Luigi Minafra1, Valentina Bravatà1, Giorgio Russo2, Giusi Irma Forte2, Francesco Paolo Cammarata2, Marilena Ripamonti2, Giuliana Candiano2, Melchiorre Cervello3, Agata Giallongo3, Giovanni Perconti3, Cristina Messa4, Maria Carla Gilardi5. 1. Institute of Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR) -LATO, Cefalù, Italy valentina.bravata@ibfm.cnr.it luigi.minafra@ibfm.cnr.it. 2. Institute of Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR) -LATO, Cefalù, Italy. 3. Institute of Biomedicine and Molecular Immunology "Alberto Monroy"-National Research Council (IBIM-CNR), Palermo, Italy. 4. Institute of Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR) -LATO, Cefalù, Italy Nuclear Medicine Center, San Gerardo Hospital, Monza, Italy Department of Health Sciences, Tecnomed Foundation, University of Milano-Bicocca, Milan, Italy. 5. Institute of Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR) -LATO, Cefalù, Italy Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy Department of Health Sciences, Tecnomed Foundation, University of Milano-Bicocca, Milan, Italy.
Abstract
BACKGROUND/AIM: Intraoperative electron radiation therapy (IOERT) is a therapeutic approach that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells as well as to preserve healthy surrounding tissue from the side-effects of radiation therapy. The radiobiology of the healthy tissue response to IR is a topic of interest which may contribute to avoiding impairment of normal tissue and organ function and to reducing the risks of secondary cancer. The purpose of the study was to highlight cell and gene expression responses following IOERT treatment in the human non-tumorigenic MCF10A cell line in order to find new potential biomarkers of radiosensitivity/radioresistance. MATERIAL AND METHODS: Gene-expression profiling of MCF10A cells treated with 9 and 23 Gy doses (IOERT boost and exclusive treatment, respectively), was performed by whole-genome cDNA microarrays. Real-time quantitative reverse transcription (qRT-PCR), immunofluorescence and immunoblot experiments were carried out to validate candidate IOERT biomarkers. Clonogenic tests and morphological evaluations to examine cellular effects induced by radiation were also conducted. RESULTS: The study revealed a dose-dependent gene-expression profile and specific key genes that may be proposed as novel markers of radiosensitivity. Our results show consistent differences in non-tumorigenic cell tolerance and in the molecular response of MCF10A cells to different IOERTs. In particular, after 9 Gy of exposure, the selection of a radioresistant cell fraction was observed. CONCLUSION: The possibility of clarifying the molecular strategies adopted by cells in choosing between death or survival after IR-induced damage opens-up new avenues for the selection of a proper personalized therapy schedule. Copyright
BACKGROUND/AIM: Intraoperative electron radiation therapy (IOERT) is a therapeutic approach that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells as well as to preserve healthy surrounding tissue from the side-effects of radiation therapy. The radiobiology of the healthy tissue response to IR is a topic of interest which may contribute to avoiding impairment of normal tissue and organ function and to reducing the risks of secondary cancer. The purpose of the study was to highlight cell and gene expression responses following IOERT treatment in the human non-tumorigenic MCF10A cell line in order to find new potential biomarkers of radiosensitivity/radioresistance. MATERIAL AND METHODS: Gene-expression profiling of MCF10A cells treated with 9 and 23 Gy doses (IOERT boost and exclusive treatment, respectively), was performed by whole-genome cDNA microarrays. Real-time quantitative reverse transcription (qRT-PCR), immunofluorescence and immunoblot experiments were carried out to validate candidate IOERT biomarkers. Clonogenic tests and morphological evaluations to examine cellular effects induced by radiation were also conducted. RESULTS: The study revealed a dose-dependent gene-expression profile and specific key genes that may be proposed as novel markers of radiosensitivity. Our results show consistent differences in non-tumorigenic cell tolerance and in the molecular response of MCF10A cells to different IOERTs. In particular, after 9 Gy of exposure, the selection of a radioresistant cell fraction was observed. CONCLUSION: The possibility of clarifying the molecular strategies adopted by cells in choosing between death or survival after IR-induced damage opens-up new avenues for the selection of a proper personalized therapy schedule. Copyright
Authors: Valentina Bravatà; Luigi Minafra; Francesco Paolo Cammarata; Pietro Pisciotta; Debora Lamia; Valentina Marchese; Giada Petringa; Lorenzo Manti; Giuseppe Ap Cirrone; Maria Carla Gilardi; Giacomo Cuttone; Giusi Irma Forte; Giorgio Russo Journal: Br J Radiol Date: 2018-07-05 Impact factor: 3.039
Authors: Francesco P Cammarata; Filippo Torrisi; Giusi I Forte; Luigi Minafra; Valentina Bravatà; Pietro Pisciotta; Gaetano Savoca; Marco Calvaruso; Giada Petringa; Giuseppe A P Cirrone; Anna L Fallacara; Laura Maccari; Maurizio Botta; Silvia Schenone; Rosalba Parenti; Giacomo Cuttone; Giorgio Russo Journal: Int J Mol Sci Date: 2019-09-24 Impact factor: 5.923
Authors: Theodora-Dafni Michalettou; Ioannis Michalopoulos; Sylvain V Costes; Christine E Hellweg; Megumi Hada; Alexandros G Georgakilas Journal: Life (Basel) Date: 2021-02-03
Authors: Valentina Bravatà; Claudia Cava; Luigi Minafra; Francesco Paolo Cammarata; Giorgio Russo; Maria Carla Gilardi; Isabella Castiglioni; Giusi Irma Forte Journal: Int J Mol Sci Date: 2018-04-04 Impact factor: 5.923