Title: | Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer |
Other Titles: | Nanoparticle Therapy using EBUS-TBNA in Lung Cancer |
Authors: | Kato, Tatsuya Browse this author |
Lee, Daiyoon Browse this author |
Huang, Huang Browse this author |
Cruz, William Browse this author |
Ujiie, Hideki Browse this author |
Fujino, Kosuke Browse this author |
Wada, Hironobu Browse this author |
Patel, Priya Browse this author |
Hu, Hsin-pei Browse this author |
Hirohashi, Kentaro Browse this author |
Nakajima, Takahiro Browse this author |
Sato, Masaaki Browse this author |
Kaji, Mitsuhito Browse this author |
Kaga, Kichizo Browse this author →KAKEN DB |
Matsui, Yoshiro Browse this author →KAKEN DB |
Chen, Juan Browse this author |
Zheng, Gang Browse this author |
Yasufuku, Kazuhiro Browse this author |
Keywords: | therapeutic target genes |
short interfering RNA (siRNA) |
endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) |
nanoparticle |
lung cancer |
Issue Date: | Jan-2018 |
Publisher: | American Association for Cancer Research |
Journal Title: | Molecular cancer research |
Volume: | 16 |
Issue: | 1 |
Start Page: | 47 |
End Page: | 57 |
Publisher DOI: | 10.1158/1541-7786.MCR-16-0341 |
PMID: | 28993508 |
Abstract: | Inhibiting specific gene expression with siRNA provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1)-expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy. The relevance of these genes was evaluated by means of siRNA experiments in cancer cell growth. To establish a therapeutic model, kinesin family member-11 (KIF11) was selected as a target gene. A total of 356 lung cancers were analyzed immunohistochemically for its clinicopathologic significance. The antitumor effect of HPPS-conjugated siRNA was evaluated in vivo using xenograft tumor models. Inhibition of gene expression for these targets effectively suppressed lung cancer cell growth. SCARB1 was highly expressed in a subset of tumors from the lung large-cell carcinoma (LCC) and small-cell lung cancer (SCLC) patients. High-level KIF11 expression was identified as an independent prognostic factor in LCC and squamous cell carcinoma (SqCC) patients. Finally, a conjugate of siRNA against KIF11 and HPPS nanoparticles induced downregulation of KIF11 expression and mediated dramatic inhibition of tumor growth in vivo. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/72287 |
Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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