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
|
リソース情報 |
ヒト・動物細胞 |
A431 |