Susannah G Ellsworth, Alison Ross, Kevin R Y Shiue, Pranav Murthy, Miranda L Byrne-Steel, Ravi Patel, Richard C Zellars, Feng-Ming Spring Kong, Amy Miller, Kristen A Russ, Michael T Lotze
{"title":"Survey of Changes in Absolute Lymphocyte Counts and Peripheral Immune Repertoire Diversity after External Beam Radiotherapy.","authors":"Susannah G Ellsworth, Alison Ross, Kevin R Y Shiue, Pranav Murthy, Miranda L Byrne-Steel, Ravi Patel, Richard C Zellars, Feng-Ming Spring Kong, Amy Miller, Kristen A Russ, Michael T Lotze","doi":"10.1667/RADE-24-00010.1","DOIUrl":"10.1667/RADE-24-00010.1","url":null,"abstract":"<p><p>Radiation-induced lymphopenia (RIL) is associated with worse outcomes in patients with multiple solid tumors. Hypofractionated radiation therapy (HFRT) reduces RIL compared with conventionally fractionated radiation therapy (CFRT). However, fractionation effects on immune repertoire (IR) diversity are unknown. RNA-based T- and B-cell receptor sequencing was performed on peripheral lymphocytes collected prospectively before radiation therapy and <4 weeks after the final radiation fraction. Patients received CFRT (≤3 Gy/day × ≥10 days ± chemotherapy, n = 13) or HFRT (≥5 Gy/day × ≤5 days, n = 10), per institutional standards of care. Immune repertoire diversity parameters analyzed were number of unique CDR3 receptors (uCDR3), Shannon entropy, and sample clonality (percentage of all receptors represented by the top 10 clones). RIL was severe with concurrent chemotherapy (median %Δ ALC -58.8%, -12.5%, and -28.6% in patients treated with CFRT and chemo, CFRT alone, and HFRT, respectively). CFRT and concurrent chemotherapy was associated with more severe diversity restriction in all examined parameters than either HFRT or CFRT alone. Increased immune repertoire diversity despite decreased ALC was more common in patients treated with HFRT than CFRT and significantly less common in patients treated with concurrent chemotherapy (P < 0.001). Radiation-induced changes in immune repertoire diversity are variably reflected in the peripheral ALC. Both HFRT and CFRT caused RIL, but HFRT was associated with improved immune repertoire diversity despite RIL. The addition of chemotherapy may potentiate radiation-induced restriction in immune repertoire diversity. As immune repertoire diversity is associated with response to immunotherapy, these findings may have implications for radiation therapy/chemotherapy/immunotherapy combinations. Further studies are required to understand the relationship between radiation, circulating lymphocyte populations, immune repertoire diversity and response to treatment.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"837-846"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547083","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":"Hepatic Stellate Cell-mediated Increase in CCL5 Chemokine Expression after X-ray Irradiation Determined In Vitro and In Vivo.","authors":"Masataka Taga, Kengo Yoshida, Shiho Yano, Keiko Takahashi, Seishi Kyoizumi, Megumi Sasatani, Keiji Suzuki, Tomohiro Ogawa, Yoichiro Kusunoki, Tatsuaki Tsuruyama","doi":"10.1667/RADE-23-00127.1","DOIUrl":"10.1667/RADE-23-00127.1","url":null,"abstract":"<p><p>Radiation exposure causes hepatitis which induces hepatic steatosis and fibrosis. Although hepatic stellate cells (HSCs) have been considered potential pathological modulators for the development of hepatitis due to viral and microbial infections, their involvement in radiation-induced hepatitis is yet to be determined. This study aimed to clarify the relationship between radiation exposure and expressions of inflammatory cytokines and chemokines in HSCs in vitro and in vivo. HSCs were obtained from 1-week-old mice, known to be highly sensitive to radiation-induced hepatocellular carcinoma, using a newly established method combining liver perfusion, cell dissociation, and density gradient centrifugation, followed by magnetic negative selection of hematopoietic and endothelial cells with anti-CD45.2 and CD146 antibodies. The isolated HSCs were confirmed by the expression of desmin and glial fibrillary acidic protein (GFAP). We demonstrated that primary cultured HSCs, exposed to X-ray irradiation (0, 1.9, and 3.8 Gy) and cultured for 3 and 7 days, produced elevated levels of C-C motif chemokine ligand 5 (CCL5, also known as RANTES) inflammatory chemokine in a dose-dependent manner. An in vivo immunofluorescence method confirmed that increased CCL5 signals were observed in GFAP-positive HSCs in mouse livers 7 days after whole-body X-ray irradiation (1.9 and 3.8 Gy). Adequate expression of C-C motif chemokine receptor 5 (Ccr5), a receptor for CCL5, was also detected using real-time PCR in the liver of both irradiated and non-irradiated mice. Taken together, our data suggest that HSCs may drive hepatitis via CCL5/CCR5 axis in the liver under radiation-induced stress. Furthermore, this newly established experimental protocol can help evaluate the expression of other inflammatory cytokines in primary cultures of HSCs isolated from infant mice.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"862-869"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506819","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}
Ignacia B Tanaka, Satoshi Tanaka, Rei Nakahira, Jun-Ichiro Komura
{"title":"Transgenerational Effects on Lifespan and Pathology of Paternal Pre-conceptional Exposure to Continuous Low-dose-rate Gamma Rays in C57BL/6J Mice.","authors":"Ignacia B Tanaka, Satoshi Tanaka, Rei Nakahira, Jun-Ichiro Komura","doi":"10.1667/RADE-24-00093.1","DOIUrl":"10.1667/RADE-24-00093.1","url":null,"abstract":"<p><p>The present work investigates the multigenerational effects of paternal pre-conceptional exposure to continuous low-dose-rate gamma rays in C56BL/6J mice. Male C57BL/6J (F0 sires) mice were exposed to low dose rates of 20, 1, and 0.05 mGy/day for 400 days, to total accumulated doses of 8,000, 400, and 20 mGy, respectively. Upon completion of the radiation exposure, the F0 male mice were immediately bred to non-irradiated 8-week-old C57BL/6J females (F0 dams) to produce the first-generation (F1) mice. Randomly selected F1 males and females were then bred to produce the second-generation (F2) mice. All the mice, except the F0 dams, were subjected to pathological examination upon natural death. Reproductive parameters, lifespan, causes of death, neoplasm incidences and non-neoplastic disease incidences were used as parameters to evaluate the biological effects of continuous pre-conceptional exposure of the sires (F0) to continuous low-dose-rate radiation. There were no significant differences in the pregnancy and weaning rates among the parent (F0) generation. Average litter size and average number of weaned pups (F1) from dams bred to males (F0) exposed to 20 mGy/day were significantly decreased compared to the non-irradiated controls. Significant lifespan shortening in the sires (F0) was observed only in the 20 mGy/day group due to early death from malignant lymphomas. Life shortening was also observed in the F1 progeny of sires (F0) exposed to 20 and 1 mGy/day, but could not be attributed to a specific cause. No significant differences in the causes of death were found between dose groups in any generation. The number of primary tumors per mouse was significantly increased only in the F0 males exposed to 20 mGy/day. Except for the increased incidence rate for Harderian gland neoplasms in sires (F0) exposed to 20 mGy/day, there was no significant difference in neoplasm incidences and tumor spectra in all 3 generations in each sex regardless of radiation exposure. No multi- or transgenerational effects in the parameters examined were observed in the F1 and F2 progeny of sires exposed to 0.05 mGy/day for 400 days.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"870-887"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547084","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}
Lawrence T Dauer, Michael T Mumma, Julie C Lima, Sarah S Cohen, Daniel Andresen, Amir A Bahadori, Michael Bellamy, David A Bierman, Steve Blattnig, Benjamin French, Eric Giunta, Kathryn Held, Nolan Hertel, Laura Keohane, Richard Leggett, Loren Lipworth, Kathleen B Miller, Ryan B Norman, Caleigh Samuels, Kali S Thomas, Sergei Y Tolmachev, Linda Walsh, John D Boice
{"title":"A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.","authors":"Lawrence T Dauer, Michael T Mumma, Julie C Lima, Sarah S Cohen, Daniel Andresen, Amir A Bahadori, Michael Bellamy, David A Bierman, Steve Blattnig, Benjamin French, Eric Giunta, Kathryn Held, Nolan Hertel, Laura Keohane, Richard Leggett, Loren Lipworth, Kathleen B Miller, Ryan B Norman, Caleigh Samuels, Kali S Thomas, Sergei Y Tolmachev, Linda Walsh, John D Boice","doi":"10.1667/RADE-23-00186.1","DOIUrl":"10.1667/RADE-23-00186.1","url":null,"abstract":"<p><p>The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"847-861"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506818","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}
Emma Kosowski, John D Olson, Jean Gardin, George W Schaaf, Denise Nishita, Simon Authier, Polly Chang, David J Brenner, Albert J Fornace, J Mark Cline, Evagelia C Laiakis
{"title":"Long-term Radiation Signal Persistence in Urine and Blood: A Two-year Analysis in Non-human Primates Exposed to a 4 Gy Total-Body Gamma-Radiation Dose.","authors":"Emma Kosowski, John D Olson, Jean Gardin, George W Schaaf, Denise Nishita, Simon Authier, Polly Chang, David J Brenner, Albert J Fornace, J Mark Cline, Evagelia C Laiakis","doi":"10.1667/RADE-23-00261.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00261.1","url":null,"abstract":"<p><p>National security concerns regarding radiological incidents, accidental or intentional in nature, have increased substantially over the past few years. A primary area of intense planning is the assessment of exposed individuals and timely medical management. However, exposed individuals who receive survivable radiation doses may develop delayed effects of acute radiation exposure many months or years later. Therefore, it is necessary to identify such individuals and determine whether their symptoms may have been initiated by radiation and require complex medical interventions. We previously developed early response metabolomic biosignatures in biofluids from non-human primates exposed to a total body gamma radiation dose of 4 Gy (up to 60 days). A follow-up of these animals has been ongoing with samples consistently collected every few months for up to 2 years after exposure, providing a unique cohort to determine if a radiation signal persists longer than 2 months. Metabolic fingerprinting in urine and serum determined that exposed animals remain metabolically different from pre-exposure levels and from age-matched controls, and the pre-determined biosignature maintains high sensitivity and specificity. Significant perturbations in tricarboxylic acid intermediates, cofactors and nucleotide metabolism were noted, signifying energetic changes that could be attributed to or perpetuate altered mitochondrial dynamics. Importantly, these animals have begun developing diseases such as hypertension much earlier than their age-matched controls, further emphasizing that radiation exposure may lead to accelerated aging. This NHP cohort provides important information and highlights the potential of metabolomics in determining persistent changes and a radiation-specific signature that can be correlated to phenotype.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591417","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":"Harnessing Senescence for Antitumor Immunity to Advance Cancer Treatment.","authors":"Pataje G S Prasanna","doi":"10.1667/RADE-24-00098.1","DOIUrl":"10.1667/RADE-24-00098.1","url":null,"abstract":"<p><p>Considering the limitations and complexities of the cell-killing-based cancer treatment approaches, one could aim to integrate symbiotic advances in many energy delivery technologies and transformational pieces of evidence in research on senescence and immunomodulators to advance cancer treatment. Although senescent cells contribute to drug tolerance, resistance to therapy, tumorigenesis, maladapting cancer phenotypes, tumor relapse, recurrence, and metastasis, emerging pieces of evidence also demonstrate that acutely induced senescent cells in tumors can elicit a strong and lasting antitumor immune response juxtaposed to the immunologically silent apoptotic cells. This commentary is to help develop an unconventional conceptual framework to advance cancer treatment. Accordingly, it will involve transiently inducing senescent cells in tumors at optimal levels to prime the immune system with radiation, then eliminating senescent cells with senolytics (drugs that specifically eliminate senescent cells) to disrupt their positive feedback accumulation (to prevent tumor maladaptation and adverse effects in healthy cells) and unleash long-lasting antitumor immunity with immunomodulators. The approach is reasonably speculative and will require scientifically rigorous \"fit-for-purpose,\" well-controlled preclinical research and development involving dose and schedule optimization of radiation and drugs, using representative in vitro and in vivo cancer models to obtain high-quality data to proceed to clinical studies.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"727-733"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081411","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}
Jessica A Stering, Amy E Biggs, Tara E Carney, Megan E Oest, Brittany A Simone
{"title":"Caloric Restriction Diet Attenuates Systemic Bone Fragility after Radiotherapy.","authors":"Jessica A Stering, Amy E Biggs, Tara E Carney, Megan E Oest, Brittany A Simone","doi":"10.1667/RADE-23-00227.1","DOIUrl":"10.1667/RADE-23-00227.1","url":null,"abstract":"<p><p>Bone fragility is a well-documented long-term side effect of radiotherapy, which currently has no preventative treatments. In this study, we applied a caloric restriction (CR) diet to attenuate both local and systemic bone loss after irradiation (RTx) in an established female Balb/c mouse model (4 consecutive daily doses of 5 Gy to the right hindlimb only). CR mice were tapered down to a 30% reduced calorie diet (RTx/CR) one week before irradiation, while regular diet (RD) mice received food ad libitum (RTx/RD). Unirradiated (sham) mice received either a 30% CR diet (SH/CR) or received food ad libitum (SH/RD). Irradiated, contralateral, and unirradiated hindlimbs were evaluated at 2, 4, and 8 weeks postirradiation using micro-computed tomography (μCT) to assess bone morphology and 3-point bending to quantify femur strength. Histological analysis of irradiated and unirradiated tibiae was performed to examine general bone tissue cytology and serum biomarker analysis was performed using terminal blood draw samples. After treatment, femur strength and metaphyseal bone quantity was decreased in irradiated and contralateral femora of RTx/RD mice compared to SH/RD femurs; this finding is consistent with previous studies. RTx/CR mice had positive effects when compared to RTx/RD mice, including increased strength relative to body mass in both the irradiated and contralateral limb, increased trabecular bone mass, and decreased marrow adiposity. However, a number of adverse effects were also observed, including a significant decrease in body mass and decreased cortical bone. Overall, CR shows promise as a preventative treatment for postirradiated bone fragility, yet questions remain to be addressed in future studies. Ideal diet duration, impact to normal tissue, and mechanism of action must be explored to better understand the clinical implication of a CR diet.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"765-774"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294082","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}
Qiu Wang, Binyan Cao, Junwei Zhan, Xinyu Hu, Yang Yu, Xueyu Li, Ying Liu
{"title":"Sea Buckthorn Oil Promotes the PI3K-Akt-ERK Signaling Pathway and Macrophage M2 Polarization to Reduce Radiation-induced Skin Injury.","authors":"Qiu Wang, Binyan Cao, Junwei Zhan, Xinyu Hu, Yang Yu, Xueyu Li, Ying Liu","doi":"10.1667/RADE-23-00100.1","DOIUrl":"10.1667/RADE-23-00100.1","url":null,"abstract":"<p><p>In this work, we explored the role and mechanism of sea buckthorn oil in reducing radiation-induced skin damage. The radiation-induced rat skin injury model was established using strontium-90. Rats were treated with sea buckthorn oil twice a day postirradiation, and skin damage was observed at different times and evaluated using an injury score. Skin pathological changes were observed using hematoxylin and eosin (H&E) staining. Western blotting and immunohistochemistry were used to detect the expression of vascular growth and pathway proteins. ELISA was used to detect the secretion level of inflammatory factors. Immunohistochemistry was used to detect macrophage polarization marker proteins. We found that sea buckthorn oil can alleviate radiation-induced skin damage, accelerate skin vascular regeneration, and promote the up-regulation of vascular endothelial growth factor (VEGF) and its receptor (VEGFR). These results demonstrate the beneficial effects of sea buckthorn oil on radiation-induced skin damage. Furthermore, the levels of IL-1β and TNF-α in the sea buckthorn oil treatment group were significantly lower than those in the control group, while the levels of IL-4 and IL10 were significantly higher (P < 0.05). CD206 expression also increased in the sea buckthorn oil treatment group, while CD16 expression decreased compared to the control group (P < 0.05). Western blotting showed that PI3K, Akt and ERK expression increased in the sea buckthorn oil treatment group (P < 0.05). The beneficial effect of sea buckthorn oil in reducing the inflammatory response in irradiated rats was diminished when they were treated with PI3K inhibitor. We conclude that sea buckthorn oil may regulate macrophage M2 polarization by increasing the PI3K-Akt-ERK signaling pathway, thereby inhibiting the inflammatory response and promoting skin vascular regeneration to prevent and treat radiation-induced skin damage.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"785-794"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352749","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":"Disulfiram Upgrades the Radiosensitivity of Osteosarcoma by Enhancing Apoptosis and P53-Induced Cell Cycle Arrest.","authors":"Qiujian Lian, Fengmei Chen, Zhilin Sha, Haonan Zhao, Jingyan Li, Tongjiang Chen, Chang Liu, Bingxuan Wang, Zhiwei Wang, Suchi Qiao","doi":"10.1667/RADE-24-00046.1","DOIUrl":"10.1667/RADE-24-00046.1","url":null,"abstract":"<p><p>The prognosis of osteosarcoma has not been improved for decades. As radioresistance is one of the major reasons, effective radiotherapy sensitization drugs need to be discovered. HOS and K7M2 osteosarcoma cell lines were treated with disulfiram (DSF) and radiation to assess cell viability, proliferation, migration ability, apoptosis level, ROS and Ca2+ level, and cell cycle in vitro. A HOS-derived subcutaneous tumor mouse model was constructed to evaluate tumor growth after DSF combined with radiation, and the Tunel assay and immunohistochemistry of Ki67 were conducted. Western blot was used to evaluate the protein expression level. The IC50 and working concentration of DSF in osteosarcoma cell lines were ascertained. When combined with radiation, DSF effectively suppressed cell viability, proliferation, and migration, while enhancing apoptosis in osteosarcoma cells. The cell cycle postirradiation exhibited a downward shift in the G1 phase, but the addition of DSF counteracted this trend. The combination of DSF and radiation exhibited inhibitory effects on tumor growth in vivo, which was corroborated by Ki67 staining and Tunel assay. Western blot analysis revealed that DSF upregulated the expression of P53, P21, CDKN2C, BAX, and cleaved Caspase-3 while downregulating BCL2, CDK4/6, and CyclinD1 after irradiation. Our results document that DSF exerts its radiosensitization effects in vivo and in vitro, and is a valuable radiosensitizing drug option for osteosarcoma. The radiosensitization effect is mainly achieved by activating the apoptotic pathway and promoting cell cycle arrest induced by P53/P21 and CDKN2C after irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"752-764"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294083","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}
Alizeh Z Khan, Cheyanne M Scholl, Joshua G Henry, Parminder S Basran
{"title":"A Comparative Study on Radiosensitivity of Canine Osteosarcoma Cell Lines Subjected to Spatially Fractionated Radiotherapy.","authors":"Alizeh Z Khan, Cheyanne M Scholl, Joshua G Henry, Parminder S Basran","doi":"10.1667/RADE-24-00168.1","DOIUrl":"10.1667/RADE-24-00168.1","url":null,"abstract":"<p><p>Canine appendicular osteosarcoma (OSCA) is a highly aggressive cancer, constituting 85% of all bone tumors in dogs, predominantly affecting larger breeds and exhibiting a high metastatic rate. This disease also shares many genomic similarities with human osteosarcomas, making it an ideal comparative model for treatment discovery. In this study, we characterized the radiobiological properties of several OSCA cell lines when subjected to spatially fractionated radiation therapy (SFRT) and chemotherapy. Specifically, we focused on lower (peak) doses from SFRT ranging from 1 to 10 Gy. These canine OSCA cell lines serve as useful models for osteosarcoma research that can be utilized to find translational treatments for both canine and human patients. This study reaffirms established clinical wisdom regarding the notoriously radioresistant profile of osteosarcomas but additionally offers compelling evidence supporting SFRT as a promising treatment option that could be used in conjunction with other cytotoxic agents.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"745-751"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294081","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}