset analysis, in the patients whose tumor location was the colon (p = 0.016) and whose preoperative lymphocyte percentage was below 18.7% (p = 0.017), RFS was significantly better in the PSK group. Adverse drug reactions were rarely observed. All the adverse reactions were grade 2 or below, with no severe reactions. The present retrospective study suggests a possible efficacy of postoperative adjuvant therapy with UFT plus PSK in elderly patients over 70 years of age with resected colorectal cancer.