論文 - 詳細
| RRC ID | 2063 |
|---|---|
| 著者 | Manabe T, Mizumoto K, Nagai E, Matsumoto K, Nakamura T, Nukiwa T, Tanaka M, Matsuda T. |
| タイトル | Cell-based protein delivery system for the inhibition of the growth of pancreatic cancer: NK4 gene-transduced oral mucosal epithelial cell sheet. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:Pancreatic resection for pancreatic cancer is the only curative modality, but the high incidence of local recurrence after surgery results in a very poor prognosis. This study aims to develop a new therapeutic tool that could inhibit the growth of remnant cancer cells, which is based on local delivery of NK4 (hepatocyte growth factor antagonist) secreted from an NK4 gene-transduced oral mucosal epithelial cell (OMEC) sheet (NK4-sheet), which is adhered to the resected surface. EXPERIMENTAL DESIGN:OMECs, harvested and cultured according to 3T3 feeder layer technique, were seeded on a collagen mesh-overlayered, biodegradable VICRYL mesh to produce an OMEC sheet. NK4 gene transduction was mediated by recombinant adenovirus (Ad-NK4). Applicability of OMECs for cell-based NK4 delivery was examined. An experimental model using nude mice was established to determine the effect of an NK4-sheet on both tumor growth and angiogenesis. RESULTS:NK4 secreted from Ad-NK4-transduced OMECs suppressed MRC-5-induced invasion of pancreatic cancer cell lines. Heterotopically implanted gene-transduced OMECs remained for >/==" BORDER="0:10 days while gradually decreasing. NK4-sheets inhibited both angiogenesis and tumor growth in vivo. CONCLUSION:Autologous OMEC was found to be suited to this purpose because of no secretion of hepatocyte growth factor, ease in harvesting from a patient, reasonably high proliferation potential, and no immune reaction. Although NK4-sheets under development exhibited a low level and short period of NK4 secretion, it is expected that this system may have a great potentiality of protein delivery system to target tissue at clinical situations when it is loaded with multilayered OMECs. |
| 巻・号 | 9(8) |
| ページ | 3158-66 |
| 公開日 | 2003-8-1 |
| PMID | 12912968 |
| MeSH | Adenoviridae / genetics Animals Biocompatible Materials Cell Adhesion Cell Division Cell Line, Tumor Collagen / chemistry Collagen / metabolism Epithelial Cells / metabolism* Female Gene Transfer Techniques* Hepatocyte Growth Factor / genetics* Hepatocyte Growth Factor / metabolism Humans Mice Mice, Nude Mitogens* Models, Biological Mouth Mucosa / pathology* Neoplasm Invasiveness Neoplasm Transplantation Neovascularization, Pathologic Pancreatic Neoplasms / therapy* Polyglactin 910 / chemistry Prognosis Rats Reverse Transcriptase Polymerase Chain Reaction Time Factors |
| IF | 10.107 |
| 引用数 | 13 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MRC-5 |