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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Non-invasive Monitoring of Sorafenib Effects on Tumor Growth and Angiogenesis by Dynamic Contrast-Enhanced CT Scans and Immunohistological Correlations

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  • E. Bettina F. Schwarz - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Clemens C. Cyran - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Philipp M. Paprottka - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • S. Sourbron - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Jobst von Einem - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Rabea Hinkel - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Oliver Dietrich - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Bernd Wintersberger - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Konstantin Nikolaou - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Maximilian F. Reiser - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Karl-Walter Jauch - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Christiane J. Bruns - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch632

doi: 10.3205/11dgch632, urn:nbn:de:0183-11dgch6326

Published: May 20, 2011

© 2011 Schwarz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Inhibiting tumor growth and angiogenesis, the oral multikinase inhibitor sorafenib is used for the treatment of advanced HCC and RCC. Despite promising clinical results, there is no sufficient data on its anti-angiogenic, anti-proliferative and pro-apoptotic effects concerning (pre-) clinical therapy courses in other tumor entities. Our aim was to investigate those effects on experimental prostate carcinomas in rats by dynamic contrast-enhanced CT scans of endothelial permeability and tumor vascularity correlated with standard immunohistological analysis.

Materials and methods: 16 male Copenhagen rats (control n=8, therapy n=8) were implanted with subcutaneous prostate carcinoma allografts (6*106 MLLB-2 cells in matrigel). The animals were imaged at baseline and after a one-week treatment course of sorafenib (10 mg/d/kg bw) by dynamic CT following enhancement with Ultravist®. Quantitative assessments of tumor plasma flow (tumor perfusion PF; ml/100ml/min) and tumor vascularity (plasma volume PV, %) were calculated based on a two-compartment model. Histological stainings for HE, RECA-1, Ki-67 and TUNEL were done.

Results: Sorafenib significantly suppressed tumor perfusion (endothelial permeability) in prostate carcinoma allografts over the treatment course of 7 days (PFday0 47,934 ± 36,855 to PFday7 24,374 ± 18,494 ml/100ml/min, p<0.05). The tumor plasma volume decreased significantly over the treatment course (PVbaseline=5.1 ± 1.0, PVday7=0.56 ± 0.48; p<0.01). Histological analysis demonstrated a significant reduction of vital tumor tissue (HE) (-27.03%, p<0.017), cell proliferation (Ki-67-,) (-45.16%, p<3.59E-8) and RECA-1 positive cells (MVD) (-40.82%; p<2.73E-5) in the treated animals. Significantly more TUNEL positive cells could be detected in sorafenib-treated tumors (+149.89%, p<0.013)

Conclusion: Endothelial permeability and tumor vascularity are significantly reduced under sorafenib in this tumor model as assayed by DCE-CTs. Results indicate a significant anti-angiogenic, anti-proliferative and pro-apoptotic effect of sorafenib as validated by correlating IHC data. DCE-CT could prove valuable for monitoring the anti-angiogenic effects of targeted therapy on an individual patient basis.