| RRC ID |
67501
|
| 著者 |
Une N, Takano-Kasuya M, Kitamura N, Ohta M, Inose T, Kato C, Nishimura R, Tada H, Miyagi S, Ishida T, Unno M, Kamei T, Gonda K.
|
| タイトル |
The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.
|
| ジャーナル |
Med Oncol
|
| Abstract |
The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
|
| 巻・号 |
38(6)
|
| ページ |
60
|
| 公開日 |
2021-4-21
|
| DOI |
10.1007/s12032-021-01503-z
|
| PII |
10.1007/s12032-021-01503-z
|
| PMID |
33881631
|
| MeSH |
Angiogenesis Inhibitors / pharmacology*
Animals
Blood Vessels / diagnostic imaging
Blood Vessels / drug effects
Blood Vessels / pathology
Carcinoma, Hepatocellular / blood supply*
Carcinoma, Hepatocellular / diagnostic imaging
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / radiotherapy
Female
Liver Neoplasms, Experimental / blood supply*
Liver Neoplasms, Experimental / diagnostic imaging
Liver Neoplasms, Experimental / drug therapy
Liver Neoplasms, Experimental / radiotherapy
Mice, Inbred BALB C
Phenylurea Compounds / pharmacology*
Quinolines / pharmacology*
Sorafenib / pharmacology
Tumor Hypoxia / drug effects
X-Ray Microtomography
|
| IF |
2.834
|
| リソース情報 |
| ヒト・動物細胞 |
Hepa 1-6(RCB1638) |
