title: In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy.
abstract: BACKGROUND
  We previously visualized in vivo responses to chemotherapy in a colorectal liver metastatic xenograft model using in vivo real-time and time-series intravital two-photon laser scanning microscopy (TPLSM). In this study, we established the method for evaluating the response of peritoneal xenografts to chemotherapy of metastatic gastric cancer using intravital TPLSM.
  
  
  METHODS
  Red fluorescent protein-expressing gastric cancer cells (NUGC4) were inoculated into the peritoneal cavity of green fluorescent protein nude mice.
  
  
  RESULTS
  Laparotomy revealed that 2 weeks after inoculation, macroscopic peritoneal metastatic nodules were formed. The first intravital TPLSM session revealed that they were composed of red tumor cell clusters and green surrounding stroma. Paclitaxel was administered intraperitoneally after the first TPLSM three times a week for 7 days in the treatment group. At the second laparotomy, there were significantly fewer and smaller nodules in the treated mice than in the controls. The second intravital TPLSM session showed tumor cell fragmentation, swelling, and nuclear condensation in the metastatic nodules--a response to chemotherapy. There were multinuclear tumor cells in the paclitaxel-treated living mice.
  
  
  CONCLUSIONS
  Our method may become a powerful tool for evaluating the efficacy of novel anti-gastric cancer drugs in a preclinical murine model with minimum interindividual variation.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, t-shimura@clin.medic.mie-u.ac.jp.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Shimura
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Okigami
authors.forename: Shozo
authors.initials: S
authors.lastname: Ide
authors.forename: Takahito
authors.initials: T
authors.lastname: Kitajima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Araki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D000097573:Red Fluorescent Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D017239:Paclitaxel; D000097573:Red Fluorescent Protein