S. Kanamori et al., Induction of vascular endothelial growth factor (VEGF) by hyperthermia and/or an angiogenesis inhibitor, INT J HYPER, 15(4), 1999, pp. 267-278
Intratumoral localization of vascular endothelial growth factor (VEGF) foll
owing administration of hyperthermia (HT) and/or anti-angiogenic drugs (TNP
-470) was evaluated using SCC VII rumours in C3H/He mice. Hyperthermia at 4
4.0 degrees C for 30 min was given with a water bath on day 0. TNP-470 (100
mg/kg) was administered alone or after HT on day 0 and day 3. Histological
changes on day 4 were evaluated by haematoxylin-eosin (HE) staining and im
munohistochemical staining for VEGF. The percentage of the necrotic area re
lative to the entire tumour area (the % necrotic area) was measured on HE s
tains. The average % necrotic area of the untreated SCC VII tumours was 7%,
while those of tumours treated with TNP-470 alone and HT alone were 27 or
65%, respectively. When HT and TNP-470 were combined, the % necrotic area w
as 82%, which was significantly higher than that caused by HT alone (p < 0.
05).
Immunohistochemical staining for VEGF in untreated SCC VII tumours was weak
, although strong staining for VEGF was noted in untreated EMT-6 rumours of
BALB/c mice, which have spontaneous central necrosis. After administration
of HT and/or TNP-470, layer-shaped staining by VEGF was observed in the re
sidual SCC VII tumour cells adjacent to the necrotic area. In conclusion, t
he expression of VEGF increased in response to administration of HT and/or
TNP-470. Hypoxia caused by heat-induced vascular damage may be attributable
to increased expression of VEGF in SCC VII tumours.