Item type:Thesis, Open Access

Peritumorale Entzündung, chronische Pankreatitis und Chemoresistenz von Gemcitabin bei der Therapie des Pankreaskarzinoms – Evaluation am transgenen Tumormausmodell

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2014-09-08

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Philipps-Universität Marburg
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Abstract

BACKGROUND AND AIMS: Gemcitabine is the standard therapy for patients with pancreatic cancer with metastatic disease. Patients with metastatic pancreatic cancer presenting with increased values of C-reactive protein do not respond to gemcitabine. So far, no studies have evaluated the correlation between chronic pancreatitis, systemic inflammatory response syndrome, and the loss of chemotherapeutic benefit. METHODS: Pdx-1-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ mice were assigned into four groups: 1) Sixteen animals received a daily intraperitoneal injection of caerulein from their ninth week of life on. 2) Sixteen mice were additionally given gemcitabine. 3) Twelve animals received gemcitabine only. 4) Saline-treated control group. Furthermore, human Paca44 pancreatic ductal adenocarcinoma cells were seeded and cultured in 0.5% FBS containing growth medium plus/minus 1 μM gemcitabine plus/minus recombinant human interleukin (IL)-6. RESULTS: Induced systemic inflammatory response syndrome and a mild chronic pancreatitis diminished the beneficial effects of gemcitabine upon median overall survival. In median, the monogemcitabine group survived 191 days, whereas the caerulein-mono group survived 114, the control group 121, and the caerulein gemcitabine group 127 days (P < .05). In vitro, the induction of STAT3 phosphorylation by recombinant human IL-6 promoted pancreatic ductal adenocarcinoma cell survival during gemcitabine treatment. CONCLUSION: We could demonstrate for the first time that an improvement in median overall survival with gemcitabine is significantly abolished by a persistent mild chronic pancreatitis and a systemic inflammatory response syndrome. In particular, the inflammation biomarkers C-reactive protein, IL-6, and IL-1α could indicate the prognostic benefit of gemcitabine chemotherapy and should now be tested in prospective patient-controlled trials.

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Dates
Created: 2014Issued: 2014-09-08Updated: 2014-09-08
DOI
https://doi.org/10.17192/z2014.0573
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Interleukin-1aC-reaktives ProteinInterleukin-6ChemotherapySIRSPersonalisierte MedizinSIRSInterleukin-6. CRPInterleukin-1abiomarkersPancreatic cancerGemcitabine
DFG-subjects
BauchspeicheldrüsenkrebsGemcitabinChronische BauchspeicheldrüsenentzündungChemotherapieBiomarker
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2014.0573
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Knoop, Richard F. (1056825308): Peritumorale Entzündung, chronische Pankreatitis und Chemoresistenz von Gemcitabin bei der Therapie des Pankreaskarzinoms – Evaluation am transgenen Tumormausmodell. : Philipps-Universität Marburg 2014-09-08. DOI: https://doi.org/10.17192/z2014.0573.

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This item has been published with the following license: In Copyright