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Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

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Authors
Jin, Hua; Kim, Tae Hee; Hwang, Soon-Kyung; Chang, Seung-Hee; Kim, Hyun Woo; Anderson, Hanjo K.; Lee, Han-Woong; Lee, Kee-Ho; Colburn, Nancy H.; Yang, Hsin-Sheng; Cho, Myung-Haing; Cho, Chong Su
Issue Date
2006
Publisher
American Association for Cancer Research
Citation
Mol Cancer Ther 2006;5:1041–49
Keywords
Aerosol deliveryPDCD4UACLung cancerK-ras null mice
Abstract
The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid–modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase–mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.
ISSN
1535-7163
http://dx.doi.org/10.1158/1535-7163.MCT-05-0433
Language
English
URI
http://hdl.handle.net/10371/6128
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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