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

Jin, Huajun; Cx, Xu; Hw, Kim; Ys, Chung; Shin, J-Y; Chang, Sung‐Pil; Park, Sung Jin; Es, Lee; Hwang, S-K; Kwon, Jung-Taek; Minai-Tehrani, Arash; Woo, Min Ah; Noh, M-S; Youn, Hee Jeong; Kim, Dae-Yong; Yoon, Byung–Il; Kh, Lee; Kim, Tae Hee; Cs, Cho; Cho, Myung‐Haing

doi:10.1038/sj.cgt.7701116

Cited by 49 publications

(28 citation statements)

References 31 publications

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“…Our results are supported by a recent report indicating that redundantly activated Akt could contribute to carcinogenesis in the lungs (50). Also, PTEN inactivation could accelerate K-ras-initiated lung tumorigenesis (51), and K-ras mutation-induced lung tumorigenesis could be suppressed by PTEN gene transfection (52). Moreover, CTMP acts as a negative regulator by suppressing Akt activity (53).…”

Section: Discussionsupporting

confidence: 78%

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

Jin

Xu²,

Lim³

et al. 2009

Am J Respir Crit Care Med

127

103

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Rationale: Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. Objectives: The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development. Methods: Experiments were performed on 5-week-old male K-ras LA1 lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods. Measurement and Main Results: A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras LA1 mice. Conclusions: Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.

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Section: Discussionsupporting

confidence: 78%

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

Jin

Xu²,

Lim³

et al. 2009

Am J Respir Crit Care Med

127

103

View full text Add to dashboard Cite

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“…RNA concentration and integrity were determined by measuring the absorbance at 260 nm and by electrophoresis on a 1% agarose gel. For reverse transcription (RT)-PCR, 5 mg of total RNA was reverse transcribed using SUPERSCRIPT RT (Invitrogen) and an oligo (dT) [12][13][14][15][16][17][18] primer (Invitrogen). Real-time RT-PCR was performed in an iCycler detection system (Bio-Rad, Hercules, CA).…”

Section: Evaluation Of Tumor Burdenmentioning

confidence: 99%

“…RNA concentration and integrity were determined by measuring the absorbance at 260 nm and by electrophoresis on 1% agarose gel. For RT-PCR, 5 mg of total RNA was reverse transcribed using SUPERSCRIPT RT (Invitrogen) and oligo (dT) [12][13][14][15][16][17][18] 48 The primer sequences designed for amplification of a b-actin cDNA fragment (541 bp) were 5 0 -GTGGGGCGCCCCAGGCACCA-3 0 and 5 0 -GTCCT TAATGTCACGCACGATTTC-3 0 . Amplification was performed according to Laux et al 49 PCR products were analyzed by electrophoresis on a 0.8% agarose gel and visualized by ethidium bromide (Anco and Rhenium Industries Ltd, Jerusalem, Israel).…”

Section: Rt-pcrmentioning

confidence: 99%

“…By contrast, aerosol delivery is more efficient and a simpler mode of gene therapy transport to the lungs. Aerosol delivery also has the advantages of uniform gene therapy agent distribution, lower risk of lung injury and access to a larger bronchial epithelium surface area 7,8 Intranasal aerosol delivery of biological agents has been successfully shown for interleukin-12, 13,14 p53, 3 the therapeutic antibody cetuximab, 15 PTEN, 16 interleukin-2 17 and granulocyte macrophage colony-stimulating factor. 18 Several chemotherapeutic agents have also been tested for aerosol delivery to patients with lung carcinoma, including cisplatin and doxorubicin.…”

Section: Introductionmentioning

confidence: 99%

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WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

et al. 2009

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The Wilms' tumor gene 1 (WT1) is a universal tumor antigen and consequently a good therapeutic target for the development of gene therapy strategies. Earlier, we reported the in vitro efficacy of WT1 RNAi in the inhibition of B16F10 murine melanoma cell line growth. In this study, we used an aerosol system to deliver WT1 RNAi complexes, polyethyleneimine (PEI)-WT1-1 or PEI-WT1-2, to the lungs of mice with B16F10 lung metastasis. This treatment produced a statistically significant (P ¼ 0.020) reduction in the number and size of lung tumor foci, resulting in decreased lung weight and tumor index in treated mice compared with controls. The WT1 RNAi treatment also reduced the number and size of tumor blood vessels, suggesting decreased angiogenesis. Furthermore, the treated lung tissue showed cells in the tumor infiltrations undergoing apoptosis and elevated expression of the proapoptotic genes Bcl-xS and Bax, suggesting an activation of the intrinsic apoptotic pathway. Overall, WT1-1 treatment prolonged the mean survival time of tumor-bearing mice in comparison with the control and WT1-2-treated mice. Our data show that WT1 gene silencing in vivo by aerosol delivery of PEI-WT1 RNAi complexes is an effective therapeutic strategy for the treatment of lung metastases.

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“…The results indicated that UAC/PCD4 complexes suppressed tumor angiogenesis, facilitated apoptosis, and inhibited pathways important for cell proliferation, compared with vector control. In addition, they delivered UAC/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) complexes into a K-ras lung cancer mouse model through an aerosol route [61]. UAC/PTEN complexes were found to significantly suppress lung tumors by nuclear complex formation between PTEN and p53 through Akt-related signal pathways as well as cell cycle arrest.…”

Section: Imidazolementioning

confidence: 99%

Polymeric Nanoparticles of Chitosan Derivatives as DNA and siRNA Carriers

Kim

Jiang

Choi

et al. 2011

Advances in Polymer Science

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The success of gene therapy is dependent on finding effective carrier systems. Viral vectors have been widely used in vivo and in clinical trials due to their high transfection efficiency; however, they have several disadvantages, including immunogenicity, potential infectivity, inflammation, and complicated production. Therefore, non-viral vectors have recently been tried as an alternative. Among non-viral vectors, chitosan and chitosan derivatives have been investigated due to several advantages, including biocompatibility, biodegradability, and low toxicity. However, the low transfection efficiency of DNA (or low gene silencing of siRNA) and the low cell specificity of chitosan as a gene carrier need to be overcome before clinical trials. The objective of this review is to discuss the use of chitosan and chitosan derivatives in gene therapy, and the effect of several parameters on transfection efficiency of DNA (or gene silencing of siRNA). Also, specific ligand and pH-sensitive modifications of chitosan for improvement of cell specificity and transfection efficiency (or gene silencing) are explained.

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

Cited by 49 publications

References 31 publications

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

Polymeric Nanoparticles of Chitosan Derivatives as DNA and siRNA Carriers

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