Abstract | PURPOSE: METHODS AND MATERIAL: Potential radiosensitization by SAHA was assessed in MRT xenografts by analysis of tumor growth delay, necrosis (HE), apoptosis (TUNEL), proliferation (ki-67) and γH2AX expression as well as dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG -PET) after treatment with either SAHA alone, single-dose (10 Gy) or fractionated XRT (3 × 3Gy) solely as well as in combination with SAHA compared to controls. RESULTS: SAHA only had no significant effect on tumor growth. Combination of SAHA for 8 days with single-dose XRT resulted in a higher number of complete remissions, but failed to prove a significant growth delay compared to XRT only. In contrast fractionated XRT plus SAHA for 3 weeks did induce significant tumor growth delay in MRT-xenografts. The histological examination showed a significant effect of XRT in tumor necrosis, expression of Ki-67, γH2AX and apoptosis. SAHA only had no significant effect in the histological examination. Comparison of xenografts treated with XRT and XRT plus SAHA revealed a significantly increased γH2AX expression and apoptosis induction in the mice tumors after combination treatment with single-dose as well as fractionated XRT. The combination of SAHA with XRT showed a tendency to increased necrosis and decrease of proliferation compared to XRT only, which, however, was not significant. The 18F-FDG-PET results showed no significant differences in the standard uptake value or glucose transport kinetics after either treatment. CONCLUSION: SAHA did not have a significant effect alone, but proved to enhance the effect of XRT in our MRT in vivo model.
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Authors | Markus Thiemann, Susanne Oertel, Volker Ehemann, Wilko Weichert, Albrecht Stenzinger, Marc Bischof, Klaus-J Weber, Ramon Lopez Perez, Uwe Haberkorn, Andreas E Kulozik, Jürgen Debus, Peter E Huber, Claudia Battmann |
Journal | Radiation oncology (London, England)
(Radiat Oncol)
Vol. 7
Pg. 52
(Mar 29 2012)
ISSN: 1748-717X [Electronic] England |
PMID | 22458853
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Radiation-Sensitizing Agents
- Vorinostat
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Topics |
- Animals
- Apoptosis
(drug effects, radiation effects)
- Chemoradiotherapy
(methods)
- Disease Models, Animal
- Female
- Flow Cytometry
- Histone Deacetylase Inhibitors
(pharmacology)
- Humans
- Hydroxamic Acids
(pharmacology)
- Immunohistochemistry
- In Situ Nick-End Labeling
- Mice
- Mice, Nude
- Positron-Emission Tomography
- Radiation-Sensitizing Agents
(pharmacology)
- Radiotherapy
- Rhabdoid Tumor
(diagnostic imaging, drug therapy, radiotherapy)
- Vorinostat
- Xenograft Model Antitumor Assays
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