International journal of radiation biology最新文献

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.

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.

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

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.

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.

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.

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 LD_70/30 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.

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.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo.

Methods: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo.

Results: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect.

Conclusion: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Purpose: A U. S. and European joint effort fostering the development of medical countermeasures (MCMs) operable in case of radiological or nuclear emergencies.

Methods: Based on the joint engagement between the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the French Institut de Radioprotection et de Sûreté Nucléaire (IRSN), a Statement of Intent to Collaborate was signed in 2014 and a series of working group meeting were established. In December 2022, the NIAID and IRSN hosted a five-day, U.S./European meeting titled 'Radiation-Induced Cutaneous and Gastrointestinal Injuries: Advances in Understanding Pathologies, Assessment, and Clinically Accepted Practices' in Paris, France. The goals of the meeting were to bring together U.S. and European investigators to explore new research avenues for the medical management of skin and gastrointestinal injuries, including specific diagnostics for each organ system, animal models, and promising medical countermeasures (MCMs) to mitigate radiation damage. There was also an emphasis on exploring additional areas of medicine and response to understand best practices from other emergency scenarios, which could be leveraged to improve radiation preparedness, and the importance of accurate dosimetry in preclinical work.

Results: Subsequent to the workshop, seven collaborative projects, funded by both organizations, were established on topics ranging from MCMs and predictive biomarkers, and using physical methods to assess cutaneous radiation injuries, to mechanistic studies to understand radiation-induced damage in multiple organ systems. The importance of accurate dosimetry in preclinical works was highlighted and two recently published U.S./European commentaries that focus on the need for dosimetry standardization in the reported literature had their origins in this meeting. This commentary summarizes the workshop and open discussions among academic investigators, industry researchers, and U.S. and IRSN program representatives.

Conclusions: Given the substantive progress made due to these interactions, both groups plan to expand out these meetings by incorporating high-level investigators from across the globe, while endeavoring to maintain the informal setting that was conducive to in-depth scientific discussion and enhanced the state of the science in radiation research.