title: Antitumor effects in gastrointestinal stromal tumors using photodynamic therapy with a novel glucose-conjugated chlorin.
abstract: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5,10,15,20-tetrakis [4-[β-d-glucopyranosylthio-2,3,5,6-tetrafluorophenyl]-2,3,[methano[N-methyl] iminomethano] chlorin (H(2)TFPC-SGlc), for the GIST treatment. Various photosensitizers were administered in vitro to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation and antitumor effects of these photosensitizers in vivo. In vitro, the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of H(2)TFPC-SGlc, and apoptosis mediated by PDT with H(2)TFPC-SGlc were significantly higher in GIST-T1 than in WI-38 cells. In vivo, H(2)TFPC-SGlc accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT. PDT with novel H(2)TFPC-SGlc is potentially useful for clinical applications about the treatment of GIST.
authors.affiliation: Authors' Affiliations: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya; Graduate School of Materials Science, Nara Institute of Science and Technology, Nara; Office of Society-Academia Collaboration for Innovation, Kyoto University, Kyoto; Division of Materials and Manufacturing Science, Osaka University, Osaka; Research Institute of Natural Sciences, Okayama University of Science, Okayama; and Division of Human Health and Medical Science, Graduate School of Kuroshio Science, Kochi University Nankoku, Kochi, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kataoka
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ohi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Moriwaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Akashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Hamano
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mori
authors.forename: Eiji
authors.initials: E
authors.lastname: Kubota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanida
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006001:Glycoconjugates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D005464:Fluorobenzenes; D005466:Fluorocarbons
chemical_list: D000970:Antineoplastic Agents; D005960:Glucosides; D006001:Glycoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C000593331:5,10,15,20-tetrakis(4-(glucopyranosylthio-2,3,5,6-tetrafluorophenyl)-2,3-(methano(N-methyl)iminomethano)chlorin; C000593332:5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(methano(N-methyl)iminomethano))chlorin; D005464:Fluorobenzenes; D005466:Fluorocarbons; C006969:chlorin