論文 - 詳細
| RRC ID | 68547 |
|---|---|
| 著者 | Yagi H, Ueda M, Jinno H, Aiura K, Mikami S, Tada H, Seno M, Yamada H, Kitajima M. |
| タイトル | Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties. |
| ジャーナル | Cancer Sci |
| Abstract |
It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent. |
| 巻・号 | 97(12) |
| ページ | 1315-20 |
| 公開日 | 2006-12-1 |
| DOI | 10.1111/j.1349-7006.2006.00336.x |
| PII | CAS336 |
| PMID | 17032310 |
| MeSH | Angiogenesis Inhibitors / therapeutic use* Animals Female Fibroblast Growth Factor 2 / genetics* Fibroblast Growth Factor 2 / metabolism Humans Immunoenzyme Techniques Mice Mice, Inbred BALB C Neoplasms, Experimental / drug therapy* Neoplasms, Experimental / pathology Neovascularization, Pathologic / prevention & control* Plasmids Recombinant Fusion Proteins / therapeutic use* Ribonuclease, Pancreatic / genetics* Ribonuclease, Pancreatic / metabolism Tumor Cells, Cultured |
| IF | 4.966 |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 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 | A431 |