Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n ¼ 123) or III (n ¼ 82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6 -80.4%) with PSK (n ¼ 137) and 58.8% (95% CI 47.1 -70.5%) in the controls (n ¼ 68) (P ¼ 0.016). POLYSACCHARIDE K reduced the recurrence by 43.6% (95% CI 4.5 -66.7%) and mortality by 40.2% (95% CI À12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3 -88.2%) in the PSK group and 72.1% (95% CI 61.4 -82.7%) in the control group (P ¼ 0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1 -72.9%) and 74.6% (95% CI 63.0 -86.1%) in the PSK group as compared with 32.1% (95% CI 14.8 -49.4%) and 46.4% (95% CI 28.0 -64.9%) in the controls (P ¼ 0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P ¼ 0.02; odds ratio 0.27; 95% CI 0.09 -0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712 -5.165; Po0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221 -3.633; P ¼ 0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017 -19.014; P ¼ 0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.
We report the inhibitory effect of topical application of extracts of a traditional Chinese herbal prescription on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Methanol and water extracts obtained from 22 traditional Chinese herbal prescriptions were assayed and their inhibition ratios calculated. In general, the methanol extracts produced more effective inhibition than the water extracts. Of the various traditional Chinese herbal prescriptions, the methanol extract of Rikkunshi-to was more effective than other prescriptions as far as inhibition of TPA-induced inflammation was concerned. Hoelen, Glycyrrhizae Radix, Atractylodis Rhizoma, components of Rikkunshi-to markedly inhibited the inflammatory activity involved by TPA in mice. Furthermore, topical application of the methanol extract of Rikkunshi-to markedly inhibited TPA-induced tumor promotion in two-stage carcinogenesis in mouse skin.
Acute gastric mucosal lesions are often observed after the intravenous administration of high doses of anticancer drugs. To investigate the acute toxic effects of such anticancer therapy on the gastric mucosa, 5-fluorouracil (5-FU) was administered intravenously to anesthetized rats. Gastric mucosal blood flow (GMBF) was measured continuously using laser Doppler velocimetry. Acid secretion was measured using a perfusion method for 1 h after the administration of 5-FU. No significant change was observed with a low dose of 5-FU (50 mg/kg), but a high doses of 5-FU (100 or 200 mg/kg) caused a significant decrease in GMBF in a dose-dependent manner. The selective antagonist of the muscarinic acetylcholine receptor, pirenzepine, prevented the decrease in GMBF with high doses of 5-FU. Acid secretion decreased after the administration of 5-FU, but not significantly. This study indicates that a decrease in GMBF may be an important factor in gastric mucosal injury induced by chemotherapy. Pirenzepine may prevent the gastric mucosal lesions which are induced by the administration of 5-FU.
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