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Enhanced induction of abnormal telomere FISH signals in response to oxidative DNA damage. 氧化 DNA 损伤会增强端粒 FISH 异常信号的诱导。
IF 2 4区 医学 Q2 BIOLOGY Pub Date : 2024-03-22 DOI: 10.1093/jrr/rrad102
Yoshimi Sakamoto, Kazunori Shiraishi, Seiji Kodama

Telomere dysfunction induces chromosomal instability, which is a driving force in the development of cancers. To examine X-irradiation's effect on telomere integrity, we investigated X-ray-induced abnormalities in telomere signals detected by fluorescence in situ hybridization (telomere FISH) in mouse embryo fibroblast cells. The abnormalities were categorized as either extra telomere signals (ETSs) or loss of telomere signals (LTSs). The results indicated that low doses (0.3-0.5 Gy) of X-rays significantly induced ETS but not LTS and that ETS induction was saturated at doses above 0.5 Gy. In addition, treatment with hydrogen peroxide also induced ETS but not LTS. To clarify the involvement of radicals in inducing ETS, we examined the effect of ascorbic acid (AsA) on telomere FISH signals and found that pre-treatment with AsA (5 mM, 2 h), but not post-treatment, significantly suppressed the induction of ETS by X-irradiation. Importantly, neither pre- nor post-treatment with AsA affected X-ray-induced chromosome aberrations. These results suggest that oxidative DNA damage induced by radicals is involved in the induction of ETS. Furthermore, combined treatment with aphidicolin, a DNA replication inhibitor, elevated the induction of ETS by X-irradiation. This observation suggests that DNA replication stress, potentially triggered by oxidative DNA lesions within telomeres, may contribute to the induction of ETS resulting from X-irradiation. Based on these results, we propose that ETS is a sensitive biological marker of oxidative DNA damage in telomere structures.

端粒功能障碍会诱发染色体不稳定性,而染色体不稳定性是癌症发生的驱动力。为了研究 X 射线对端粒完整性的影响,我们通过荧光原位杂交(端粒 FISH)检测了小鼠胚胎成纤维细胞中 X 射线诱导的端粒信号异常。这些异常可分为端粒额外信号(ETS)和端粒丢失信号(LTS)。结果表明,低剂量(0.3-0.5 Gy)的 X 射线能显著诱导 ETS,而不能诱导 LTS;当剂量超过 0.5 Gy 时,ETS 的诱导达到饱和。此外,过氧化氢处理也能诱导 ETS,但不能诱导 LTS。为了澄清自由基在诱导 ETS 中的作用,我们研究了抗坏血酸(AsA)对端粒 FISH 信号的影响,结果发现,AsA(5 mM,2 h)的前处理(而非后处理)能显著抑制 X 射线对 ETS 的诱导。重要的是,AsA 处理前后都不会影响 X 射线诱导的染色体畸变。这些结果表明,自由基诱导的 DNA 氧化损伤参与了 ETS 的诱导。此外,与 DNA 复制抑制剂蚜虫霉素联合处理会增强 X 射线诱导的 ETS。这一观察结果表明,端粒内的 DNA 氧化病变可能引发 DNA 复制压力,从而导致 X 射线照射诱导 ETS。基于这些结果,我们认为 ETS 是端粒结构中 DNA 氧化损伤的敏感生物标记。
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引用次数: 0
Comparison of external dose estimates using different retrospective dosimetry methods in the settlements located near Semipalatinsk Nuclear Test Site, Republic of Kazakhstan. 在哈萨克斯坦共和国塞米巴拉金斯克核试验场附近居民点使用不同回顾性剂量学方法进行的外剂量估计比较。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad082
Valeriy Stepanenko, Sergey Shinkarev, Andrey Kaprin, Kazbek Apsalikov, Sergey Ivanov, Peter Shegay, Evgenia Ostroumova, Ausrele Kesminiene, Alexandra Lipikhina, Viktoria Bogacheva, Kassym Zhumadilov, Masayoshi Yamamoto, Aya Sakaguchi, Satoru Endo, Nariaki Fujimoto, Bernd Grosche, Vladimir Iatsenko, Alla Androsova, Zukhra Apsalikova, Noriyuki Kawano, Masaharu Hoshi

For correct assessment of health risks after low-dose irradiation, calculation of radiation exposure estimates is crucial. To verify the calculated absorbed doses, instrumental methods of retrospective dosimetry are used. We compared calculated and instrumental-based estimates of external absorbed doses in the residents of Dolon, Mostik and Cheremushki villages, Kazakhstan, affected by the first nuclear weapon test performed at the Semipalatinsk Nuclear Test Site (SNTS) on August 29, 1949. The 'instrumental' doses were retrospectively estimated using the Luminescence Retrospective Dosimetry (LRD) and Electron Spin Resonance (ESR) methods. Correlation between the calculated individual cumulative external absorbed whole-body doses based on typical input data and ESR-based individual doses in the same people was strong (r = 0.782). It was even stronger between the calculated doses based on individual questionnaires' input data and the ESR-based doses (r = 0.940). Application of the LRD method is useful for validation of the calculated settlement-average cumulated external absorbed dose to air. Reconstruction of external exposure can be supplemented with the data from later measurements of soil contamination with long-lived radionuclides, such as, 137Cs. Our results show the reliability of the calculational method used for the retrospective assessment of individual external doses.

为了正确评估低剂量辐照后的健康风险,辐射照射估计的计算至关重要。为了验证计算的吸收剂量,使用回顾性剂量测定的仪器方法。我们比较了1949年8月29日在塞米巴拉金斯克核试验场(SNTS)进行的第一次核武器试验对哈萨克斯坦Dolon、Mostik和Cheremushki村居民外部吸收剂量的计算和基于仪器的估计。使用发光回顾性剂量法(LRD)和电子自旋共振(ESR)方法对“仪器”剂量进行回顾性估计。基于典型输入数据计算的个体累积外部吸收全身剂量与基于esr的同一人群个体剂量之间存在很强的相关性(r = 0.782)。基于个人问卷输入数据计算的剂量与基于esr的剂量之间的相关性更强(r = 0.940)。LRD法的应用有助于验证计算的沉降-平均累积外空气吸收剂量。外部暴露的重建可以用后来对土壤污染的长寿命放射性核素(如137Cs)的测量数据加以补充。我们的结果表明,用于个体外剂量回顾性评估的计算方法是可靠的。
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引用次数: 0
Real-time tumor-tracking radiotherapy with SyncTraX for primary liver tumors requiring isocenter shift†. SyncTraX实时肿瘤跟踪放疗治疗原发性肝肿瘤的等中心移位
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad088
Yusuke Uchinami, Naoki Miyamoto, Daisuke Abo, Ryo Morita, Koji Ogawa, Tatsuhiko Kakisaka, Ryusuke Suzuki, Tomohiko Miyazaki, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama

The SyncTraX series enables real-time tumor-tracking radiotherapy through the real-time recognition of a fiducial marker using fluoroscopic images. In this system, the isocenter should be located within approximately 5-7.5 cm from the marker, depending on the version, owing to the limited field of view. If the marker is placed away from the tumor, the isocenter should be shifted toward the marker. This study aimed to investigate stereotactic body radiotherapy (SBRT) outcomes of primary liver tumors treated with SyncTraX in cases where the isocenter was shifted marginally or outside the planning target volume (PTV). Twelve patients with 13 liver tumors were included in the analysis. Their isocenter was shifted toward the marker and was placed marginally or outside the PTV. The prescribed doses were generally 40 Gy in four fractions or 48 Gy in eight fractions. The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method. All patients completed the scheduled SBRT. The median distance between the fiducial marker and PTV centroid was 56.0 (interquartile range [IQR]: 52.7-66.7) mm. By shifting the isocenter toward the marker, the median distance between the marker and isocenter decreased to 34.0 (IQR: 33.4-39.7) mm. With a median follow-up period of 25.3 (range: 6.9-70.0) months, the 2-year OS and LC rates were 100.0% (95% confidence interval: 100-100). An isocenter shift makes SBRT with SyncTraX feasible in cases where the fiducial marker is distant from the tumor.

SyncTraX系列通过使用透视图像实时识别基准标记物,实现实时肿瘤跟踪放疗。在这个系统中,由于视野有限,根据版本的不同,等心应该位于距离标记大约5-7.5 cm的范围内。如果标记物被放置在远离肿瘤的地方,则等中心应向标记物移动。本研究旨在探讨SyncTraX治疗原发性肝肿瘤的立体定向体放疗(SBRT)结果,当等中心轻微移位或超出计划靶体积(PTV)时。12例13例肝脏肿瘤纳入分析。他们的等心向标记物移动,放置在PTV边缘或外面。处方剂量一般为40戈瑞,分4次或48戈瑞,分8次。采用Kaplan-Meier法计算总生存期(OS)和局部控制率(LC)。所有患者均完成了预定的SBRT。基准标记物与PTV质心之间的中位距离为56.0(四分位数间距[IQR]: 52.7-66.7) mm。通过将等中心向标记物移动,标记物与等中心之间的中位距离降至34.0 (IQR: 33.4-39.7) mm。中位随访时间为25.3(范围:6.9-70.0)个月,2年OS和LC率为100.0%(95%置信区间:100-100)。等中心移位使得SyncTraX联合SBRT在基准标志物离肿瘤较远的情况下可行。
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引用次数: 0
Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study. 每日剂量调整放疗策略避免延长早期声门鳞状细胞癌的总治疗时间:一项单机构回顾性研究。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad080
Yasuhiro Dekura, Koichi Yasuda, Hideki Minatogawa, Yusuke Uchinami, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takashi Mori, Kentaro Nishioka, Keiji Kobashi, Norio Katoh, Akihiro Homma, Hidefumi Aoyama

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.

本研究的目的是确定早期声门鳞状细胞癌(EGSCC)的根治性放疗的结果,在放疗期间增加放疗分数的策略,同时预计总治疗时间(OTT)会延长。研究纳入了2008年至2019年期间在北海道大学医院接受根治性放疗的临床诊断为T1-2N0M0 EGSCC的患者。我们的标准方案是T1组患者接受66 Gy,分33组治疗,T2组患者接受70 Gy,分35组治疗(常规组[UG])。如果预期OTT延长bb0.1周,则从放疗开始或放疗期间剂量分数大小从2.0 Gy增加到2.5 Gy(调整组[AG])。此时,我们对UG和AG进行了统计分析。共确定116例患者,调整29例患者的治疗方案。中位随访时间为60.9个月。T1组5年累积局部失败率AG为12.0%,UG为15.4%,T2组AG为40.7%,UG为25.3%。AG与UG之间无显著差异。同样,在总生存率和无进展生存率方面也没有观察到显著差异。我们对EGSCC患者的单机构回顾性分析表明,从开始或过程中调整放疗计划以增加分数大小的方法可能有效地维持治疗结果。
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引用次数: 0
Gamma-irradiated Aspergillus conidia show a growth curve with a reproductive death phase. γ射线照射的曲霉菌分生孢子显示出具有生殖死亡阶段的生长曲线。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad081
Shigetoshi Horikiri, Mami Harada, Ryoko Asada, Tetsuaki Tsuchido, Masakazu Furuta

In this study, we evaluated the effects of gamma irradiation on the germination of Aspergillus conidia and mycelial growth using microscopy and predictive microbiological modeling methods. A dose of 0.4 kGy reduced the germination rate by 20% compared to the untreated control, indicating interphase death due to the high radiation dose. The number of colonies formed (5.5%) was lower than the germination rate (69%), suggesting that most colonies died after germination. Microscopic observations revealed that mycelial elongation ceased completely in the middle of the growth phase, indicating reproductive death. The growth curves of irradiated conidia exhibited a delayed change in the growth pattern, and a decrease in slope during the early stages of germination and growth at low densities. A modified logistic model, which is a general purpose growth model that allows for the evaluation of subpopulations, was used to fit the experimental growth curves. Dose-dependent waveform changes may reflect the dynamics of the subpopulations during germination and growth. These methods revealed the occurrence of two cell death populations resulting from gamma irradiation of fungal conidia and contribute to the understanding of irradiation-induced cell death in fungi.

在本研究中,我们使用显微镜和预测微生物建模方法评估了伽马辐射对曲霉菌分生孢子萌发和菌丝生长的影响。与未处理的对照相比,0.4 kGy的剂量使发芽率降低了20%,表明由于高辐射剂量导致的间期死亡。形成的菌落数(5.5%)低于发芽率(69%),表明大多数菌落在发芽后死亡。显微镜观察表明,菌丝体的伸长在生长期中期完全停止,表明生殖死亡。辐照分生孢子的生长曲线在发芽和低密度生长的早期阶段表现出生长模式的延迟变化和斜率的降低。使用一个改进的逻辑模型来拟合实验生长曲线,该模型是一个通用的生长模型,可以评估亚群。剂量依赖性波形变化可能反映了亚群在发芽和生长过程中的动态。这些方法揭示了真菌分生孢子的伽马辐射导致的两个细胞死亡群体的发生,并有助于理解辐射诱导的真菌细胞死亡。
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引用次数: 0
MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature. MTDH通过促进基于预后特征的铁下垂来增强头颈部鳞状细胞癌的放射敏感性。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad074
Xiang Cao, Yizhi Ge, Zhenyu Yan, Xinyu Hu, Fanyu Peng, Yujie Zhang, Xia He, Dan Zong

Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan-Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.

电离辐射(IR)诱导头颈部鳞状细胞癌(HNSCC)的铁下垂。但是,尚不清楚铁下垂是否会影响HNSCC患者放疗后的预后。本研究旨在建立一种铁下垂特征来预测HNSCC的放射敏感性和预后。从ferdb数据库、the Cancer Genome Atlas和GEO数据库中获取铁中毒相关基因、临床数据和RNA表达谱。通过随机生存森林、单变量Cox回归、Kaplan-Meier和ROC分析确定预后基因。采用主成分分析、多变量Cox回归、nomogram和DCA分析来评估其预测能力。通过功能富集和免疫相关分析,探索潜在的生物学机制和肿瘤免疫微环境。通过流式细胞术、实时荧光定量PCR和克隆生存试验验证hub基因对铁下垂和放射敏感性的影响。我们构建了一个与铁中毒相关的特征,包括IL6、NCF2、metadherin (MTDH)和CBS。根据风险评分将患者分为高危组(HRisk)和低危组(low-risk)。风险评分被证实是总生存(OS)的独立预测因子。结合临床分期与风险评分,建立OS预测图。此外,HRisk主要富集与肿瘤发生和肿瘤免疫抑制相关的通路。MTDH被证实对ir诱导的铁下垂有有效的作用,从而促进了放射敏感性。我们构建了一个与铁中毒相关的特征来预测HNSCC患者的放射敏感性和OS。MTDH被认为是放射耐药HNSCC患者的一个有希望的治疗靶点。
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引用次数: 0
Development of local-power-free, remote α-particle detection using optical fibers. 基于光纤的局部无电源、远程α粒子检测技术的发展。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad092
Kent B Pfeifer, Thomas M Weber, James E Martin

We demonstrate the application of fluorescence optical fiber coupled to a telecom grade fiber as a sensor for alpha particles using alpha-specific ZnS(Ag) scintillation materials whose wavelength is down-shifted into a low-loss region of the telecom grade fiber transmission band. Telecom-grade fiber optics offer a solution for sensing alpha radiation in deep repositories and cask storage for radioactive materials due to the stability of SiO2 under normal environmental conditions and its relative radiation hardness at low radiation doses. Long-term nuclear waste storage facilities require sensors for the detection of leakage of radioactive materials that are maintenance-free, do not require power and can survive with no 'wear out' mechanisms for decades. By accomplishing the wavelength transformation, we maximize efficiencies in the detection of α-particles and signal transport and can detect alpha scintillation at distances on the order of >1 km with a sensor that is ~3% efficient and can be easily scaled as a sensor array. This paper describes the construction and testing of the sensor including manufacture of the controlled thickness films, verification of the wavelength shift from 450 to 620 nm and optimization of the sensitivity as a function of thickness. We also model the relative sensitivity of the film as a function of film thickness, and we demonstrate a signal-to-noise ratio of 10 at a range of greater than 1 km.

我们演示了将荧光光纤耦合到电信级光纤上作为α粒子传感器的应用,该传感器使用α特异性ZnS(Ag)闪烁材料,其波长被下移到电信级光纤传输频带的低损耗区域。由于SiO2在正常环境条件下的稳定性及其在低辐射剂量下的相对辐射硬度,电信级光纤为深库和桶储存放射性物质提供了一种感应α辐射的解决方案。长期核废料储存设施需要用于检测放射性物质泄漏的传感器,这些传感器无需维护,不需要电力,并且可以在没有“磨损”机制的情况下存活数十年。通过完成波长变换,我们最大限度地提高了α-粒子和信号传输的检测效率,并且可以在>1 km的距离上使用效率约为3%的传感器检测α闪烁,并且可以很容易地扩展为传感器阵列。本文介绍了传感器的结构和测试,包括控制厚度薄膜的制作,波长从450到620nm的位移验证以及灵敏度随厚度的函数的优化。我们还将薄膜的相对灵敏度建模为薄膜厚度的函数,并证明在大于1公里的范围内信噪比为10。
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引用次数: 0
Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study. 用调强放疗治疗头皮或面部血管肉瘤的临床结果:一项多中心研究
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad089
Takahiro Iwai, Toshiyuki Imagumbai, Shinya Hiraoka, Takahiro Kishi, Shun Okabayashi, Ryo Ashida, Takamasa Mitsuyoshi, Yukinori Matsuo, Takashi Ishigaki, Takashi Mizowaki, Masaki Kokubo

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

包括放射治疗(RT)在内的综合治疗是头皮或面部血管肉瘤的常用治疗方法。虽然调强放疗(IMRT)可以向头皮或面部提供均匀剂量,但临床数据有限。这项多中心研究旨在评估头皮或面部血管肉瘤接受最终或术后IMRT治疗的效果。我们回顾性分析了2015年1月至2020年3月在三家机构接受头皮或面部血管肉瘤IMRT治疗的患者的数据。评估局部控制率(LC)、总生存期(OS)、无进展生存期(PFS)、复发模式和毒性。15名患者在研究期间接受了IMRT。10例患者行终期放射治疗,5例患者行术后放射治疗。1年LC率为85.7%(95%可信区间[CI], 53.9-96.2%)。1年OS和PFS率分别为66.7% (95% CI, 37.5-84.6%)和53.3% (95% CI, 26.3%-74.4%)。单因素分析显示,临床靶体积大于500 cm3与LC不良相关。远处转移是最常见的复发方式。所有患者均发生2级或3级放射性皮炎,5例患者发生≥3级皮肤溃疡。一名接受帕唑帕尼维持治疗的患者出现5级皮肤溃疡。Fisher精确检验显示,术后RT与≥3级皮肤溃疡风险增加显著相关。这些结果表明,IMRT是头皮或面部血管肉瘤的一种可行和有效的治疗方法,尽管≥3级的皮肤溃疡是接受术后RT的患者常见的不良事件。
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引用次数: 0
Role of microbiota in radiation-induced small-bowel damage. 微生物群在辐射诱发的小肠损伤中的作用。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad084
Yi-Fan Chen, Sung-Chou Li, Eng-Yen Huang

Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.

辐射引起的胃肠损伤是一种常见的急性辐射综合征。先前的研究强调,半乳糖凝集素-1和白细胞介素-6 (IL-6)与小肠绒毛脱落和肠道放射抵抗有关。因此,我们的目标是研究受半乳糖凝集素-1或IL-6调节的肠道细菌是否可以减轻辐射引起的小肠损伤。在本研究中,通过微生物组阵列分析了半乳糖凝集素-1、sgp130调控和野生型(WT)小鼠之间的差异。观察18 Gy全腹辐射对厚壁菌门/拟杆菌门(F/B)比值及门水平细菌分布比例的影响。采用粪便菌群移植法在WT小鼠体内植入耐辐射肠道菌群,免疫组化观察存活小肠隐窝灶数量。将半乳糖凝集素-1基因敲除和sgp130基因转基因小鼠的粪便移植到WT小鼠体内,使其具有更高的辐射抗性,显著增加了小肠隐窝的存活数量。这种通过基因调控产生的抗辐射能力不受F/B比的影响。我们最初发现,接受耐辐射小鼠粪便细菌的WT小鼠的小肠绒毛在辐射暴露后表现出更好的修复结果。这些结果表明,有必要将重点放在鉴定和应用优良的耐辐射菌株上。在我们的实验室,我们将进一步研究特定的耐药菌株,以减轻放射治疗的急性副作用,提高患者的免疫能力和术后生活质量。
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引用次数: 0
An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy. 体积重扫和分割治疗对肝癌质子治疗剂量均匀性影响的研究。
IF 1.9 4区 医学 Q2 BIOLOGY Pub Date : 2024-01-19 DOI: 10.1093/jrr/rrad093
Pei-Yi Lee, Bing-Shen Huang, Shen-Hao Lee, Tsz-Yui Chan, Eric Yen, Tsair-Fwu Lee, I-Chun Cho

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, 'TOPAS,' and an image registration toolbox, 'Elastix,' to calculate 4D dose distributions from 5 patients' four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn't significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2-3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.

铅笔束扫描(PBS)技术在现代粒子治疗中提供了高度适形的剂量分布,但由于呼吸诱导的器官运动和PBS之间的相互作用而面临挑战。本研究评估了不同体积重扫描策略在肝癌质子治疗中减轻这种影响的有效性。我们使用基于geant4的蒙特卡罗模拟工具包“TOPAS”和图像配准工具箱“Elastix”来计算5名患者的四维计算机断层扫描(4DCT)的四维剂量分布。我们分析了临床肿瘤体积(CTV)在不同重新扫描次数和治疗时间下的均匀性指数(HI)值。我们的研究结果表明,剂量均匀性在治疗一周后稳定在低点,这意味着重新扫描和分步治疗都有助于减轻相互作用。值得注意的是,重新扫描次数的增加并没有显著降低正常组织的平均剂量,但有效地防止了CTV附近组织的高局部剂量。基于统计平均的重新扫描技术不需要额外的设备或患者的合作,因此可以广泛使用。然而,扫描次数、肿瘤位置、横膈膜运动和治疗分级显著影响其有效性。因此,在决定重扫描次数时,应考虑到光束数、治疗分数大小和总递送时间,以避免在没有显著临床效益的情况下不必要地延长治疗时间。结果显示,2-3个扫描在临床上更适合肝癌患者接受质子治疗。
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Journal of Radiation Research
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