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Arash Minai-Tehrani,
Seung-Hee Chang,
Jung-Taek Kwon,
Soon-Kyung Hwang,
Ji-Eun Kim,
Ji-Young Shin,
Kyeong-Nam Yu, Sung-Jin Park,
Hu-Lin Jiang,
Ji-Hye Kim,
Seong-Ho Hong,
Bitna Kang,
Duyeoul Kim,
Chan-Hee Chae,
Kee-Ho Lee,
George R Beck,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Osteopontin (OPN) is a secreted glycophosphoprotein that has been implicated in the regulation of cancer development. The function of OPN is primarily regulated through post-translational modification such as glycosylation. As yet, however, the relationship between OPN glycosylation and lung cancer development has not been investigated. In this study, we addressed this issue by studying the effect of a triple mutant (TM) of OPN, which is mutated at three O-glycosylation sites, on lung cancer development in K-ras (LA1) mice, a murine model for human non-small cell lung cancer. METHODS: Aerosolized lentivirus-based OPN TM was delivered into the lungs of K-ras (LA1) mice using a nose-only-inhalation chamber 3 times/wk for 4 wks. Subsequently, the effects of repeated delivery of OPN TM on lung tumorigenesis and its concomitant OPN-mediated signaling pathways were investigated. RESULTS: Aerosol-delivered OPN TM inhibited lung tumorigenesis. In addition, the OPN-mediated Akt signaling pathway was inhibited. OPN TM also decreased NF-κB activity and the phosphorylation of 4E-BP1, while facilitating apoptosis in the lungs of K-ras (LA1) mice. CONCLUSIONS: Our results show that aerosol delivery of OPN TM successfully suppresses lung cancer development in the K-ras (LA1) mouse model and, therefore, warrant its further investigation as a possible therapeutic strategy for non-small cell lung cancer.
Cellular oncology (Dordrecht). 10/2012;
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Arash Minai-Tehrani,
Young-Chan Park,
Soon-Kyung Hwang,
Jung-Taek Kwon,
Seung-Hee Chang, Sung-Jin Park,
Kyeong-Nam Yu,
Ji-Eun Kim,
Ji-Young Shin,
Ji-Hye Kim,
Bitna Kang,
Seong-Ho Hong,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.
Journal of veterinary science (Suwŏn-si, Korea) 12/2011; 12(4):309-17. · 0.89 Impact Factor
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Kyeong-Nam Yu,
Arash Minai-Tehrani,
Seung-Hee Chang,
Soon-Kyung Hwang,
Seong-Ho Hong,
Ji-Eun Kim,
Ji-Young Shin, Sung-Jin Park,
Ji-Hye Kim,
Jung-Taek Kwon,
Hu-Lin Jiang,
Bitna Kang,
Duyeol Kim,
Chan-Hee Chae,
Kee-Ho Lee,
Tae-Jong Yoon,
George R Beck,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.
Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.
Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.
PLoS ONE 01/2010; 5(12):e15623. · 4.09 Impact Factor
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Cheng Xiong Xu,
Hua Jin,
Youn Sun Chung,
Ji Young Shin,
Soon Kyung Hwang,
Jung Taek Kwon, Sung Jin Park,
Eun Sun Lee,
Arash Minai-Tehrani,
Seung Hee Chang,
Min Ah Woo,
Mi Suk Noh,
Gil Hwan An,
Kee Ho Lee,
Myung Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health.
Journal of veterinary science (Suwŏn-si, Korea) 07/2009; 10(2):105-13. · 0.89 Impact Factor
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Hyun Sun Cho,
Seung Hee Chang,
Youn Sun Chung,
Ji Young Shin, Sung Jin Park,
Eun Sun Lee,
Soon Kyung Hwang,
Jung Taek Kwon,
Arash Minai Tehrani,
Minah Woo,
Mi Sook Noh,
Huda Hanifah,
Hua Jin,
Cheng Xiong Xu,
Myung Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.
Journal of Veterinary Science 04/2009; 10(1):23-8. · 1.16 Impact Factor
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Min-Ah Woo,
Sang-Myung Lee,
Gunsung Kim,
JongHo Baek,
Mi Suk Noh,
Ji Eun Kim, Sung Jin Park,
Arash Minai-Tehrani,
Se-Chang Park,
Yeong Tai Seo,
Yong-Kwon Kim,
Yoon-Sik Lee,
Dae Hong Jeong,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Immunoassays using nanomaterials have been rapidly developed for the analysis of multiple biomolecules. Highly sensitive and biocompatible surface enhanced Raman spectroscopy-active nanomaterials have been used for biomolecule analysis by many research groups in order to overcome intrinsic problems of conventional immunoassays. We used fluorescent surface-enhanced Raman spectroscopic dots (F-SERS dots) to detect biomolecules in this study. The F-SERS dots are composed of silver nanoparticle-embedded silica nanospheres, organic Raman tagging materials, and fluorescent dyes. The F-SERS dots demonstrated highly sensitive, selective, and multifunctional characteristics for multiplex targeting, tracking, and imaging of cellular and molecular events in the living organism. We successfully applied F-SERS dots for the detection of three cellular proteins, including CD34, Sca-1, and SP-C. These proteins are simultaneously expressed in bronchioalveolar stem cells (BASCs) in the murine lung. We analyzed the relative expression ratios of each protein in BASCs since external standards were used to evaluate SERS intensity in tissue. Quantitative comparisons of multiple protein expression in tissue were first attempted using SERS-encoded nanoprobes. Our results suggested that immunoassays using F-SERS dots offered significant increases in sensitivity and selectivity. Such immunoassays may serve as the primary next-generation labeling technologies for the simultaneous analysis of multiple biomolecules.
Analytical Chemistry 01/2009; 81(3):1008-15. · 5.86 Impact Factor
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Hua Jin,
Hyun-Woo Kim,
Cheng-Xiong Xu,
Jung-Taek Kwon,
Soon-Kyung Hwang,
Eun-Sun Lee,
Seung-Hee Chang, Sung-Jin Park,
Mi-Suk Noh,
Min-Ah Woo,
Kyeong-Nam Yu,
Hu-Jang Lee,
Joon-Weon Choi,
Don-Ha Choi,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Previously we reported that cadalene extracted from Zelkova serrata inhibited lung tumorigenesis in mice. However, the precise mechanism has not yet investigated. Here, we examined the effects of cadalene on signal pathways important for apoptosis, cell cycle, and protein translation in lung cancer cells. Our results showed that cadalene suppressed the expression of Akt and its phosphor-forms through controlling PI3K and PTEN. Cadalene also induced apoptosis through facilitating proapoptotic protein expression. In addition, cadalene caused cell cycle arrest and decreased mTOR-mediated protein translation. Taken together, cadalene may be developed as a lung cancer therapeutic agent in the future.
BioFactors 12/2008; 29(2‐3):67 - 75. · 4.93 Impact Factor
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Hua Jin,
Cheng-Xiong Xu,
Hwang-Tae Lim, Sung-Jin Park,
Ji-Young Shin,
Youn-Sun Chung,
Se-Chang Park,
Seung-Hee Chang,
Hee-Jeong Youn,
Kee-Ho Lee,
Yeon-Sook Lee,
Yoon-Cheol Ha,
Chan-Hee Chae,
George R Beck,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: 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.
The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development.
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.
A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b 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.
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.
American Journal of Respiratory and Critical Care Medicine 11/2008; 179(1):59-68. · 11.08 Impact Factor
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Cheng-Xiong Xu,
Dhananjay Jere,
Hua Jin,
Seung-Hee Chang,
Youn-Sun Chung,
Ji-Young Shin,
Ji-Eun Kim, Sung-Jin Park,
Yong-Hoon Lee,
Chan-Hee Chae,
Kee Ho Lee,
George R Beck,
Chong-Su Cho,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for the development of novel therapeutic options. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.
To demonstrate the feasibility and emphasize the importance of noninvasive aerosol delivery of Akt1 small interfering RNA (siRNA) as an effective and selective option for lung cancer treatment.
Nanosized poly(ester amine) polymer was synthesized and used as a gene carrier. An aerosol of poly(ester amine)/Akt1 siRNA complex was delivered into K-ras(LA1) and urethane-induced lung cancer models through a nose-only inhalation system. The effects of Akt1 siRNA on lung cancer progression and Akt-related signals were evaluated.
The aerosol-delivered Akt1 siRNA suppressed lung tumor progression significantly through inhibiting Akt-related signals and cell cycle.
The use of poly(ester amine) serves as an effective carrier, and aerosol delivery of Akt1 siRNA may be a promising approach for lung cancer treatment and prevention.
American Journal of Respiratory and Critical Care Medicine 08/2008; 178(1):60-73. · 11.08 Impact Factor
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Jun-Sung Kim,
Kyeong Nam Yu,
Mi Suk Noh,
Min-Ah Woo, Sung-Jin Park,
Jin Hong Park,
Jin Hua,
Hyun Sun Cho,
Soon Kyung Hwang,
Eun-Sun Lee,
Youn-Sun Chung,
In-Young Choi,
Se-Chang Kwon,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 x : 30 microg/kg and 50 x : 150 microg/kg). A slight anti-tumoral effect was observed in all 10 x groups compared to the control. In the 50 x groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-beta. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition.
Journal of Veterinary Science 04/2008; 9(1):45-50. · 1.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Inorganic phosphate (Pi) plays a key role in diverse physiological functions. Several studies indicate that Pi may affect lung cell development through Na/Pi cotransporter (NPT). Several NPT subtypes have been identified in mammalian lung, and considerable progress has been made in our understanding of their function and regulation. Therefore, current study was performed to elucidate the potential effects of high dietary Pi on lungs of developing mice. Our results clearly demonstrate that high dietary Pi may affect the lung of developing mice through Akt-related cap-dependent protein translation, cell cycle regulation, and angiogenesis. Our results support the hypothesis that Pi works as a critical signal molecule for normal lung growth and suggest that careful restriction of Pi consumption may be important in maintaining a normal development.
Toxicological Sciences 12/2007; 100(1):215-23. · 4.65 Impact Factor
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Jun Sung Kim,
Eunye Kuk,
Kyeong Nam Yu,
Jong-Ho Kim, Sung Jin Park,
Hu Jang Lee,
So Hyun Kim,
Young Kyung Park,
Yong Ho Park,
Cheol-Yong Hwang,
Yong-Kwon Kim,
Yoon-Sik Lee,
Dae Hong Jeong,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: The antimicrobial effects of silver (Ag) ion or salts are well known, but the effects of Ag nanoparticles on microorganisms and antimicrobial mechanism have not been revealed clearly. Stable Ag nanoparticles were prepared and their shape and size distribution characterized by particle characterizer and transmission electron microscopic study. The antimicrobial activity of Ag nanoparticles was investigated against yeast, Escherichia coli, and Staphylococcus aureus. In these tests, Muller Hinton agar plates were used and Ag nanoparticles of various concentrations were supplemented in liquid systems. As results, yeast and E. coli were inhibited at the low concentration of Ag nanoparticles, whereas the growth-inhibitory effects on S. aureus were mild. The free-radical generation effect of Ag nanoparticles on microbial growth inhibition was investigated by electron spin resonance spectroscopy. These results suggest that Ag nanoparticles can be used as effective growth inhibitors in various microorganisms, making them applicable to diverse medical devices and antimicrobial control systems.
Nanomedicine: nanotechnology, biology, and medicine 04/2007; 3(1):95-101. · 5.44 Impact Factor
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Hua Jin,
Hyun-Woo Kim,
Cheng-Xiong Xu,
Jung-Taek Kwon,
Soon-Kyung Hwang,
Eun-Sun Lee,
Seung-Hee Chang, Sung-Jin Park,
Mi-Suk Noh,
Min-Ah Woo,
Kyeong-Nam Yu,
Hu-Jang Lee,
Joon-Weon Choi,
Don-Ha Choi,
Myung-Haing Cho
[show abstract]
[hide abstract]
ABSTRACT: Previously we reported that cadalene extracted from Zelkova serrata inhibited lung tumorigenesis in mice. However, the precise mechanism has not yet investigated. Here, we examined the effects of cadalene on signal pathways important for apoptosis, cell cycle, and protein translation in lung cancer cells. Our results showed that cadalene suppressed the expression of Akt and its phosphor-forms through controlling PI3K and PTEN. Cadalene also induced apoptosis through facilitating pro-apoptotic protein expression. In addition, cadalene caused cell cycle arrest and decreased mTOR-mediated protein translation. Taken together, cadalene may be developed as a lung cancer therapeutic agent in the future.
BioFactors 02/2007; 29(2-3):67-75. · 4.93 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The development of technology enables the reduction of material size in science. The use of particle reduction in size from micro to nanoscale not only provides benefits to diverse scientific fields but also poses potential risks to humans and the environment. For the successful application of nanomaterials in bioscience, it is essential to understand the biological fate and potential toxicity of nanoparticles. The aim of this study was to evaluate the biological distribution as well as the potential toxicity of magnetic nanoparticles to enable their diverse applications in life science, such as drug development, protein detection, and gene delivery. We recently synthesized biocompatible silica-overcoated magnetic nanoparticles containing rhodamine B isothiocyanate (RITC) within a silica shell of controllable thickness [MNPs@SiO2(RITC)]. In this study, the MNPs@SiO2(RITC) with 50-nm thickness were used as a model nanomaterial. After intraperitoneal administration of MNPs@SiO2(RITC) for 4 weeks into mice, the nanoparticles were detected in the brain, indicating that such nanosized materials can penetrate blood-brain barrier (BBB) without disturbing its function or producing apparent toxicity. After a 4-week observation, MNPs@SiO2(RITC) was still present in various organs without causing apparent toxicity. Taken together, our results demonstrated that magnetic nanoparticles of 50-nm size did not cause apparent toxicity under the experimental conditions of this study.
Toxicological Sciences 02/2006; 89(1):338-47. · 4.65 Impact Factor
