78 NEOADJUVANT ANTI-ANGIOGENIC TREATMENT OF RENAL CELL CANCER AND ITS EFFECT ON TUMOR BLOOD VESSELS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 201078 NEOADJUVANT ANTI-ANGIOGENIC TREATMENT OF RENAL CELL CANCER AND ITS EFFECT ON TUMOR BLOOD VESSELS Derya Tilki, Nicolas Haseke, Oliver Reich, Michael Seitz, Christian Stief, Michael Staehler, and Süleyman Ergün Derya TilkiDerya Tilki Munich, Germany More articles by this author , Nicolas HasekeNicolas Haseke Munich, Germany More articles by this author , Oliver ReichOliver Reich Munich, Germany More articles by this author , Michael SeitzMichael Seitz Munich, Germany More articles by this author , Christian StiefChristian Stief Munich, Germany More articles by this author , Michael StaehlerMichael Staehler Munich, Germany More articles by this author , and Süleyman ErgünSüleyman Ergün Essen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.126AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The majority of renal cell carcinomas (RCC) are hypervascularized. To date, four substances have been approved to control angiogenesis in RCC: sunitinib, sorafenib, temsirolimus, and the combination of bevacizumab and interferon alpha. Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. Anti-angiogenic treatment leads to vascular remodelling processes and subsequent influence on tumor growth, which, however, are not sufficiently studied in RCC yet. METHODS Vascular morphogenesis in 15 renal specimen after neoadjuvant anti-angiogenic treatment and 9 matched cases without anti-angiogenic treatment was studied by light microscopy and immunohistochemistry for the vascular markers CD31, CD34, a-smooth muscle actin (a-SMA) and human endostatin/collagen 18. RESULTS Histological examination of tumor tissue by conventional light microscopic evaluation revealed an extensive necrosis, particularly at the central part of the tumors which was significantly enhanced in tumors treated with anti-angiogenic substances. However, within the necrotic areas few surviving tumor cells were found to be organized around blood vessels which appeared to be greater in diameter in comparison to those in the tumor marginal area. Immunostaining for CD31, CD34 and a-SMA revealed a regular integration of smooth muscle cells into the vascular wall in treated tumors. Also, the immunostaining for the endogenous angiogenesis inhibitor endostatin in the wall of tumor blood vessels was stronger in treated tumors. The number of such stabilized blood vessels was increased under anti-angiogenic therapy while the general vascular density was significantly reduced. CONCLUSIONS The results indicate for the first time that anti-angiogenic therapy of human tumors induces vascular stabilization which is associated with an extensive vascular remodelling and necrosis of tumor tissue. Persistent tumor cells around larger vessels may be of therapeutic relevance. Therapeutic acceleration and sustainment of the processes of vascular stabilization in tumors would enable new strategies in tumor therapy and imaging. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e33 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Derya Tilki Munich, Germany More articles by this author Nicolas Haseke Munich, Germany More articles by this author Oliver Reich Munich, Germany More articles by this author Michael Seitz Munich, Germany More articles by this author Christian Stief Munich, Germany More articles by this author Michael Staehler Munich, Germany More articles by this author Süleyman Ergün Essen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...