In vivo efficacy of the histone deacetylase inhibitor suberoylanilide hydroxamic acid in combination with radiotherapy in a malignant rhabdoid tumor mouse model
| العنوان: | In vivo efficacy of the histone deacetylase inhibitor suberoylanilide hydroxamic acid in combination with radiotherapy in a malignant rhabdoid tumor mouse model |
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| المؤلفون: | Jürgen Debus, Wilko Weichert, Volker Ehemann, Susanne Oertel, Andreas E. Kulozik, Albrecht Stenzinger, Claudia Battmann, Marc Bischof, Peter E. Huber, Markus Thiemann, Klaus-J Weber, Uwe Haberkorn, Ramon Lopez Perez |
| المصدر: | Radiation Oncology, Vol 7, Iss 1, p 52 (2012) Radiation Oncology (London, England) |
| بيانات النشر: | BMC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | lcsh:Medical physics. Medical radiology. Nuclear medicine, Radiation-Sensitizing Agents, Necrosis, medicine.drug_class, medicine.medical_treatment, lcsh:R895-920, Malignant rhabdoid tumor, Mice, Nude, Standardized uptake value, Apoptosis, Hydroxamic Acids, Histone deacetylase inhibition, lcsh:RC254-282, Mice, In vivo, In Situ Nick-End Labeling, Medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Rhabdoid Tumor, Suberoylanilide hydroxamic acid, Vorinostat, Radiotherapy, business.industry, Research, Histone deacetylase inhibitor, Chemoradiotherapy, Flow Cytometry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Xenograft Model Antitumor Assays, Radiation therapy, Histone Deacetylase Inhibitors, Disease Models, Animal, Oncology, Radiology Nuclear Medicine and imaging, Positron-Emission Tomography, Immunology, Cancer research, Tumor necrosis factor alpha, Female, medicine.symptom, business |
| الوصف: | Purpose Histone deacetylase inhibitors are promising new substances in cancer therapy and have also been shown to sensitize different tumor cells to irradiation (XRT). We explored the effect as well as the radiosensitizing properties of suberoylanilide hydroxamic acid (SAHA) in vivo in a malignant rhabdoid tumor (MRT) mouse model. 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. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62a9e2ef5bc09ddfadf4f8724134ee85 http://www.ro-journal.com/content/7/1/52 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62a9e2ef5bc09ddfadf4f8724134ee85 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |