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Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

311 records · Page 18Linked to original sources

Oral HCFU for prevention of hepatic metastasis in an experimental colorectal carcinoma.

BACKGROUND: An animal experimental study was performed to clarify the preventive effect of oral HCFU (1-hexylcarbamoyl-5-fluorouracil) on hepatic metastasis. MATERIALS AND METHODS: A total of 180 BALB/C mice received intraportal injection of Colon26 cancer cells followed by oral daily administration of HCFU to 5 groups divided according to the dose of HCFU, ranging from 0 (controls) to 7.5 mg/Kg for 21 days. These groups were independently assigned to 3 sets to investigate survival rates and degree of hepatic metastasis. RESULTS: Mean survivals in the treated groups were statistically longer than the controls except the 7.5 mg/Kg group. HCFU 7.5 and 5 mg/Kg groups showed the minimum liver weight on the 12th and 16th day, respectively these were significantly smaller than those of controls (p < 0.0001 in both). CONCLUSION: It is considered that oral HCFU could effectively suppress hepatic metastasis of the colon26 cancer cells and prolong the life of animals. This finding suggests the promising clinical application of oral HCFU for colorectal cancer after curative resection.

Administration, Oral↗

Effects of interferon-beta in combination with 5-fluorouracil on the growth of esophageal cancer cells in vitro.

The possible antiproliferative potency of human recombinant interferon-beta (hIFN-beta) towards ten human esophageal cancer cell lines was examined in comparison with the activity of the factor towards human malignant melanoma cell lines. The cell growth of esophageal cancer cell lines was inhibited by hIFN-beta in a dose- and time- dependent manner. The 50% inhibitory concentrations (IC50) of hIFN-beta on nine cell lines out of ten ranged between 23 to 332 IU/ml of culture medium. The remaining cell line, T.Tn, was less sensitive to the interferon (IC50, 611 IU/ml). Under the same culture conditions, the melanoma cell lines tested differed markedly in their sensitivity to hIFN-beta. When the esophageal cancer cells were treated with 5-fluorouracil (5-FU) in the presence of a low concentration of hIFN-beta, the effectiveness of 5-FU was markedly enhanced. In particular, the rate of growth inhibition of T.Tn cells was more than the added potencies of 5-FU and hIFN-beta indicating that the interferon is an effective biomodulator of 5-FU. All these data suggest that combination therapy with hIFN-beta and the anticancer drug 5-FU would be beneficial for the treatment of carcinoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗

Antihypertensive effect of MK-421 in rats. Role of the renal kallikrein-kinin system.

To study the hypotensive mechanism of the new oral converting-enzyme inhibitor, MK-421, we evaluated the antihypertensive effect of MK-421 in rats with hypertension induced by chronic administration of norepinephrine (NE) or vasopressin and measured urinary kallikrein and kinin excretions as indices of the renal kallikrein-kinin system. When 6 mg/kg/day of MK-421 was administered simultaneously with 1.8 mg/kg/day of NE, the systolic blood pressure of conscious rats rose on Day 1 to only 122.6 +/- 3.4 mm Hg compared with the rise to 146.3 +/- 1.6 mm Hg when NE alone was infused (p less than 0.001). Similarly, when the same dose of MK-421 was administered simultaneously with 7.2 U/kg/day of vasopressin, the systolic blood pressure of conscious rats rose on Day 1 to only 117.4 +/- 3.8 mm Hg compared with the rise to 141.6 +/- 3.4 mm Hg when vasopressin alone was infused (p less than 0.01). The antihypertensive effect of MK-421 was sustained for 6 days in rats infused with NE or vasopressin. Infusion of NE alone resulted in a small but significant increase in urinary kallikrein excretion and no change in urinary kinin excretion. The combined administration of NE with MK-421 induced additional increases in urinary kallikrein and kinin excretions. Vasopressin alone resulted in marked decreases in urinary kallikrein and kinin excretions. The combined administration of vasopressin with MK-421 induced no additional changes in urinary kallikrein and kinin excretion. These results indicate that the hypotensive effect of MK-421 may depend on a reduced sensitivity of the peripheral arteries to vasoconstrictor substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

The association of metastasis with the expression of adhesion molecules in cell lines derived from human gastric cancer.

Peritoneal dissemination and hepatic metastasis commonly occur after patients with gastric cancer have undergone surgery. The presence of metastasis after surgery is sure to affect the prognosis of patients with gastric cancer. We conducted in vitro and in vivo studies to assess the role of adhesion molecules in this process, using 2 cell lines derived from human gastric cancer. Although both cell lines expressed several adhesion molecules to varying degrees, NUGC-4 cells, which disseminated early after inoculation into the abdominal cavity of nude mice accompanied by the formation of bloody ascitic fluid, predominantly expressed CD44H. However, MKN74 cells, which demonstrated hematogenous metastasis in the liver after inoculation into the spleen of nude mice, strongly expressed the sialyl Lewis(x) antigen (s-Le(x)), but did not express CD44H at all. When the binding of both these cancer cells to human umbilical vein endothelial cells was examined it was found that MKN74 cells adhered more strongly than NUGC-4 cells. The adhesion of cancer cells to endothelial cells was inhibited by treatment with antibodies against s-Le(x) and E-selectin. In the liver metastasis model of nude mice, treatment with anti-s-Le(x) antibodies significantly inhibited the development of MKN74 cell liver metastasis, both in the number of tumor nodules and in liver weight. NUGC-4 cells adhered to monolayers of mesothelial cells more strongly than MKN74 cells. The adhesion of NUGC-4 cells to these cells was partially inhibited by antibodies either against CD44H or the beta 1 subunit of integrin, but was completely blocked by a combination of these 2 antibodies. These antibodies markedly inhibited the dissemination of NUGC-4 cells in the peritoneal cavity of nude mice, and prolonged their mean survival time. These findings suggest that s-Le(x) and E-selectin mediate the adhesion of gastric cancer cells to endothelial cells, and CD44H and beta 1 integrin play important roles in the initial attachment of gastric cancer cells to mesothelial cells. It is possible that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of gastric cancer metastasis.

Animals↗