| Residential College | false |
| Status | 已發表Published |
| Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3 | |
Zhaoxia Zou1; Yufang Yin1; Jenny Lin1; Li-chen J. Hsu1; Vanessa L. Brandon1; Fan Yang1; Richard Jove1; Rahul Jandial1; Gang Li2 ; Mike Y. Chen1
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| 2016 | |
| Source Publication | JOURNAL OF NEUROSURGERY
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| ISSN | 0022-3085 |
| Volume | 124Issue:5Pages:1310-1318 |
| Abstract | OBJECTDespite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODSMelanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTSThe results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 −/− cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONSThe data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents. |
| Keyword | Sorafenib Convection-enhanced Delivery Stat3 Melanoma Brain Mice Oncology |
| DOI | 10.3171/2015.3.JNS132040 |
| Indexed By | SCIE |
| Language | 英語English |
| WOS Research Area | Neurosciences & Neurology ; Surgery |
| WOS Subject | Clinical Neurology ; Surgery |
| WOS ID | WOS:000374723000013 |
| Scopus ID | 2-s2.0-84975168232 |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | Faculty of Health Sciences |
| Affiliation | 1.Division of Neurosurgery, Department of Surgery, City of Hope National Medical Center, Duarte, California 2.Faculty of Health Sciences, University of Macau, China |
| Recommended Citation GB/T 7714 | Zhaoxia Zou,Yufang Yin,Jenny Lin,et al. Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3[J]. JOURNAL OF NEUROSURGERY, 2016, 124(5), 1310-1318. |
| APA | Zhaoxia Zou., Yufang Yin., Jenny Lin., Li-chen J. Hsu., Vanessa L. Brandon., Fan Yang., Richard Jove., Rahul Jandial., Gang Li., & Mike Y. Chen (2016). Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3. JOURNAL OF NEUROSURGERY, 124(5), 1310-1318. |
| MLA | Zhaoxia Zou,et al."Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3".JOURNAL OF NEUROSURGERY 124.5(2016):1310-1318. |
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