原创力文档combined anti-angiogenic therapy targeting pdgf and vegf receptors lowers the interstitial fluid pressure in a murine experimental carcinoma结合抗血管生成疗法针对pdgf和vegf受体降低了孔隙流体压力在小鼠实验癌.pdfVIP
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combined anti-angiogenic therapy targeting pdgf and vegf receptors lowers the interstitial fluid pressure in a murine experimental carcinoma结合抗血管生成疗法针对pdgf和vegf受体降低了孔隙流体压力在小鼠实验癌
Combined Anti-Angiogenic Therapy Targeting PDGF and
VEGF Receptors Lowers the Interstitial Fluid Pressure in a
Murine Experimental Carcinoma
1. 1. 1 ˚ 1 2
Agnieszka Kłosowska-Warde˛ ga *, Yoko Hasumi , Mikhail Burmakin , Aive Ahgren , Linda Stuhr ,
Ingrid Moen2, Rolf K. Reed2, Kristofer Rubin3, Carina Hellberg 1, Carl-Henrik Heldin 1
1 Biomedical Center, Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden, 2 Department of Biomedicine, University of Bergen, Jonas Lies vei 91,
Bergen, Norway, 3 Biomedical Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Abstract
Elevation of the interstitial fluid pressure (IFP) of carcinoma is an obstacle in treatment of tumors by chemotherapy and
correlates with poor drug uptake. Previous studies have shown that treatment with inhibitors of platelet-derived growth
factor (PDGF) or vascular endothelial growth factor (VEGF) signaling lowers the IFP of tumors and improve chemotherapy. In
this study, we investigated whether the combination of PDGFR and VEGFR inhibitors could further reduce the IFP of KAT-4
human carcinoma tumors. The tumor IFP was measured using the wick-in-needle technique. The combination of STI571 and
PTK/ZK gave an additive effect on the lowering of the IFP of KAT-4 tumors, but the timing of the treatment was crucial. The
lowering of IFP following combination therapy was accompanied by vascular remodeling and decreased vascular leakiness.
The effects of the inhibitors on the therapeutic efficiency of Taxol were investigated. Whereas the anti-PDGF and anti-VEGF
treatment did not significantly inhibit
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