PURPOSE: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. METHODS AND MATERIALS: MRT was performed using a lattice of 25 mum-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-microm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of gamma-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. RESULTS: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. CONCLUSIONS: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT. (c) 2010 Elsevier Inc. All rights reserved.
PURPOSE: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. METHODS AND MATERIALS: MRT was performed using a lattice of 25 mum-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-microm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of gamma-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. RESULTS: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. CONCLUSIONS: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT. (c) 2010 Elsevier Inc. All rights reserved.
Authors: Matthew D Belley; Ian N Stanton; Mike Hadsell; Rachel Ger; Brian W Langloss; Jianping Lu; Otto Zhou; Sha X Chang; Michael J Therien; Terry T Yoshizumi Journal: Med Phys Date: 2015-04 Impact factor: 4.071
Authors: Lei Zhang; Hong Yuan; Christina Inscoe; Pavel Chtcheprov; Michael Hadsell; Yueh Lee; Jianping Lu; Sha Chang; Otto Zhou Journal: Expert Rev Anticancer Ther Date: 2014-12 Impact factor: 4.512
Authors: Lei Zhang; Hong Yuan; Laurel M Burk; Christy R Inscoe; Michael J Hadsell; Pavel Chtcheprov; Yueh Z Lee; Jianping Lu; Sha Chang; Otto Zhou Journal: Phys Med Biol Date: 2014-02-20 Impact factor: 3.609
Authors: Hong Yuan; Lei Zhang; Jonathan E Frank; Christina R Inscoe; Laurel M Burk; Mike Hadsell; Yueh Z Lee; Jianping Lu; Sha Chang; Otto Zhou Journal: Radiat Res Date: 2015-08-25 Impact factor: 2.841
Authors: Annique C Dombrowsky; Karin Burger; Ann-Kristin Porth; Marlon Stein; Martin Dierolf; Benedikt Günther; Klaus Achterhold; Bernhard Gleich; Annette Feuchtinger; Stefan Bartzsch; Elke Beyreuther; Stephanie E Combs; Franz Pfeiffer; Jan J Wilkens; Thomas E Schmid Journal: Radiat Environ Biophys Date: 2019-10-26 Impact factor: 1.925