title: In vivo real-time imaging of chemotherapy response on the liver metastatic             tumor microenvironment using multiphoton microscopy.
abstract: In vivo real-time visualization of chemotherapy response at the cellular             level provides us with direct evidence of what happens on the tumor microenvironment             of metastatic organs. We imaged the response of metastatic tumor cells and host             stromal cells to chemotherapeutics on liver metastatic xenografts in living mice             using intravital two-photon laser scanning microscopy (TPLSM). Red fluorescent             protein-expressing human colorectal cancer cells (HT29) was inoculated to the             spleen of green fluorescent protein-expressing nude mice. 5-Fluorouracil or irinotecan             was intraperitoneally administered after the formation of macroscopic liver metastases.             Intravital TPLSM was performed at multiple time-points for time-series imaging             of liver metastatic xenografts in the same mice. Under the 1st TPLSM, HT29 cells             were visualized in hepatic sinusoids at the single cell level. Liver metastatic             nodules consisting of viable cancer cells and surrounding stroma with tumor vessels             were visualized under the 2nd TPLSM. After chemotherapy, tumor cell fragmentation,             condensation, swelling and intracellular vacuoles were observed under the 3rd             TPLSM. There was no obvious morphological difference in tumor response between             these chemotherapeutics. Time-series intravital TPLSM imaging on the metastatic             tumor xenografts may be useful for screening and evaluating new chemotherapeutics             with less interindividual variability.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. qouji@clin.medic.mie-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masato
authors.initials: M
authors.lastname: Okigami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Mikio
authors.initials: M
authors.lastname: Kawamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Araki
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; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D005472:Fluorouracil / Q000627:therapeutic use; D049452:Green Fluorescent Proteins; D019073:HT29 Cells; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008164:Luminescent Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000187:drug effects*; D000097573:Red Fluorescent Protein
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D049452:Green Fluorescent Proteins; D002955:Leucovorin; D008164:Luminescent Proteins; D009944:Organoplatinum Compounds; D000097573:Red Fluorescent Protein