This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background and Objective: Oral carcinogenesis is a multistep process in which genetic events cause disruption of the normal regulatory pathways controlling basic cellular function. Multiple genetic events lead to oral cancer, and various cellular genes are upregulated in oral squamous cell carcinoma. Goal of these studies was to image and quantify expression of specific biomarkers known to play a role in the vascular and extracellular matrix (ECM) changes. Study Design/Materials and Methods: In the hamster cheek model (10 hamsters) throughout carcinogenesis, in vivo multi-wavelength multi-photon fluorescence (MPM) and second harmonic generated (SHG) techniques were used to image surface and subsurface fluorescence prior to and after the injection of biomarkers: Vascular Endothelial Growth Factor (VEGF); urinase type Plasminogen Activator (uPA) and Inhibitor (PAI-1); Matrix Metalloproteinases 1,2,9 (MMPs). At 4,6,8,10,12 weeks, one animal was sacrificed., Histopathological sections were prepared and pathology evaluated on a scale of 0-6. Results: Carcinogenesis-related structural and vascular changes were clearly visible. Biomarker expression was clearly identified, localized and quantified at all timepoints throughout carcinogenesis, providing important new information on the carcinogenesis process. Conclusion: Time- and spatially-resolved determination of (1) specific biomarker expression, (2) vascular and ECM remodeling throughout oral carcinogenesis provide valuable information on mechanisms of dysplastic and malignant change.
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