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Sex differences in radiation research. 会议报告辐射研究中的性别差异。
Pub Date : 2024-01-01 Epub Date: 2023-11-27 DOI: 10.1080/09553002.2023.2283089
Lanyn P Taliaferro, Rajeev K Agarwal, C Norman Coleman, Andrea L DiCarlo, Kimberly A Hofmeyer, Shannon G Loelius, Olivia Molinar-Inglis, Dana C Tedesco, Merriline M Satyamitra

Purpose: The Sex Differences in Radiation Research workshop addressed the role of sex as a confounder in radiation research and its implication in real-world radiological and nuclear applications.

Methods: In April 2022, HHS-wide partners from the Radiation and Nuclear Countermeasures Program, the Office of Research on Women's Health National Institutes of Health Office of Women's Health, U.S. Food and Drug Administration, and the Radiological and Nuclear Countermeasures Branch at the Biomedical Advanced Research and Development Authority conducted a workshop to address the scientific implication and knowledge gaps in understanding sex in basic and translational research. The goals of this workshop were to examine sex differences in 1. Radiation animal models and understand how these may affect radiation medical countermeasure development; 2. Biodosimetry and/or biomarkers used to assess acute radiation syndrome, delayed effects of acute radiation exposure, and/or predict major organ morbidities; 3. medical research that lacks representation from both sexes. In addition, regulatory policies that influence inclusion of women in research, and the gaps that exist in drug development and device clearance were discussed. Finally, real-world sex differences in human health scenarios were also considered.

Results: This report provides an overview of the two-day workshop, and open discussion among academic investigators, industry researchers, and U.S. government representatives.

Conclusions: This meeting highlighted that current study designs lack the power to determine statistical significance based on sex, and much is unknown about the underlying factors that contribute to these differences. Investigators should accommodate both sexes in all stages of research to ensure that the outcome is robust, reproducible, and accurate, and will benefit public health.

目的:辐射研究中的性别差异讲习班讨论了性别在辐射研究中作为混杂因素的作用及其在现实世界放射和核应用中的意义。方法:2022年4月,来自hhs范围内的辐射与核对策项目、妇女健康研究办公室、国家卫生研究院妇女健康办公室、美国食品和药物管理局以及生物医学高级研究与发展管理局的辐射与核对策部门的合作伙伴举办了一次研讨会,以解决在基础研究和转化研究中理解性别的科学含义和知识差距。这次研讨会的目的是研究1。辐射动物模型并了解这些模型如何影响辐射医学对策的发展;2. 用于评估急性辐射综合征、急性辐射暴露的延迟效应和/或预测主要器官病变的生物剂量学和/或生物标志物;3.缺乏男女代表的医学研究。此外,还讨论了影响妇女参与研究的监管政策,以及药物开发和器械审批方面存在的差距。最后,还考虑了现实世界中人类健康状况的性别差异。结果:本报告概述了为期两天的研讨会,以及学术研究人员、行业研究人员和美国政府代表之间的公开讨论。结论:本次会议强调,目前的研究设计缺乏确定基于性别的统计显著性的能力,造成这些差异的潜在因素还有很多未知之处。调查人员应在研究的所有阶段考虑两性,以确保结果是可靠的、可重复的和准确的,并将有利于公共卫生。
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引用次数: 0
Effects of ionising radiation exposure in offspring and next generations: dosimetric aspects and uncertainties. 电离辐射暴露对后代和下一代的影响:剂量学方面和不确定性。
Pub Date : 2024-01-01 Epub Date: 2023-11-16 DOI: 10.1080/09553002.2023.2280017
Ämilie Degenhardt, Sara Dumit, Augusto Giussani

Purpose: The impact of the exposure to ionizing radiation in the offspring and next generation has been investigated in the last decades and currently is the subject of study of the ICRP Task Group 121. Studying the effects of radiation exposure in pre-conceptional and post-conceptional phases can be a challenge since potential effects to the fetus vary depending on the stage of fetal development. Epidemiology and radiobiology studies are the two sources of information one can use to correlate the radiation dose to the human body and tissues and the resulting effects. For a proper evaluation of the outcomes of such studies, and a correct appraisal of the exposure/dose-effect relationship, (i) reliable dosimetry, (ii) accurate reporting, and (iii) reproducibility of results are required. Although variables related to dose, including for instance source of radiation, geometry of irradiation, dose rate etc., are usually known, especially in radiobiology studies, often important details of the irradiation are not reported.

Conclusions: Based on standards developed by the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Disease (NIAID) and the National Institute of Standards and Technology (NIST), a review of the scientific studies used by the UNSCEAR to estimate the risk of hereditary effects, and by the ICRP in its current recommendations, was conducted to evaluate the way dosimetry was reported. Dosimetry and the related uncertainties were not adequately described in the vast majority of those studies. This does not necessarily mean that they do not provide relevant information, however it prevents from a thorough verification and reproduction of their findings. In order to guarantee the reliability and robustness of the process of revision of the estimates of risk and detriment it is therefore considered mandatory to include a careful check of the new relevant literature with regard to the criteria on the completeness and reproducibility of the dosimetric information.

目的:近几十年来,人们一直在研究电离辐射照射对后代和下一代的影响,目前这是ICRP第121工作组的研究主题。研究孕前和孕后阶段辐射暴露的影响可能是一个挑战,因为对胎儿的潜在影响因胎儿发育阶段而异。流行病学和放射生物学研究是人们可以用来将辐射剂量与人体和组织及其产生的影响联系起来的两个信息来源。为了正确评估这类研究的结果,并正确评估暴露/剂量效应关系,需要(i)可靠的剂量测定法,(ii)准确的报告,以及(iii)结果的可重复性。虽然与剂量有关的变数,包括例如辐射源、照射的几何形状、剂量率等,通常是已知的,特别是在放射生物学研究中,但辐照的重要细节往往没有报告。结论:根据国家癌症研究所(NCI)、国家过敏和传染病研究所(NIAID)和国家标准与技术研究所(NIST)制定的标准,对UNSCEAR用于估计遗传影响风险的科学研究以及ICRP在其当前建议中使用的科学研究进行了审查,以评估剂量学报告的方式。在这些研究中,绝大多数都没有充分描述剂量学和相关的不确定性。这并不一定意味着它们不提供有关资料,但这妨碍彻底核查和复制它们的调查结果。因此,为了保证对风险和危害估计的修订过程的可靠性和稳健性,认为有必要对有关剂量学资料的完整性和可重复性标准的新相关文献进行仔细检查。
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引用次数: 0
The efficacy of coaxial percutaneous iodine-125 seed implantation combined with arterial infusion chemotherapy for advanced pancreatic cancer: a randomized clinical trial. 同轴经皮碘-125粒子植入联合动脉灌注化疗治疗晚期胰腺癌的疗效:随机临床试验。
Pub Date : 2024-01-01 Epub Date: 2024-04-30 DOI: 10.1080/09553002.2024.2347357
HongXiang Yao, Ying ZhuGe, ShiXiang Jin, ShuiBing Chen, HengYiTing Zhang, Dong Zhang, ZhiGang Chen

Background: This study aimed to evaluate the clinical efficacy of coaxial percutaneous Iodine-125 (125I) seed implantation in combination with arterial infusion chemotherapy for the treatment of advanced pancreatic cancer (PC) through a randomized controlled trial.

Methods: A total of 101 patients with advanced PC were randomized into two groups: control group treated with systemic intravenous chemotherapy and experimental group that received 125I seed implantation in combination with arterial infusion chemotherapy. Outcomes, including tumor control, abdominal pain relief, and survival time were compared between these two groups (Trial Registration No. KYKT2018-65).

Results: Pretreatment abdominal pain scores were comparable between the two groups, whereas the abdominal pain scores at 1- and 3-month post-treatment were significantly lower in the control group than those in the experimental group (1-month: 3.74 ± 1.54 vs. 4.48 ± 1.46, p = .015; 3-month: 3.64 ± 2.21 vs. 5.40 ± 1.56, p < .001). At 3-month post-treatment, computed tomography (CT) scan revealed a significantly higher disease control rate in the experimental group than that in the control group (94.0% vs. 74.5%, p = .007). The median survival time in the experimental group was significantly longer than that in the control group (15-month vs. 9-month, p < .001).

Conclusion: The combination of coaxial percutaneous 125I seed implantation with arterial infusion chemotherapy could significantly alleviate abdominal pain, improve tumor control rates, and prolong survival time in patients with advanced PC.

研究背景本研究旨在通过随机对照试验评估同轴经皮碘-125(125I)粒子植入联合动脉灌注化疗治疗晚期胰腺癌(PC)的临床疗效:共有101名晚期胰腺癌患者被随机分为两组:对照组接受全身静脉化疗,实验组接受125I粒子植入联合动脉灌注化疗。对两组患者的肿瘤控制、腹痛缓解和生存时间等结果进行比较(试验登记号:KYKT2018-65):结果:两组患者治疗前的腹痛评分相当,而治疗后1个月和3个月的腹痛评分,对照组明显低于实验组(1个月:3.74 ± 1.54 vs 3.74 ± 1.54):1 个月:3.74 ± 1.54 vs. 4.48 ± 1.46,p = .015;3 个月3.64 ± 2.21 vs. 5.40 ± 1.56,p vs. 74.5%,p = .007)。实验组的中位生存时间明显长于对照组(15 个月 vs. 9 个月,p 结论:实验组的中位生存时间明显长于对照组(15 个月 vs. 9 个月):同轴经皮 125I 粒子植入联合动脉灌注化疗可明显缓解晚期 PC 患者的腹痛,提高肿瘤控制率,延长生存时间。
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引用次数: 0
Comparative analysis of the yields of dicentrics and chromosomal translocations. 双中心和染色体易位产量的比较分析。
Pub Date : 2024-01-01 Epub Date: 2024-07-02 DOI: 10.1080/09553002.2024.2369077
Dorota Młynarczyk, Pedro Puig, Joan F Barquinero, Carmen Armero, Virgilio Gómez-Rubio

Purpose: Chromosomal dicentrics and translocations are commonly employed as biomarkers to estimate radiation doses. The main goal of this article is to perform a comparative analysis of yields of both types of aberrations. The objective is to determine if there are relevant distinctions between both yields, allowing for a comprehensive assessment of their respective suitability and accuracy in the estimation of radiation doses.

Materials and methods: The analysis involved data from a partial-radiation simulation study with the calibration data obtained through two scoring methods: conventional and PAINT modified. Subsequently, a Bayesian bivariate zero-inflated Poisson model was employed to compare the posterior marginal density of the mean of dicentrics and translocations and assess the differences between them.

Results: When employing the conventional method of scoring, the findings indicate that there is no notable disparity between the yield of observed translocations and dicentrics. However, when utilizing the PAINT modified method, a notable discrepancy is observed for higher doses, indicating a relevant difference in the mean number of the two types of aberrations.

Conclusions: The choice of scoring method significantly influences the analysis of radiation-induced aberrations, especially when distinguishing between complex and simple chromosomal formations. Further research and analysis are necessary to gain a deeper understanding of the factors and mechanisms impacting the formation of dicentrics and translocations.

目的:染色体二中心和易位通常被用作估算辐射剂量的生物标记。本文的主要目的是对这两种畸变的检出率进行比较分析。目的是确定这两种畸变率之间是否存在相关区别,从而全面评估它们各自在估算辐射剂量方面的适用性和准确性:分析涉及部分辐射模拟研究的数据,校准数据通过两种评分方法获得:传统评分法和 PAINT 改良评分法。随后,采用贝叶斯双变量零膨胀泊松模型来比较二中心和易位平均值的后验边际密度,并评估它们之间的差异:结果:采用传统的评分方法时,研究结果表明观察到的易位和二中心的产量之间没有明显的差异。然而,当使用 PAINT 改良方法时,观察到较高剂量时存在明显差异,这表明这两种畸变的平均数量存在相关差异:结论:评分方法的选择对辐射诱导畸变的分析有很大影响,尤其是在区分复杂和简单染色体畸变时。要更深入地了解影响双中心和易位形成的因素和机制,还需要进一步的研究和分析。
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引用次数: 0
Mutations induced in some Egyptian cowpea varieties with yield characteristics and high nutritional value using gamma rays and evaluation by microsatellite markers. 利用伽马射线诱导一些具有产量特征和高营养价值的埃及豇豆品种发生变异,并通过微卫星标记进行评估。
Pub Date : 2024-01-01 Epub Date: 2024-07-11 DOI: 10.1080/09553002.2024.2374912
M Adly, A Ezzat, A Awad, A El-Fiki

Purpose: In order to achieve mutations with enhanced economic, productive, and nutritional characteristics in the two Egyptian cowpea varieties, Dokki 331 and Kaha 1, the application of gamma irradiation at different doses is employed. Additionally, this method aids in distinguishing between these mutations using simple sequence repeat (SSR) analysis.

Materials and methods: Two different cowpea cultivars were subjected to varying doses of gamma radiation ranging from 50 to 300 Gy. In order to analyze the effects of radiation, both unirradiated and irradiated seeds from both cultivars were planted using a randomized complete block design. This experiment was conducted over a span of six generations, namely M1, M2, M3, M4, M5, and M6, starting from April 2017 and continuing until 2022. Among the various radiation doses, the cultivar Kaha 1 produced promising traits when exposed to a dose of 150 Gy, while the cultivar Dokki 331 showed favorable traits when exposed to a dose of 300 Gy. These traits were further cultivated and studied until the M6 generation.

Results: Induced mutations in two Egyptian cowpea varieties, Kaha 1 and Dokki 331, are subjected to varying doses of gamma radiation (0, 50, 100, 150, 200, 250, and 300 Gy). Morphological and genetic variations were observed, with mutations being induced at doses of 150 Gy for Kaha 1 and 300 Gy for Dokki 331. The mutation in Kaha 1 (beam 1) resulted in dwarfism, altered leaf shape, early flowering, increased peduncles, pods, and pod seed numbers, ultimately leading to enhanced seed production and acreage productivity. In Dokki 331, the mutations primarily affected pod color, resulting in greenish-brown pods with mosaic seeds, segregating black and gray seeds from the mosaic ones. These mutations led to an increase in the nutritional value of the seeds, including higher nitrogen content, total free amino acids, crude protein, total carbohydrates, and total sugars. The genetic diversity of the seven cowpea mutations was assessed using 20 microsatellite markers. The analysis revealed a total of 60 alleles, with an average of three alleles per locus. The allele frequency ranged from 0.2857 to 1.0, with an average of 0.6036. Gene diversity varied from 0.0 to 0.8163, while the heterozygosity was mostly zero, except for one primer (VM 37) with an average of 0.0071. The polymorphic information content (PIC) ranged from 0.7913 to 0.0, with an average of 0.4323. The Marker Index value ranged from 0.36 to 0.0, with an average of 0.152. Overall, our findings demonstrate the successful induction of mutations in Egyptian cowpea varieties using gamma rays, resulting in improved yield characteristics and nutritional value.

Conclusions: Radiation as a physical mutagen is highly regarded for its effectiveness, affordability, speed, and safety in inducing mutations. Utilizing gamma rays, we successfully derived a novel cowpea v

目的:为了在两个埃及豇豆品种 Dokki 331 和 Kaha 1 中获得经济、高产和营养特性更强的突变,采用了不同剂量的伽马辐照。此外,这种方法还有助于利用简单序列重复(SSR)分析来区分这些突变:对两种不同的豇豆栽培品种进行了不同剂量的伽马射线辐射,辐射范围从 50 到 300 Gy 不等。为了分析辐射的影响,采用随机完全区组设计法种植了两个品种未受辐射和受辐射的种子。该实验从 2017 年 4 月开始,持续到 2022 年,共进行了六代,即 M1、M2、M3、M4、M5 和 M6。在各种辐射剂量中,栽培品种 "Kaha 1 号 "在 150 Gy 的辐射剂量下表现出良好的性状,而栽培品种 "Dokki 331 "在 300 Gy 的辐射剂量下表现出良好的性状。这些性状被进一步培养和研究,直到 M6 代:对两个埃及豇豆品种 Kaha 1 和 Dokki 331 进行不同剂量的伽马射线辐射(0、50、100、150、200、250 和 300 Gy),诱发了突变。观察到了形态和遗传变异,Kaha 1 号和 Dokki 331 分别在 150 Gy 和 300 Gy 的剂量下诱发了突变。Kaha 1(光束 1)的突变导致矮化、叶形改变、早花、花序梗、豆荚和豆荚种子数量增加,最终提高了种子产量和种植面积生产力。在多基 331 中,突变主要影响豆荚颜色,导致豆荚呈绿褐色,种子呈马赛克状,黑色和灰色种子与马赛克种子分离。这些突变提高了种子的营养价值,包括更高的氮含量、总游离氨基酸、粗蛋白、总碳水化合物和总糖。使用 20 个微卫星标记评估了七个豇豆突变的遗传多样性。分析结果显示共有 60 个等位基因,平均每个位点有 3 个等位基因。等位基因频率从 0.2857 到 1.0 不等,平均为 0.6036。基因多样性从 0.0 到 0.8163 不等,除一个引物(VM 37)的平均杂合度为 0.0071 外,其他引物的杂合度大多为零。多态信息含量(PIC)从 0.7913 到 0.0 不等,平均为 0.4323。标记指数值从 0.36 到 0.0 不等,平均为 0.152。总之,我们的研究结果表明,利用伽马射线成功诱导了埃及豇豆品种的突变,从而改善了其产量特性和营养价值:辐射作为一种物理诱变剂,因其诱导突变的有效性、经济性、快速性和安全性而备受推崇。利用伽马射线,我们成功培育出了一个名为beam 1突变的豇豆新品种,并获得了埃及农业部的批准。
{"title":"Mutations induced in some Egyptian cowpea varieties with yield characteristics and high nutritional value using gamma rays and evaluation by microsatellite markers.","authors":"M Adly, A Ezzat, A Awad, A El-Fiki","doi":"10.1080/09553002.2024.2374912","DOIUrl":"10.1080/09553002.2024.2374912","url":null,"abstract":"<p><strong>Purpose: </strong>In order to achieve mutations with enhanced economic, productive, and nutritional characteristics in the two Egyptian cowpea varieties, Dokki 331 and Kaha 1, the application of gamma irradiation at different doses is employed. Additionally, this method aids in distinguishing between these mutations using simple sequence repeat (SSR) analysis.</p><p><strong>Materials and methods: </strong>Two different cowpea cultivars were subjected to varying doses of gamma radiation ranging from 50 to 300 Gy. In order to analyze the effects of radiation, both unirradiated and irradiated seeds from both cultivars were planted using a randomized complete block design. This experiment was conducted over a span of six generations, namely M1, M2, M3, M4, M5, and M6, starting from April 2017 and continuing until 2022. Among the various radiation doses, the cultivar Kaha 1 produced promising traits when exposed to a dose of 150 Gy, while the cultivar Dokki 331 showed favorable traits when exposed to a dose of 300 Gy. These traits were further cultivated and studied until the M6 generation.</p><p><strong>Results: </strong>Induced mutations in two Egyptian cowpea varieties, Kaha 1 and Dokki 331, are subjected to varying doses of gamma radiation (0, 50, 100, 150, 200, 250, and 300 Gy). Morphological and genetic variations were observed, with mutations being induced at doses of 150 Gy for Kaha 1 and 300 Gy for Dokki 331. The mutation in Kaha 1 (beam 1) resulted in dwarfism, altered leaf shape, early flowering, increased peduncles, pods, and pod seed numbers, ultimately leading to enhanced seed production and acreage productivity. In Dokki 331, the mutations primarily affected pod color, resulting in greenish-brown pods with mosaic seeds, segregating black and gray seeds from the mosaic ones. These mutations led to an increase in the nutritional value of the seeds, including higher nitrogen content, total free amino acids, crude protein, total carbohydrates, and total sugars. The genetic diversity of the seven cowpea mutations was assessed using 20 microsatellite markers. The analysis revealed a total of 60 alleles, with an average of three alleles per locus. The allele frequency ranged from 0.2857 to 1.0, with an average of 0.6036. Gene diversity varied from 0.0 to 0.8163, while the heterozygosity was mostly zero, except for one primer (VM 37) with an average of 0.0071. The polymorphic information content (PIC) ranged from 0.7913 to 0.0, with an average of 0.4323. The Marker Index value ranged from 0.36 to 0.0, with an average of 0.152. Overall, our findings demonstrate the successful induction of mutations in Egyptian cowpea varieties using gamma rays, resulting in improved yield characteristics and nutritional value.</p><p><strong>Conclusions: </strong>Radiation as a physical mutagen is highly regarded for its effectiveness, affordability, speed, and safety in inducing mutations. Utilizing gamma rays, we successfully derived a novel cowpea v","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1117-1125"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Docetaxel radiosensitizes castration-resistant prostate cancer by downregulating CAV-1. 多西他赛通过下调CAV-1对去势抵抗性前列腺癌症放射增敏。
Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/09553002.2023.2263553
Kevin J Tu, Sanjit K Roy, Zachery Keepers, Manas R Gartia, Hem D Shukla, Nrusingh C Biswal

Purpose: Docetaxel (DXL), a noted radiosensitizer, is one of the few chemotherapy drugs approved for castration-resistant prostate cancer (CRPC), though only a fraction of CRPCs respond to it. CAV-1, a critical regulator of radioresistance, has been known to modulate DXL and radiation effects. Combining DXL with radiotherapy may create a synergistic anticancer effect through CAV-1 and improve CRPC patients' response to therapy. Here, we investigate the effectiveness and molecular characteristics of DXL and radiation combination therapy in vitro.

Materials and methods: We used live/dead assays to determine the IC50 of DXL for PC3, DU-145, and TRAMP-C1 cells. Colony formation assay was used to determine the radioresponse of the same cells treated with radiation with/without IC50 DXL (4, 8, and 12 Gy). We performed gene expression analysis on public transcriptomic data collected from human-derived prostate cancer cell lines (C4-2, PC3, DU-145, and LNCaP) treated with DXL for 8, 16, and 72 hours. Cell cycle arrest and protein expression were assessed using flow cytometry and western blot, respectively.

Results: Compared to radiation alone, combination therapy with DXL significantly increased CRPC death in PC3 (1.48-fold, p < .0001), DU-145 (1.64-fold, p < .05), and TRAMP-C1 (1.13-fold, p < .05) at 4 Gy of radiation. Gene expression of CRPC treated with DXL revealed downregulated genes related to cell cycle regulation and upregulated genes related to immune activation and oxidative stress. Confirming the results, G2/M cell cycle arrest was significantly increased after treatment with DXL and radiation. CAV-1 protein expression was decreased after DXL treatment in a dose-dependent manner; furthermore, CAV-1 copy number was strongly associated with poor response to therapy in CRPC patients.

Conclusions: Our results suggest that DXL sensitizes CRPC cells to radiation by downregulating CAV-1. DXL + radiation combination therapy may be effective at treating CRPC, especially subtypes associated with high CAV-1 expression, and should be studied further.

目的:多西他赛(dox)是一种著名的放射增敏剂,是为数不多的被批准用于去势耐受性癌症(CRPC)的化疗药物之一,尽管只有一小部分CRPC对其有反应。CAV-1是一种重要的放射耐受调节因子,已知可调节dox和辐射效应。将dox与放疗相结合可以通过CAV-1产生协同抗癌作用,并改善CRPC患者对治疗的反应。在这里,我们在体外研究dox和放射联合治疗的有效性和分子特征。材料和方法:我们使用活/死分析来测定dox对PC3、DU-145和TRAMP-C1细胞的IC50。集落形成测定法用于测定用IC50-dox(4,8,12 Gy)。我们对从用dox治疗8、16和72天的人源性前列腺癌症细胞系(C4-2、PC3、DU-145、LNCaP)收集的公共转录组数据进行了基因表达分析 小时。分别使用流式细胞术和蛋白质印迹评估细胞周期停滞和蛋白质表达。结果:与单独放疗相比,dox联合治疗显著增加了PC3患者的CRPC死亡(1.48倍,p 结论:我们的研究结果表明,dox通过下调CAV-1使CRPC细胞对辐射敏感。Dox + 放射联合治疗可能对治疗CRPC有效,尤其是与CAV-1高表达相关的亚型,应进一步研究。
{"title":"Docetaxel radiosensitizes castration-resistant prostate cancer by downregulating CAV-1.","authors":"Kevin J Tu, Sanjit K Roy, Zachery Keepers, Manas R Gartia, Hem D Shukla, Nrusingh C Biswal","doi":"10.1080/09553002.2023.2263553","DOIUrl":"10.1080/09553002.2023.2263553","url":null,"abstract":"<p><strong>Purpose: </strong>Docetaxel (DXL), a noted radiosensitizer, is one of the few chemotherapy drugs approved for castration-resistant prostate cancer (CRPC), though only a fraction of CRPCs respond to it. CAV-1, a critical regulator of radioresistance, has been known to modulate DXL and radiation effects. Combining DXL with radiotherapy may create a synergistic anticancer effect through CAV-1 and improve CRPC patients' response to therapy. Here, we investigate the effectiveness and molecular characteristics of DXL and radiation combination therapy in vitro.</p><p><strong>Materials and methods: </strong>We used live/dead assays to determine the IC<sub>50</sub> of DXL for PC3, DU-145, and TRAMP-C1 cells. Colony formation assay was used to determine the radioresponse of the same cells treated with radiation with/without IC<sub>50</sub> DXL (4, 8, and 12 Gy). We performed gene expression analysis on public transcriptomic data collected from human-derived prostate cancer cell lines (C4-2, PC3, DU-145, and LNCaP) treated with DXL for 8, 16, and 72 hours. Cell cycle arrest and protein expression were assessed using flow cytometry and western blot, respectively.</p><p><strong>Results: </strong>Compared to radiation alone, combination therapy with DXL significantly increased CRPC death in PC3 (1.48-fold, <i>p</i> < .0001), DU-145 (1.64-fold, <i>p</i> < .05), and TRAMP-C1 (1.13-fold, <i>p</i> < .05) at 4 Gy of radiation. Gene expression of CRPC treated with DXL revealed downregulated genes related to cell cycle regulation and upregulated genes related to immune activation and oxidative stress. Confirming the results, G2/M cell cycle arrest was significantly increased after treatment with DXL and radiation. CAV-1 protein expression was decreased after DXL treatment in a dose-dependent manner; furthermore, CAV-1 copy number was strongly associated with poor response to therapy in CRPC patients.</p><p><strong>Conclusions: </strong>Our results suggest that DXL sensitizes CRPC cells to radiation by downregulating CAV-1. DXL + radiation combination therapy may be effective at treating CRPC, especially subtypes associated with high CAV-1 expression, and should be studied further.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"256-267"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The relationship of body mass index to setup errors, dosimetric parameters and incidence of radiation pneumonitis in non-small cell lung cancer patients undergoing intensity-modulated radiation therapy: a single-center observational study. 癌症非小细胞肺癌患者的体重指数与设置误差、剂量测定参数和放射性肺炎发病率的关系:一项单中心观察性研究。
Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/09553002.2023.2261549
Xinrui Rao, Hongyuan Liu, Yuewen Zhang, Yaqiong Xie, Geng Wang, Sheng Zhang, Gang Wu, Ye Wang, Rui Zhou

Background: The relationship among body mass index (BMI), setup error and radiation pneumonitis is not clearly illustrated.

Objective: The present study aimed to investigate the role of BMI in non-small cell lung cancer (NSCLC) patients' radiation treatment, focusing on its relationship with setup error of patient positioning, the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and the incidence of radiation pneumonitis.

Methods: This prospective observational study included 523 cases of NSCLC patients during 2020-2022. Patients were divided into different groups by different BMI. The setup error was obtained by cone beam CT (CBCT) at three positions, lateral (LAT), longitudinal (LNG) and vertical (VRT). IMRT dosimetric parameters of V5, V20, and mean dose were collected.

Results: Patients with BMI ≥28 kg/m2 showed significantly higher absolute values of LAT, LNG and VRT, higher V5, V20, mean dose, as well as higher total incidence of radiation pneumonitis and grade III radiation pneumonitis compared with patients with BMI <24 kg/m2 or 24-28 kg/m2. Spearman's analysis demonstrated that the absolute values of LAT, LNG and VRT were positively correlated with BMI, and positive correlation existed among BMI, dosimetric parameters and setup errors. ROC curves showed that LAT in setup errors and V5 in dosimetric parameters had the best diagnostic value for prediction of radiation pneumonitis. Only BMI, LAT, V5 and V20 were the independent risk factors for radiation pneumonitis.

Conclusions: Setup error caused by higher BMI might be associated with the dosimetric parameters, as well as the incidence of radiation pneumonitis in NSCLC patients.

背景:身体质量指数(BMI)、设置误差和放射性肺炎之间的关系尚不清楚。目的:本研究旨在探讨BMI在NSCLC患者放射治疗中的作用,重点探讨其与患者定位设置误差、调强放射治疗(IMRT)剂量参数和放射性肺炎发病率的关系。方法:这项前瞻性观察性研究纳入了2020年523例非小细胞肺癌患者 ∼ 2022年。根据不同的体重指数(BMI)将患者分为不同的组。设置误差通过锥形束CT(CBCT)在三个位置获得,即横向(LAT)、纵向(LNG)和垂直(VRT)。收集V5、V20和平均剂量的IMRT剂量测定参数。结果:BMI≥28的患者 与BMI<24的患者相比,kg/m2的LAT、LNG和VRT绝对值显著更高,V5、V20平均剂量更高,放射性肺炎和III级放射性肺炎的总发病率也更高 kg/m2或24 ∼ 28 Spearman分析表明,LAT、LNG和VRT的绝对值与BMI呈正相关,BMI、剂量测量参数和设置误差之间存在正相关。ROC曲线显示,设置误差中的LAT和剂量测定参数中的V5对预测放射性肺炎具有最佳的诊断价值。只有BMI、LAT、V5和V20是放射性肺炎的独立危险因素。结论:高BMI引起的设置错误可能与NSCLC患者的剂量测量参数以及放射性肺炎的发生率有关。
{"title":"The relationship of body mass index to setup errors, dosimetric parameters and incidence of radiation pneumonitis in non-small cell lung cancer patients undergoing intensity-modulated radiation therapy: a single-center observational study.","authors":"Xinrui Rao, Hongyuan Liu, Yuewen Zhang, Yaqiong Xie, Geng Wang, Sheng Zhang, Gang Wu, Ye Wang, Rui Zhou","doi":"10.1080/09553002.2023.2261549","DOIUrl":"10.1080/09553002.2023.2261549","url":null,"abstract":"<p><strong>Background: </strong>The relationship among body mass index (BMI), setup error and radiation pneumonitis is not clearly illustrated.</p><p><strong>Objective: </strong>The present study aimed to investigate the role of BMI in non-small cell lung cancer (NSCLC) patients' radiation treatment, focusing on its relationship with setup error of patient positioning, the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and the incidence of radiation pneumonitis.</p><p><strong>Methods: </strong>This prospective observational study included 523 cases of NSCLC patients during 2020-2022. Patients were divided into different groups by different BMI. The setup error was obtained by cone beam CT (CBCT) at three positions, lateral (LAT), longitudinal (LNG) and vertical (VRT). IMRT dosimetric parameters of <i>V</i><sub>5</sub>, <i>V</i><sub>20</sub>, and mean dose were collected.</p><p><strong>Results: </strong>Patients with BMI ≥28 kg/m<sup>2</sup> showed significantly higher absolute values of LAT, LNG and VRT, higher <i>V</i><sub>5</sub>, <i>V</i><sub>20</sub>, mean dose, as well as higher total incidence of radiation pneumonitis and grade III radiation pneumonitis compared with patients with BMI <24 kg/m<sup>2</sup> or 24-28 kg/m<sup>2</sup>. Spearman's analysis demonstrated that the absolute values of LAT, LNG and VRT were positively correlated with BMI, and positive correlation existed among BMI, dosimetric parameters and setup errors. ROC curves showed that LAT in setup errors and <i>V</i><sub>5</sub> in dosimetric parameters had the best diagnostic value for prediction of radiation pneumonitis. Only BMI, LAT, <i>V</i><sub>5</sub> and <i>V</i><sub>20</sub> were the independent risk factors for radiation pneumonitis.</p><p><strong>Conclusions: </strong>Setup error caused by higher BMI might be associated with the dosimetric parameters, as well as the incidence of radiation pneumonitis in NSCLC patients.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"248-255"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Co60 gamma irradiation reduces rooting ability in M1V1 Salvia uliginosa while inducing leaf variegation. Co60 伽马辐照降低了 M1V1 丹参的生根能力,同时诱导叶片变色。
Pub Date : 2024-01-01 Epub Date: 2024-01-24 DOI: 10.1080/09553002.2024.2304852
Rebekah C I Maynard, John M Ruter

Purpose: Salvia uliginosa is a desirable ornamental shrub for the landscape with blue flowers and the ability to attract pollinators, but limited variation is commercially available in this species. Mutation breeding is a valuable tool to induce variation in ornamental species. However, many deleterious effects are associated with mutation breeding, including reduced rooting ability of vegetative cuttings.

Materials and methods: Cuttings of S. uliginosa were randomly assigned into groups of 10 and exposed to 0, 10, 20, 30, 40, or 50 Gy of gamma rays from a cobalt-60 source to determine an appropriate treatment rate. A follow-up experiment treated 25 S. uliginosa cuttings at 35 Gy to induce favorable mutations.

Results and conclusions: Root quality, survival, and plant height were reduced at higher levels of gamma radiation in the M1V1. However, rooting ability was not impacted in M1V2 selections. Additionally, one mutant was isolated from the 35 Gy treatment with variegated leaves for a mutation rate of 4%. Our research determined a treatment rate that induced a dominant mutation in S. uliginosa while minimizing the deleterious influence of gamma radiation.

目的:丹参(Salvia uliginosa)是一种理想的景观观赏灌木,开蓝色花,能吸引传粉昆虫,但该物种的商业变异非常有限。突变育种是诱导观赏物种变异的重要工具。然而,突变育种会产生许多有害影响,包括降低无性扦插的生根能力:扦插的 S. uliginosa 被随机分配成 10 人一组,分别暴露于 0、10、20、30、40 或 50 Gy 的钴-60 伽玛射线,以确定适当的处理率。后续实验用 35 Gy 处理了 25 株 S. uliginosa 插条,以诱导有利的突变:在 M1V1 中,较高水平的伽马辐射会降低根的质量、存活率和植株高度。然而,M1V2的生根能力没有受到影响。此外,从 35 Gy 处理中分离出一个突变体,其叶片呈杂色,突变率为 4%。我们的研究确定了一种既能诱导 S. uliginosa 发生显性突变,又能将伽马射线的有害影响降至最低的处理率。
{"title":"Co<sup>60</sup> gamma irradiation reduces rooting ability in M<sub>1</sub>V<sub>1</sub> <i>Salvia uliginosa</i> while inducing leaf variegation.","authors":"Rebekah C I Maynard, John M Ruter","doi":"10.1080/09553002.2024.2304852","DOIUrl":"10.1080/09553002.2024.2304852","url":null,"abstract":"<p><strong>Purpose: </strong><i>Salvia uliginosa</i> is a desirable ornamental shrub for the landscape with blue flowers and the ability to attract pollinators, but limited variation is commercially available in this species. Mutation breeding is a valuable tool to induce variation in ornamental species. However, many deleterious effects are associated with mutation breeding, including reduced rooting ability of vegetative cuttings.</p><p><strong>Materials and methods: </strong>Cuttings of <i>S. uliginosa</i> were randomly assigned into groups of 10 and exposed to 0, 10, 20, 30, 40, or 50 Gy of gamma rays from a cobalt-60 source to determine an appropriate treatment rate. A follow-up experiment treated 25 <i>S. uliginosa</i> cuttings at 35 Gy to induce favorable mutations.</p><p><strong>Results and conclusions: </strong>Root quality, survival, and plant height were reduced at higher levels of gamma radiation in the M<sub>1</sub>V<sub>1</sub>. However, rooting ability was not impacted in M<sub>1</sub>V<sub>2</sub> selections. Additionally, one mutant was isolated from the 35 Gy treatment with variegated leaves for a mutation rate of 4%. Our research determined a treatment rate that induced a dominant mutation in <i>S. uliginosa</i> while minimizing the deleterious influence of gamma radiation.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"663-668"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements. 审查作为膳食补充剂的肌酸和精氨酸的辐射防护潜力证据。
Pub Date : 2024-01-01 Epub Date: 2024-04-29 DOI: 10.1080/09553002.2024.2345098
Lyudmila Nersesova, Mariam Petrosyan, Gohar Tsakanova

Purpose: Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups.

Conclusions: Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.

目的:肌酸(Cr)和精氨酸(L-arginine)是天然存在的胍类化合物,通常用作增强体力的膳食补充剂。肌酸和精氨酸还具有一些与能量无关的特性,如抗氧化、抗凋亡和抗炎特性,这些特性有助于它们对氧化应激(OS)起到保护作用。在这方面,许多研究都强调了铬对氧化应激的保护作用,因为氧化应激是在衰老过程中、在运动员增加运动负荷的过程中以及在一些神经系统疾病和与异种生物和紫外线照射有关的毒性效应中产生的。在此背景下,由于电离辐射会导致细胞内的OS,从而产生辐射毒性,因此人们越来越有兴趣了解铬是否具有作为有效辐射防护剂的全部潜力。通过广泛的文献检索,我们没有找到任何有关这一问题的数据。在这篇叙述性综述中,我们总结了过去几年发表的一些有关铬的辐射防护作用的实验数据。此外,我们还回顾了其他研究小组早些时候提供的有关精氨酸辐射调节作用的现有数据:肌酸具有明显的辐射防护潜力,包括:(1)对接受急性全身 X 射线照射(LD70/30 剂量为 6.5 Gy,(2) 对外周血细胞群组成的辐射保护作用,(3) 对外周血单核细胞 DNA 损伤的辐射保护作用,(4) 对肝细胞核-核小体的辐射保护作用,以及 (5) 对相应动物的大脑和肝脏 Cr-Cr 激酶系统的辐射保护作用。考虑到铬的这些细胞保护、基因保护、肝脏保护和能量刺激特性,以及它对大鼠存活率的显著辐射保护作用,可以认为它是一种有潜力的辐射保护剂,可用于进一步的临床前和临床研究。对目前现有的有关精氨酸放射修饰作用的数据进行的回顾表明,精氨酸作为一种放射保护剂、放射诱导剂和放射增敏剂具有很大的潜力。然而,要证明精氨酸(Arg)作为放射保护剂的有效性,似乎有必要扩大和深化相关的临床前研究,最重要的是增加概念验证临床试验的数量,而目前显然还缺乏这种临床试验。
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引用次数: 0
Defining the role of Tip60 in the DNA damage response of glioma cell lines. 确定 Tip60 在胶质瘤细胞系 DNA 损伤反应中的作用。
Pub Date : 2024-01-01 Epub Date: 2024-10-03 DOI: 10.1080/09553002.2024.2409668
K Bannik, A Sak, M Groneberg, M Stuschke

Purpose: Glioblastomas are resistant to conventional therapies, including radiotherapy. Our previous study proved that epigenetic regulation influences the radiation response of glioma cells. This study evaluated the role of the acetyltransferase Tip60 on the radiation response.

Material and methods: Tip60 expression was down-regulated by transfecting specific siRNA's in A7 and MO59K cells with high and low expression of Tip60, respectively, and its effect on survival was assessed. DNA repair was analyzed by foci scoring (γH2AX, Rad51, 53BP1, pATM). The interaction of Tip60 with ATM and DNA-PK was investigated using the specific inhibitors KU55933 and NU7441, respectively.

Results: Knockdown of Tip60 significantly (p < .001) reduced survival in both cell lines, but the effect was more pronounced in A7 cells. ATMi and DNA-PKi significantly reduced the surviving fraction following irradiation. However, no further effect of siTip60 on the radiosensitivity of ATMi treated A7 cells was observed. In contrast, DNA-PKi effectively enhanced the sensitizing effect of siTip60. Mechanistically, siTip60 reduced the number of initial Rad51 and ATM foci formation after irradiation and prevented their dissolution at 24 h. siTip60 had no impact on the formation of 53BP1 and γH2AX foci and did not further affect these end-points if combined with ATMi or DNA-PKi.

Conclusions: Downregulation of Tip60 enhances the radiation sensitivity of both glioma cells and markedly elevates the radiation sensitivity when combined with DNA-PKi. Therefore, treatment with DNA-PK inhibitors represents a promising approach to augment the radiation sensitivity of glioma cell lines with deficient Tip60 activity in a synergistic manner.

目的:胶质母细胞瘤对包括放疗在内的传统疗法具有抗药性。我们之前的研究证明,表观遗传调控会影响胶质瘤细胞的放射反应。本研究评估了乙酰转移酶 Tip60 对放射反应的作用:通过转染特异性 siRNA,分别下调 Tip60 高表达的 A7 细胞和低表达的 MO59K 细胞中 Tip60 的表达,并评估其对存活率的影响。DNA修复通过病灶评分(γH2AX、Rad51、53BP1、pATM)进行分析。分别使用特异性抑制剂 KU55933 和 NU7441 研究了 Tip60 与 ATM 和 DNA-PK 的相互作用:结果:敲除 Tip60 会显著降低两种细胞系的存活率(p < .001),但这种影响在 A7 细胞中更为明显。ATMi和DNA-PKi能明显降低照射后的存活率。然而,siTip60 对经 ATMi 处理的 A7 细胞的放射敏感性没有进一步的影响。相比之下,DNA-PKi能有效增强siTip60的增敏作用。siTip60 对 53BP1 和 γH2AX 病灶的形成没有影响,如果与 ATMi 或 DNA-PKi 结合使用,也不会进一步影响这些终点:结论:下调Tip60可增强两种胶质瘤细胞的辐射敏感性,与DNA-PKi联合使用可显著提高辐射敏感性。因此,用DNA-PK抑制剂治疗是一种很有前景的方法,能以协同方式增强Tip60活性不足的胶质瘤细胞系的辐射敏感性。
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引用次数: 0
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International journal of radiation biology
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