Induction of vascular endothelial growth factor (VEGF) by hyperthermia and/or an angiogenesis inhibitor

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.