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anticoagulant warfarin has also shown promise in the management of vascular
rejection. Metastatic renal cell carcinoma and transitional cell carcinoma, forexample, often contain large numbers of tumor-derived microemboli, which can bedetected in the cardiac ventricles by echocardiography.[@R39] The presence ofmicroemboli in these patients is associated with a high mortality rate.[@R41]
Encouragingly, preliminary studies have demonstrated a reduction in microemboliafter the administration of the anticoagulant warfarin[@R42] and this has been
associated with a clinical benefit in patients with metastatic renal cellcarcinoma.[@R43] Because renal cell carcinoma is a tumor that generates a highlevel of microemboli, the first objective of clinical trials in this disease was to assess
the microemboligenic potential of experimental therapeutic agents. As outlined byJason et al.[@R44] the assessment of microemboli in the tumor using
echocardiography is a promising approach that should be considered an integralcomponent of preclinical studies. The use of anti-angiogenic agents in renal cell
carcinoma {#s3-2} ---------------------------------------------------------- The vascularendothelial growth factor (VEGF) pathway has been demonstrated to be a major
driver of malignant neovascularization in a number of tumor types including renal
cell carcinoma.[@R45] As a result, small molecule inhibitors of VEGF signalling(for example, sunitinib, sorafenib and pazopanib) have been developed. Theseagents have been shown to have significant effects on tumor vasculature in clinical
trials and their activity has been confirmed in xenograft models.[@R45] The
efficacy of VEGF inhibitors in renal cell carcinoma has been assessed in a numberof clinical trials (for example, [clinicaltrials.gov](clinicaltrials.gov) NCT01057780,NCT01067684, NCT01028137). However, an analysis of the results of these trials
has revealed that the activity of VEGF inhibitors is largely dependent on the tumor
microenvironment. In the VEGF inhibitors' first line use in metastatic renal cell
carcinoma, responses were observed in only 30% of patients[@R49] and a

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