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Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer

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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)
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)
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)

Submitter: 加藤 達哉

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