Marine Potez1, Cristian Fernandez-Palomo1, Audrey Bouchet2, Verdiana Trappetti1, Mattia Donzelli3, Michael Krisch4, Jean Laissue1, Vladislav Volarevic5, Valentin Djonov6. 1. Institute of Anatomy, University of Bern, Bern, Switzerland. 2. Institute of Anatomy, University of Bern, Bern, Switzerland; Synchrotron Radiation for Biomedicine, INSERM UA7, 71 rue des Martyrs, 38000 Grenoble, France. 3. Biomedical Beamline ID17, European Synchrotron Radiation Facility, Grenoble, France; Joint Department of Physics, The Institute of Cancer Research and the Royal Marsden Hospital, London, United Kingdom. 4. Biomedical Beamline ID17, European Synchrotron Radiation Facility, Grenoble, France. 5. Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia. 6. Institute of Anatomy, University of Bern, Bern, Switzerland. Electronic address: valentin.djonov@ana.unibe.ch.
Abstract
PURPOSE: Synchrotron microbeam radiation therapy (MRT) is a method that spatially distributes the x-ray beam into several microbeams of very high dose (peak dose), regularly separated by low-dose intervals (valley dose). MRT selectively spares normal tissues, relative to conventional (uniform broad beam [BB]) radiation therapy. METHODS AND MATERIALS: To evaluate the effect of MRT on radioresistant melanoma, B16-F10 murine melanomas were implanted into mice ears. Tumors were either treated with MRT (407.6 Gy peak; 6.2 Gy valley dose) or uniform BB irradiation (6.2 Gy). RESULTS: MRT induced significantly longer tumor regrowth delay than did BB irradiation. A significant 24% reduction in blood vessel perfusion was observed 5 days after MRT, and the cell proliferation index was significantly lower in melanomas treated by MRT compared with BB. MRT provoked a greater induction of senescence in melanoma cells. Bio-Plex analyses revealed enhanced concentration of monocyte-attracting chemokines in the MRT group: MCP-1 at D5, MIP-1α, MIP-1β, IL12p40, and RANTES at D9. This was associated with leukocytic infiltration at D9 after MRT, attributed mainly to CD8 T cells, natural killer cells, and macrophages. CONCLUSIONS: In light of its potential to disrupt blood vessels that promote infiltration of the tumor by immune cells and its induction of senescence, MRT could be a new therapeutic approach for radioresistant melanoma.
PURPOSE: Synchrotron microbeam radiation therapy (MRT) is a method that spatially distributes the x-ray beam into several microbeams of very high dose (peak dose), regularly separated by low-dose intervals (valley dose). MRT selectively spares normal tissues, relative to conventional (uniform broad beam [BB]) radiation therapy. METHODS AND MATERIALS: To evaluate the effect of MRT on radioresistant melanoma, B16-F10 murinemelanomas were implanted into mice ears. Tumors were either treated with MRT (407.6 Gy peak; 6.2 Gy valley dose) or uniform BB irradiation (6.2 Gy). RESULTS: MRT induced significantly longer tumor regrowth delay than did BB irradiation. A significant 24% reduction in blood vessel perfusion was observed 5 days after MRT, and the cell proliferation index was significantly lower in melanomas treated by MRT compared with BB. MRT provoked a greater induction of senescence in melanoma cells. Bio-Plex analyses revealed enhanced concentration of monocyte-attracting chemokines in the MRT group: MCP-1 at D5, MIP-1α, MIP-1β, IL12p40, and RANTES at D9. This was associated with leukocytic infiltration at D9 after MRT, attributed mainly to CD8 T cells, natural killer cells, and macrophages. CONCLUSIONS: In light of its potential to disrupt blood vessels that promote infiltration of the tumor by immune cells and its induction of senescence, MRT could be a new therapeutic approach for radioresistant melanoma.
Authors: Sarah Sabatasso; Cristian Fernandez-Palomo; Ruslan Hlushchuk; Jennifer Fazzari; Stefan Tschanz; Paolo Pellicioli; Michael Krisch; Jean A Laissue; Valentin Djonov Journal: Cancers (Basel) Date: 2021-04-27 Impact factor: 6.639
Authors: Soha Bazyar; Edward Timothy O'Brien; Thad Benefield; Victoria R Roberts; Rashmi J Kumar; Gaorav P Gupta; Otto Zhou; Yueh Z Lee Journal: Cancers (Basel) Date: 2021-12-29 Impact factor: 6.639
Authors: Pavel Lobachevsky; Helen B Forrester; Alesia Ivashkevich; Joel Mason; Andrew W Stevenson; Chris J Hall; Carl N Sprung; Valentin G Djonov; Olga A Martin Journal: Front Oncol Date: 2021-05-21 Impact factor: 6.244