Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen <i>in vivo</i>
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- Fumitaka Takeshita
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Yoshiko Minakuchi
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Shunji Nagahara
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Kimi Honma
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Hideo Sasaki
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Kotaro Hirai
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Takumi Teratani
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Nachi Namatame
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Yusuke Yamamoto
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Koji Hanai
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Takashi Kato
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Akihiko Sano
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
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- Takahiro Ochiya
- Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Formulation Research Laboratories, Sumitomo Pharmaceutical, Osaka 567-0878, Japan; Koken Bioscience Institute, Tokyo 115-0051, Japan; and Department of Biology, School of Education, Waseda University, Tokyo 169-0051, Japan
この論文をさがす
説明
<jats:p> Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3′-hydroxykinase p110-α-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-α levels was not associated with the <jats:italic>in vivo</jats:italic> administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 102 (34), 12177-12182, 2005-08-09
Proceedings of the National Academy of Sciences
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キーワード
- Male
- Drug Carriers
- Reverse Transcriptase Polymerase Chain Reaction
- Polycomb Repressive Complex 2
- Prostatic Neoplasms
- Bone Neoplasms
- Genetic Therapy
- DNA-Binding Proteins
- Gene Expression Regulation, Neoplastic
- Mice
- Phosphatidylinositol 3-Kinases
- Cell Line, Tumor
- Animals
- Humans
- Enhancer of Zeste Homolog 2 Protein
- Collagen
- RNA, Small Interfering
- Luciferases
- Transcription Factors
詳細情報 詳細情報について
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- CRID
- 1361981468609324672
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- NII論文ID
- 80017604766
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- ISSN
- 10916490
- 00278424
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- PubMed
- 16091473
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- データソース種別
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