title: Intraperitoneal delivery of a small interfering RNA targeting NEDD1 prolongs the survival of scirrhous gastric cancer model mice.
abstract: The prognosis of patients with advanced diffuse-type gastric cancer (GC), especially scirrhous gastric cancer (SGC) remains extremely poor. Peritoneal carcinomatosis is a frequent form of metastasis of SGC. With survival rates of patients with peritoneal metastasis at 3 and 5 years being only 9.8% and 0%, respectively, development of a new treatment is urgently crucial. For such development, the establishment of a therapeutic mouse model is required. Among the 11 GC cell lines we examined, HSC-60 showed the most well-preserved expression profiles of the Hedgehog and epithelial-mesenchymal transition pathways found in primary SGCs. After six cycles of harvest of ascitic tumor cells and their orthotopic inoculation in scid mice, a highly metastatic subclone of HSC-60, 60As6 was obtained, by means of which we successfully developed peritoneal metastasis model mice. The mice treated with small interfering (si) RNA targeting NEDD1, which encodes a gamma-tubulin ring complex-binding protein, by the atelocollagen-mediated delivery system showed a significantly prolonged survival. Our mouse model could thus be useful for the development of a new therapeutic modality. Intraperitoneal administration of siRNAs of targeted genes such as NEDD1 could provide a new opportunity in the treatment of the peritoneal metastasis of SGC.
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Takao
authors.initials: T
authors.lastname: Nishimura
authors.forename: Misato
authors.initials: M
authors.lastname: Takigahira
authors.forename: Fumiko
authors.initials: F
authors.lastname: Chiwaki
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D002293:Adenocarcinoma, Scirrhous / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen / Q000008:administration & dosage; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays; D050807:ets-Domain Protein Elk-1 / Q000235:genetics
chemical_list: C494112:ELK1 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D008869:Microtubule-Associated Proteins; C509189:NEDD1 protein, human; D034741:RNA, Small Interfering; C059821:atelocollagen; D050807:ets-Domain Protein Elk-1; C086844:Nedd1 protein, mouse; D003094:Collagen