Radiation research最新文献

{"title":"Evaluation of Cell Cycle-Dependent Migration Activity after X-ray Exposure: A Radiobiological Approach for Optimization of Radiotherapy with Cell Cycle-Targeting Agents.","authors":"Ryosuke Seino, Hisanori Fukunaga","doi":"10.1667/RADE-23-00213.1","DOIUrl":"10.1667/RADE-23-00213.1","url":null,"abstract":"<p><p>Radiotherapy with cell cycle-specific anticancer agents has become an important option in the control of both primary tumors and metastases. Here, we used image analysis algorithms that enable quick segmentation and tracking to describe a radiobiological approach for the optimized selection of cell cycle-targeting anticancer drugs for radiotherapy. We confirmed cell cycle-synchronization using human cervical cancer HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) as a cell cycle-monitoring probe. Cells synchronized in the G1 and G2 phases were irradiated with X rays at 0.5-2 Gy. Each cell was identified using Cellpose, a deep learning-based algorithm for cellular segmentation, and the velocity and direction of migration were analyzed using the TrackMate plugin in Fiji ImageJ. G1 phase synchronized cells showed a dose-dependent decrease in velocity after irradiation, while G2 cells tended to increase their velocity. The migration pattern of all cells appeared to be a random walk model, regardless of the exposure dose. In addition, we used cisplatin to arrest the cell cycle. HeLa-FUCCI cells arrested at the G2 phase via cisplatin treatment showed enhanced cell migration after X-ray exposure. These results indicated that anticancer agents that arrest the cell cycle of cancer cells in a specific phase may enhance cell migration after radiotherapy. Our approach, using cellular segmentation and tracking algorithms, could enhance the radiobiological assessment of cell cycle-specific migration after irradiation to aid in optimizing radiotherapy using cell cycle-targeting agents.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892389","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 Novel TGFβ Receptor Inhibitor, IPW-5371, Prevents Diet-induced Hepatic Steatosis and Insulin Resistance in Irradiated Mice.","authors":"Alexandria M Szalanczy, Chrissy Sherrill, Katherine M Fanning, Barry Hart, David Caudell, Ashley W Davis, Jordyn Whitfield, Kylie Kavanagh","doi":"10.1667/RADE-23-00202.1","DOIUrl":"10.1667/RADE-23-00202.1","url":null,"abstract":"<p><p>As the number of cancer survivors increases and the risk of accidental radiation exposure rises, there is a pressing need to characterize the delayed effects of radiation exposure and develop medical countermeasures. Radiation has been shown to damage adipose progenitor cells and increase liver fibrosis, such that it predisposes patients to developing metabolic-associated fatty liver disease (MAFLD) and insulin resistance. The risk of developing these conditions is compounded by the global rise of diets rich in carbohydrates and fats. Radiation persistently increases the signaling cascade of transforming growth factor β (TGFβ), leading to heightened fibrosis as characteristic of the delayed effects of radiation exposure. We investigate here a potential radiation medical countermeasure, IPW-5371, a small molecule inhibitor of TGFβRI kinase (ALK5). We found that mice exposed to sub-lethal whole-body irradiation and chronic Western diet consumption but treated with IPW-5371 had a similar body weight, food consumption, and fat mass compared to control mice exposed to radiation. The IPW-5371 treated mice maintained lower fibrosis and fat accumulation in the liver, were more responsive to insulin and had lower circulating triglycerides and better muscle endurance. Future studies are needed to verify the improvement by IPW-5371 on the structure and function of other metabolically active tissues such as adipose and skeletal muscle, but these data demonstrate that IPW-5371 protects liver and whole-body health in rodents exposed to radiation and a Western diet, and there may be promise in using IPW-5371 to prevent the development of MAFLD.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076528","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":"Revisiting an Inverse Dose-Fractionation Effect of Ionizing Radiation Exposure for Ischemic Heart Disease: Insights from Recent Studies.","authors":"Lydia B Zablotska, Mark P Little, Nobuyuki Hamada","doi":"10.1667/RADE-00230.1","DOIUrl":"10.1667/RADE-00230.1","url":null,"abstract":"<p><p>Over the last two decades, there has been emerging evidence suggesting that ionizing radiation exposures could be associated with elevated risks of cardiovascular disease (CVD), particularly ischemic heart disease (IHD). Excess CVD risks have been observed in a number of exposed groups, with generally similar risk estimates both at low and high radiation doses and dose rates. In 2014, we reported for the first time significantly higher risks of IHD mortality when radiation doses were delivered over a protracted period of time (an inverse dose-fractionation effect) in the Canadian Fluoroscopy Cohort Study. Here we review the current evidence on the dose-fractionation effect of radiation exposure, discuss potential implication for radiation protection policies and suggest further directions for research in this area.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11260496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rainer Kurt Sachs 1932-2024.","authors":"David J Brenner, Lynn R Hlatky","doi":"10.1667/RADE-24-00RKS.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00RKS.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555410","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":"Dr. Stanley Bartlett Curtis (1932-2024).","authors":"Walter Schimmerling, Francis A Cucinotta, Jack Miller, Mark Shavers","doi":"10.1667/RADE-24-00110.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00110.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555409","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":"Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.","authors":"Frederick A Valeriote, Stephen L Brown, Joseph Media, Pin Li, Mani Maheshwari, Jiajiu Shaw","doi":"10.1667/RADE-22-00030.1","DOIUrl":"10.1667/RADE-22-00030.1","url":null,"abstract":"<p><p>We report on a new radioprotector, UTS-1401, a small molecule that was synthesized (by one of us, JS) and evaluated here for its radioprotective effect against total-body irradiation (TBI). Female and male NIH Swiss mice were subjected to TBI at doses of 6.5, 7.5 and 8.5 Gy either with or without a 24 h pretreatment of UTS-1401 given ip and observed for 30 days. Survival rates were significantly increased when mice were treated with UTS-1401 compared to those not treated. The radioprotective effect of UTS-1401 was drug-dose dependent for male mice exposed to 8.5 Gy TBI with 150 mg/kg of UTS-1401 as the optimal dose. The radioprotective effect of UTS-1401 on female mice exposed to 8.5 Gy TBI was observed at 50, 100, and 150 mg/kg, with no dose response relationship noted. Female mice were more radioresistant than male mice with LD50/30 values of 7.8 Gy vs. 6.8 Gy, respectively. Weight changes after UTS-1401 alone showed a significant body weight increase at 150 mg/kg. Both the ip and iv route for UTS-1401 were similarly effective for male mice exposed to 8 Gy TBI. Further analysis using an endogenous spleen colony assay demonstrated that pretreatment of UTS-1401 for up to 72h prior to TBI protected both spleen weight and hematopoietic stem cells with a treated/untreated ratio between 2.0 and 3.2 for the latter for times between 0.5 h and 72 h. A separate in vivo study showed that pretreatment of UTS-1401 protected bone marrow CFU-GM for mice exposed to TBI. In summary, UTS-1401 is a promising small-molecule radioprotective agent as demonstrated by whole animal, hematopoietic stem cell and bone marrow myeloid progenitor cell survival.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157950","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":"Mechanism of the Radioresistant Colorectal Cancer Cell Line SW480RR Established after Fractionated X Irradiation.","authors":"Koya Yamashita, Hironobu Yasui, Tomoki Bo, Masaki Fujimoto, Osamu Inanami","doi":"10.1667/RADE-23-00021.1","DOIUrl":"10.1667/RADE-23-00021.1","url":null,"abstract":"<p><p>Radioresistant cancer cells are risk factors for recurrence and are occasionally detected in recurrent tumors after radiotherapy. Intratumor heterogeneity is believed to be a potential cause of treatment resistance. Heterogeneity in DNA content has also been reported in human colorectal cancer; however, little is known about how such heterogeneity changes with radiotherapy or how it affects cancer radioresistance. In the present study, we established radioresistant clone SW480RR cells after fractionated X-ray irradiation of human colorectal cancer-derived SW480.hu cells, which are composed of two cell populations with different chromosome numbers, and examined how cellular radioresistance changed with fractionated radiotherapy. Compared with the parental cell population, which mostly comprised cells with higher ploidy, the radioresistant clones showed lower ploidy and less initial DNA damage. The lower ploidy cells in the parental cell population were identified as having radioresistance prior to irradiation; thus, SW480RR cells were considered intrinsically radioresistant cells selected from the parental population through fractionated irradiation. This study presents a practical example of the emergence of radioresistant cells from a cell population with ploidy heterogeneity after irradiation. The most likely mechanism is the selection of an intrinsically radioresistant population after fractionated X-ray irradiation, with a background in which lower ploidy cells exhibit lower initial DNA damage.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082287","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 Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.","authors":"Thomas Welzel, Maria Saager, Peter Peschke, Jürgen Debus, Christian P Karger","doi":"10.1667/RADE-23-00151.1","DOIUrl":"10.1667/RADE-23-00151.1","url":null,"abstract":"<p><p>Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the in vivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred. The differences in the diffusion pattern of the GM of the cervical spinal cord were examined until the endpoint of the study, occurrence of paresis grade II of both forelimbs was reached. In both radiation techniques, the same order of the occurrence of MR-morphological pathologies was observed - from edema formation to a blood spinal cord barrier (BSCB) disruption to paresis grade II of both forelimbs. However, carbon-ion irradiation showed a significant increase of the mean apparent diffusion coefficient (ADC; P = 0.031) with development of a BSCB disruption in the GM. Animals with paresis grade II as a late radiation response had a highly significant increase in mean ADC (P = 0.0001) after carbon-ion irradiation. At this time, a tendency was observed for higher mean ADC values in the GM after 12C irradiation as compared to photon irradiation (P = 0.059). These findings demonstrated that carbon-ion irradiation leads to greater structural damage to the GM of the rat cervical spinal cord than photon irradiation due to its higher linear energy transfer (LET) value.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899507","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":"Single-dose Administration of Recombinant Human Thrombopoietin Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated with 3 Gy Gamma Radiation.","authors":"Jinkun Yang, Hao Luan, Xing Shen, Guolin Xiong, Xun Wang, Xuewen Zhang, Wenyu Ji, Ying Jiang, Yangyang Dai, Enqi Zhang, Hongling Ou, Yuwen Cong, Xinru Wang, Shuang Xing, Zuyin Yu","doi":"10.1667/RADE-23-00206.1","DOIUrl":"10.1667/RADE-23-00206.1","url":null,"abstract":"<p><p>We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 μg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 μg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 μg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 μg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852508","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":"Comparison of Novel Proteomic Expression Profiles for Radiation Exposure in Male and Female C57BL6 Mice.","authors":"M Sproull, Y Fan, Q Chen, D Meerzaman, K Camphausen","doi":"10.1667/RADE-23-00180.1","DOIUrl":"10.1667/RADE-23-00180.1","url":null,"abstract":"<p><p>There is a need for point-of-care diagnostics for future mass casualty events involving radiation exposure. The development of radiation exposure and dose prediction algorithms for biodosimetry is needed for screening of large populations during these scenarios, and exploration of the potential effects which sex, age, genetic heterogeneity, and physiological comorbidities may have on the utility of biodosimetry diagnostics is needed. In the current study, proteomic profiling was used to examine sex-specific differences in age-matched C57BL6 mice on the blood proteome after radiation exposure, and the usefulness of development and application of biodosimetry algorithms using both male and female samples. Male and female mice between 9-11 weeks of age received a dose of total-body irradiation (TBI) of either 2, 4 or 8 Gy and plasma was collected at days 1, 3 and 7 postirradiation. Plasma was then screened using the SomaScan v4.1 assay for ∼7,000 protein analytes. A subset panel of protein biomarkers demonstrated significant (FDR < 0.05 and |logFC| > 0.2) changes in expression after radiation exposure. All proteins were used for feature selection to build predictive models of radiation exposure using different sample and sex-specific cohorts. Both binary (prediction of any radiation exposure) and multidose (prediction of specific radiation dose) model series were developed using either female and male samples combined or only female or only male samples. The binary series (models 1, 2 and 3) and multidose series (models 4, 5 and 6) included female/male combined, female only and male only respectively. Detectable values were obtained for all ∼7,000 proteins included in the SomaScan assay for all samples. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. Overall predictive accuracies in the binary model series was ∼100% at the model training level, and when tested with fresh samples, 97.9% for model 1 (female and male) and 100% for model 2 (female only) and model 3 (male only). When sex-specific models 2 and 3 were tested with the opposite sex, the overall predictive accuracy rate dropped to 62.5% for model 2 and remained 100% for model 3. The overall predictive accuracy rate in the multidose model series was 100% for all models at the model training level and, when tested with fresh samples, 83.3%, 75% and 83.3% for Multidose models 4-6, respectively. When sex-specific model 5 (female only) and model 6 (male only) were tested with the opposite sex, the overall predictive accuracy rate dropped to 52.1% and 68.8%, respectively. These models represent novel predictive panels of radiation-responsive proteomic biomarkers and illustrate the utility and necessity of considering sex-specific differences in development of radiation biodosimetry prediction algorithms. As sex-specific differences were observed in this study, and as use of point-of-care radiati","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}