Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery

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Abstract

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery.

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Abbreviations

BLS:

bright-light surgery

FGS:

fluorescent-guided surgery

GFP:

green fluorescent protein

PDOX:

patient-derived orthotopic xenograft

RFP:

red fluorescent protein.

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Acknowledgements

This study was supported in part by the National Cancer Institute grant CA132971 and CA142669. This study was also supported in part by grants-in-Aid from the Ministry of Education, Science and Culture, Japan, and grants from the Ministry of Health and Welfare, Japan.

Author Contributions

SY, YH and AM performed the experiments. SY and RMH wrote the paper. All the authors analyzed the data.

Author information

Correspondence to R M Hoffman.

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Competing interests

YU is the President and CEO of Oncolys BioPharma, the manufacturer of OBP-401 (Telomescan). HT and TF are consultants of Oncolys BioPharma. The remaining authors declare no conflict of interest.

Additional information

This paper is dedicated to the memory of AR Moossa, MD.

Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Yano, S., Hiroshima, Y., Maawy, A. et al. Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery. Cancer Gene Ther 22, 344–350 (2015) doi:10.1038/cgt.2015.26

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