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      1. Author :
        Takeshita, Fumitaka; Minakuchi, Yoshiko; Nagahara, Shunji; Honma, Kimi; Sasaki, Hideo; Hirai, Kotaro; Teratani, Takumi; Namatame, Nachi; Yamamoto, Yusuke; Hanai, Koji; Kato, Takashi; Sano, Akihiko; Ochiya, Takahiro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Proceedings of the National Academy of Sciences of the United States of America
      6. Products :
      7. Volume :
        102
      8. Issue :
        34
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Bone Neoplasms; Cell Line, Tumor; Collagen; DNA-Binding Proteins; Drug Carriers; Gene Expression Regulation, Neoplastic; Gene Therapy; Humans; Luciferases; Male; Mice; PC-3M-luc; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Transcription Factors
      12. Abstract :
        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-alpha-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-alpha levels was not associated with the in vivo 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.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16091473
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8979