title: Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma.
abstract: Fluorescence-guided surgery (FGS) of cancer is an emerging technology. We have previously shown the importance of resecting both the tumor and the tumor microenvironment (TME) for curative FGS. We also previously developed a syngeneic model using the mouse lymphoma cell line EL-4, expressing red fluorescent protein (EL-4-RFP), growing in green fluorescent protein (GFP) transgenic mice, which we have used in the present report to develop FGS of the tumor microenvironment.
  
  
  
  EL-4-RFP lymphoma cells were injected subcutaneously in C57/BL6 GFP transgenic mice. EL-4-RFP cells subsequently formed tumors by 35 days after cell transplantation. Using the portable hand-held Dino-Lite digital imaging system, subcutaneous tumors were resected by FGS. Resected tumor tissues were visualized with the Olympus FV1000 confocal microscope.
  
  
  
  Using the Dino-Lite, subcutaneous tumors and the tumor microenvironment were clearly visualized and resected. In the resected tumor, host stromal cells, including adipocyte-like cells and blood vessels with lymphocytes, were observed by confocal microscopy in addition to cancer cells by color-coded confocal imaging. The cancer cells and stromal cells in the TME were deeply intermingled in a highly-complex pattern.
  
  
  
  Color-coded FGS is an effective method to completely resect cancer cells along with the stromal cells in the TME which interact in a highly-complex pattern. Microscopically, cancer cells invade the TME and vice versa. To prevent tumor recurrence, it is necessary to resect the TME along with the tumor.
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan AntiCancer, Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. all@anticancer.com asue@gifu-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.affiliation: Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. all@anticancer.com asue@gifu-u.ac.jp.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003116:Color; D004195:Disease Models, Animal; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008164:Luminescent Proteins / Q000737:chemistry; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods*; D009364:Neoplasm Recurrence, Local; D009368:Neoplasm Transplantation; D025321:Surgery, Computer-Assisted / Q000379:methods; D059016:Tumor Microenvironment; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: Dino-Lite; RFP; TME; Tumor microenvironment; color-coded; fluorescence-guided surgery; imaging; transgenic GFP mouse