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

Jin, Hua; Kim, Tae Hee; Hwang, Sung‐Joo; Chang, Simyung; Kim, Hyun Woo; Anderson, Hanjo K.; Lee, Han-Woong; Lee, Kee-Ho; Colburn, Nancy H.; Yang, Huiling; Cho, Myung‐Haing; Cho, Chong Su

doi:10.1158/1535-7163.mct-05-0433

Cited by 90 publications

(68 citation statements)

References 35 publications

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“…8,9 Briefly, chitosan was coupled with UA (70 mol %) via an active ester intermediate using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (Peptide Institute, Osaka, Japan). The free amino groups of UAC were determined by ninhydrin assay using glucosamine standard, and the composition of UAC was verified by nuclear magnetic resonance spectroscopy (600 MHz, Bruker BioSpin, Munchen, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…For gene delivery, mice were placed in nose-only exposure chamber and exposed to the aerosol based on the methods used previously. 8,18 For the effects of PTEN against lung cancer development, the K-ras LA1 mice were divided into three groups (three mice per group). Control group was not treated with anything and other two groups were exposed to aerosol containing UAC with PTEN expression vector pcDNA3.0-PTEN (PTEN-treated group) or pcDNA3.0 vector alone (vector control), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…7 In these regards, we have already shown that urocanic acid (UA)-modified chitosan (UAC) is an effective delivery vehicle due to degradability, ability to form a complex with DNA and its physicochemical properties as a gene delivery system with little toxicity and enhanced gene transfection efficiency. 8,9 Approximately 30% of human tumors carry ras gene mutations. Of the three members of ras family-K-ras, N-ras and H-ras-K-ras are found to be the most frequently mutated members in human tumors, including lung adenocarcinomas (25-50%).…”

Section: Introductionmentioning

confidence: 99%

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Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice

Jin

et al. 2008

Cancer Gene Ther

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The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras LA1 lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice

Jin

et al. 2008

Cancer Gene Ther

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“…Most reports showed that PDCD4 was a pro-apoptosis gene. [27][28][29][30] However, recently a study showed that PDCD4 was an antiapoptotic regulator that inhibited the translation of procaspase-3 mRNA in cells. 31 In our study, there was no significant difference in hepatocyte apoptosis between PDCD4-deficient mice and WT mice at 0 h after LPS/D-GalN injection.…”

Section: Discussionmentioning

confidence: 99%

The inhibitory action of PDCD4 in lipopolysaccharide/D-galactosamine-induced acute liver injury

Wang

Zhang

Wei

et al. 2013

Laboratory Investigation

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Programmed cell death 4 (PDCD4) acts as a tumor suppressor gene, which suppresses tumor growth, infiltration and metastasis. Our previous studies demonstrated that PDCD4 had an important role in the development of ovarian cancer and glioma. Recent studies show that PDCD4 is also involved in various inflammatory diseases. However, its exact effect on inflammation remains unclear. In our current study, we explored the role of PDCD4 in acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) using wild-type (WT) mice and PDCD4-deficient mice. Our results showed that liver-to-body weight ratios, as well as serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly increased in PDCD4-deficient mice than WT mice. Histological examination, immunohistochemical and TUNEL analysis revealed PDCD4-deficient mice had more necrotic and apoptotic hepatocytes, inflammatory cells infiltration and liver internal hemorrhage than WT mice. In addition, some inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) in the serum and liver tissues were also significantly increased in PDCD4-deficient mice. More importantly, we found that the aggravation of liver tissue injury in PDCD4-deficient mice was due to excessive mitogen-activated protein kinase and NF-kB activation, which induced the release of more inflammatory factors, and consequently resulted in higher levels of hepatocyte necrosis and apoptosis. These results indicate that PDCD4 has a protective role in LPS/D-GalN-induced acute liver injury. This finding may present new opportunities for PDCD4 to be explored as a therapeutic target in acute liver injury.

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“…(14) In addition, our previous data showed that aerosol-delivered Pdcd4 regulated lung cancer growth through increasing the cell cycle inhibitors, such as p21 and p27, while suppressing cell proliferation proteins, such as cyclin-dependent kinase 4 and proliferating cell nuclear antigen. (29) p21(Waf1=Cip1) has originally been identified as an inhibitor of G1 cyclin-dependent kinases that mediates the p53-induced growth arrest following DNA damage. (30) In addition, there are several reports showing that p21 (Waf1=Cip1) may also influence cell proliferation in a positive manner.…”

mentioning

confidence: 99%

Decreased Level of PDCD4 (Programmed Cell Death 4) Protein Activated Cell Proliferation in the Lung of A/J Mouse

Hwang

Minai-Tehrani

Lim

et al. 2010

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Programmed cell death 4 (PDCD4), a protein that binds to eukaryotic initiation factor 4A (eIF4A), inhibits the initiation of translation. Although a number of tumor suppressors target transcription, Pdcd4 is the first suppressor targeting protein translation, and has also been suggested to function as a tumor suppressor gene in human cancer. The majority of tumor suppressors are mutationally inactivated, but the expression of Pdcd4 is downregulated with progression in a number of human cancer sites, including the lung. Methods: An aerosol of lentivirus-shRNA Pdcd4 was delivered into A=J mice, through a nose-only inhalation system twice a week for 1 month. Results and Conclusions: Downregulated Pdcd4 resulted in increase levels of antiapoptotic and uPA-regulated proteins.We also found that downregulated Pdcd4 induced the mTOR=p70S6K pathway and cell-cycle proteins. Our results suggest that Pdcd4 may perform a critical function in the regulation of lung cancer cell proliferation.

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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

Cited by 90 publications

References 35 publications

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice

The inhibitory action of PDCD4 in lipopolysaccharide/D-galactosamine-induced acute liver injury

Decreased Level of PDCD4 (Programmed Cell Death 4) Protein Activated Cell Proliferation in the Lung of A/J Mouse

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