Item type:Thesis, Open Access

Evaluation des oral verfügbaren Smoothened-Antagonisten LDE225 zur Therapie von Inselzelltumoren in der transgenen Rip1Tag2-Maus

Thumbnail Image

Files

dwd.pdf (2.74 MB)

Date

2013-11-25

Authors

Publisher

Philipps-Universität Marburg
DOI

Supervisors

Abstract

Recent studies were able to identify the Hedgehog-pathway and its receptor Smoothened as a potential therapeutic target in pancreatic neuroendocrine neoplasms. The goal of this study was to evaluate the orally bioavailable Smo-antagonist LDE225 as a new therapeutic agent. Such an evaluation had not been performed for islet cell tumors. To investigate in vivo effectiveness, Rip1Tag2 transgenic mice were treated from week 5 till death with a dose of 80 mg/kg/d. Resected pancreata from treated and untreated mice were microscopically and immunohistochemically evaluated. Additionally, quantitative real-time-PCR for Hh target genes was performed on cDNA synthesized from isolated islet RNA. Microscopically, the treatment reduced tumor size by 95%. Median survival was significantly prolonged in treated mice (p<0,05). Quantitative real-time-PCR showed a clear downregulation of Hh target genes Gli1, Ptch1 and Hip1, confirming effective pharmacologic levels within the desired tissue site in vivo. The findings of this study suggest that the orally bioavailable Smo-antagonist LDE225 might provide new options in the therapy of pancreatic neuroendocrine neoplasms.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2013Issued: 2013-11-25Updated: 2013-11-25
DOI
https://doi.org/10.17192/z2013.0677
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Rip1Tag2PankreasHedgehogpancreasRip1Tag2transgenicneuroendocrine tumortransgen
DFG-subjects
Neuroendokriner TumorHedgehog
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2013.0677
show more
Wiese, Dominik (1045591130): Evaluation des oral verfügbaren Smoothened-Antagonisten LDE225 zur Therapie von Inselzelltumoren in der transgenen Rip1Tag2-Maus. : Philipps-Universität Marburg 2013-11-25. DOI: https://doi.org/10.17192/z2013.0677.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright