| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The combination of tirapazamine (TPZ), hypoxia specific cytotoxin, and mild temperature hyperthermia (MTH ; 40℃, 30 min) was useful for sensitizing tumor cells in vivo, including quiescent (Q) cells. TPZ combined radiotherapy and TPZ combined thermo-radiotherapy at mild temperatures were promising for sensitizing tumor cells, including Q tumor cells. Combined treatment with TPZ and MTH, whether other cytotoxic treatments such as γ-ray irradiation or chemotherapy agents were combined or not, was useful for sensitizing tumor cells, even after anti-angiogenic agent TNP-470 treatment. The use of TPZ in the treatment of solid tumors causes a shift from the proliferating (P) to Q state in vivo in contrast to X-ray irradiation that causes a shift from the Q to P state.
After thermal neutron irradiation, combination with ^<10>B-compound, especially p-boronophenylalanie-^<10>B (BPA), widened the difference in the extent of reoxygenation between Q and total (P+Q) tumor cells, and delayed reoxygen
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ation phenomena, compared with thermal neutron irradiation alone. γ-Ray irradiation and neutron irradiation with BPA induced larger repair capacities in each cell population. In contrast, thermal neutron irradiation without ^<10>B-compound induced the smallest repair capacity in both cell populations. The use of ^<10>B-compound, especially BPA, resulted in an increase in repair capacity in both cell populations. In addition, the use of ^<10>B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population. All these findings suggested the difficulty in distribution of ^<10>B-compound, especially BPA, in Q cells and the heterogeneity in intratumor distribution of ^<10>B-compound. As a result, the intratumor phenomena after thermal neutron irradiation with BPA were similar to those after γ-ray irradiation.
In SCC VII tumors, TPZ and cisplatin reduced the hypoxic fraction (HF) after treatment, especially in Q cells. In contrast, bleomycin increased the HF after treatment. Both reoxygenation following γ-ray irradiation or bleomycin treatment and rehypoxiation following TPZ or cisplatin treatment occurred more rapidly in total cells than in Q cells. Based on our previous report that total and Q cells within this tumor have large acutely and chronically HFs, respectively, acute hypoxic cells play a major role in reoxygenation and rehypoxiation in SCC VII tumors. Less
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