Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer
| Autor: | Hideki Ujiie, Priya Patel, Mitsuhito Kaji, William Cruz, Tatsuya Kato, Gang Zheng, Takahiro Nakajima, Hsin-pei Hu, Kentaro Hirohashi, Hironobu Wada, Daiyoon Lee, Yoshiro Matsui, Kazuhiro Yasufuku, Masaaki Sato, Huang Huang, Kichizo Kaga, Kosuke Fujino, Juan Chen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Small interfering RNA Lung Neoplasms 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Carcinoma medicine Humans RNA Small Interfering Lung cancer Endoscopic Ultrasound-Guided Fine Needle Aspiration Molecular Biology Lymph node business.industry Cancer medicine.disease SCARB1 030104 developmental biology medicine.anatomical_structure Oncology Lymphatic Metastasis 030220 oncology & carcinogenesis Cancer cell Cancer research Nanoparticles Lymph Nodes business |
| Zdroj: | Molecular Cancer Research. 16:47-57 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | 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. Implications: This approach showed delivering personalized cancer-specific siRNAs via the appropriate nanocarrier may be a novel therapeutic option for patients with advanced lung cancer. Mol Cancer Res; 16(1); 47–57. ©2017 AACR. |
| Databáze: | OpenAIRE |
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