Tumor site prediction using spatiotemporal detection of subclinical hyperemia in experimental photocarcinogenesis

摘要

We demonstrate that a spatial and temporal analysis of subclinical hyperemia reliably predicts specific areas at high risk for skin tumor development during photocarcinogenesis. To determine detailed spatiotemporal patterns of inflammatory angiogenesis foci in a relatively large area, we developed a mesoscopic (between microscopic and macroscopic) imaging approach. This method relies on our earlier finding that the combination of a spectral analysis of hemoglobin with diffuse-light-suppressed imaging can increase the image resolution, contrast and penetration depth to visualize microvasculature Hgb content in the large tissue area. In our recent study, SKHI hairless albino mice were irradiated for 10 weeks with a carcinogen dose of UVB. Using our newly developed mesoscopic imaging methods, we imaged the mice over 20 - 30 weeks after stopping UVB, and excised hyperemicon-hyperemic areas at several different time-points. We show that persistent hyperemic foci can predict future tumor formation. In particular, our imaging approach allows us to assess the spatial and temporal extent of subclinical inflammatory foci, which in turn can predict sites of future overlying tumor formation. In addition, although COX-2 inhibitors are known to suppress skin cancer development in humans, it remains unclear whether the chemopreventive activity of COX-2 inhibitors are chiefly attributable to their anti-inflammatory effects. Our study provides evidence that subclinical subepithelial inflammatory foci occur prior to overt tumor formation, and that these areas are highly predictive for future tumor formation, that celecoxib's ability to suppress tumorigenesis is tightly linked to its ability to reduce the area of subclinical inflammatory foci.