Antitumor effect of S-1 on DMH induced colon cancer in rats.

The aim of this study was to establish an autochthonous colon cancer model in the rat as an in vivo secondary screen for the general evaluation of new anticancer agents against colorectal cancer, and also to evaluate practically the antitumor activity of 1M tegafur-0.4M 5- chloro-2,4-dihydroxypyridine-1M potassium oxonate(S-1), a new p.o. fluoropyrimidine. Thirty-two Sprague-Dawley rats received dimethlhydrazine(40 mg/kg) s.c. once weekly for 10 weeks to induce colon cancer.20 weeks after beginning the carcinogen treatment, a barium enema was performed to visualize tumors. The animals were divided into a control group and S-1 treatment group. After 5 weeks of treatment, the barium enema was repeated. The mean doubling time of 24 tumors in the control group was 19.0 + 8.4 (SD) days. Response to S-1 was judged as effective when the doubling time exceeded 35.8 days, calculated from the mean + 2SDs in the control group. The response rate of S-1 was 55%, 34% of the tumors were decreased in size after treatment. This figure was higher than that of clinically-used 5-fluorouracil(5-FU) derivatives; 5-FU;6%, Tegafur(FT):6%, 1M tegafur-4M uracil(UFT):14%, reported in our previous study. An autochthonous colon cancer model is useful to evaluate the clinical therapeutic efficacy of drugs for colorectal cancer, and S-1 is expected to have a high therapeutic effect on human colorectal cancer.

[A model for sensitivity determination of anticancer agents against chemical-induced colon cancer in rats].

Chemically-induced colon cancer was used to test the sensitivity of tumors to chemotherapeutic agents. Thirty-four Sprague-Dawley rats received dimethylhydrazine (40 mg/kg) s.c. once weekly for 10 weeks to induce colon cancer. Twenty weeks after beginning the carcinogen treatment, a barium enema was performed to determine the size of colon tumors. The animals were divided into CDDP group and CPT-11 group, in which the maximum tolerable dose of each drug was given. After 5 weeks of treatment, the barium enema was repeated. "Response" was assessed on the basis of tumor doubling time. Response rates in the CDDP and CPT-11 groups were 6% and 35%, respectively. This reflects the clinical data of those drugs and confirms the results of our previous study. The present study may be a predictive model for screening anticancer drugs for human colorectal malignancy.

Growth rate of experimental colon cancer in the absence of fecal stream and antitumor effect of UFT in rats.

Growth rate of a chemically-induced colon tumor in the absence of fecal stream was investigated and the tumors to a chemotherapeutic agent tested. Eighty Sprague-Dawley rats received dimethylhydrazine (40 mg/kg) s.c. once weekly for 10 wk to induce colon cancer. Then a colostomy was performed to produce a defunctioning colon without fecal stream. 22 wk after beginning the carcinogen treatment, a barium enema was performed to visualize tumors in the defunctionalized colon. 29 rats died postoperatively and 16 had no tumor radiographically. The remaining 35 rats were divided into a control group and UFT treatment group. After 5 wk of treatment, the barium enema was repeated. The mean doubling time of 19 tumors in the control group was 9.8 days +/- 4.0 (SD). Response to UFT was judged as effective when the doubling time exceeded 17.8 days, calculated from the mean +/- 2SDs in the control group. The response rate of UFT was 48%. The growth rate of colon tumors without fecal stream was faster and more stable than those with fecal stream; as a result, the sensitivity to UFT became higher than that in tumors with fecal stream (36%), which was reported in our previous study. The present experimental system may be more accurate for assessing the response to chemotherapeutic agents.

A model for sensitivity determination of anticancer agents against chemically-induced colon cancer in rats.

Chemically-induced colon cancer was used to test the sensitivity of tumors to chemotherapeutic agents. Seventy-one Sprague-Dawley rats received dimethylhydrazine (20mg/kg) s.c. once weekly for 20 weeks to induce colon cancer. Then a barium enema was performed to see the size of colon tumors. The animals were divided into three groups that were subjected to the following treatments: 5-fluorouracil (5 FU); 1-(2-tetrahydrofuryl)-5 FU(FT); and a mixture of FT and uracil (UFT). After 5 weeks of treatment, the barium enema was repeated. "Response" was assessed on the basis of tumor doubling time. Response rates in the 5-FU, FT, and UFT groups were 25%, 33% and 36%, respectively and this reflects the clinical data of these drugs. The present system may be a predictive model for screening anticancer drugs for human colorectal cancer.

Reduced growth rate of dimethylhydrazine-induced colon tumors in rats.

alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.

[Growth rate of experimental colonic cancer in rats].

Colonic cancers were induced in rats by subcutaneous injection of 1,2-Dimethylhydrazine. Tumor growth patterns were estimated by means of a double contrast barium enema technique. Tumor growth was almost exponential and the average doubling time was 20 +/- 5 (m +/- S.D.) days, at which time three different types of tumor growth patterns: Constant type, decreasing type and reaccelerating type, were noted. Serial double contrast barium enema technique appeared to be an useful method of studying in vivo primary colonic cancer growth patterns in rats.

Sonotubometric measurement of the eustachian tube function by means of band noise. A clinical view of the acoustic measurement of the eustachian tube.

The Eustachian tube is well known as an organ serving the ventilation and drainage of the tympanic cavity and mastoid. Ventilation is carried out by the opening and closing of the Eustachian tube accompanying swallowing movements. Until now there has been no instrument to quantify these motor activities of the tube necessary for its function as a ventilator. The author developed a generally applicable sonotubometer Model WIO-01 with the help of Siemens Hearing Institute K.K. for automatic measurement of the aforesaid tubal function with the use of 7 kHz full-octave band noise. In a sonotubometric trial with 32 adult female subjects, the duration of patency of the Eustachian tube was 288.5 +/- 1.38.5 ms, and the amplitude eliciting response was 16.4 +/- 8.3 dB. The positive response rate was 89.1%. In 89 children aged 4-12 years, a positive response was detected in 117 ears (61.9%). The mean duration of patency was 337.7 +/- 154.4 ms, and the amplitude 16.3 +/- 7.2 dB. It is physiological to have tubal opening and closing during natural swallowing. It is therefore important to understand the tubal function when dealing with tympanoplasty and diseases caused by tubal dysfunction.