Yutaka Yukawa

Microangiographic and histologic analysis of the effects of hyperthermia on murine tumor vasculature

The effects of hyperthermia on murine tumor vasculature were studied by microangiography and histological examination. The tumors used were SCC VII carcinoma and mammary adenocarcinoma of syngeneic C3H/He mice. For the quantitative analysis of microangiographic changes, the percent (%) vascular area, which was defined as the percentage of opacified tumor vessel area to the entire tumor area, was determined in each microangiogram. The % vascular area after heating in a water bath at 44 degrees C for 30 min was minimized 24 hr after heating in both types of tumors. The histologic study revealed that the initial decrease of the % vascular area was due to congestion, thrombosis, and rupture of tumor vessels, and its subsequent increase was due to angiogenesis. SCC VII was more heat sensitive than mammary adenocarcinoma in terms of tumor growth delay, and tumor vessels of SCC VII were more vulnerable to heat than those of mammary adenocarcinoma. Histological examinations showed a marked difference in the architecture of vessels between the two types of tumors. Tumor vessels of mammary adenocarcinoma were supported by a connective tissue band, whereas those of SCC VII consisted of a single endothelial cell layer. Our findings suggest that the tumor vessels supported by a connective tissue band are less sensitive to heat than those without such support. The vascular damage of SCC VII was temperature dependent, and the critical temperature at which dramatic vascular damage appeared was between 42.7 degrees C and 43.7 degrees C.

Studies on the radioprotective effects of superoxide dismutase in mice.

Abstract Protective effects of superoxide dismutase (SOD) on radiation-induced skin reactions of mice were examined as a function of the drug concentration and the modes of its administration. The anti-inflammatory effects of SOD was most prominent when 1 mg/mouse of SOD was given i.p. one hour before and one hour after irradiation, followed by 0.5 mg/mouse daily. Protective effects of SOD as a function of radiation dose were examined using deforming scores for the mouse leg as a measure of response. Protective effects of the drug was observed in the range of 40–70 Gy, while no effect was obtained in the dose level less than 40 Gy. The dose required to kill 50 % of the SOD treated mice within 30 days (LD sol50 30 ) was 7.84 Gy as compared to 7.54 Gy for the control group of mice.

In vivo radiosensitizing activity of a new fluorinated hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation☆

Since most clinical radiotherapy is given as multiple small irradiation fractions, the present study was undertaken to test the in vivo radiosensitizing activity of a new hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. Radiosensitizing activity was measured by a growth delay assay using a transplanted mammary tumor in C3H/He mice, and by an in vivo-in vitro assay using the SCC VII tumor. KU-2285 was injected intraperitoneally 30 min before irradiation in all experiments. The in vivo-in vitro assay using SCC VII tumors showed that 12.5 micrograms/g of KU-2285 sensitized the tumors to irradiation (5 Gy/fr x 5 fr/48 hr or 6 Gy/fr x 3 fr/48 hr). KU-2285 also sensitized the transplanted mammary tumors to fractionated irradiation. We concluded that KU-2285 was able to sensitize two different murine tumors when given in combination with radiation dose fractionation.