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.

نویسندگان

  • Hua Jin
  • Tae Hee Kim
  • Soon-Kyung Hwang
  • Seung-Hee Chang
  • Hyun Woo Kim
  • Hanjo K Anderson
  • Han-Woong Lee
  • Kee-Ho Lee
  • Nancy H Colburn
  • Hsin-Sheng Yang
  • Myung-Haing Cho
  • Chong Su Cho
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Impact of Duration and Severity of Persistent Pain on Programmed Cell Death

Programmed cell death is a highly regulated form of cell death, mostly distinguished by the activation of a family of cystein-aspartate proteases (caspases) that cleave various proteins resulting in morphological and biochemical changes characteristic of this form of cell death. Several recent studies have addressed the role of programmed cell death in inflammatory and chronic pain states. Casp...

متن کامل

Impact of Duration and Severity of Persistent Pain on Programmed Cell Death

Programmed cell death is a highly regulated form of cell death, mostly distinguished by the activation of a family of cystein-aspartate proteases (caspases) that cleave various proteins resulting in morphological and biochemical changes characteristic of this form of cell death. Several recent studies have addressed the role of programmed cell death in inflammatory and chronic pain states. Casp...

متن کامل

Cell cycle and apoptosis: A review

Cancer is characterized by abnormally excessive cell proliferation. Cell proliferation, the process by which a cell grows and divides to produce two daughter cells. Each of these daughter cells divides to produce two new cells, steps that are called cell cycle. Meanwhile, apoptosis is a highly regulated process of cell death, which is involved not only in the development of shape and morphogene...

متن کامل

Antibacterial loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections.Chitosan polyelectrolyte complex...

متن کامل

Antibacterial loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections.Chitosan polyelectrolyte complex...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Molecular cancer therapeutics

دوره 5 4  شماره 

صفحات  -

تاریخ انتشار 2006