eprintid: 19431
rev_number: 22
eprint_status: archive
userid: 1589
dir: disk0/00/01/94/31
datestamp: 2015-12-22 10:32:34
lastmod: 2024-04-30 08:24:51
status_changed: 2015-12-22 10:32:34
type: article
metadata_visibility: show
creators_name: Blattmann, Claudia
creators_name: Oertel, Susanne
creators_name: Thiemann, Markus
creators_name: Dittmar, Anne
creators_name: Roth, Eva
creators_name: Kulozik, Andreas E.
creators_name: Ehemann, Volker
creators_name: Weichert, Wilko
creators_name: Huber, Peter E.
creators_name: Stenzinger, Albrecht
creators_name: Debus, Jürgen
title: Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy
subjects: 610
divisions: 910500
divisions: 911400
divisions: 912000
abstract: Background: Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model.   Methods: Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated.   Results: Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21Waf1/Cip1, inhibition of proliferation and angiogenesis compared to tumors treated with HIT only.   Conclusion: HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials.  
date: 2015
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1656480301
own_urn: urn:nbn:de:bsz:16-heidok-194313
language: eng
bibsort: BLATTMANNCHISTONEDEA2015
full_text_status: public
publication: Radiation Oncology
volume: 10
number: 146
place_of_pub: London
pagerange: 1-11
issn: 1748-717X
citation:   Blattmann, Claudia ; Oertel, Susanne ; Thiemann, Markus ; Dittmar, Anne ; Roth, Eva ; Kulozik, Andreas E. ; Ehemann, Volker ; Weichert, Wilko ; Huber, Peter E. ; Stenzinger, Albrecht ; Debus, Jürgen  (2015) Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy.  Radiation Oncology, 10 (146).  pp. 1-11.  ISSN 1748-717X     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19431/1/13014_2015_Article_455.pdf