التفاصيل البيبلوغرافية
| العنوان: |
Fractionated radiotherapy is the main stimulus for the induction of cell death and of Hsp70 release of p53 mutated glioblastoma cell lines |
| المؤلفون: |
Rubner, Yvonne, Muth, Carolin, Strnad, Annedore, Derer, Anja, Sieber, Renate, Buslei, Rolf, Frey, Benjamin, Fietkau, Rainer, Gaipl, Udo S |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Glioblastoma multiforme, Fractionated radiotherapy, Temozolomide, Valproic acid, Clonogenic potential, G2 cell cycle arrest, Apoptosis, Necrosis, Hsp70, Immunogenic cell death |
| الوصف: |
Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Despite a multimodal therapy consisting of resection followed by fractionated radiotherapy (RT) combined with the chemotherapeutic agent (CT) temozolomide (TMZ), its recurrence is almost inevitable. Since the immune system is capable of eliminating small tumor masses, a therapy should also aim to stimulate anti-tumor immune responses by induction of immunogenic cell death forms. The histone deacetylase inhibitor valproic acid (VPA) might foster this. Methods Reflecting therapy standards, we applied in our in vitro model fractionated RT with a single dose of 2Gy and clinically relevant concentrations of CT. Not only the impact of RT and/or CT with TMZ and/or VPA on the clonogenic potential and cell cycle of the glioblastoma cell lines T98G, U251MG, and U87MG was analyzed, but also the resulting cell death forms and release of danger signals such as heat-shock protein70 (Hsp70) and high-mobility group protein B1 (HMGB1). Results The clonogenic assays revealed that T98G and U251MG, having mutated tumor suppressor protein p53, are more resistant to RT and CT than U87MG with wild type (WT) p53. In all glioblastoma cells lines, fractionated RT induced a G2 cell cycle arrest, but only in the case of U87MG, TMZ and/or VPA alone resulted in this cell cycle block. Further, fractionated RT significantly increased the number of apoptotic and necrotic tumor cells in all three cell lines. However, only in U87MG, the treatment with TMZ and/or VPA alone, or in combination with fractionated RT, induced significantly more cell death compared to untreated or irradiated controls. While necrotic glioblastoma cells were present after VPA, TMZ especially led to significantly increased amounts of U87MG cells in the radiosensitive G2 cell cycle phase. While CT did not impact on the release of Hsp70, fractionated RT resulted in significantly increased extracellular concentrations of Hsp70 in p53 mutated and WT glioblastoma cells. ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| Relation: |
http://www.ro-journal.com/content/9/1/89 |
| الاتاحة: |
http://www.ro-journal.com/content/9/1/89 |
| Rights: |
Copyright 2014 Rubner et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.A0D4CF77 |
| قاعدة البيانات: |
BASE |