{"data":{"id":"10.6084/m9.figshare.3205228.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.3205228.v1","prefix":"10.6084","suffix":"m9.figshare.3205228.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Alessio, Nicola","nameType":"Personal","givenName":"Nicola","familyName":"Alessio","affiliation":[],"nameIdentifiers":[]},{"name":"Capasso, Stefania","nameType":"Personal","givenName":"Stefania","familyName":"Capasso","affiliation":[],"nameIdentifiers":[]},{"name":"Bernardo, Giovanni Di","nameType":"Personal","givenName":"Giovanni Di","familyName":"Bernardo","affiliation":[],"nameIdentifiers":[]},{"name":"Cappabianca, Salvatore","nameType":"Personal","givenName":"Salvatore","familyName":"Cappabianca","affiliation":[],"nameIdentifiers":[]},{"name":"Casale, Fiorina","nameType":"Personal","givenName":"Fiorina","familyName":"Casale","affiliation":[],"nameIdentifiers":[]},{"name":"Calarco, Anna","nameType":"Personal","givenName":"Anna","familyName":"Calarco","affiliation":[],"nameIdentifiers":[]},{"name":"Cipollaro, Marilena","nameType":"Personal","givenName":"Marilena","familyName":"Cipollaro","affiliation":[],"nameIdentifiers":[]},{"name":"Peluso, Gianfranco","nameType":"Personal","givenName":"Gianfranco","familyName":"Peluso","affiliation":[],"nameIdentifiers":[]},{"name":"Galderisi, Umberto","nameType":"Personal","givenName":"Umberto","familyName":"Galderisi","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Mesenchymal stromal cells having inactivated \u003ci\u003e\u003cb\u003eRB1\u003c/b\u003e\u003c/i\u003e survive following low irradiation and accumulate damaged DNA: hints for side effects following radiotherapy"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2016,"subjects":[{"subject":"Biophysics"},{"subject":"29999 Physical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Physical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Physical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Medicine"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Developmental Biology"},{"subject":"Cancer"},{"subject":"Hematology"},{"subject":"Computational Biology"}],"contributors":[],"dates":[{"date":"2016-04-28","dateType":"Created"},{"date":"2016-04-28","dateType":"Updated"},{"date":"2016","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15384101.2016.1175798","relatedIdentifierType":"DOI"},{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.3205228","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1864060 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Following radiotherapy, bone sarcomas account for a significant percentage of recurring tumors. This risk is further increased in patients with hereditary retinoblastoma that undergo radiotherapy. We analyzed the effect of low and medium dose radiation on mesenchymal stromal cells (MSCs) with inactivated \u003ci\u003eRB1\u003c/i\u003e gene to gain insights on the molecular mechanisms that can induce second malignant neoplasm in cancer survivors. MSC cultures contain subpopulations of mesenchymal stem cells and committed progenitors that can differentiate into mesodermal derivatives: adipocytes, chondrocytes, and osteocytes. These stem cells and committed osteoblast precursors are the cell of origin in osteosarcoma, and \u003ci\u003eRB1\u003c/i\u003e gene mutations have a strong role in its pathogenesis. Following 40 and 2000 mGy X-ray exposure, MSCs with inactivated \u003ci\u003eRB1\u003c/i\u003e do not proliferate and accumulate high levels of unrepaired DNA as detected by persistence of gamma-H2AX foci. In samples with inactivated \u003ci\u003eRB1\u003c/i\u003e the radiation treatment did not increase apoptosis, necrosis or senescence versus untreated cells. Following radiation, CFU analysis showed a discrete number of cells with clonogenic capacity in cultures with silenced \u003ci\u003eRB1\u003c/i\u003e. We extended our analysis to the other members of retinoblastoma gene family: \u003ci\u003eRB2/P130\u003c/i\u003e and \u003ci\u003eP107\u003c/i\u003e. Also in the MSCs with silenced \u003ci\u003eRB2/P130\u003c/i\u003e and \u003ci\u003eP107\u003c/i\u003e we detected the presence of cells with unrepaired DNA following X-ray irradiation. Cells with unrepaired DNA may represent a reservoir of cells that may undergo neoplastic transformation. Our study suggests that, following radiotherapy, cancer patients with mutations of retinoblastoma genes may be under strict controls to evaluate onset of secondary neoplasms following radiotherapy.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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