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Low doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissues

dc.contributor.authorGil Marques, Filipa
dc.contributor.authorPoli, Maria Esmeralda
dc.contributor.authorMalaquias, João
dc.contributor.authorCarvalho, Tânia
dc.contributor.authorPortêlo, Ana
dc.contributor.authorRamires, Afonso
dc.contributor.authorAldeia, Fernando
dc.contributor.authorRibeiro, Ruy M.
dc.contributor.authorVitorino, Emília
dc.contributor.authorDiegues, Isabel
dc.contributor.authorCosta, Luis
dc.contributor.authorCoutinho, João
dc.contributor.authorPina, Maria Filomena
dc.contributor.authorMareel, Marc
dc.contributor.authorSantos, Susana Constantino Rosa
dc.date.accessioned2020-12-02T11:52:02Z
dc.date.available2020-12-02T11:52:02Z
dc.date.issued2020
dc.description© 2020 Published by Elsevier B.V.pt_PT
dc.description.abstractPurpose: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8 Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. Material and methods: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of angiogenic, pro-inflammatory, adhesion and oxidative stress genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. Results: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC and down-regulating the pro-inflammatory IL8 marker. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. Conclusions: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRadiother Oncol. 2020 Oct;151:322-327. Epub 2020 Sep 28. Erratum for: Radiother Oncol. 2019 Dec;141:256-261.pt_PT
dc.identifier.doi10.1016/j.radonc.2020.06.038pt_PT
dc.identifier.issn0167-8140
dc.identifier.urihttp://hdl.handle.net/10451/45061
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/radiotherapy-and-oncologypt_PT
dc.relation.publisherversionhttps://www.thegreenjournal.com/pt_PT
dc.subjectAngiogenesispt_PT
dc.subjectEndothelial cell activationpt_PT
dc.subjectIonizing radiationpt_PT
dc.subjectMicrovasculature.pt_PT
dc.subjectRadiotherapypt_PT
dc.titleLow doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissuespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage327pt_PT
oaire.citation.startPage322pt_PT
oaire.citation.titleRadiotherapy and Oncologypt_PT
oaire.citation.volume151pt_PT
person.familyNameGil Marques
person.familyNamePoli
person.familyNameCarvalho
person.familyNameRibeiro
person.familyNameCosta
person.familyNamePina
person.familyNameConstantino Rosa Santos
person.givenNameFilipa
person.givenNameMaria Esmeralda
person.givenNameTânia
person.givenNameRuy Miguel
person.givenNameLuis
person.givenNameMaria Filomena Brazão Carvalho De
person.givenNameSusana
person.identifier1814324
person.identifier.ciencia-id4C10-5743-02F8
person.identifier.ciencia-id9A15-E40B-738F
person.identifier.ciencia-id041E-4ADE-FB64
person.identifier.ciencia-idB311-FEB7-B1D3
person.identifier.ciencia-idF11D-8C75-78BF
person.identifier.orcid0000-0001-8715-6988
person.identifier.orcid0000-0002-7544-7726
person.identifier.orcid0000-0002-5283-5013
person.identifier.orcid0000-0002-3988-8241
person.identifier.orcid0000-0002-4782-7318
person.identifier.orcid0000-0002-5711-1292
person.identifier.ridG-6776-2015
person.identifier.ridJ-3656-2013
person.identifier.scopus-author-id25653983600
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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