Radiation research最新文献

{"title":"The Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cell-derived Exosomes in Acute Radiation Intestinal Injury.","authors":"Jianping Yu, Gaosheng Yang, Yanping Yang, Xiaopeng Han, Jinbao Wang, Hongyu Wang, Yanjie Li, Weikai Chen","doi":"10.1667/RADE-25-00020.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00020.1","url":null,"abstract":"<p><p>Radiation-induced bowel injury is a common complication of radiation therapy for pelvic or abdominal cancers, with its occurrence increasing worldwide. Current treatments face significant challenges, and the limitations of conventional methods highlight the urgent need for new therapeutic strategies and drugs. Mesenchymal stem cell-derived exosomes show promising potential in treating inflammatory diseases. In this study, an acute radiation-induced intestinal injury model was created in rats after exposure to a 10 Gy X-ray dose, after administration of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-exo) via tail vein injection. The results showed that these exosomes (exos) enhanced survival, aided in functional recovery, reduced inflammation, decreased enterocyte death, and helped regenerate the intestinal lining. Additionally, bioinformatic analyses of gene expression and gene ontology (GO) enrichment were performed. Molecular validation revealed a significant increase in pyroptosis-related factors in the intestinal tissues after irradiation, indicating that cellular pyroptosis is a key mechanism. In conclusion, HUC-MSC-exos help maintain intestinal integrity and promote cell growth, suggesting they could be an effective treatment for radiation-induced intestinal injury.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691735","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 Bioluminescence Tomography System Compatible with CBCT-guided Small Animal Irradiators for High-Precision Preclinical Radiation Research.","authors":"Zhishen Tong, Zijian Deng, Xiangkun Xu, Ciara Newman, Xun Jia, Yuncheng Zhong, Merle Reinhart, Paul Tsouchlos, Tim Devling, Hamid Dehghani, Iulian Iordachita, Debabrata Saha, James Kim, John W Wong, Ken Kang-Hsin Wang","doi":"10.1667/RADE-25-00114","DOIUrl":"https://doi.org/10.1667/RADE-25-00114","url":null,"abstract":"<p><p>Widely used cone-beam computed tomography (CBCT)-guided irradiators struggle to localize soft-tissue targets due to low imaging contrast. While bioluminescence tomography (BLT) offers a promising functional imaging solution, its adoption in pre-clinical radiotherapy research has been limited. To address this, we developed MuriGlo, a novel BLT system compatible with CBCT-guided small animal irradiators to support high-precision radiation studies. We demonstrate MuriGlo's capabilities in supporting both in vitro and in vivo experiments. MuriGlo consists of a detachable mouse bed, thermostatic control, mirrors, filters, and a charge-coupled device (CCD) camera, enabling multi-projection and multi-spectral bioluminescence imaging (BLI). The detachable bed facilitates animal transfer between MuriGlo and an irradiator for BLT-guided radiation study. We evaluated the thermostatic control's ability and demonstrated that it can maintain a consistent animal body temperature at 37°C throughout imaging. We also quantified detection sensitivity via signal-to-noise ratio (SNR) in detecting minimal cell quantities using glioblastoma (GL261) cells with Luc2 and AkaLuc reporters. The optical system can detect as few as 1173 GL261-Luc2 and 61 GL261-AkaLuc cells in vitro at SNR = 5. For image-guided capabilities, we present BLT-guided 5-arc, BLT-guided 2-field box, and BLI-guided single-field plans. The high conformal 5-arc plan fully covers gross tumor volume (GTV) at prescribed dose with minimal normal tissue exposure from moderate to high dose range, while the simplified, high-throughput BLT-guided 2-field box achieves 100% GTV coverage but results in larger normal tissue exposure. The choice of the planning strategy should therefore depend on the specific requirements for radiation accuracy and experimental throughput. Moreover, we compared MuriGlo's tumor localization accuracy for widely used irradiators, SARRP and SmART+. The localization accuracy of MuriGlo for both SARRP and SmART+ irradiators is < 1 mm with GTV coverage > 97%. This universal, BLT-guided platform enables plug-and-play integration with commercial irradiators, supporting functional image guidance and enhancing high-precision preclinical radiation research.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691805","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":"Apigenin Enhances the Radiosensitivity of TNBC Cells by Improving cGAS-STING Pathway Activity.","authors":"Xiongxiong Liu, Youming Zhu, Tong Zheng, Ting Zhao, Ping Li, Dan Xu, Hui Wang, Chao Sun","doi":"10.1667/RADE-25-00117.1","DOIUrl":"10.1667/RADE-25-00117.1","url":null,"abstract":"<p><p>Apigenin inhibits proliferation and induces apoptosis in triple-negative breast cancer (TNBC) cells, processes linked to DNA damage. However, the combined effect of apigenin and radiation on TNBC cells remains unclear. This study aimed to determine whether apigenin enhances the radiosensitivity of TNBC cells by activating the cGAS-STING pathway. Human TNBC cell lines MDA-MB-231 and MDA-MB-468 were X-ray irradiated, and the optimal apigenin concentration was determined by CCK-8 assay. Protein expression was analyzed by western blot, and cGAS or STING was knocked down using siRNA. DNA damage was assessed by immunofluorescence quantification of γH2AX and cytoplasmic dsDNA foci, while apoptosis was measured by flow cytometry. At 15 μM, apigenin showed minimal toxicity and enhanced radiosensitivity in both cell lines. Ionizing radiation increased cytosolic dsDNA levels and micronuclei formation, which was associated with upregulated cGAS-STING-TBK1-IRF3 pathway activity. Apigenin further enhanced this pathway by increasing radiation-induced cytosolic dsDNA and micronuclei, thereby promoting TNBC cell apoptosis. Moreover, knockdown of cGAS or STING significantly attenuated the apoptotic response induced by the combination of apigenin and radiation. These findings suggest that apigenin enhances the radiosensitivity of TNBC cells by activating the tumor cell-intrinsic cGAS-STING pathway.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"502-512"},"PeriodicalIF":2.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646175","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":"Lattice Radiation Therapy Delays Progression and Extends Survival for Dogs with Macroscopic Soft Tissue Sarcoma.","authors":"V R Morales, J N Bryan, S Chu, A B Barbour, D Y Kim, J Bryant, N Andruska, J Kavanaugh, M B Spraker, C A Maitz","doi":"10.1667/RADE-25-00208.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00208.1","url":null,"abstract":"<p><p>Soft tissue sarcomas are common tumors in dogs with many pathologic and molecular cross-species similarities existing between dogs and humans. Spatially fractionated radiotherapy, utilizing an intensity-modulated technique known as Lattice radiation therapy, enables the safe delivery of hypofractionated, dose-escalated treatment to large tumors and has been associated with increased response rates and the induction of immune responses. Seven dogs were prospectively randomized to receive either palliative (n = 3, 20 Gy in 5 consecutive daily fractions) or lattice (n = 4, 20 Gy to 95% of the PTV with a simultaneous integrated boost of 66.7 Gy delivered every other day) radiation therapy. Tumor biopsies were performed before the first dose of radiation, and at the end of the final dose of radiation. Peripheral blood mononuclear cells were collected before the first dose of radiation, and at the end of the final dose of radiation, as well as 2 weeks after completion of treatment. Analysis of immune response within the tumor microenvironment was analyzed using the Nanostring Canine IO panel. An overall response rate of 50% was noted in the Lattice group. While no local tumor progression was observed in the lattice group, all 3 (100%) dogs in the palliative radiation cohort had evidence of local tumor progression at 21, 35 and 150 days postirradiation. Median overall survival was 436 days in dogs receiving lattice radiation therapy compared with 194 days in the palliative cohort. These results suggest that lattice radiation therapy can be safely administered to dogs with large macroscopic sarcomas and may confer improved local control and survival outcomes compared with conventional palliative radiotherapy. These findings also suggest that dogs with naturally occurring tumors can serve as valuable translational models to bridge current gaps in our understanding and help accelerate clinical translation of spatial fractionation approaches.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646137","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":"Impact of Dose Administration Schedule and Orthovoltage X-ray Beam Quality on Survival and Dose Response Relationships in C57BL/6J Mouse Models of Acute Radiation Syndrome.","authors":"Tyler Beach, Tyson J McDonald, Autumn Rassmusen, James Bakke, Harold S Javitz, Paul Burkander, Denise Nishita, Shweta Kapur, Deborah I Bunin, Polly Y Chang","doi":"10.1667/RADE-25-00209.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00209.1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Total-body irradiation (TBI) and partial-body irradiation (PBI) mouse models have been used for many years to develop safe and effective medical countermeasures (MCMs) against the acute radiation syndrome (ARS). ARS MCM development will benefit from a demonstration of the impact on survival from (a) the handling stress associated with repeat dose administrations, and (b) radiation beam quality with additional filtering of the orthovoltage X-ray beam, which we provide here. An open source \"R\" statistical tool is also provided to aid in generating dose response relationships (DRR) for establishing institutional lethality profiles. Compiled results from 27 TBI and 28 PBI studies in C57BL/6J male and female mice show the impact of the number of vehicle dose administrations and beam hardening on survival. For dose administration frequency, irradiated, non-dosed groups were compared with groups receiving increasing numbers of vehicle doses. Linear probit plots and lethality estimates were generated for the Thoraeus filter (tin, copper and aluminum) with and without 5 days of twice daily (5 × BID) dosing and for the aluminum filter without vehicle administration. A Wald test compared the slopes and intercepts of the probit estimates to assess differences in estimated lethality. Log-rank tests were used to determine the impact of vehicle administrations on observed lethality. A statistically significant reduction in survival was observed with increasing numbers of vehicle doses in the TBI model and for females in the PBI model using aluminum filtration. Repeated vehicle administrations (5× BID) also resulted in lower survival than in non-dosed males and females with the Thoraeus filter. Probit estimates of lethality when comparing non-dosed and 5× BID dosed groups indicate lower radiation doses were needed to achieve lethality in the 5× BID dosed groups, which were statistically significant in most log rank tests. When comparing the impact of filtration on survival, there was a statistically significant difference in intercepts for the estimated lethality values for each filter type, and the hardened Thoraeus-filtered beam required nearly 2 Gy of additional radiation dose to achieve the same survival as the aluminum filter. Lastly, our freely available \"R\" tool accurately generated probit estimates and confidence intervals (CI) when compared with estimates and CIs generated by a certified statistician using the STATA STS statistical package. Our results show that handling stress should be taken into consideration in designing ARS MCM development studies. Beam hardening with the removal of the low-energy photons and characteristic X rays resulted in a consistent shift in the DRRs for both males and females, with the \"softer\" aluminum beam resulting in greater mortality as compared to the Thoraeus-filtered beam. These findings will inform effective dose administration strategies in the design of ARS MCM development studies and aid in radiation dose h","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646118","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":"Low-Dose Ionizing Radiation Modulates Translation Efficiency in Human Lung Fibroblasts.","authors":"Rosette N Tamaddon, Martin Roffe, Antonella Bertucci, Huy-Dung Hoang, Tyson E Graber, Benoit Le Tallec, Dmitry Klokov, Yi Wang, Tommy Alain","doi":"10.1667/RADE-25-00220","DOIUrl":"https://doi.org/10.1667/RADE-25-00220","url":null,"abstract":"<p><p>Understanding the cellular responses to low-dose ionizing radiation exposure (≤ 0.1 Gy) is essential for developing evidence-based radiation protection policies. Unlike high-dose radiation exposure, which is known to alter gene expression and protein synthesis, the cellular impact of low-dose exposure remains less defined. To address this gap, ribosome profiling was performed on normal human lung fibroblast cells exposed to low (0.1 Gy) and high (1 Gy) doses of 60Cobalt gamma (γ) rays. At 1 and 6 h postirradiation, global protein synthesis remained unchanged at low dose; however, specific mRNAs showed altered translation efficiency. These translational shifts occurred despite minimal changes at the transcriptional level, indicating that translation offers a more sensitive readout of early low-dose γ-radiation effects. The small GTP-binding protein RAB33B was identified as a translationally upregulated target. This study emphasizes that conventional transcriptome analyses do not fully capture gene expression dynamics and suggests that selective translation could contribute to a distinct cellular response to low-dose irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616591","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":"Bias in Low Dose Risk Estimation due to the Constant RBE Assumption in RERF Studies.","authors":"Richard Sposto","doi":"10.1667/RADE-25-00113","DOIUrl":"https://doi.org/10.1667/RADE-25-00113","url":null,"abstract":"<p><p>Radiation exposure from the atomic bombs in Hiroshima and Nagasaki consisted of both gamma and neutron radiation. Because the main goal of analyzing Radiation Effects Research Foundation (RERF) data is to estimate the increased risk from gamma radiation alone, the analysis approach has been to weight the typically more potent neutron dose with a constant relative biological effectiveness (RBE) factor and add it to the gamma dose to form a weighted total dose, which is considered equivalent to a pure gamma dose. However, in many experimental systems, it has been shown that the RBE of neutron radiation relative to gamma radiation is not constant. The possibly incorrect assumption of constant RBE can lead to bias in estimating the excess risk due to gamma radiation exposure. We investigated analytically the potential bias resulting from the constant RBE assumption over a range of organ doses, assuming constant RBE and true limiting maximum RBE values and gamma and neutron dose response curvatures, with particular attention to risk estimation in the low dose range. The results of the analytic investigation are confirmed in a simulation study. We show that in the low dose range, the relationship between excess relative risk (ERR) and weighted total dose depends on the assumed constant RBE, the true limiting maximum RBE, the curvatures of the gamma and neutron dose responses, and the moments of the distribution of gamma radiation dose conditional on the weighted total dose. Assuming a constant RBE in analysis that equals the true limiting maximum RBE does not guarantee negligible bias unless there is no curvature in the dose response. The existence of positive curvature in this case induces negative bias. However, at very low doses, which may be of interest, e.g., 0.1 Gy, the bias will be small. At higher doses, assuming a constant RBE can still lead to significant bias, even if its value matches the true limiting maximum RBE. When interpreting the estimated excess risk from analyses of RERF data, it is important to recognize the bias that may come from assuming a constant RBE-weighted neutron dose.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593703","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":"De novo Copy Number Variations in the Offspring of Male Mice Chronically Exposed to Various Low Dose-Rates of Ionizing Radiation.","authors":"Keiji Ogura, Yoshiko Ayabe, Chihiro Harada, Ignacia Braga Tanaka, Satoshi Tanaka, Jun-Ichiro Komura","doi":"10.1667/RADE-24-00194","DOIUrl":"https://doi.org/10.1667/RADE-24-00194","url":null,"abstract":"<p><p>Previously, we conducted a large-scale pathology study on the transgenerational effects of ionizing radiation, examining the lifespan and causes of death in the first- (F1) and second- (F2) generation offspring of male C57BL/6J mice (F0) 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. Studies on de novo copy number variations (CNVs) using chromosomal microarray analysis in a subset of the F1 mice showed an increase in the frequency of the F1 mice with de novo CNVs born from the 20 mGy/day irradiated males compared to the non-irradiated controls. The present study illustrates the difficulty of detecting increases of de novo CNVs in F1 mice born from the males exposed to lower dose-rates of 1 and 0.05 mGy/day. These genetic analyses, combined with the pathology analyses in a larger number of mice, provide insights regarding the importance of population size and statistical power in studies on the transgenerational effects of low-dose-rate radiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593919","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":"The FLASH Effect in 3D and 2D Models: Preserving Tumor Control while Reducing Apoptosis in Normal Cells.","authors":"Andrea Scarmelotto, Emma Lambert, Victor Delprat, Charbel Koumeir, Carine Michiels, Stéphane Lucas, Anne-Catherine Heuskin","doi":"10.1667/RADE-25-00051.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00051.1","url":null,"abstract":"<p><p>Irradiation at ultra-high dose rates is gaining increased attention due to its ability to limit damage to surrounding healthy tissues, thereby preventing radiation-induced side effects. Although there are some exceptions, this protective effect (the FLASH effect) has been demonstrated in many preclinical models, primarily after low-LET irradiation and high-dose irradiation. Here, we report that both ultra-high dose rate (UHDR) and conventional dose rate (CONV) irradiations produce similar growth delays in 3D tumor spheroids (composed of HCT116 and T98G, colorectal carcinoma or glioblastoma cell lines), indicating comparable efficacy in tumor control. In normal cells (HIEC-6, a non-malignant epithelial cell line from the small intestine), UHDR and CONV irradiation induced comparable senescence, while a lower induction of apoptosis was observed after UHDR irradiation at clinically relevant doses and early time points postirradiation. Collectively, these findings highlight the potential of UHDR irradiation to modulate normal tissue responses while achieving comparable tumor control.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532446","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":"TSPAN8-mediated Epithelial-mesenchymal Transition Drives Acquired Radioresistance in Cervical Cancer.","authors":"Jing-Nan Wang, Ling-Li Liao, Fan Yang, Ru Wang, Lei Zhang, Ao-Xue Li, Peng-Jie Yu, Ruo-Tong Wu, Nuo Chen, Yu-Qiao Xu, Yong-Chun Zhou","doi":"10.1667/RADE-25-00233.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00233.1","url":null,"abstract":"<p><p>Acquired radioresistance remains a major obstacle to effective radiotherapy for cervical cancer, often driven by epithelial-mesenchymal transition (EMT). This study reveals TSPAN8 as a novel regulator of EMT-mediated radioresistance, offering new insights for overcoming treatment failure. Radioresistant subclones of HeLa-R25 and SiHa-R25 cells were established by repeated 2 Gy fractions. Radioresistance, apoptosis, EMT, and stemness were assessed by clonogenic survival, flow cytometry, immunoblotting, and immunofluorescence. Differentially expressed genes were identified by microarray, validated by protein-protein interaction analysis and co-immunoprecipitation, and functionally examined via TSPAN8 overexpression/knockdown, xenograft models, and immunohistochemistry of primary, metastatic, and recurrent post-radiotherapy specimens. Prognostic relevance was analyzed in the TCGA-CESC cohort. Fractionated irradiation induced EMT and radioresistance, with significantly higher clonogenic survival in R25 cells (P < 0.05), characterized by E-cadherin loss, N-cadherin/Vimentin upregulation, and increased CD44/Oct4. TSPAN8 was the most upregulated gene and directly interacted with E-cadherin. Overexpression enhanced EMT, invasion, and resistance to apoptosis, while knockdown reversed these effects and restored radiosensitivity in vivo. TSPAN8 knockdown in radioresistant xenografts significantly suppressed tumor growth (P < 0.05), and combined knockdown with irradiation further reduced tumor volume (P < 0.05). In patient samples, post-radiotherapy recurrences and metastases exhibited high TSPAN8 and vimentin with reduced E-cadherin. TCGA data confirmed that elevated TSPAN8 was associated with worse outcomes, including shorter disease-specific survival (HR = 2.02, 95% CI 1.01-3.71, P = 0.02) and progression-free survival (HR = 3.09, 95% CI 1.80-5.30, P < 0.001). These data suggest that TSPAN8 drives EMT-mediated radioresistance in cervical cancer, is associated with recurrence and poor survival, and represents a potential biomarker and therapeutic target. Targeting TSPAN8 may enhance radiosensitivity and improve personalized radiotherapy outcomes.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":"205 5","pages":"513-527"},"PeriodicalIF":2.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842066","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}