Modification of radio-thermo-chemotherapy by AK-2123 and hydralazine in tumor bearing mice.
The effects of chemical modifiers of hypoxic radiosensitizer, a 3-nitrotriazole derivative AK-2123 (200 mg/kg) before treatment, and vasodilator of hydralazine (HDZ; 5.0 mg/kg) after treatment on tumor growth of SCCVII of mice were investigated in the radio-thermotherapy combined with mitomycin C (MMC; 2.0 mg/kg) or adriamycin (ADM; 3 mg/kg). The tumor treated by 10 Gy alone (tumor doubling time = 7.5 days), MMC alone (6.9 days), and hyperthermia (43 degrees C, 30 min; HT) alone (8.0 days) showed a slight growth delay (control: 5.6 days). Prolonged growth delay (23.2 days) was observed by MMC-radio-thermotherapy (MMC-10Gy/HT) than that (12.4 days) by 10 Gy/HT. The modification of MMC-radio-thermotherapy by HDZ administered between 10 Gy and HT (MMC-10 Gy/HDZ/HT) resulted in the significant prolongation of tumor growth delay (31.7 days). AK-2123 administration before this treatment, (MMC-AK-2123)-10 Gy/HDZ/HT), enhanced a further tumor growth delay (37.6 days) which is equal to that by 50 Gy alone and resulted in the highest dose modifying factor (DMF) of 5.2. While modification of ADM-radio-thermotherapy by AK-2123 and HDZ, (ADM-AK-2123)-10 Gy/HDZ/HT, gave the equal tumor growth delay to that by 30 Gy alone (DMF = 3.1). These high efficacies of radio-thermo-chemotherapy modified by AK-2123 and HDZ may be caused by tumor blood flow reduction.
Kunugita
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N
Department of Radiation Biology and Health, University of Occupational and Environmental Health, Japan.
Mei
N
N
Norimura
T
T
Kagiya
T V
TV
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D006979:Hyperthermia, Induced; D051379:Mice; D008809:Mice, Inbred C3H; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D014230:Triazoles; C072690:AK 2123; D006830:Hydralazine