Abstract
BACKGROUND
Radiotherapy, combined with surgical resection and chemotherapy, remains a first-line treatment for infiltrative gliomas. However, these tumors are not surgically curable, and ...often recur, even within the prior radiation field, and may demonstrate a more aggressive phenotype. Importantly, high grade gliomas display diverse molecular phenotypes, and whether this genetic variability leads to divergent behaviour in the radiated tumor microenvironment is unknown. Herein, we characterize the effects of the irradiated brain microenvinroment on nine additional unique GBM cell lines to better understand the nuances of how tumor molecular phenotypes influence cellular dynamics.
METHODS
Female athymic nude mice were randomly divided into cranial radiation (15 Gy) and non-radiated groups. Mice then underwent intracranial implantation with one of the selected patient-derived xenograft (PDX) GBM cell lines (GBM 6, 10, 12, 39, 46, 76, 123, 164, 196; total n=8-15, per group, per line). Kaplan-Meyer (K-M) and log-rank tests were performed to compare the survival between irradiated and non-irradiated groups.
RESULT
Of nine previously untested human GBM lines, we found that five demonstrated shorter survival in the pre-radiated brain (GBM 6, 46, 76, 164, 196). However, two lines yielded prolonged survival in the pre-radiated brain (GBM 10, 12); GBM 39, 123 whose rate of growth was not impacted by the radiated brain.
CONCLUSION
These results highlight the likely critical impact of the irradiated microenvironment on tumor behaviour, yet illustrate that different tumors may exhibit opposing responses. Although further evaluation will be needed to understand mechanisms of divergent behavior, our data suggest the increased rate of growth in the radiated microenvironment may not apply to the fastest-growing tumor lines, which could instead demonstrate a paradoxical response.
To investigate the radiation-induced abscopal effect in terms of oxidative stress, apoptosis and DNA damage in the spleen cells following cranial X-rays irradiation of rats.
Rats were cranially ...irradiated using 2 Gy X-rays. Another group was whole-body irradiated with 2 Gy X-rays and a third group was exposed to scattered radiation (measured to be 3 mGy). 24 hours following irradiation, sections from the spleen of the rats were dissected as well as plasma samples. The samples were examined for the desired endpoints.
The cranially irradiated animals showed a significant increase in the levels of glutathione, superoxide dismutase and catalase with no significant change in the lipid peroxidation product in the spleen cells with a significant increase in the C-reactive protein level the plasma. Apoptotic cell death in the spleen cells was demonstrated as indicated by the decrease of Bcl-2; the increase of p53, Bax, caspase-3 and caspase-8 and induction of DNA damage in the spleen in both of the cranially irradiated rats and whole body exposed rats. The exposure to 3 mGy scattered radiation increased the plasma level of C-RP and also induced apoptosis in the spleen cells.
Cranial irradiation-induced abscopal effect in distant spleen cells. Very low doses of radiation can induce apoptosis in the spleen cells. Advances in knowledge: This paper provides an evidence on the incidence of radiation abscopal effect. Also, the results shed light of the effect very low doses of radiation as low as 3 mGy.
Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept ...of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even though there is now a large number of animal studies demonstrating its marked therapeutic potential with an exceptional normal tissue sparing effect. Furthermore, MRT is conceptually similar to macroscopic grid based radiation therapy which has been used in clinical practice for decades. In this review, the potential clinical applications of MRT are analysed for both malignant and non-malignant diseases.
Radiation dose is central to much of radiobiological research. Precision and accuracy of dose measurements and reporting of the measurement details should be sufficient to allow the work to be ...interpreted and repeated and to allow valid comparisons to be made, both in the same laboratory and by other laboratories. Despite this, a careful reading of published manuscripts suggests that measurement and reporting of radiation dosimetry and setup for radiobiology research is frequently inadequate, thus undermining the reliability and reproducibility of the findings. To address these problems and propose a course of action, the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Standards and Technology (NIST) brought together representatives of the radiobiology and radiation physics communities in a workshop in September, 2011. The workshop participants arrived at a number of specific recommendations as enumerated in this paper and they expressed the desirability of creating dosimetry standard operating procedures (SOPs) for cell culture and for small and large animal experiments. It was also felt that these SOPs would be most useful if they are made widely available through mechanism(s) such as the web, where they can provide guidance to both radiobiologists and radiation physicists, be cited in publications, and be updated as the field and needs evolve. Other broad areas covered were the need for continuing education through tutorials at national conferences, and for journals to establish standards for reporting dosimetry. This workshop did not address issues of dosimetry for studies involving radiation focused at the sub-cellular level, internally-administered radionuclides, biodosimetry based on biological markers of radiation exposure, or dose reconstruction for epidemiological studies.
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