By Andrew D Shaw; et al
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Effects of blocking platelet-derived growth factorreceptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst 2003; 19:458–470. 39. Veenendall LM, Jin H, Ran S, Cheung L, Navone N, Marks JW, Waltenberger J, Thorpe P, Rosenblum MG. In vitro and in vivo studies of a VEGF121=r Gelonin chimeric fusion toxin targeting the neovasculature of solid tumors. Proc Natl Acad Sci USA 2002; 99: 7866–7871. 40. Suhardja A, Hoffman H. Role of growth factors and their receptors in proliferation of microvascular endothelial cells.
The use of TKI was taken a step further when Baker et al. (91) showed that combining PTK787 (VEGF-R TKI) plus PKI-166 (EGF-R TKI) in combination with gemcitabine resulted in a 97% reduction of pancreatic tumor volume in the orthotopic animal model, and the efﬁcacy correlated with a decrease in circulating proangiogenic molecules (VEGF, IL-8) decreases in staining for dividing cells as measured by proliferating cell nuclear antigen and increases in apoptosis of tumor cells and endothelial cells.
14. Ravdin PM, Tandon AK, Allred DG, Clark GM, Fuqua SA, Hilsenbeck SH, Chamness GC, Osborne CK.