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Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status

TitleAbscopal effect of radiation therapy: Interplay between radiation dose and p53 status
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2014
AuthorsStrigari, L., Mancuso Mariateresa, Ubertini V., Soriani A., Giardullo Paola, Benassi M., D'Alessio D., Leonardi Simona, Soddu S., and Bossi G.
JournalInternational Journal of Radiation Biology
Volume90
Pagination248-255
ISSN09553002
Keywordsanimal experiment, animal model, Animals, Apoptosis, article, Bystander Effect, cancer cell, cancer growth, cancer radiotherapy, Cell Line, colon cancer, controlled study, Dose-Response Relationship, electron beam, Electrons, Female, Gamma rays, HCT116 Cells, human, human cell, Humans, immunohistochemistry, irradiation, Mice, mouse, Neoplasm Transplantation, Neoplasms, nonhuman, Nude, nude mouse, priority journal, protein p53, Radiation, radiation dose, radiometry, radiotherapy, signal transduction, Tumor, Tumor Suppressor Protein p53
Abstract

Purpose: This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals. Material and methods: Wild-type (wt)-p53 or p53-null HCT116 human colon cancer cells were xenografted into both flanks of athymic female nude mice. When tumours reached a volume of 0.2 cm3, irradiation was performed, under strict dose monitoring, with a dedicated mobile accelerator designed for intra-Operative-RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron beam, was delivered to a tumour established in one side flank, leaving the other non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry out short-term molecular analyses. Results: All directly-irradiated tumours, showed a dose-dependent delayed and reduced regrowth, independent of the p53 status. Importantly, a significant effect on tumour-growth inhibition was also demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a moderate effect also evident after 10 Gy-irradiation. In contrast, no significant difference was observed in the NIR p53-null tumours, independent of the dose delivered. Molecular analyses indicate that p53-dependent signals might be responsible for the abscopal effect in our model system, via a pro-apoptotic pathway. Conclusions: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells. © 2014 Informa UK, Ltd.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84896780423&doi=10.3109%2f09553002.2014.874608&partnerID=40&md5=8b0600a471c0ad08b0dd98a1f24023f6
DOI10.3109/09553002.2014.874608
Citation KeyStrigari2014248