Echinococcus multilocularis: the impact of ionizing radiation on metacestodes

Alveolar echinococcosis is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. Current chemotherapeutical options for the treatment of echinococcosis are not satisfactory, and novel drugs and/or other potential means of therapy are needed. E. multilocularis metacestodes are characterized by almost potentially unlimited growth, and also display other features of cancerous tumours. In this study, we exposed metacestodes that were generated in vitro to 50-100 Gy ionizing irradiation, and subsequently investigated the short-term (10-12 days post-treatment) and long-term (14 weeks post-treatment) effects. We found, that in the short-term, no release of alkaline phosphatase (EmAP) activity as a measure for potentially induced damage and loss of viability could be detected, and that the protein expression pattern and protease activities in vesicle fluids and medium supernatants did not alter dramatically following irradiation. However, irradiation was associated with distinct morphological and ultrastructural alterations in the tissue of metacestodes, affecting most notably cell-cell contacts, mitochondrial shape, glycogen-storage cells and lipid droplet formation. These could be detected already at 10 days following treatment and remained as such also in the long-term. In addition, as determined after 14 weeks of culture, irradiation affected the proliferation and the growth of E. multilocularis metacestodes. Thus, we demonstrate that radiotherapy does not have a clear-cut parasitocidal effect, but can lead to metabolic impairment of E. multilocularis metacestodes, as reflected by the distinct morphological and structural alterations induced by irradiation treatment.

Chalcone JAI-51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors

Microbeam radiation therapy (MRT), a preclinical form of radiosurgery, uses spatially fractionated micrometre-wide synchrotron-generated X-ray beams. As MRT alone is predominantly palliative for animal tumors, the effects of the combination of MRT and a newly synthesized chemotherapeutic agent JAI-51 on 9L gliosarcomas have been evaluated. Fourteen days (D14) after implantation (D0), intracerebral 9LGS-bearing rats received either MRT, JAI-51 or both treatments. JAI-51, alone or immediately after MRT, was administered three times per week. Animals were kept up to ∼20 weeks after irradiation or sacrificed at D16 or D28 after treatment for cell cycle analysis. MRT plus JAI-51 increased significantly the lifespan compared with MRT alone (p = 0.0367). JAI-51 treatment alone had no effect on rat survival. MRT alone or associated with JAI-51 induced a cell cycle blockade in G2/M (p < 0.01) while the combined treatment also reduced the proportion of G0/G1 cells. At D28 after irradiation, MRT and MRT/JAI-51 had a smaller cell blockade effect in the G2/M phase owing to a significant increase in tumor cell death rate (<2c) and a proportional increase of endoreplicative cells (>8c). The combination of MRT and JAI-51 increases the survival of 9LGS-bearing rats by inducing endoreduplication of DNA and tumor cell death; further, it slowed the onset of tumor growth resumption two weeks after treatment.

Statistical modeling of the eye for multimodal treatment planning for external beam radiation therapy of intraocular tumors

Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors.

Prognostic importance of Gleason 7 disease among patients treated with external beam radiation therapy for prostate cancer: results of a detailed biopsy core analysis

To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT).

Radiation exposure in whole-body computed tomography of multiple trauma patients: bearing devices and patient positioning

Whole-body computed tomography (WBCT) plays an important role in the management of severely injured patients. We evaluated the radiation exposure of WBCT scans using different positioning boards and arm positions.

Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing radiation exposure in nonhuman primates by mass spectrometry-based metabolomics

Mass spectrometry-based metabolomics has previously demonstrated utility for identifying biomarkers of ionizing radiation exposure in cellular, mouse and rat in vivo radiation models. To provide a valuable link from small laboratory rodents to humans, γ-radiation-induced urinary biomarkers were investigated using a nonhuman primate total-body-irradiation model. Mass spectrometry-based metabolomics approaches were applied to determine whether biomarkers could be identified, as well as the previously discovered rodent biomarkers of γ radiation. Ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry analysis was carried out on a time course of clean-catch urine samples collected from nonhuman primates (n = 6 per cohort) exposed to sham, 1.0, 3.5, 6.5 or 8.5 Gy doses of (60)Co γ ray (∼0.55 Gy/min) ionizing radiation. By multivariate data analysis, 13 biomarkers of radiation were discovered: N-acetyltaurine, isethionic acid, taurine, xanthine, hypoxanthine, uric acid, creatine, creatinine, tyrosol sulfate, 3-hydroxytyrosol sulfate, tyramine sulfate, N-acetylserotonin sulfate, and adipic acid. N-Acetyltaurine, isethionic acid, and taurine had previously been identified in rats, and taurine and xanthine in mice after ionizing radiation exposure. Mass spectrometry-based metabolomics has thus successfully revealed and verified urinary biomarkers of ionizing radiation exposure in the nonhuman primate for the first time, which indicates possible mechanisms for ionizing radiation injury.

The role of olfactory cues in the sequential radiation of a gall-boring beetle

Species diversity itself may cause additional species diversity. According to recent findings, some species modify their environment in such a way that they facilitate the creation of new niches for other species to evolve to fill. Given the vast speciesdiversity of insects, the occurrence of such sequential radiation of species is likely common among herbivorous insects and the species that depend on them, many of them being insects as well. Herbivorous insects often have close associations with specific host plants and their preferences for mating and ovipositing on a specific host-plant species can reproductively isolate host-specific populations, facilitating speciation. Previous research by our laboratory has established that there are two distinct populations of thegall fly, Eurosta solidaginis (Tephritidae), which attack different species of goldenrods, Solidago altissima (Asteraceae) and S. gigantea. The gall fly’s host-associated differentiation is facilitating the divergence and potential speciation of twosubpopulations of the gall-boring beetle Mordellistena convicta (Mordellidae) by providing new resources (galls on stems of the galdenrods) for the gall-boring beetles. These beetles exist as two host-plant associated populations of inquilines that inhabit the galls induced by the gall fly. While our previous research has provided genetic and behavioral evidence for host-race formation, little is known about the role of their host plants in assortative mating and oviposition-site selection of the gall-boring beetles’ hostassociated populations. Volatile emissions from host plants can play a major role in assisting herbivores to locate their natal host plants and thus facilitate assortative mating and host-specific oviposition. The present study investigated the role of host-plant volatiles in host fidelity (mating on the host plant) and oviposition preference of M. convicta by measuring its behavioral responses to the host-plant volatile emissions using Y-tube olfactometers. In total, we tested behavioral responses of 615 beetles. Our resultsshow that M. convicta adults are attracted to their natal host galls (67% of S. altissima-emerging beetles and 70% of S. gigantea-emerging beetles) and avoid the alternate host galls (75% of S. altissima-emerging beetles and 66% of S. gigantea-emerging beetles),while showing no preference for, or avoidance of, ungalled plants from either species. This suggests that the gall beetles can orient to the volatile chemicals emitted by the galls and can potentially use them to identify suitable sites for mating and/or oviposition. Thus, host-associated mating and oviposition may play a role in the sequential speciation of the gall-boring beetle.

Paleoenvironment and Paleoecology of a Late Paleocene High-Latitude Terrestrial Succession, Arkose Ridge Formation at Box Canyon, Southern Talkeetna Mountains, Alaska

Paleogene sedimentary rocks of the Arkose Ridge Formation (Talkeetna Mountains, Alaska) preserve a record of a fluvial-lacustrine depositional environment and its forested ecosystem in an active basin among the convergent margin tectonic processes that shaped southern Alaska. An -800 m measured succession at Box Canyon indicates braid-plain deposition with predominantly gravelly deposits low in the exposure to sandy and muddy facies associations below an overlying lava flow sequence. U-Pb geochronology on zircons from a tuff and a sandstone within the measured section, as well as an Ar/Ar date from the overlying lava constrain the age of the sedimentary succession to between similar to 59 Ma and 48 Ma Fossil plant remains occur throughout the Arkose Ridge Formation as poorly-preserved coalified woody debris and fragmentary leaf impressions. At Box Canyon, however, a thin la-custrine depositional lens of rhythmically laminated mudrocks yielded fish fossils and a well-preserved floral assemblage including foliage and reproductive organs representing conifers, sphenopsids, monocots, and dicots. Leaf physiognomic methods to estimate paleoclimate were applied to the dicot leaf collection and indicate warm temperate paleotemperatures (-11-15 +/- -4 degrees C MAT) and elevated paleoprecipitation (-120 cm/yr MAP) estimates as compared to modem conditions; results that are parallel with previously published estimates from the partly coeval Chickaloon Formation deposited in more distal depositional environments in the same basin. The low abundance of leaf herbivory in the Box Canyon dicot assemblage (-9% of leaves damaged) is also similar to the results from assemblages in the meander-plain depositional systems of the Chickaloon. This new suite of data informs models of the tectonostratigraphic evolution of southern Alaska and the developing understanding of terrestrial paleoecology and paleoclimate at high latitudes during the Late Paleocene-Early Eocene greenhouse climate phase. (c) 2014 Elsevier B.V. All rights reserved.

The role of radiation therapy in resected T2 N0 esophageal cancer: a population-based analysis

The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy.