Item type:Doctoral Thesis, Open Access

Untersuchungen zur Chemo- und Radiosensitivität und deren Auswirkungen auf Zellzyklus, Apoptoseinduktion und Genexpression in neuroendokrinen Pankreastumorzellen

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Date

2005-07-25

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Philipps-Universität Marburg
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Abstract

Treatment of patients with dissiminated functional pancreatic endocrine tumors is palliative. It includes the use of biotherapeutics, as well as application of chemotherapy to relieve symptoms and to reduce tumor volume. At present, the combination of streptozotocin and doxorubicin is the regimen of choice. In rapidly growing anaplastic small cell neuroendocrine tumors, the combination of cisplatin and etoposide seems to be more effective. However, response to chemotherapy and survival benefit is limited and often impaired by substantial side effects. In order to identify potential more effective agents in neuroendocrine pancreatic tumors in this study, the endocrine pancreatic tumor cell line BON I was treated with different conventional chemotherapeutic agents and cell cycle perturbation, induction of apoptosis and gene and protein expression were assessed. It was shown that paclitaxel elicts a strong antiproliferative effect with an early time and dose-dependent induction of G2/M arrest and concomitant induction of apoptosis. Furthermore, a slight radiosensitizing effect of paclitaxel was observed, though being limited to a defined drug and radiation dose level. Gen expression analysis with RT-PCR and cDNA arrays revealed upregulation of several cyclins, cdk s, cdki s and different cell-cycle and apoptosis related genes after 48h of treatment. Although a few p53-associated genes were overexpressed, there was no indication of p53 transcription-dependent cell death. Also, no evidence for death receptor-mediated apoptosis was found. Despite a strong G2/M arrest was also shown with some of the other drugs, no other agent used had such a marked induction of apoptosis at any of the examined time and dose intervals than paclitaxel. In respect to the obtained in vitro findings, a superior antiproliferative effect of paclitaxel may also be conceivable in vivo and should be addressed in clinical studies.

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Dates
Created: 2005Issued: 2005-07-25Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2005.0360
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Neuroendocrine pancreatic tumorApoptosisGastroenteropancreatic neuroendocrine tumorRadiosensitivitätneuroendokriner pankreatischer TumorCarcinoid tumor5-aza-2'-deoxycytidingastroenteropankreatische neuroendokrine TumorenCell cycleInselzelltumor
DFG-subjects
Neurosekretorische ZelleDifferentielle GenexpressionDecitabin ,CarcinoidInselzellcarcinomZellzyklusApoptosisTaxolGenexpression
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2005.0360
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Robbel, Christian (130186716): Untersuchungen zur Chemo- und Radiosensitivität und deren Auswirkungen auf Zellzyklus, Apoptoseinduktion und Genexpression in neuroendokrinen Pankreastumorzellen. : Philipps-Universität Marburg 2005-07-25. DOI: https://doi.org/10.17192/z2005.0360.

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