Abscopal mutagenic effect of low-energy-ions in Arabidopsis Thaliana seeds

Abstract

Purpose: To demonstrate the abscopal mutagenic effect of low-energy-ion irradiation in dormant plant seeds, and its dependence on the targeted portion of seeds.

Materials and methods: Arabidopsis thaliana-lines transgenic for b-glucuronidase (GUS) recombination substrates and A. thaliana RADiation54 (AtRAD54) promoter::GUS were adopted. The seeds were irradiated from four specialised orientations with 30 KeV ⁴⁰Ar⁺ ions. The homologous recombination frequency (HRF) and the expression levels of the AtRAD54 genein non-irradiated aerial plants were measured. Moreover, several post-embryonic developments, such as growth of primary roots, differentiation of root hairs, and germination of seeds and growth of true leaves, were also analysed.

Results: It was shown that low-energy-ion irradiation of seeds led to significant increases in HRF in the non-irradiated aerial parts of irradiated plants and the aerial parts of naïve plants from irradiated progenitors. The low-energy-ion irradiation was also shown to induce an elevated expression of AtRAD54 gene in aerial plants, and to inhibit the post-embryonic developments of seeds. Moreover, the changes in HRF, expression level of the AtRAD54 gene and post-embryonic developments depended largely on the orientation of seeds with regard to low-energy-ion irradiation; and the root apical meristem (RAM)-orientated irradiation exhibited the largest effects on all biological endpoints assayed here.

Conclusions: Low-energy-ion irradiation can induce an abscopal mutagenic effect in dormant plant seeds, the extent of which depends greatly on the targeted portion of seeds.     

Toward electron-beam sterilization of a pre-assembled Boston keratoprosthesis

PurposeTo evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization.MethodsHuman donor corneas and corneas pre-assembled in BK devices were immersed in recombinant human serum albumin (rHSA) media and E-beam irradiated at 25 kGy. Mechanical (tensile strength and modulus, and compression modulus), chemical, optical, structural, and degradation properties of the corneal tissue after irradiation and after 6 months of preservation were evaluated.ResultsThe mechanical evaluation showed that E-beam irradiation enhanced the tensile and compression moduli of human donor corneas, with no impact on their tensile strength. By chemical and mechanical analysis, E-beam irradiation caused a minor degree of crosslinking between collagen fibrils. No ultrastructural changes due to E-beam irradiation were observed. E-beam irradiation slightly increased the stability of the cornea against collagenase-induced degradation and had no impact on glucose diffusion. The optical evaluation showed transparency of the cornea was maintained. E-beam irradiated corneal tissues and BK-cornea pre-assembled devices were stable for 6 months after room-temperature preservation.ConclusionsE-beam irradiation generated no detrimental effects on the corneal tissues or BK-cornea pre-assembled devices and improved native properties of the corneal tissue, enabling prolonged preservation at room temperature. The pre-assembly of BK in a donor cornea, followed by E-beam irradiation, offers the potential for an off-the-shelf, ready to implant keratoprosthesis device.     

mTOR通路激活后上调SNCG表达水平抑制 乳腺癌细胞辐射 敏感性的研究

目的：探讨乳腺癌T47D细胞通过激活mTOR通路调控SNCG表达水平，从而抑制乳腺癌细胞辐射敏感性的分子机制。方法：检测不同剂量γ射线照射后的T47D乳腺癌细胞中mTOR蛋白表达水平。在细胞培养液中加入不用浓度磷脂酸（PA，mTOR通路激活剂）进行培养，以常规培养细胞为对照组，采用Western blot法检测对照组和激活剂组细胞SNCG蛋白的表达。对照组和激活组细胞采用4 Gy γ射线照射24 h，检测照射后SNCG mRNA和蛋白的表达情况，并采用平板细胞克隆形成实验检测克隆形成率。同时，将转染SNCG siRNA的乳腺癌T47D细胞株分成激活组和对照组，验证SNCG在乳腺癌细胞辐射敏感性抵抗中的生物学功能。结果：不同剂量射线照射后，mTOR蛋白表达水平显著升高。mTOR激活剂PA处理后的细胞对乳腺癌细胞放射敏感性具有明显的抑制作用，同时Western blot显示γ射线照射处理后的乳腺癌细胞中SNCG蛋白的表达水平异常。Western blot和qPCR方法检测发现，T47D对照组和干扰SNCG基因的T47D细胞实验组中，激活mTOR或γ射线照射均能引起SNCG蛋白和mRNA表达增加。克隆形成实验进一步证明，降低SNCG的表达可显著抑制T47D细胞克隆形成能力。结论：在乳腺癌细胞中，mTOR介导的SNCG表达调控对乳腺癌细胞抗辐射起着重要作用，降低SNCG的表达可提高辐射敏感性，提示在临床治疗中有可能通过使用SNCG抑制剂或mTOR抑制剂提高乳腺癌细胞在放化疗中的敏感性。     

Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review

BackgroundThe head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted.MethodsPubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated.ResultsEleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0–5.9%, 95% CI 1.6–3.5%). The incidence of cRF correlated only with T-stage (p = 0.008), and involvement of midline (p = 0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p = 0.344).ConclusionThe incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups.     

The dosimetric impact of respiratory breast movement and daily setup error on tangential whole breast irradiation using conventional wedge,field-in-field and irregular surface compensator techniques

To evaluate the dosimetric impact of respiratory breast motion and daily setup error on whole breast irradiation (WBI) using three irradiation techniques; conventional wedge (CW), field-in-field (FIF) and irregular surface compensator (ISC). WBI was planned for 16 breast cancer patients. The dose indices for evaluated clinical target volume (CTV_evl), lung, and body were evaluated. For the anterior-posterior (AP) respiratory motion and setup error of a single fraction, the isocenter was moved according to a sine function, and the dose indices were averaged over one period. Furthermore, the dose indices were weighted according to setup error frequencies that have a normal distribution to model systematic and random setup error for the entire treatment course. In all irradiation techniques, AP movement has a significant impact on dose distribution. CTV_evlD₉₅ (the minimum relative dose that covers 95 % volume) and V₉₅ (the relative volume receiving 95 % of the prescribed dose) were observed to significantly decrease from the original ISC plan when simulated for the entire treatment course. In contrast, the D₉₅, V₉₅ and dose homogeneity index did not significantly differ from those of the original plans for FIF and CW. With regard to lung dose, the effect of motion was very similar among all three techniques. The dosimetric impact of AP respiratory breast motion and setup error was largest for the ISC technique, and the second greatest effect was observed with the FIF technique. However, these variations are relatively small.     

Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long‐established ones. This retrospective matched‐pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa‐based (n = 121) or a cyclophosphamide/total body irradiation‐based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA‐matched sibling or an unrelated donor. With a median follow‐up of 44 months, the outcome was similar in both groups. Acute graft‐versus‐host disease grade II‐IV was observed in 25% after thiotepa‐containing regimen versus 35% after TBI (P = 0.06). The 2‐yr cumulative incidence of chronic graft‐versus‐host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non‐relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia‐free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.     

A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fields and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans.