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|Daniel U Reimer|
|Medical University Innsbruck, Austria|
|Keynote: Gynecol Obstet (Sunnyvale)|
|Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of this study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by gene array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinumsensitivity and survival were analyzed and associated to Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (P<0.001). Vav1 and Vav2 did not prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1 expression correlated with higher FIGO stage and residual disease. Furthermore, Vav3.1 overexpression was associated with poor progression-free (HR=2.820, P=0.0001) and overall survival (HR=2.842, P=0.0001). Subgroup analyses revealed an impact of Vav3.1 on survival only in type-II but not in type-I cancers. Notably, platinum-refractory cancers showed marked overexpression of Vav3.1 compared to other subsets of platinum-sensitivity (15.848 vs. 6.653, P=0.0001). In conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is clinically relevant in the pathophysiology of ovarian cancer. The N-terminal truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi-drug resistance.|
Daniel U Reimer finished his Medical study at Medical University Innsbruck in 1998. After a Post-doc position at the Division of Biochemical Pharmacology, MUI (1998- 2001) he did his specialization in Obstetrics and Gynecology at the Department of Obstetrics and Gynecology, MUI. From 2008-2011, he performed an ESGO accredited sub-specialization in Gynecologic Oncology. After his habilitation in 2012, he worked as Senior Consultant at the Department of Gynecology and Oncologic Surgery, Charité Berlin from 2012-2014. To date he is working as Senior Consultant in Gynecologic Oncology at the Deaprtment of Obstetrics and Gynecology in Innsbruck and as Senior Scientist at Charité Berlin.
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