title: Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice.
abstract: BACKGROUND
  Difficulties in achieving long-term survival of patients with lung cancer treated with conventional therapies suggest that novel approaches are required. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.
  
  
  OBJECTIVE
  To investigate the repeated effect of carboxyl-terminal modulator protein (CTMP) on multistage lung tumorigenesis. In this study, we addressed this question by studying the effects of lentivirus-based CTMP in the lungs of 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer.
  
  
  METHODS
  An aerosol of lentivirus-based CTMP was delivered into 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer, through a nose-only inhalation system twice a week for 4 weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated.
  
  
  RESULTS
  Long-term repeated delivery of CTMP effectively reduced tumor progression in the lungs at different stages of development. Lentiviral-CTMP inhibited protein synthesis and cell cycle and altered Akt signaling pathway in the lungs of 9-week-old K-ras(LA1) mice, and increased apoptosis was observed in the lungs of 13-week-old K-ras(LA1) mice.
  
  
  CONCLUSIONS
  Long-term repeated viral delivery of CTMP may provide a useful tool for designing lung tumor treatment.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Soon-Kyung
authors.initials: SK
authors.lastname: Hwang
authors.forename: Hwang-Tae
authors.initials: HT
authors.lastname: Lim
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Lee
authors.forename: Jongmin
authors.initials: J
authors.lastname: Park
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Park
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000336:Aerosols; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D011905:Genes, ras; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010170:Palmitoyl-CoA Hydrolase; D016896:Treatment Outcome
chemical_list: D000336:Aerosols; D002352:Carrier Proteins; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase