| Research Abstract |
It was found that hyperthermia at low temperatures (= mild hyperthermia) oxygenates preferentially tumor cells in chronically hypoxic fraction (HF), compared with those in acutely HF within solid tumors. Reduction of hypoxic cells induced by mild hyperthermia in quiescent (03 cell populations and in total (P+Q) cell populations was maintained approximately for 1 week and for 2 days, respectively. Therefore, irradiation to solid tumors within 12 hours following mild hyperthermia may be clinically useful from the viewpoint of tumor control.
Although the sensitivity to cisplatin of Q cells is lower than that of total cells within solid tumors, the combination with mild hyperthermia could effectively sensitize Q cells, which are rich in chronically HF.In addition, from the point of the effect on total tumor cells as a whole, the combination with nicotinamide (NA), an acute hypoxia-releasing agent, was also effective. Further, from the viewpoint of the sensitization of Q cells, the combinati
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on with tirapazamine (TPZ), a hypoxia-specific cytotoxin, was again effective. On the other hand, mild hyperthermia could significantly increase the uptake dose of ^<195m>mPt-radiolabeled cisplatin, that had been synthesized at our institute, by total cells in EMT6/KU tumors compared with that in SCC VII tumors, probably because of a larger chronically HF included in EMT6/KU than in SCC VII tumors.
It is true that the DNA-damaging effect of TPZ alone on Q cells was larger than that on total cells, but the combination with mild hyperthermia could enhance the DNA-damaging effect both cell fractions in contrast with NA, which reduced the effect. The effect of TPZ on total cells was observed in EMT6/KU tumors more remarkably than in SCC VII tumors, mainly because of a larger chronically HF in EMT6/KU than that in SCC VII tumors.
In neutron capture therapy (NCT), which has been clinically performed at our institute, the simultaneous combination with mild hyperthermia at the time of administration of a neutron capture compound was thought to increase the uptake dose of the compound in Q cells to some extent. Additionally, the combination with TPZ suggested the possibility of enhancing the sensitivity of Q cells and reducing the widened difference in sensitivity between total and Q cells induced by the combined use of neutron capture compounds in NCT. Less
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