{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:36:09Z","timestamp":1793439369382,"version":"4.5.0"},"reference-count":65,"publisher":"Radiation Research Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2021,4,15]]},"abstract":"<jats:p>Thoracic exposure to ionizing radiation can lead to delayed injuries to the heart and lung that are serious and even life-threatening. These injuries are difficult to predict since they manifest over many weeks and months. To identify noninvasive, tissue-specific biomarkers for the early detection of late radiation injury, circulating microRNA (miRNA) levels were measured in non-human primates (NHP, Macaca mulatta) that received a single exposure of whole-thorax lung irradiation (WTLI) at a dose likely to result in 20% or 75% mortality within 180 days (9.8 or 10.7 Gy). Animals were observed for 270 days after WTLI. Approximately 58% of 9.8 Gy WTLI animals (7 of 12) and 94% of 10.7 Gy WTLI animals (15 out of 16) did not survive to the primary end point. Evidence of pulmonary fibrosis\/pneumonitis was observed in all animals. Animals that received 10.7 Gy WTLI experienced more severe and early-onset pneumonitis, as indicated by reduced aerated lung volume, high non-sedated respiratory rate, earlier and more frequent dexamethasone treatments, and evidence of onset of heart disease. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days postirradiation, before the manifestation of symptoms, and included miRNA sequences known to regulate pathways associated with pulmonary fibrosis (TGF-\u03b2\/SMAD signaling) and pneumonitis\/inflammation (p53 signaling). The abundance of several circulating miRNA differentially expressed at day 6 or 15, such as miR-199a-3p and miR-25-3p, correlated with statistically significant differences in survival. This study supports the hypothesis that it is feasible to use plasma miRNA profiles to identify individuals at high risk of organ-specific late radiation injury. These miRNA profiles could improve radiation oncology clinical practice and serve as biomarkers to predict who might develop late complications in the aftermath of a radiological or nuclear (RAD-NUC) incident.<\/jats:p>","DOI":"10.1667\/rade-20-00031.1","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T07:38:35Z","timestamp":1635406715000},"page":"510-522","source":"Crossref","is-referenced-by-count":14,"title":["Identification of miRNA Associated with Reduced Survival after Whole-Thorax Lung Irradiation in Non-Human Primates"],"prefix":"10.1667","volume":"196","author":[{"given":"Claude J.","family":"Rogers","sequence":"first","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Espoir M.","family":"Kyubwa","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes I.","family":"Lukaszewicz","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Yamada-Hanff","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Starbird","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Miller","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asa A.","family":"Phelps","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Wallack","sequence":"additional","affiliation":[{"name":"Veterinary Imaging Center of San Diego, San Diego, California 92111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikanth","family":"Mahendra","sequence":"additional","affiliation":[{"name":"Northwest Medical Physics Center, Lynnwood, Washington 98036"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Thrall","sequence":"additional","affiliation":[{"name":"Altasciences Preclinical Seattle LLC, Everett, Washington 98203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Menon","sequence":"additional","affiliation":[{"name":"ChromoLogic LLC, Monrovia, California 91016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"40","doi-asserted-by":"crossref","unstructured":"CJ Rogers, AI Lukaszewicz, J Yamada-Hanff, et al.  \"PLoS One.\"  15, \"Identification of miRNA signatures associated with radiation-induced late lung injury in mice.\" e0232411 (2020)","DOI":"10.1371\/journal.pone.0232411"},{"key":"1","doi-asserted-by":"crossref","unstructured":"TJ MacVittie, A Bennett, C Booth, et al.  \"Health Phys.\"  103, \"The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.\" (2012)","DOI":"10.1097\/HP.0b013e318266eb4c"},{"key":"2","unstructured":"BR. 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Cohen, BP Katz, et al.  \"Health Phys.\"  103, \"A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.\" (2012)","DOI":"10.1097\/HP.0b013e31825f75a7"},{"key":"43","doi-asserted-by":"crossref","unstructured":"EB De Faria, KR Barrow, BT Ruehle, et al.  \"Health Phys.\"  109, \"The evolving mcart multimodal imaging core: Establishing a protocol for computed tomography and echocardiography in the rhesus macaque to perform longitudinal analysis of radiation-induced organ injury.\" (2015)","DOI":"10.1097\/HP.0000000000000344"},{"key":"44","doi-asserted-by":"crossref","unstructured":"KD Thrall, S Mahendra, MK Jackson, et al.  \"Health Phys.\"  116, \"A comparative dose-response relationship between sexes for mortality and morbidity of radiation-induced lung injury in the rhesus macaque.\" (2019)","DOI":"10.1097\/HP.0000000000000925"},{"key":"45","doi-asserted-by":"publisher","unstructured":"GA Parker, N Li, K Takayama, et al.  \"Health Phys.\"  116, \"Lung and heart injury in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing: Histopathological evidence of lung and heart injury.\" 383 (2019)","DOI":"10.1097\/HP.0000000000000936"},{"key":"46","doi-asserted-by":"crossref","unstructured":"MB Kirschner, SC Kao, JJ Edelman, et al.  \"PLoS One.\"  6, \"Haemolysis during sample preparation alters microRNA content of plasma.\" e24145 (2011)","DOI":"10.1371\/journal.pone.0024145"},{"key":"47","doi-asserted-by":"crossref","unstructured":"CW Law, Y Chen, W Shi, et al.  \"Genome Biol.\"  15, \"Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts.\" 1 (2014)","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"48","doi-asserted-by":"crossref","unstructured":"IS Vlachos, K Zagganas, MD Paraskevopoulou, et al.  \"Nucleic Acids Res.\"  43, \"DIANA-miRPath v3.0: deciphering microRNA function with experimental support.\" (2015)","DOI":"10.1093\/nar\/gkv403"},{"key":"49","unstructured":"N. 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Cooley, TN Yee, et al.  \"PLoS One.\"  8, \"Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.\" e57603 (2013)","DOI":"10.1371\/journal.pone.0057603"},{"key":"24","doi-asserted-by":"crossref","unstructured":"MJ Aryankalayil, S Chopra, A Makinde, et al.  \"Biomarkers.\"  23, \"Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.\" 689 (2018)","DOI":"10.1080\/1354750X.2018.1479771"},{"key":"4","doi-asserted-by":"crossref","unstructured":"ED Micewicz, K Kim, KS Iwamoto, et al.  \"PLoS One.\"  12, \"4-(Nitrophenylsulfonyl)piperazines mitigate radiation damage to multiple tissues.\" e0181577 (2017)","DOI":"10.1371\/journal.pone.0181577"},{"key":"36","doi-asserted-by":"crossref","unstructured":"J Wang, J Chen, S Sen,  \"J Cell Physiol.\"  231, \"MicroRNA as biomarkers and diagnostics.\" 25 (2016)","DOI":"10.1002\/jcp.25056"},{"key":"53","doi-asserted-by":"crossref","unstructured":"TJ MacVittie, A Gibbs, AM Farese, et al.  \"Radiat Res.\"  187, \"AEOL 10150 mitigates radiation-induced lung injury in the nonhuman primate: Morbidity and mortality are administration schedule-dependent.\" 298 (2017)","DOI":"10.1667\/RR4413.1"},{"key":"19","doi-asserted-by":"crossref","unstructured":"MJ Aryankalayil, S Chopra, J Levin, et al.  \"Radiat Res.\"  189, \"Radiation-induced long noncoding RNAs in a mouse model after whole-body irradiation.\" 251 (2018)","DOI":"10.1667\/RR14891.1"},{"key":"26","doi-asserted-by":"crossref","unstructured":"W Fendler, B Malachowska, K Meghani, et al.  \"Sci Transl Med.\"  9, \"Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates.\" eaal2408 (2017)","DOI":"10.1126\/scitranslmed.aal2408"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:25:53Z","timestamp":1793438753000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-196\/issue-5\/RADE-20-00031.1\/Identification-of-miRNA-Associated-with-Reduced-Survival-after-Whole-Thorax\/10.1667\/RADE-20-00031.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,11,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00031.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]}}}