title: Single-injection ornithine decarboxylase-directed antisense therapy using atelocollagen to suppress human cancer growth.
abstract: BACKGROUND
  Substantial evidence supports a direct role of ornithine decarboxylase (ODC) in the development and maintenance of human tumors. Although antisense oligonucleotide therapy targeting various genes are useful for cancer treatment, 1 of the major limitations is the problem of delivery. A novel antisense oligonucleotide delivery method is described that allows prolonged sustainment and release of ODC antisense oligonucleotides in vivo using atelocollagen.
  
  
  METHODS
  The effect of ODC antisense oligonucleotides in the atelocollagen on cell growth of gastrointestinal cancer (MKN 45 and COLO201) and rhabdomyosarcoma (RD) was studied in vitro using a cell-counting method with a hemocytometer. In vivo, the effect of intratumoral, intramuscular, and intraperitoneal single administration of ODC antisense oligonucleotides in the atelocollagen on tumor growth of MKN45, COLO201, and RD cells was studied. ODC activity and polyamine contents were measured.
  
  
  RESULTS
  In vitro, ODC antisense oligonucleotides in the atelocollagen remarkably suppressed MKN45, COLO201, and RD cell growth. A single administration of antisense oligonucleotides in the atelocollagen via 3 routes remarkably suppressed the growth of MKN45, COLO201, and RD tumor over a period of 35-42 days.
  
  
  CONCLUSIONS
  As various human cancers significantly express ODC, the results strongly suggest that this new antisense method may be of considerable value for treatment of human cancers.
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nemoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hata
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Seyama
authors.forename: Shunji
authors.initials: S
authors.lastname: Nagahara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagai
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Kubota
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D009955:Ornithine Decarboxylase / Q000235:genetics; D065108:Ornithine Decarboxylase Inhibitors
chemical_list: D016376:Oligonucleotides, Antisense; D065108:Ornithine Decarboxylase Inhibitors; C059821:atelocollagen; D003094:Collagen; D009955:Ornithine Decarboxylase