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- Yong Qin
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Jason Roszik
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Chandrani Chattopadhyay
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Yuuri Hashimoto
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Chengwen Liu
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Zachary A. Cooper
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Jennifer A. Wargo
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Patrick Hwu
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Suhendan Ekmekcioglu
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Elizabeth A. Grimm
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
抄録
<jats:title>Abstract</jats:title> <jats:p>Melanoma is molecularly and structurally heterogeneous, with some tumor cells existing under hypoxic conditions. Our cell growth assays showed that under controlled hypoxic conditions, BRAF(V600E) melanoma cells rapidly became resistant to vemurafenib. By employing both a three-dimensional (3D) spheroid model and a two-dimensional (2D) hypoxic culture system to model hypoxia in vivo, we identified upregulation of HGF/MET signaling as a major mechanism associated with vemurafenib resistance as compared with 2D standard tissue culture in ambient air. We further confirmed that the upregulation of HGF/MET signaling was evident in drug-resistant melanoma patient tissues and mouse xenografts. Pharmacologic inhibition of the c-Met/Akt pathway restored the sensitivity of melanoma spheroids or 2D hypoxic cultures to vemurafenib. Mol Cancer Ther; 15(10); 2442–54. ©2016 AACR.</jats:p>
収録刊行物
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- Molecular Cancer Therapeutics
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Molecular Cancer Therapeutics 15 (10), 2442-2454, 2016-10-01
American Association for Cancer Research (AACR)