Error bars show one standard deviation from the mean

d, and Amezinium metilsulfate site sunitinib inhibited tumor growth of Caki-1 xenograft tumors knocked down for IL13RA2 in vivo. Additionally, growth 15 / 20 IL13RA2 and Resistance to Sunitinib in ccRCC of xenograft tumors was promoted by upregulation of IL13RA2 and suppressed by silencing of IL13RA2. And moreover, MVD was also decreased by sunitinib treatment independent of IL13RA2 expression level. These data suggested that the mechanisms of PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19741226 acquired resistance related with PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19740122 IL13RA2 expression were not associated with re-angiogenesis in tumors despite the observations in previous reports. It was reported that tumor apoptosis was induced by upregulation of IL13RA2 in glioblastoma cells. Another report showed that sunitinib induced apoptosis by inhibition of STAT3. In our model, overexpression of IL13RA2 inhibited tumor apoptosis induced by sunitinib and silencing of IL13RA2 promoted tumor apoptosis induced by sunitinib. These data suggested that IL13RA2 expression was related to acquired resistance to sunitinib through inhibiting tumor apoptosis, not via tumor re-angiogenesis. These findings were also seen in our primary xenograft model. Recent studies showed that targeting IL13RA2 may be a new therapy for glioblastoma and head and neck squamous cell carcinoma. We conclude our observation suggests that IL13RA2 could mediate resistance to sunitinib in certain population of ccRCC by avoiding sunitinib-induced apoptosis. This is an unknown mechanism for acquiring resistance to sunitinib in addition to previous reports and suggests that IL13RA2 could be a potential target to help overcome sunitinib resistance. ~~ T cells develop in the thymus through a complex multistage process. It is well known that two major checkpoints exist during T cell development in the thymus. The first checkpoint is selection at the CD4-CD8-CD25hiCD44low stage, and the other is repertoire selection at the CD4+CD8+ double positive stage. Progression through both stages is dependent on pre-TCR or TCR complexes, therefore many TCR signal-related molecules are involved in these checkpoints. RhoH belongs to the Rho family small GTPases, which play crucial roles in the development of thymocytes. RhoH is an atypical small G protein that lacks GTPase activity, and is expressed exclusively in hematopoietic lineage cells. We and others have demonstrated that RhoH acts as an adaptor protein associating with the Src-family protein tyrosine kinase Lck, c-Src tyrosine kinase Csk, and Syk-family protein tyrosine kinase Zap70 and Syk. Because RhoH is anchored to the plasma membrane through myristoylation, it is able to recruit Lck, ZAP70, and Syk to the membrane to facilitate membrane proximal signal transduction. 1 / 13 RhoH Can Bypass the Pre-TCR Checkpoint Ligation of TCR by MHC/peptide complexes induces phosphorylation of TCR-z chain ITAMs by Lck, thereby initiating TCR-dependent signal transduction. Zap70 is recruited to these phosphorylated Immunoreceptor tyrosine-based activation motifs, where Zap70 is phosphorylated and converts to the catalytically active form that phosphorylates SLP76 and LAT which then transduce signals to their downstream targets. Since RhoH controls these two proximal kinases important for the initiation of TCR signaling, it is crucial for T cell development and activation. Consequently, TCR-mediated signal transduction in RhoH deficient T cells is almost completely abolished, resulting in defective T cell development through impaired -selection, positive selection, and negativ