PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 25, 2001
Poster Session 28 Tumor Physiology and Microenvironments
Room: Exhibition Center
(P28-375) Combined Effects of Anti-VEGF Neutralizing Antibody and Ionizing Radiation on Tumor Growth and Hypoxic Fraction.
Itasaka, Satoshi1, Oya, Natsuo1, Sasai, Keisuke2, Nihei, Keiji3, Asano, Makoto4, Hiraoka, Masahiro1, 1 2 3 4
ABSTRACT-
[Purpose] The efficacy of the combination of antiangiogenic agents and radiotherapy should be further investigated, because the possible decrease in tumor oxygenation due to the blood supply depletion may be associated with increased tumor radioresistance. In the present study, we examined the combined effects of anti-VEGF neutralizing antibody (MV833) and radiation on tumor growth, using a murine tumor model. [Materials and Methods] HT1080 human fibrosarcomas in the hind limbs of nude mice (Balb/c, nu/nu) received 8 Gy of local irradiation, before or after 5-days daily subcutaneous injection of 100ug of MV833. Tumor growth delay was compared among the combination group, irradiation alone group and MV833 alone group. In addition, the change of the hypoxic fraction in HT1080 tumors after 5-days daily intraperitoneal injection of 25ug of MV833 was determined by the paired survival curve assay. [Results] The time required for the tumor to reach two times the initial volume was 4.1 +/- 0.6 days in the control, 8.5 +/- 1.7 days in the MV833 alone group, 21.3 +/- 1.3 days in the irradiation alone group, 27.3 +/- 1.6 days in the combination (irradiation then MV833) group and 24.6 +/- 1.5 days in the combination (MV833 then irradiation) group. The growth delay time after irradiation then MV833 was significantly longer than that after irradiation alone. Hypoxic fraction was estimated to be 9.4% in the tumors treated with MV833 and 10.1% in the untreated tumors, between which no significant difference was observed. [Conclusion] It was suggested that MV833, anti-VEGF neutralizing antibody, enhanced the anti-tumor effect of irradiation, particularly when it was administered after irradiation. Also when MV833 was administered before irradiation, it did not reduce the effect of irradiation, which was consistent with the results that MV833 did not increase the hypoxic fraction of the tumor. Therefore, it was at least concluded that the use of anti-VEGF neutralizing antibody has no negative impact on the effect of irradiation.
KEYWORDS: anti-VEGF neutralizing antibody, irradiation, hypoxic fraction