Antiangiogenetische Therapie beim humanen Pankreaskarzinom nach orthotoper Implantation in die Nacktmaus durch einen Mikrotubuli-Inhibitor

Friedrich, Michael (2006): Antiangiogenetische Therapie beim humanen Pankreaskarzinom nach orthotoper Implantation in die Nacktmaus durch einen Mikrotubuli-Inhibitor. Dissertation, LMU München: Faculty of Medicine

Abstract

ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic diseases, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic diseases could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: ZD6126, Pankreaskarzinom, Gemzar, Mikrotubuli-Inhibitor, Antiangiogenese
• Subjects: 600 Technology, Medicine > 610 Medical sciences and medicine; 600 Technology, Medicine
• Faculties: Faculty of Medicine
• Language: German
• Date of oral examination: 2. February 2006
• 1. Referee: Jauch, Karl-Walter
• Signature of the printed copy: 0700/UMD 11526