Abstract
The aim of this study is to determine if ultraviolet light (UVC) irradiation in combination with fluorescence-guided surgery (FGS) can eradicate metastatic human pancreatic cancer in orthotopic nude–mouse models. Two weeks after orthotopic implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3 treatment groups; BLS-only (n = 8) or FGS (n = 8) or FGS-UVC (n = 8). The residual tumors were resected using a hand-held portable imaging system under fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical resection bed was irradiated with 2700 J/m2 UVC (254 nm) in the mice treated with FGS-UVC. The average residual tumor area after FGS (n = 16) was significantly smaller than after BLS only (n = 24) (0.135±0.137 mm2 and 3.338±2.929 mm2, respectively; p = 0.007). The BLS treated mice had significantly reduced survival compared to FGS- and FGS-UVC-treated mice for both relapse-free survival (RFS) (p<0.001 and p<0.001, respectively) and overall survival (OS) (p<0.001 and p<0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to FGS-only treated mice (p = 0.008 and p = 0.025, respectively); with RFS lasting at least 150 days indicating the animals were cured. The results of the present study suggest that UVC irradiation in combination with FGS has clinical potential to increase survival.
Highlights
Complete tumor resection can improve overall survival of pancreatic cancer patients [1], which is presently 5% at five years
We have previously showed that fluorescence-guided surgery (FGS) for pancreatic cancer decreased the residual tumor burden and improved overall and disease-free survival in mouse models [3,4,5]
We showed that murine Lewis lung carcinoma (LLC) and human U87 glioma cells, expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, were more sensitive to UVC light than non-colored LLC and U87 cells, suggesting that the expression of fluorescent proteins in cancer cells can enhance the photodynamic effect of UVC on cancer cells
Summary
Complete tumor resection can improve overall survival of pancreatic cancer patients [1], which is presently 5% at five years. We have previously showed that fluorescence-guided surgery (FGS) for pancreatic cancer decreased the residual tumor burden and improved overall and disease-free survival in mouse models [3,4,5]. We showed that murine Lewis lung carcinoma (LLC) and human U87 glioma cells, expressing GFP in the nucleus and RFP in the cytoplasm, were more sensitive to UVC light than non-colored LLC and U87 cells, suggesting that the expression of fluorescent proteins in cancer cells can enhance the photodynamic effect of UVC on cancer cells
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