This result offered at least a mechanism for the difference in the efficacy of sunitinib SRT2104 order between clinical and preclinical trials. It should be considered if sunitinib acts via some of its targets on B16 cells. Previous studies reported that B16 cells did not express VEGFR1, VEGFR2, VEGFR3 [54, 55],

PDGFRα and PDGFRβ [56] but no more than 10% of B16 cells expressed c-Kit [57]. Whether sunitinib acts on B16 cells through the c-Kit target remains to be investigated in the further study. Chronic stress has been demonstrated to promote development and progression of tumors in several human cancer cells in xenografts including prostate cancer, ovarian cancer and SGC-CBP30 breast cancer [9, 13, 15, 46, 58], whereas no date regarding the influence of chronic stress in cancer models under sunitinib in vivo has been reported so far. This study showed that consecutive NE pumped stimulated the growth of primary tumor in a mouse melanoma model and could be blocked by propranolol. This result provided a piece of evidence for the discrepancy in the efficacy of sunitinib between clinical and preclinical

trials and was consistent with the results in the other studies in our laboratory (mouse colon cancer CT26 homograft and human colon cancer SW480 and HT-29 xenografts, unpublished Selleckchem EPZ5676 date not shown). To further investigate stress-induced angiogenesis in vivo, we analysed the immunoreactivity for VEGF and CD31, counted the MVD and measured the protein levels of VEGF, IL-8 and IL-6 in mouse serums. As expected, in accordance with the results in vivo as mentioned in the previous paragraph, chronic stress promoted angiogenesis and neovascularization in B16F1 tumors, thus withstood Farnesyltransferase the anti-angiogenic treatment of sunitinib. Interestingly, relatively low VEGF expression was found in tumor and endothelial cells while stronger VEGF expression usually found in peri-necrotic tumors cells mainly by reason of hypoxia as reported in the other study [59]. In clinic, the serum levels of VEGF, IL-8 and IL-6 have been suggested as potentially

predictive markers for survival in cancer patients under sunitinib. Bauerschlag et al. [60] found that 18 cases with a decrease in VEGF serum concentration out of 29 ovarian cancer patients with sunitinib therapy had a longer progression-free survival (PFS) compared to 11 cases with an increase in VEGF serum concentration (10.5 VS 2.9 months). Likewise, the lower serum VEGF level was reported to be associated with longer PFS and objective response rate in patients under sunitinib with bevacizumab-refractory metastatic renal cancer [61]. Bellmunt et al. [62] announced that the low serum IL-8 level was related to long median time to progression in urothelial cancer patients receiving sunitinib as first-line treatment.