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Exploiting the unique interaction characteristics of fast neutrons for improved cancer therapy: A radiobiological perspective 利用快中子独特的相互作用特性改进癌症治疗。放射生物学视角
Radiation Medicine and Protection Pub Date : 2024-03-01 DOI: 10.1016/j.radmp.2023.12.004
Festo Kiragga, Konstantin Brazovskiy
{"title":"Exploiting the unique interaction characteristics of fast neutrons for improved cancer therapy: A radiobiological perspective","authors":"Festo Kiragga,&nbsp;Konstantin Brazovskiy","doi":"10.1016/j.radmp.2023.12.004","DOIUrl":"10.1016/j.radmp.2023.12.004","url":null,"abstract":"<div><p>Fast neutrons have sufficient energy to liberate recoil protons, alpha particles, and other products when they interact with the nuclei of the target material through scattering and absorption processes. Physical interactions with biological tissues occur mainly with hydrogen nuclei and as the protons interact with the hydrogen in tissues, they create dense ionization chains along their tracks thus depositing energy. Fast neutron therapy was pioneered by Robert Stone in 1938 a few years after the discovery of the neutron. Its main advantage is the limited sensitivity to hypoxia and treatment of slow-growing tumors hence better local control. This is where photon therapy has yet to have much success. Energy deposition by fast neutrons in living tissues is higher than in conventional radiotherapy using mega voltage (MV) photon beams. This higher energy deposition gives fast neutrons a higher relative biological effectiveness (RBE) in dealing with certain tumors. Fast neutrons also have a higher linear energy transfer (LET) and can reach deep-sited tumors better than photon therapy. The main challenge with Fast neutron therapy has been extreme toxicity in late-reacting tissues. Overall, fast neutron therapy holds potential for the treatment of certain tumors by leveraging the unique interaction characteristics of fast neutrons with biological tissues. This review therefore intends to bring this uniqueness to light to enhance the understanding of the radiobiological properties of fast neutrons and the advantages associated with its therapy.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"5 1","pages":"Pages 24-29"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266655572300076X/pdfft?md5=8c0678a50adb5b7c173eb0d673d995be&pid=1-s2.0-S266655572300076X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139125223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
YWHAZ gene contributes to the radioresistance of oral squamous cell carcinoma cells YWHAZ基因导致口腔鳞状细胞癌细胞的放射抗性
Radiation Medicine and Protection Pub Date : 2024-03-01 DOI: 10.1016/j.radmp.2024.02.005
Songling Hu , Cong Chen , Hengheng Chen , Xin Yu , Xiaofei Li , Yang Bai , Chunlin Shao
{"title":"YWHAZ gene contributes to the radioresistance of oral squamous cell carcinoma cells","authors":"Songling Hu ,&nbsp;Cong Chen ,&nbsp;Hengheng Chen ,&nbsp;Xin Yu ,&nbsp;Xiaofei Li ,&nbsp;Yang Bai ,&nbsp;Chunlin Shao","doi":"10.1016/j.radmp.2024.02.005","DOIUrl":"https://doi.org/10.1016/j.radmp.2024.02.005","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells.</p></div><div><h3>Methods</h3><p>The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ).</p></div><div><h3>Results</h3><p>GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. <em>In vitro</em> experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (<em>t</em> ​= ​18.89, <em>P</em> ​&lt; ​0.01) and radioresistant CAL-27R cells (<em>t</em> ​= ​25.70, <em>P</em> ​&lt; ​0.01). Knockdown of YWHAZ gene significantly increased radiation-induced cell killing effect, apoptosis induction, and γH2AX foci formation in CAL-27R and HSC-3 cells. Moreover, siRNA YWHAZ transfection also reduced the invasion and migration abilities of the irradiated CAL-27R [(<em>t</em> ​= ​21.09, <em>P</em>&lt;0.01 (migration); <em>t</em> ​= ​6.16, <em>P</em>&lt;0.05 (invasion)] and HSC-3 ​cells [(<em>t</em> = 34.53, <em>P</em> &lt; 0.001 (migration); <em>t</em> ​= ​4.92, <em>P</em> ​&lt; ​0.05 (invasion)] and attenuated radiation-induced expressions of metastasis-related proteins.</p></div><div><h3>Conclusion</h3><p>YWHAZ contributes to the radioresistance of oral squamous cells and thus it may applicable to be a potential target for OSCC radiotherapy.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"5 1","pages":"Pages 30-36"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555724000078/pdfft?md5=1c6ce5286911c99a1e86ada6597e6db8&pid=1-s2.0-S2666555724000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140164080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computed tomography-based delta-radiomics enabling early prediction of short-term responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer 基于计算机断层扫描的δ-放射组学可早期预测非小细胞肺癌患者对同期化放疗的短期反应
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.002
Fengqin Zhou , Jianping Bi , Shen Wu , Yi Ding , Jun Chen , Mengting Yuan , Yaoyao He , Guang Han , Zilong Yuan
{"title":"Computed tomography-based delta-radiomics enabling early prediction of short-term responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer","authors":"Fengqin Zhou ,&nbsp;Jianping Bi ,&nbsp;Shen Wu ,&nbsp;Yi Ding ,&nbsp;Jun Chen ,&nbsp;Mengting Yuan ,&nbsp;Yaoyao He ,&nbsp;Guang Han ,&nbsp;Zilong Yuan","doi":"10.1016/j.radmp.2023.10.002","DOIUrl":"10.1016/j.radmp.2023.10.002","url":null,"abstract":"<div><h3>Objective</h3><p>To explore the potential of computed tomography (CT)-based delta-radiomics in predicting early short-term responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer (NSCLC), in order to determine the optimal time point for the prediction.</p></div><div><h3><em>M</em>ethods</h3><p>A total of 20 patients with pathologically confirmed NSCLC were prospectively enrolled in this study, who did not receive surgical treatment between February 2021 and February 2022. For each case, a total of 1,210 radiomic features (RFs) were extracted from both planning CT (pCT) images along with each of the subsequent three weeks of CT images. Effective ΔRFs were selected using intra-class correlation coefficient (ICC) analysis, Pearson's correlation, ANOVA test (or Mann-Whitney <em>U</em>-test), and univariate logistic regression. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the potential to predict short-term responses of different time points.</p></div><div><h3>Results</h3><p>Among the 1,210 ΔRFs for 1–3 weeks, 121 common features were retained after processing using ICC analysis and Pearson's correlation. These retained features included 54 and 58 of all time points that differed significantly between the response and non-response groups for the first and third months, respectively (<em>P</em> ​&lt; ​0.05). After univariate logistic regression, 11 and 44 features remained for the first and third months, respectively. Finally, eight ΔRFs (<em>P</em> ​&lt; ​0.05, AUC ​= ​0.77–0.91) that can discriminate short-term responses in both at 1 and 3 months with statistical accuracy were identified.</p></div><div><h3>Conclusion</h3><p>CT-based delta-radiomics has the potential to provide reasonable biomarkers of short-term responses to concurrent chemoradiotherapy for NSCLC patients, and it can help improve clinical decisions for early treatment adaptation.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 227-235"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000540/pdfft?md5=6fd526953af19bce707bea7b42e02754&pid=1-s2.0-S2666555723000540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135605710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The clinical prospect of FLASH radiotherapy FLASH 放射治疗的临床前景
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.005
Jiyuan Liu, Guangming Zhou, Hailong Pei
{"title":"The clinical prospect of FLASH radiotherapy","authors":"Jiyuan Liu,&nbsp;Guangming Zhou,&nbsp;Hailong Pei","doi":"10.1016/j.radmp.2023.10.005","DOIUrl":"10.1016/j.radmp.2023.10.005","url":null,"abstract":"<div><p>FLASH radiotherapy (FLASH-RT) is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 ​Gy/s. Compared with conventional radiotherapy (CONV-RT), FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues, which is called the “spare” effect. The “spare” effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms. Mitochondrial homeostasis, the immune microenvironment, or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms. Concurrently, it is imperative to advance timely clinical translation efforts. Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland, with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types. While summarizing the existing FLASH experiments, this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 190-196"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000576/pdfft?md5=9ad27495afcbe4277488319946afe9ef&pid=1-s2.0-S2666555723000576-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances of radiotherapy combined with targeted therapy for nasopharyngeal carcinoma 放射治疗结合靶向治疗鼻咽癌的进展
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.001
Xiaoyan Xu , Hengzhao Zhuang , Yijun Xu , Zhongxu Xing , Yang Jiao , Lili Wang
{"title":"Advances of radiotherapy combined with targeted therapy for nasopharyngeal carcinoma","authors":"Xiaoyan Xu ,&nbsp;Hengzhao Zhuang ,&nbsp;Yijun Xu ,&nbsp;Zhongxu Xing ,&nbsp;Yang Jiao ,&nbsp;Lili Wang","doi":"10.1016/j.radmp.2023.10.001","DOIUrl":"10.1016/j.radmp.2023.10.001","url":null,"abstract":"<div><p>Nasopharyngeal carcinoma is insidious at onset, prone to lymph node metastasis, and has a high rate of locally advanced disease at initial diagnosis. Radiotherapy combined with chemotherapy is the main treatment for locally advanced nasopharyngeal carcinoma, but local recurrence and distant metastasis often lead to treatment failure, of which radioresistance caused by radiotherapy may be one of the reasons. Targeted therapy can selectively inhibit tumor proliferation and metastasis, and patients can achieve long-term survival benefits with low toxic and side effects. Targeted therapy involves a variety of tumor mechanisms, in which combination with radiotherapy may improve radioresistance and the efficacy of radiotherapy. In this review, the advantages and research progress of targeted therapy combined with radiotherapy for nasopharyngeal carcinoma were discussed.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 197-203"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000539/pdfft?md5=196d565d1df6d5800148cc3985e07d8c&pid=1-s2.0-S2666555723000539-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135605454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The application of machine learning and deep learning radiomics in the treatment of esophageal cancer 机器学习和深度学习放射组学在食管癌治疗中的应用
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.009
Jinling Yi , Yibo Wu , Boda Ning , Ji Zhang , Maksim Pleshkov , Ivan Tolmachev , Xiance Jin
{"title":"The application of machine learning and deep learning radiomics in the treatment of esophageal cancer","authors":"Jinling Yi ,&nbsp;Yibo Wu ,&nbsp;Boda Ning ,&nbsp;Ji Zhang ,&nbsp;Maksim Pleshkov ,&nbsp;Ivan Tolmachev ,&nbsp;Xiance Jin","doi":"10.1016/j.radmp.2023.10.009","DOIUrl":"10.1016/j.radmp.2023.10.009","url":null,"abstract":"<div><p>Esophageal cancer (EC) is a very aggressive disease with most cases diagnosed at advanced stages. Early detection and prognosis prediction are of clinical significance in the optimal management of EC. Genomic and proteomic technologies demonstrated limited efficacy due to the invasive nature and the inherent tumor heterogeneity. Non-invasive radiomics has achieved significant results in tumor characterization, treatment response and survival prediction for various cancers. In this article, the current application of both machine learning and deep learning based radiomics in the diagnosis, prognostic prediction and treatment outcome prediction for patients with EC were reviewed. The current challenges and prospects for the future application of radiomics in EC were also discussed.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 182-189"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000618/pdfft?md5=eaa45cac9a96203027e59008d8f0f015&pid=1-s2.0-S2666555723000618-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135455083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A new Chinese standard for testing of quality control in medical proton/heavy ion beam radiotherapy equipment 医用质子/重离子束放射治疗设备质量控制检测的新中国标准
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.007
Jilong Yuan , Xiangjie Ma , Quanfu Sun , Haikuan Liu , Shouping Xu , Yinxiangzi Sheng , Xiaoyun Ma , Xiangkui Mu , Xinguo Liu , Tao Yang , Xin Zhang , Hsiao-Ming Lu , Jinsheng Cheng
{"title":"A new Chinese standard for testing of quality control in medical proton/heavy ion beam radiotherapy equipment","authors":"Jilong Yuan ,&nbsp;Xiangjie Ma ,&nbsp;Quanfu Sun ,&nbsp;Haikuan Liu ,&nbsp;Shouping Xu ,&nbsp;Yinxiangzi Sheng ,&nbsp;Xiaoyun Ma ,&nbsp;Xiangkui Mu ,&nbsp;Xinguo Liu ,&nbsp;Tao Yang ,&nbsp;Xin Zhang ,&nbsp;Hsiao-Ming Lu ,&nbsp;Jinsheng Cheng","doi":"10.1016/j.radmp.2023.10.007","DOIUrl":"https://doi.org/10.1016/j.radmp.2023.10.007","url":null,"abstract":"<div><p>With the development of social economy and radiotherapy technique, proton/heavy ion radiotherapy has been applied widely to clinical practices. At present, there are at least 29 hospitals in China at various stages of planning, construction, commissioning or clinical operation of medical proton/heavy ion beam radiotherapy equipment. Compared with common radiotherapy accelerators used in conventional external beam radiotherapy, the proton/heavy ion therapy system has more stringent requirements for quality control so as to achieve an optimum therapeutic effect. In order to protect the health rights of patients undergoing radiotherapy, to facilitate the relevant administrative supervision departments to carry out standard-based approval and routine supervision and to promote the development of related medical undertakings, the standard for testing of quality control for medical proton/heavy ion beam radiotherapy equipment is drafted to fill the gap in this regard in China and even worldwide. The standard contains five indicators and corresponding testing methods for radiological protection and safety and 16 indicators for quality control of equipment performance. The standard is a mandatory standard and is based on the relevant Chinese legal requirements for the testing of radiotherapy equipment, so all the indicators listed in the standard shall be tested. During the drafting of the standard, the opinions from hospitals that are currently using proton/heavy ion medical accelerators for radiotherapy purpose and from the related equipment manufacturers were taken into account. The draft standard was revised with reference to these opinions and the feasibility of the related quality control requirements. The official version of the standard was released on March 7, 2023, and implementation is scheduled to begin on March 1, 2024.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 177-181"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266655572300059X/pdfft?md5=f7efef282f48d6a1a307aa5145510921&pid=1-s2.0-S266655572300059X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hexyl-pentynoic acid serves as a novel radiosensitizer for breast cancer by inhibiting UCHL3-dependent Rad51 deubiquitination 己基戊炔酸通过抑制 UCHL3 依赖性 Rad51 去泛素化,成为一种新型乳腺癌放射增敏剂
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.003
Zuchao Cai , David Lim , Beidi Jia , Guochao Liu , Wenwen Ding , Zhendong Wang , Zhujun Tian , Junxuan Peng , Fengmei Zhang , Chao Dong , Zhihui Feng
{"title":"Hexyl-pentynoic acid serves as a novel radiosensitizer for breast cancer by inhibiting UCHL3-dependent Rad51 deubiquitination","authors":"Zuchao Cai ,&nbsp;David Lim ,&nbsp;Beidi Jia ,&nbsp;Guochao Liu ,&nbsp;Wenwen Ding ,&nbsp;Zhendong Wang ,&nbsp;Zhujun Tian ,&nbsp;Junxuan Peng ,&nbsp;Fengmei Zhang ,&nbsp;Chao Dong ,&nbsp;Zhihui Feng","doi":"10.1016/j.radmp.2023.10.003","DOIUrl":"10.1016/j.radmp.2023.10.003","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effects and underlying mechanism of 2-hexyl-4-pentynoic acid (HPTA), a derivative of valproic acid (VPA), on radiotherapy in breast cancer.</p></div><div><h3>Methods</h3><p>MCF7 cells and 7,12-dimethylbenz-[α]-anthracene (DMBA)-induced transformed human normal breast cells (MCF10A–DMBA cells) were irradiated with 8 ​Gy X-rays. For both cells there were four groups: control, valproic acid (VPA)/HPTA, IR, and VPA/HPTA+IR groups. MTT and clonogenic survival assays were performed to assess cell proliferation, and comet assay was performed to evaluate DNA damage. Protein expression of γH2AX, 53BP1, Rad51, and BRCA1 was examined <em>via</em> immunofluorescence and immunoblotting. Cycloheximide chase and ubiquitination experiments were conducted to determine Rad51 ubiquitination. <em>In vivo</em> experiments involved a rat model of DMBA-induced breast cancer, with four fractionated doses of 2 ​Gy. Tumor tissue pathological changes and γH2AX, Rad51, and UCHL3 expression levels were measured by hematoxylin-eosin staining, immunohistochemistry, and immunoblotting.</p></div><div><h3>Results</h3><p>Compared with the IR group, 15 ​μmol/L HPTA reduced the cell proliferation ability of irradiated MCF7 cells (<em>t</em>=2.16, <em>P</em>&lt;0.05). The VPA/HPTA+IR group exhibited significantly increased DNA double-strand breaks relative to those in the IR group (VPA+IR <em>vs.</em> IR, <em>t</em>=13.37, <em>P</em>&lt;0.05; HPTA+IR <em>vs.</em> IR, <em>t</em>=8.48, <em>P</em>&lt;0.05). Immunofluorescence and immunoblotting experiments demonstrated that the VPA/HPTA+IR group displayed significantly increased cell foci formation, γH2AX and 53BP1 protein expression levels compared to the IR group [(γH2AX: VPA+IR <em>vs.</em> IR, <em>t</em>=8.88, <em>P</em>&lt; 0.05; HPTA+IR <em>vs.</em> IR, <em>t</em>=8.90, <em>P</em>&lt; 0.05), (53BP1, VPA+IR <em>vs.</em> IR, <em>t</em>=5.73, <em>P</em>&lt; 0.05; HPTA+IR <em>vs.</em> IR, <em>t</em>=6.40, <em>P</em>&lt; 0.05)]. Further, Rad51 expression was downregulated (VPA+IR <em>vs.</em> IR, <em>t</em>=3.12, <em>P</em>&lt; 0.05; HPTA+IR <em>vs.</em> IR, <em>t</em> ​= ​2.70, <em>P</em>&lt;0.05), and Rad51 inhibition effectively counteracted HPTA-induced radiosensitization. Ubiquitination detection further verified that HPTA inhibits Rad51 expression <em>via</em> UCHL3-dependent Rad51 deubiquitination. <em>In vivo</em> study results showed that 20 ​mg/kg HPTA significantly enhanced the radiosensitivity of breast tumors in rats by inhibiting Rad51 expression.</p></div><div><h3>Conclusions</h3><p>HPTA is a highly effective radiosensitizer that enhances the radiotherapeutic efficacy of breast cancer treatment through UCHL3-dependent deubiquitination of Rad51.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 204-213"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000552/pdfft?md5=51c139d03ab29a98dcedb40162b9492c&pid=1-s2.0-S2666555723000552-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135654952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells SWI/SNF 复合物对胚胎成纤维细胞异染色质中 DNA 损伤修复的影响
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.006
Hong Zhang , Yinyin Shu , Mintao Ji
{"title":"Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells","authors":"Hong Zhang ,&nbsp;Yinyin Shu ,&nbsp;Mintao Ji","doi":"10.1016/j.radmp.2023.10.006","DOIUrl":"10.1016/j.radmp.2023.10.006","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the impact of SWI/SNF complex on heterochromatin DNA damage repair after exposure to X-ray irradiation, in order to explore the underlying mechanism.</p></div><div><h3>Methods</h3><p>NIH3T3 and MRC5 cells were treated with 50 ​nmol/L siRNA targeting SWI/SNF complex subunits (BRM, ARID1A, BRG1 and SNF5), and YAP/TAZ. At 24 ​h after transfection, the cells were irradiated with 0.5 and 1 ​Gy of X-rays. At 20, 60 and 240 ​min post-irradiation, γH2AX assay was performed to evaluate the radiation response in total or heterochromatin. Comet assay was used to determine the role of YAP/TAZ in DNA damage when the cells were irradiated with 4 ​Gy of X-rays. NIH3T3 were treated with 50 ​nmol/L siRNA targeting BRM/BRG1 and YAP/TAZ to determine their relationship on heterochromatin DNA damage repair.</p></div><div><h3>Results</h3><p>In NIH3T3, SWI/SNF complex subunits (BRM, ARID1A and BRG1) knock-down increased γH2AX in total and heterochromatin at 1 ​Gy 60 ​min post-irradiation (<em>P</em> ​&lt; ​0.05), while SNF5 knock-down decreased heterochromatin γH2AX at 1 ​Gy 20 ​min post-irradiation (<em>P</em> ​&lt; ​0.05). In MRC5, BRM and BRG1 knock-down increased γH2AX in total and heterochromatin at 1 ​Gy 60 ​min post-irradiation (<em>P</em> ​&lt; ​0.05). Inconsistently, ARID1A knock-down did not affect it, and SNF5 knock-down increased heterochromatin γH2AX at 1 ​Gy 60 ​min post-irradiation (<em>P</em> ​&lt; ​0.05). Moreover, YAP/TAZ knock-down decreased heterochromatin γH2AX in NIH3T3 and MRC5 (<em>P</em> ​&lt; ​0.05). Meanwhile, YAP/TAZ knock-down decreased Tail Moment in comet assay at 4 ​Gy 60 ​min post-irradiation (<em>P</em> ​&lt; ​0.05). BRM/BRG1 combining with YAP/TAZ knock-down significantly decreased heterochromatin γH2AX compared with single BRM/BRG1 knock-down at 0.5 ​Gy 60 ​min post-irradiation (<em>P</em> ​&lt; ​0.05).</p></div><div><h3>Conclusions</h3><p>The SWI/SNF complex subunits exhibited varying effects on DNA damage repair. BRM/BRG1 knock-down promoted γH2AX accumulation in heterochromatin through YAP/TAZ. This study provides a novel direction for DNA damage repair and sheds light on the role of SWI/SNF complex in response to DNA damage repair in heterochromatin.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 214-220"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000588/pdfft?md5=5e3aa13519a76759b814b68a353c9457&pid=1-s2.0-S2666555723000588-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136058961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Measurement and analysis on distribution of radiation field dose inside the treatment room of TaiChi Pro multimodal integrated digital radiotherapy system 太极 Pro 多模态综合数字放射治疗系统治疗室内辐射场剂量分布测量与分析
Radiation Medicine and Protection Pub Date : 2023-12-01 DOI: 10.1016/j.radmp.2023.10.008
Meinan Yao , Zechen Feng , Bin Bai , Zhiqiang Xuan , Yongzhong Ma
{"title":"Measurement and analysis on distribution of radiation field dose inside the treatment room of TaiChi Pro multimodal integrated digital radiotherapy system","authors":"Meinan Yao ,&nbsp;Zechen Feng ,&nbsp;Bin Bai ,&nbsp;Zhiqiang Xuan ,&nbsp;Yongzhong Ma","doi":"10.1016/j.radmp.2023.10.008","DOIUrl":"10.1016/j.radmp.2023.10.008","url":null,"abstract":"<div><h3>Objective</h3><p>To examine the leakage radiation dose from the accelerator module's primary beam self-shielding, as well as stray radiation levels and distribution in the treatment room across various planes for the innovative X/γ multimodal radiotherapy system, TaiChi Pro, which is the world's first digitally integrated system that combines a linear accelerator, multi-source rotational focused gamma knife, and multi-modal image guidance, in order to formulate treatment room safety strategies and estimate additional radiation doses to patients.</p></div><div><h3>Methods</h3><p>The TaiChi Pro multi-mode integrated radiotherapy system was utilized with a 6 ​MV X-ray accelerator in the flatten-filter free (FFF) treatment mode. The system has a primary radiation beam self-shielding, and an isocenter dose rate of 800 ​cGy/min. For detection points in various planes, an <em>x, y, z</em> coordinate system was established with the isocenter as the origin. To simulate the situation of patient, water-equivalent phantom was employed. The ambient dose equivalent and ambient dose equivalent rate at detection points in the radiation field were measured using thermoluminescence dosimeters.</p></div><div><h3>Results</h3><p>The self-shielding area achieved a maximum dose of 114.0 ​mGy at 1 m distance from the target point after 3 ​min of cumulative irradiation. The leakage radiation ratios at all points remained below 0.5%, fulfilling the self-shielding design requirements. Regarding the couch, the highest radiation was observed in the opposite direction of the beam at the target point. The stray radiation on the treatment bed plane resulted in an ambient dose equivalent that did not exceed 0.5% of the ambient dose equivalent at the central point.</p></div><div><h3>Conclusion</h3><p>The levels and distribution patterns of stray and leakage radiation inside the TaiChi Pro treatment room meet the requirements of the relevant national standard. The measured values of indoor radiation levels and distribution are very useful for room shielding design and personnel protection.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 236-243"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000606/pdfft?md5=826eaa2e3c5564fab880e7d0d364e420&pid=1-s2.0-S2666555723000606-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136093026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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