Search

Exposure to high levels of radiation can cause acute, long-term health effects, such as acute radiation syndrome, cancer, and cardiovascular disease. This is an important occupational hazard in different fields, such as the aerospace and healthcare industry, as well as a crucial burden to overcome to boost space applications and exploration. Protective bulky equipment made of heavy metals is not suitable for many advanced purporses, such as mobile devices, wearable shields, and manned spacecrafts. In the latter case, the in-space manufacturing of protective shields is highly desirable and remains an unmet need. Composites made of polymers and high atomic number fillers are potential means for radiation protection due to their low weight, good flexibility, and good processability. In the present work, we developed electrospun composites based on polycaprolactone (polymer matrix) and tungsten powder for application as shielding materials. Electrospinning is a versatile technology that is easily scalable at an industrial level and allows obtaining very lightweight, flexible sheet materials for wearables. By controlling tungsten powder size, we engineered homogeneous, stable and processable suspensions to fabricate radiation composite shielding sheets. The shielding capability was assessed by an in vivo model on prototype composite sheets containing 80 w% of W filler in a polycaprolactone (PCL) fibrous matrix by means of irradiation tests (X-rays) on mice. The obtained results are promising; as expected, the shielding effectivity of the developed composite material increases with the thickness/number of stacked layers. It is worth noting that a thin barrier consisting of 24 layers of the innovative shielding material reduces the extent of apoptosis by 1.5 times compared to the non-shielded mice. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a phytoestrogen-containing standardized soy extract (SSE) on the growth of nonsmall cell lung cancer (NSCLC; A549) xenografts in female athymic mice. Tumor-bearing mice received either sterile water or SSE [50 or 100 mg/(kg-d), per os], 5 d/wk, until the mean tumor weight in each group was at least 900 mg. Treatment with SSE reduced tumor growth in the high-dose group compared with control (P < 0.01 ); tumors in both treated groups had reduced proliferation and greater apoptosis compared with controls (P < 0.05). SSE treatment also induced diffuse central necrosis, reducing the viable tissue mass within the tumor. Whereas tumor levels of epidermal growth factor receptor were comparable in control and treated mice, the expression of phosphorylated protein kinase B (p-Akt) was lower in tumors of mice treated with 100 mg SSE/(kg.d) than in controls (P < 0.01). The protein level of phosphorylated mitogen-activated protein kinase also tended to be lower (P = 0.07) in this group than in controls. Estrogen receptor (ER)[alpha] and ER[beta] were present in tumors, but their expression levels did not differ among groups. Serum insulin-like growth factor-1 concentrations also were not affected by the treatments. In conclusion, we found that soy phytochemicals slow the in vivo growth of NSCLC xenografts; the modulation of the Akt-signaling pathway observed in tumors of SSE-treated mice may have a role in the activity observed. Our research provides further support for the concept that consumption of phytoestrogens may be effective in delaying lung cancer progression.

While most of the evidence for radiation-induced late health effects relates to cancer, there has been increasing interest recently in the development of non-cancer diseases, including lens opacity, observed in populations exposed to low-dose radiation. In a recent study, we reported that mice heterozygous for the Patched1 ( Ptch1) gene represented a novel and powerful animal model for this disorder, and a useful tool for investigating the mechanisms of radiogenic cataract development. Given the ongoing and considerable uncertainty in allowable lens dose levels and the existence of a threshold for the development of cataracts, we tested the effects of a decreasing range of radiation doses (2 Gy, 1 Gy and 0.5 Gy X rays) by irradiating groups of Ptch1+/- mice at 2 days of age. Our findings showed that at this dose range, acute exposure of this highly susceptible mouse model did not induce macroscopically detectable cataracts, and only the 2 Gy irradiated mice showed microscopic alterations of the lens. Molecular analyses performed to evaluate the induction of epithelial-mesenchymal transition (EMT) and subsequent fibrotic alterations in mouse lens cells also indicated the existence of a dose threshold for such effects in the mouse model used. The mechanisms of cataractogenesis remain unclear, and further experimental studies are essential to elucidate those mechanisms specific for cataract initiation and development after irradiation, as well as the underlying genetic factors controlling cataract susceptibility. [ABSTRACT FROM AUTHOR]

With the aim to illustrate to the students what really happens in a radiobiology's laboratory, a virtual lab was created. Through an interactive simulation of both X-ray generator and mouse models, the students can expand their knowledge about the biological effects induced by ionizing radiation using new pedagogical and technological strategies. The realized multimedia product has also been inserted as a case study to promote a deeper interaction between e-learning and research. The carcinogenic effects of ionizing radiation are induced by a direct irradiation of DNA molecule, but also by not direct cells and tissues exposure (so called: Abscopal effects). Ionizing radiation exposure can also induce non-cancer effects. In this context, genetically engineered radiation-susceptible mouse models represent a powerful tool to improve both understanding of radiation effects and assessment of cancer and non-cancer risks from ionizing radiation exposure. Our research field is focused on the study of high-impact human health-related pathologies such as: Medulloblastoma, Basal Cell Carcinoma, Lens opacities and Cardiovascular disease. [ABSTRACT FROM AUTHOR]

The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present study has focused on the evaluation of the prognostic value of ERa, ERß1, ERß2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ERa/ERß1 and ERa/ERß2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ERa alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ERa/ERß1 ratio of 1 or less or an ERa/ERß2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67. In conclusion, we report here that the ERa/ERß1 and ERa/ERß2 expression ratios are independent prognostic markers of survival in endometrioid endometrial cancer; these findings suggest that phenotyping these interacting markers conjointly may better predict patient survival than each individual marker alone. [ABSTRACT FROM AUTHOR]

It has historically been accepted that incorrectly repaired DNA double strand breaks (DSBs) are the principal lesions of importance regarding mutagenesis, and long-term biological effects associated with ionizing radiation. However, radiation may also cause dysregulation of epigenetic processes that can lead to altered gene function and malignant transformation, and epigenetic alterations are important causes of miRNAs dysregulation in cancer.Patched1 heterozygous (Ptch1+/-) mice, characterized by aberrant activation of the Sonic hedgehog (Shh) signaling pathway, are a well-known murine model of spontaneous and radiation-induced medulloblastoma (MB), a common pediatric brain tumor originating from neural granule cell progenitors (GCPs). The high sensitivity of neonatal Ptch1+/- mice to radiogenic MB is dependent on deregulation of the Ptch1 gene function. Ptch1 activates a growth and differentiation programme that is a strong candidate for regulation through the non-coding genome. Therefore we carried out miRNA next generation sequencing in ex vivo irradiated and control GCPs, isolated and purified from cerebella of neonatal WT and Ptch1+/- mice. We identified a subset of miRNAs, namely let-7 family and miR-17~92 cluster members, whose expression is altered in GCPs by radiation alone, or by synergistic interaction of radiation with Shh-deregulation. The same miRNAs were further validated in spontaneous and radiation-induced MBs from Ptch1+/- mice, confirming persistent deregulation of these miRNAs in the pathogenesis of MB.Our results support the hypothesis that miRNAs dysregulation is associated with radiosensitivity of GCPs and their neoplastic transformation in vivo.

Neural stem cells are highly susceptible to radiogenic DNA damage, however, little is known about their mechanisms of DNA damage response (DDR) and the long-term consequences of genotoxic exposure. Patched1 heterozygous mice (Ptc1(+/-)) provide a powerful model of medulloblastoma (MB), a frequent pediatric tumor of the cerebellum. Irradiation of newborn Ptc1(+/-) mice dramatically increases the frequency and shortens the latency of MB. In this model, we investigated the mechanisms through which multipotent neural progenitors (NSCs) and fate-restricted progenitor cells (PCs) of the cerebellum respond to DNA damage induced by radiation, and the long-term developmental and oncogenic consequences. These responses were assessed in mice exposed to low (0.25 Gy) or high (3 Gy) radiation doses at embryonic day 13.5 (E13.5), when NSCs giving rise to the cerebellum are specified but the external granule layer (EGL) has not yet formed, or at E16.5, during the expansion of granule PCs to form the EGL. We found crucial differences in DDR and apoptosis between NSCs and fate-restricted PCs, including lack of p21 expression in NSCs. NSCs also appear to be resistant to oncogenesis from low-dose radiation exposure but more vulnerable at higher doses. In addition, the pathway to DNA repair and the pattern of oncogenic alterations were strongly dependent on age at exposure, highlighting a differentiation-stage specificity of DNA repair pathways in NSCs and PCs. These findings shed light on the mechanisms used by NSCs and PCs to maintain genome integrity during neurogenesis and may have important implications for radiation risk assessment and for development of targeted therapies against brain tumors., (Copyright © 2013 AlphaMed Press.)

Medulloblastoma (MB) is the most common pediatric tumor of the CNS, representing ∼20% of all childhood CNS tumors. Although in recent years many molecular mechanisms that control MB development have been clarified, the effects of biological factors such as sex on this tumor remain to be explained. Epidemiological data, in fact, indicate a significant difference in the incidence of MB between the 2 sexes, with considerably higher susceptibility of males than females. Besides this different susceptibility, female sex is also a significant favorable prognostic factor in MB, with girls having a much better outcome. Despite these literature data, there has been little investigation into estrogen influence on MB development. In our study, we evaluated how hormone deficiency resulting from ovariectomy and hormone replacement influences the development of early and advanced MB stages in Patched1 heterozygous mice, a well-characterized mouse model of radiation-induced MB. Susceptibility to MB development was significantly increased in ovariectomized Ptch1(+/-) females and restored to levels observed in control mice after estrogen replacement. We next investigated the molecular mechanisms by which estrogen might influence tumor progression and show that ERβ, but not ERα, is involved in modulation of MB development by estrogens. Finally, our study shows that a functional interaction between estrogen- and IGF-I-mediated pathways may be responsible for the effects observed., (Copyright © 2010 UICC.)