|Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Our method for detecting the quiescent (Q) cell response to γ-ray irradiation using proliferating (P) cell labeling with BrdU and the MN frequency assay was also applicable to apoptosis detection assay. No radiosensitization effect upon combination treatment with paclitaxel (TXL) is induced in Q tumor cells. Consequently, the use of a bioreductive agent, tirapazamine (TPZ) as an additional agent is promising when solid tumors are treated with irradiation combined with TXL, due to its potent cytotoxicity to Q tumor cell fractions that are hard to radiosensitize by TXL. It was also shown that newly developed ^<10>B containing α-amino alcohols of BPA, L- and D-ρ- boronophenylalaninol-^<10>B have good potential as ^<10>B-carriers in neutron capture therapy, especially when combined with both mild temperature hyperthermia (MTH) and TPZ.
Irrespective of p53 status of tumor cells, significant differences in sensitivity to γ-rays between total and Q tumor cells were consistently observed. From
the viewpoint of tumor control as a whole including intratumor Q tumor cell control, a treatment modality for enhancing Q cell response has to be considered. In neutron capture reaction, with ^<10>B-carriers, the sensitivity was increased for both total and quiescent tumor cells, especially for total cells. BPA increased the sensitivity for total cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. These sensitization patterns in combination with ^<10>B-carriers were clearer in wild-type p53 tumors than in mutant-type p53 tumors. The p53 status had the potential to affect the way to respond to reactor neutron beam irradiation following ^<10>B-carrier administration. With the difficulty in controlling mutated p53 status tumors and intratumor Q cells, combination treatment with MTH and/or TPZ as a cooperative modality in cancer therapy was thought to be encouraging for controlling solid tumors as a whole, because the potentiation of the killing effect on both tumor cell fractions by TPZ in combination with MTH did not depend on p53 status. Less