論文 - 詳細
| RRC ID | 77047 |
|---|---|
| 著者 | Taniguchi H, Natori Y, Miyagi Y, Hayashi K, Nagamura F, Kataoka K, Imai K. |
| タイトル | Treatment of primary and metastatic breast and pancreatic tumors upon intravenous delivery of a PRDM14-specific chimeric siRNA/nanocarrier complex. |
| ジャーナル | Int J Cancer |
| Abstract |
PRDM14 is highly expressed in several cancers but is not detected in normal tissues. It confers cancer stem cell-like properties, including chemoresistance and distant metastasis, to cancer cells. Herein, we aimed to develop a highly effective therapy against advanced stage cancer based on intravenously delivered PRDM14-targeted siRNA. First, we examined PRDM14 expression and gene amplification in breast and pancreatic tumors and cell lines. PRDM14 was expressed in breast cancer, including the triple-negative subtype, and pancreatic cancer. PRDM14 was amplified in 23.8% of patients with PRDM14+ breast cancer. Next, we investigated the inoculated tumor growth and distant metastasis following PRDM14 depletion by administering mice with PRDM14-specific chimeric siRNA combined with a novel branched PEGylated poly-L-ornithine (PLO)-based intravenous drug delivery system, designated PRDM14 unit polyion complex (uPIC) (n = 6/group). Inhibition of PRDM14 expression with PRDM14 uPIC by systemic intravenous injection effectively reduced tumor size and metastasis in vivo, thereby improving survival. Finally, pharmacokinetic/toxicokinetic analyses were performed on PRDM14 uPIC, which was intravenously administered to rats (n = 10-15/group) and cynomolgus monkeys (n = 3-5/group), twice weekly for 4 weeks. This revealed that PRDM14 uPIC was relatively nontoxic and the siRNA exposure in serum was greater than that predicted by the administered dose ratio when delivered as a uPIC. Taken together, our study indicated that PRDM14 uPIC is highly effective in suppressing malignant features of solid cancers and does not cause severe toxicity, making it a promising therapeutic agent for cancer treatment. |
| 巻・号 | 149(3) |
| ページ | 646-656 |
| 公開日 | 2021-8-1 |
| DOI | 10.1002/ijc.33579 |
| PMID | 33783816 |
| MeSH | Animals Apoptosis Breast Neoplasms / genetics Breast Neoplasms / pathology Breast Neoplasms / therapy* Cell Proliferation DNA-Binding Proteins / antagonists & inhibitors* DNA-Binding Proteins / genetics Drug Delivery Systems* Female Haplorhini Humans Injections, Intravenous Lung Neoplasms / genetics Lung Neoplasms / secondary Lung Neoplasms / therapy* Mice Nanoparticles / administration & dosage* Nanoparticles / chemistry Pancreatic Neoplasms / genetics Pancreatic Neoplasms / pathology Pancreatic Neoplasms / therapy* Prognosis RNA, Small Interfering / genetics* RNA-Binding Proteins / antagonists & inhibitors* RNA-Binding Proteins / genetics Rats Transcription Factors / antagonists & inhibitors* Transcription Factors / genetics Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 5.145 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PK-1(RCB1972) |