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130. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

30.04. - 03.05.2013, München

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Aspirin prolongs survival and reduced the number of Foxp3+ regulatory T cells in a genetically engineered mouse model of pancreatic cancer

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  • Lars Plaßmeier - Universitätsklinikum Marburg, Visceral-,Thorax- und Gefäßchirugie, Marburg
  • Richard Knoop - Universitätsklinikum Marburg, Visceral-,Thorax- und Gefäßchirugie, Marburg
  • Jens Waldmann - Universitätsklinikum Marburg, Visceral-,Thorax- und Gefäßchirugie, Marburg
  • Rebecca Kesselring - Universitätsklinikum Regensburg, Klinik Poliklinik für Chirurfie, Regensburg
  • Malte Buchholz - Universistätsklinikum Marburg, Klinik für Gastroenterologie und Endokrinologie, Marburg
  • Stefan Fichtner-Feigl - Universitätsklinikum Regensburg, Klinik Poliklinik für Chirurfie, Regensburg
  • Detlef K. Bartsch - Universitätsklinikum Marburg, Visceral-,Thorax- und Gefäßchirugie, Marburg
  • Volker Fendrich - Universitätsklinikum Marburg, Visceral-,Thorax- und Gefäßchirugie, Marburg

Deutsche Gesellschaft für Chirurgie. 130. Kongress der Deutschen Gesellschaft für Chirurgie. München, 30.04.-03.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. Doc13dgch686

doi: 10.3205/13dgch686, urn:nbn:de:0183-13dgch6860

Published: April 26, 2013

© 2013 Plaßmeier 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: Gemcitabine became the reference regimen for advanced pancreatic cancer after a randomized trial showed significant improvement in the median overall survival. Since then the combination of gemcitabine with a variety of cytotoxic and targeted agents has generally shown no significant survival advantage as compared with gemcitabine alone. Only the addition of erlotinib to gemcitabine resulted in a significant but very small improvement in overall survival, coming along with a very uncomfortable rash in the patients. Therefore, new adjuvant agents with very low toxic levels are needed. In this study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the chemotherapeutic potential of aspirin as an adjuvant agent to gemcitabine.

Material and methods: Drug treatment was initiated at the age of 3 months. LsL-KrasG12D; LsL-Trp53R172H; Pdx1-Cre transgenic mice were randomly assigned to receive either mock treatment, gemcitabine, or a combination of gemcitabine and aspirin. All mice were treated until death. The effect of aspirin was evaluated by histopathological analyses, and immunostaining.

Results: Gemcitabine prolonged overall median survival of LsL-KrasG12D; LsL-Trp53R172H; Pdx1-Cre-mice by 31 days as compared to mock treated animals (median survival 190 vs. 159 days; p=0.396). Addition of aspirin to gemcitabine even extended the survival for ten more days, leading to a prolonged survival by 41 days, reaching statistical significance vs. the control group (median survival 200 vs. 159 days; p=0.05). Furthermore, we found that administration of aspirin in combination with gemcitabine reduced the number of Foxp3+ regulatory T cells significantly.

Conclusion: In conclusion, we identified aspirin as an effective adjuvant agent to gemcitabine in the treatment of PDAC. While fundamental differences in biology suggest the need for caution in equating mouse tumors with their human counterparts, mouse models nevertheless represent an important source of insight regarding human neoplasia. Further studies are necessary to confirm the hypothesis that aspirin might be an effective well-tolerated chemotherapeutic adjuvant agent for pancreatic cancer.