Radiation research最新文献

{"title":"Targeting CXCR4 with 212Pb/203Pb-Pentixather Significantly Increases Overall Survival in Small Cell Lung Cancer.","authors":"Keegan A Christensen, Melissa A Fath, Jordan T Ewald, Claudia Robles-Planells, Stephen A Graves, Spenser S Johnson, Zeb R Zacharias, Jon C D Houtman, M Sue O'Dorisio, Michael K Schultz, Bryan G Allen, Muhammad Furqan, Yusuf Menda, Dijie Liu, Douglas R Spitz","doi":"10.1667/RADE-24-00232.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00232.1","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) has a 6% 5-year overall survival rate. C-X-C chemokine receptor 4 (CXCR4) is an attractive target for theranostic agents, is highly expressed in SCLCs, and can be targeted with pentixather using the theranostic pair 212Pb/203Pb. The hypothesis that 212Pb/203Pb-pentixather can be used safely and effectively for imaging and therapy in SCLC in xenograft models was tested. SPECT-CT imaging and biodistribution studies of tumor-bearing mice injected with 203Pb-pentixather demonstrated CXCR4 expression-dependent uptake and accumulation of radioligand in the kidneys and livers. Dosimetry calculations were performed to estimate 212Pb-pentixather uptake in tumor and normal tissue. 212Pb-Pentixather treatment (37-111 kBq/g) of SCLC xenografts (DMS273 and H69AR) significantly prolonged survival and delayed tumor growth. CBCs of mice at 30 days after treatment demonstrated adequate retention of bone marrow function. NSG mice allografted with human hCD34+ bone marrow were treated with 212Pb-pentixather (37-111 kBq/g) to assess damage to human hematopoietic stem cells, demonstrating cytopenias in peripheral blood CBCs at 13-18 days after treatment, resolving by days 28-31. Flow cytometry of bone marrow in these animals at days 28-31 demonstrated a significantly reduced frequency of the human hematopoietic marker CD45 and reconstitution of the bone marrow with murine CD45+ lineages. 203Pb-Pentixather can be used to image CXCR4-expressing SCLC xenografts. Treatment with high-LET alpha emitter 212Pb-pentixather significantly prolonged overall survival, and recovery of mouse bone marrow from 212Pb-pentixather was significantly greater than that of human bone marrow.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics: A DOE-NIH Joint Workshop Executive Summary.","authors":"Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern","doi":"10.1667/RADE-25-00MR1.1","DOIUrl":"10.1667/RADE-25-00MR1.1","url":null,"abstract":"<p><p>The DOE-NIH Joint Workshop on Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics, held on September 27, 2024, brought together experts from government, academia, and industry to address critical challenges in radionuclide production and clinical translation. The workshop emphasized interdisciplinary collaboration, particularly between the Department of Energy (DOE) and the National Institutes of Health (NIH), to strengthen the domestic isotope supply, streamline regulatory pathways, and further integrate computational tools into radiopharmaceutical therapy (RPT). Key discussions explored the role of AI-driven modeling, machine learning, and digital twin technologies in optimizing dosimetry, dynamically personalizing treatments, and reducing time to clinical adoption. Advances in predictive computational modeling were highlighted as essential for improving radionuclide yield, purity, and synthesis efficiency. Regulatory considerations and equitable access were central themes, with participants advocating for harmonized global standards, adaptive trial designs, and expanded infrastructure for clinical implementation. DOE computational and production infrastructure was emphasized. Future priorities identified include increased investment in radionuclide production infrastructure, expanded workforce development in radiopharmaceutical sciences and computational modeling, and the creation of robust public-private partnerships. The workshop concluded that continued strategic collaboration and sustained resources will be vital for advancing next-generation radiotheranostics, ensuring safe and effective therapies accessible to all patients.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"75-79"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Two Stable Biodosimeters for Absorbed Ionizing Radiation Dose Estimation in Multiple Combined Injury Models.","authors":"Le Ma, Zhihe Hu, Yan Chen, Zhuo Cheng, Chunmeng Shi","doi":"10.1667/RADE-24-00261.1","DOIUrl":"10.1667/RADE-24-00261.1","url":null,"abstract":"<p><p>Radiation damage and deposition caused by radiological or nuclear public health incidents (e.g., accidents or attacks) may lead to acute radiation syndrome and other complications. Accurate and effective radiation dose assessment is necessary for triaging irradiated patients and determining treatment plans. However, there is no systematic evaluation of whether radiation biodosimetry is affected by comorbidities. The weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEG) co-analysis of the RNA-sequencing data in human peripheral blood after irradiation from the Gene Expression Omnibus (GEO) database identified seven radiation-specific genes, including five upregulated genes and two downregulated genes. Five radiation-specific genes (CCNG1, CDKN1A, GADD45A, GZMB, PHLDA3) showed a strong linear correlation with the total-body X-ray radiation model. The above five genes were used to validate further several radiation combined injury models, including infection, trauma, and burns, while considering different sexes and ages in animal studies on the radiation response from 0 to 10 Gy. The receiving operator characteristic (ROC) curve analysis revealed that the CCNG1 and CDKN1A genes performed the best in radiation dose-response across both mice and humans. Moreover, the CCNG1 protein could accurately predict the absorbed doses for up to 28 days after exposure (>95%). Our findings suggested that the CCNG1 and CDKN1A mRNA performed optimally in radiation dose response, independent of trauma, burns, age, and sex. Additionally, the CCNG1 protein revealed a strong linear correlation between radiation dose and time postirradiation. Our study demonstrated the potential feasibility of using CCNG1 and CDKN1A as injury biomarkers in radiation accident management.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"27-45"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Experimental Platform for Gamma Knife Radiosurgery in Mouse Brains.","authors":"Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang","doi":"10.1667/RADE-24-00198.1","DOIUrl":"10.1667/RADE-24-00198.1","url":null,"abstract":"<p><p>The limited availability of post-Gamma Knife radiosurgery (GKRS) samples and the unsuitability of clinical GKRS devices for small animals highlight the need to develop devices that enable the application of a clinical GKRS device in mouse models. This study introduces a novel platform specifically designed for utilizing the Leksell Gamma Knife in mouse studies. The 3D-printed device comprises a positioning platform and a head fixation device. Six-week-old C57BL/6N mice underwent irradiation targeting the left caudate putamen (CPu) or left anterior frontobase areas. Clinical Gamma Knife prescription doses (central radiation doses of 80 Gy, 60 Gy, 50 Gy, 40 Gy, 20 Gy, and 10 Gy) were administered as single exposures. Dose conversion experiments confirmed that the actual radiation dose delivered to mice was consistently 1.5-fold higher than the planned clinical dose. MRI and H&E staining revealed clear radiation necrosis (RN) in the targeted areas when the planned clinical dose of 80 Gy was applied to the CPu and anterior frontobase, confirming the device's accuracy. γ-H2AX staining showed significant DNA double-strand breaks in the targeted region, particularly after a planned clinical dose of 40 Gy and higher. H&E staining also indicated parenchymal hemorrhage, tissue loss, and edema in the targeted areas among groups exposed to the planned clinical central doses of 80 Gy, 60 Gy, and 50 Gy. Immunofluorescence staining of CD68, IBA1, and NeuN showed significant neuroinflammation in the targeted areas of the high-dose groups (planned clinical doses of 80 Gy, 60 Gy, 50 Gy, or 40 Gy), characterized by increased microglia activation, macrophage infiltration, and neuronal death. This study developed a novel mouse platform for the Leksell Gamma Knife, enabling precise GKRS in mouse brains. For adult C57BL/6N mice, a planned clinical central dose of 40 Gy may be considered a suitable threshold for radiation-induced brain injury.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"46-58"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Changes in Preterminal Serum Samples of Rhesus Macaques Exposed to Two Different Doses of Acute Lethal Total-body Gamma Radiation.","authors":"Alana D Carpenter, Issa Melendez-Miranda, Yaoxiang Li, Jeyalakshmi Kandhavelu, Oluseyi O Fatanmi, Stephen Y Wise, Amrita K Cheema, Vijay K Singh","doi":"10.1667/RADE-25-00029.1","DOIUrl":"10.1667/RADE-25-00029.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces cellular and molecular damage, leading to a chain of events that results in tissue and organ injury. Proteomics studies help identify, validate, and quantify alterations in protein abundance downstream of radiation-induced genomic changes. The current study strives to characterize and validate the proteomic changes at the preterminal stage (moribund animals) in serum samples collected from rhesus macaques lethally and acutely irradiated with two different doses of cobalt-60 gamma-radiation. Peripheral blood samples were collected prior to exposure, after exposure, and at the preterminal stage from nonhuman primates (NHPs) that did not survive after 7.2 or 7.6 Gy total-body irradiation (LD60-80/60). Using mass spectrometry-based proteomics, we analyzed samples collected at various time points after irradiation. Our findings revealed that radiation induced significant time-dependent proteomic alterations compared to pre-exposure samples. More pronounced dysregulation in pathways related to immune response and hemostasis, specifically platelet function, was present in preterminal samples, suggesting that alterations in these pathways may indicate the preterminal phenotype. These results offer important insights for the identification and validation of biomarkers for radiation-induced lethality that would be of great importance for triage during a radiological/nuclear mass casualty event.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"59-74"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Urinary Metabolite Profiles between Survivors and Non-Survivors of Radiation-induced Lung Injury in the C57L/J Murine Model.","authors":"Evan L Pannkuk, Evagelia C Laiakis, Guy Y Garty, Igor Shuryak, Kamendra Kumar, Shubhankar Suman, Shanaz A Ghandhi, Yuewen Tan, Brian Ponnaiya, Xuefeng Wu, Sally A Amundson, David J Brenner, Albert J Fornace","doi":"10.1667/RADE-25-00066.1","DOIUrl":"10.1667/RADE-25-00066.1","url":null,"abstract":"<p><p>Novel biodosimetry assays are needed to categorize both acute ionizing radiation injury and delayed effects of radiation exposure, such as radiation-induced lung injury (RILI) -associated mortality. In this study, we utilized the C57L/J mouse model, a well-established system for replicating the clinical pathology of RILI. Lung injury was induced using a combination of neutron total-body irradiation (TBI) (30% of total dose +7% of total dose concomitant gamma rays) and whole-thoracic X-irradiation (WTI) boost for the balance of the required dose at total doses of 9, 9.5, 10 and 10.5 Gy. The animals were monitored for a period of 180 days postirradiation to evaluate the progression of injury. Both male and female mice were included in the study, with cohorts exposed to either sham dose (0 Gy) or 100% X-ray WTI at 11.35 Gy (LD50/180 dose) to serve as controls. Tissue injury was characterized using whole-body plethysmography, histopathology, and targeted lipidomics. Urinary metabolites were detected using untargeted metabolomic profiling to determine if they could serve as early predictors of RILI survival. A survival rate of 40-45% was observed at 180 days postirradiation consistent with the established LD50/180 value for WTI (11.35 Gy), except at 10.5 Gy, where survival dropped to 20%. Irradiated mice exhibited increased pulmonary immune infiltration and collagen deposition, reduced alveolar spaces, thickened bronchiolar walls, and dose-independent alterations in lipid profiles that were not sex-specific. We developed a multiplex urinary metabolite panel that was associated with RILI and radiation exposure. Some compounds were statistically different between sham-irradiated male and female mice, with sex specific differences at 120 days were observed for homocitrulline, xanthosine, acetyl-arginine, methylhistidine, niacinamide, xanthurenic acid, cyclic adenosine monophosphate, taurine, and prolyl-proline urinary metabolite levels. Baseline differences in sham-irradiated C57L/J mice show sex needs to be considered as a variable when developing biomarker panels for long-term RILI effects. However, urinary metabolite panels can provide excellent to very good sensitivity and specificity at predicting survival from RILI.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"1-14"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation Dose and Solid Cancer Mortality Risk in the Techa River and East Urals Radioactive Trace Cohorts in 1950-2016.","authors":"D L Preston, L Y Krestinina, D O Stram, S B Epifanova, E A Shishkina, B A Napier, B E Moroz, N V Startsev, M O Degteva, A V Akleyev","doi":"10.1667/RADE-24-00195.1","DOIUrl":"10.1667/RADE-24-00195.1","url":null,"abstract":"<p><p>The objective of the work was to estimate the dose dependence of mortality risk from solid cancers in a cohort that includes members of two cohorts of residents of the Southern Urals who received chronic environmental low-dose, low-dose-rate radiation exposure from releases of the Mayak Plutonium Production Association. These analyses use dose and dose uncertainty estimates from a recently developed Monte-Carlo dosimetry system. The 47,950 members of the cohort include the Techa River Cohort of people who lived in the villages on the Techa River between 1950 and the end of 1960 and the East Urals Radioactive Trace Cohort of people who lived in territories of Chelyabinsk Oblast contaminated by the explosion of a radioactive waste depository on September 29, 1957, between the date of the accident and the end of 1959. As of the end of 2016, there were 25,723 deaths, including 3,783 solid cancer deaths, with 1,392,394 person years among non-migrant cohort members. The solid cancer mortality rate dose response adjusted for the effect of smoking was estimated using an excess relative risk model. Parameter estimates and confidence intervals were computed using maximum likelihood methods. The corrected information matrix method was used to determine risk estimate confidence intervals (CI) adjusted for dose uncertainty using information on the statistical uncertainty of the parameter estimates and individual dose uncertainty information provided by the dosimetry system. The smoking-adjusted linear excess relative risk (ERR) per 100 mGy for solid cancer mortality was 0.060 (95% CI 0.018 to 0.108) at age 70. The ERR increased significantly in proportion to age to the power 3.1 (95% CI 0.44 to 6.4). The joint effect of radiation and smoking on solid cancer rates appeared to be multiplicative. Adjustment for smoking had little impact on the estimated ERR. Adjusting the ERR confidence interval for dose uncertainty slightly increased the upper confidence bound (adjusted 95% CI 0.018 to 0.120). There was no evidence of nonlinearity in the solid cancer dose response. Except for liver cancer, ERR estimates for various specific types of cancer were positive. However, they were statistically significant only for stomach and female breast cancers. Statistically significant smoking effects were seen for cancers of the lung, stomach, and esophagus. Risk estimates for the two groups in the cohort did not differ significantly. The risk estimates in this cohort were consistent with data in two major occupational cohorts, they were higher than those seen in the Mayak Worker Cohort. While the ERR estimates at age 70 are like those seen in the atomic bomb survivor life span study, the ERR age dependencies were strikingly different. These findings strengthen the evidence for low-dose, low-dose-rate radiation effects on solid cancer mortality rates.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"15-26"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Tumor Immunization Efficacy after Particle-Radiation Exposure.","authors":"Brian Ponnaiya, Naresh T Deoli, Guy Garty, Andrew D Harken, Peter W Grabham, Sally A Amundson, Elizabeth M C Hillman, David J Brenner","doi":"10.1667/RADE-24-00156.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00156.1","url":null,"abstract":"<p><p>Particle radiotherapy is successful in treating cancers that are typically refractory to conventional low-LET therapy; however, the underlying molecular mechanisms remain largely unknown. Some suggest that, in addition to local tumor control, particle radiotherapy may induce long-range systemic anti-cancer effects involving the immune system that may be responsible for the overall success of the modality. Using previously published methodology, we have assessed anti-tumor responses in vivo using an immunization model. Comparing the efficacy of tumor cells killed by X rays and high-LET ions to protect against subsequent tumor challenge in mice, we have observed that at equidoses, heavy ions are more effective at generating anti-tumor responses than X rays.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combat-Relevant Model of Traumatic Hemorrhage in Rats for the Study of Combined Radiation Injury: A Pilot Study.","authors":"Stephanie M Lipiec, Luciana N Torres, Kathy L Ryan, Thomas J Walters, Harold G Klemcke, Lusha Xiang","doi":"10.1667/RADE-25-00052.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00052.1","url":null,"abstract":"<p><p>The threat and consequences of nuclear or radiological events remain a military concern today. It is estimated that 65-70% of weapon-related injuries after a nuclear event will be radiation combined injuries, i. e., acute radiation injury along with hemorrhage and traumatic injuries such as blast or other burns, bone fractures, soft tissue injuries, blood loss, and/or hypoxia. However, little is known about most types of traumatic injuries associated with blood loss, as might occur during combat operations. The primary objective of this pilot study was to develop a new animal model that incorporates both hemorrhage and traumatic injury, combined with radiation exposure. Male Sprague-Dawley rats were divided into four groups (6/group): 1. sham; 2. radiation injury (RI); 3. traumatic hemorrhage (TH), which is hemorrhage combined with extremity trauma; and 4. RI+TH. Radiation injury consisted of a single X-ray dose of 5. 5.5 Gy delivered at a rate of 1 Gy/min. Hemorrhage involved a stepwise reduction of 37% of the estimated blood volume. Extremity trauma consisted of fibular fractures and penetrating and soft tissue injuries to a single extremity. Heart rate, mean arterial blood pressure (MAP), and blood indices were analyzed at intervals corresponding to pre-hemorrhage, end of hemorrhage, and 4 h after hemorrhage, with survival observed for 14 days. Radiation injury alone had little impact on the measured variables. Hemorrhage resulted in a 60% and 67% reduction in MAP in the traumatic hemorrhage and RI+TH groups, respectively, immediately after hemorrhage, which recovered by 4 h in the traumatic hemorrhage group but not in RI+TH group. A similar pattern was observed for blood lactate levels. Traumatic hemorrhage and radiation injury resulted in 50% mortality, although mortality occurred earlier after traumatic hemorrhage. RI+TH produced 80% mortality by day 4. No mortality was observed in the sham group. By combining a high dose of X-ray radiation with our established model of traumatic hemorrhage, we have developed a new rodent model that mimics combat casualties during nuclear or radiological events.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of p53 Mutation on Tumor Radiosensitivity Estimated by Predictive Models.","authors":"Atsushi Kaida, Hitomi Nojima, Masahiko Miura","doi":"10.1667/RADE-24-00260.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00260.1","url":null,"abstract":"<p><p>p53 gene mutations are common in various cancers and may provide insights in predicting tumor radiosensitivity. This study aimed to assess the effect of p53 mutations on radiosensitivity using the intrinsic radiosensitivity index (RSI) across publicly available cancer cohorts. Gene expression data, mutation data, and clinical information were obtained from the Cancer Genome Atlas dataset. RSI, calculated from the expression of 10 specific genes, was used to evaluate radiosensitivity. Additional models were used to assess the tumor microenvironment status. p53 mutations were prevalent in several types of cancer. Notably, RSI models indicated reduced predicted radiosensitivity in patients with p53 mutations compared to those without mutations, only in head and neck squamous cell carcinoma (HNSC). In contrast, p53 mutations did not significantly decrease predicted radiosensitivity in other cancers. The association between p53 mutations and the predicted radioresistant phenotype disappeared when the cohort was controlled for p53 and p16 status in HNSC. Similarly, the estimated tumor microenvironment status was unaffected by p53 mutations. These findings suggest that predicted radiosensitivity is more strongly influenced by p16 status than by p53 mutations, indicating that p53 status alone may not be a reliable predictive marker for radiosensitivity in HNSC.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}