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Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice.

AbstractRATIONALE:
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.
OBJECTIVES:
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.
MEASUREMENTS AND MAIN 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.
AuthorsSoon-Kyung Hwang, Hwang-Tae Lim, Arash Minai-Tehrani, Eun-Sun Lee, Jongmin Park, Seung Bum Park, George R Beck Jr, Myung-Haing Cho
JournalAmerican journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 179 Issue 12 Pg. 1131-40 (Jun 15 2009) ISSN: 1535-4970 [Electronic] United States
PMID19286625 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aerosols
  • CTMP protein, mouse
  • Carrier Proteins
Topics
  • Adenocarcinoma (genetics, pathology, therapy)
  • Aerosols
  • Animals
  • Apoptosis
  • Blotting, Western
  • Carrier Proteins (administration & dosage, biosynthesis, genetics)
  • Cell Line, Tumor
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Gene Transfer Techniques
  • Genes, ras
  • In Situ Nick-End Labeling
  • Lung Neoplasms (genetics, pathology, therapy)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental (drug therapy, genetics, pathology)
  • Treatment Outcome

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