Fractionated photodynamic therapy for a human oral squamous cell carcinoma xenograft

The aim of this study was to define the appropriate fractionation interval between photodynamic therapies (PDTs) for enhanced anti-tumour effects on human oral squamous cell carcinoma (HOSCC). Reoxygenation of HOSCC and the proliferative kinetics of the tumour cells following PDT exposure were evaluated in terms of immunohistochemical expression of vascular endothelial growth factor (VEGF) and the proliferating cell nuclear antigen (PCNA). The immunohistochemical expression of VEGF was quantitatively determined by computer-assisted image analysis. The VEGF expression and the PCNA labeling indices (LIs) of the tumour cells were assessed at varying time intervals after PDT. No significant differences were observed in PCNA LIs between the control group and experimental groups at 24, 48, and 72 h after PDT. The expression of VEGF after PDT exposure was demonstrated to be higher in the experimental group at 6 h than the control group, and then was comparable at 24 h between the both groups. These results indicate that the tumour cells surviving from PDT have proliferative potential, and that oxygenation in tumours subjected to PDT may be recovered after 24 h. In the next experiment, two protocols of laser irradiation in PDT were assessed on the basis of tumour volume between fractionated exposure with a 24-h interval and continuous exposure. Regrowth of the tumour was significantly suppressed by fractionated PDT. We propose here that fractionated light exposure with a 24-h interval should be utilized in PDT for an enhanced anti-tumour effect.