Contrast-enhanced, conebeam CT-based, fractionated radiotherapy and follow-up monitoring of orthotopic mouse glioblastoma: a proof-of-concept study.

Background: Despite aggressive treatment regimens comprising surgery and radiochemotherapy, glioblastoma (GBM) remains a cancer entity with very poor prognosis. The development of novel, combined modality approaches necessitates adequate preclinical model systems and therapy regimens that closely reflect the clinical situation. So far, image-guided, fractionated radiotherapy of orthotopic GBM models represents a major limitation in this regard.

Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice.

AEOL 10150 is a catalytic metalloporphyrin superoxide dismutase mimic being developed as a medical countermeasure for radiation-induced lung injury (RILI). The efficacy of AEOL 10150 against RILI through a reduction of oxidative stress, hypoxia and pro-apoptotic signals has been previously reported. The goal of this study was to determine the most effective dose of AEOL 10150 (daily subcutaneous injections, day 1-28) in improving 180-day survival in CBA/J mice after whole-thorax lung irradiation (WTLI) to a dose of 14.

High LET (56)Fe ion irradiation induces tissue-specific changes in DNA methylation in the mouse.

DNA methylation is an epigenetic mechanism that drives phenotype and that can be altered by environmental exposures including radiation. The majority of human radiation exposures occur in a relatively low dose range; however, the biological response to low dose radiation is poorly understood. Based on previous observations, we hypothesized that in vivo changes in DNA methylation would be observed in mice following exposure to doses of high linear energy transfer (LET) (56) Fe ion radiation between 10 and 100 cGy.

The effect of radiation quality on genomic DNA methylation profiles in irradiated human cell lines.

It has been acknowledged for many years that radiation exposure induces delayed, non-targeted effects in the progeny of the irradiated cell. Evidence is beginning to demonstrate that among these delayed effects of radiation are epigenetic aberrations, including altered DNA methylation. To test the hypothesis that differences in radiation quality affect radiation-induced DNA methylation profiles, normal AG01522 and RKO colon carcinoma cells were exposed to low-LET X rays and protons or high-LET iron ions.

Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells.

Purpose: To investigate radiation-induced bystander responses and to determine the role of gap junction intercellular communication and the radiation environment in propagating this response.

Materials And Methods: We used medium transfer and targeted irradiation to examine radiation-induced bystander effects in primary human fibroblast (AG01522) and human colon carcinoma (RKO36) cells. We examined the effect of variables such as gap junction intercellular communication, linear energy transfer (LET), and the role of the radiation environment in non-targeted responses.

Amifostine metabolite WR-1065 disrupts homologous recombination in mammalian cells.

Repair of DNA damage through homologous recombination (HR) pathways plays a crucial role in maintaining genome stability. However, overstimulation of HR pathways in response to genotoxic stress may abnormally elevate recombination frequencies, leading to increased mutation rates and delayed genomic instability. Radiation-induced genomic instability has been detected after exposure to both low- and high-linear energy transfer (LET) radiations, but the mechanisms responsible for initiating or propagating genomic instability are not known.

Heavy ions, radioprotectors and genomic instability: implications for human space exploration.

The risk associated with space radiation exposure is unique from terrestrial radiation exposures due to differences in radiation quality, including linear energy transfer (LET). Both high- and low-LET radiations are capable of inducing genomic instability in mammalian cells, and this instability is thought to be a driving force underlying radiation carcinogenesis. Unfortunately, during space exploration, flight crews cannot entirely avoid radiation exposure.

WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability.

Compounds that can protect cells from the effects of radiation are important for clinical use, in the event of an accidental or terrorist-generated radiation event, and for astronauts traveling in space. One of the major concerns regarding the use of radio-protective agents is that they may protect cells initially, but predispose surviving cells to increased genomic instability later. In this study we used WR-1065, the active metabolite of amifostine, to determine how protection from direct effects of high- and low-LET radiation exposure influences genomic stability.

Ancestral organization of the MHC revealed in the amphibian Xenopus.

With the advent of the Xenopus tropicalis genome project, we analyzed scaffolds containing MHC genes. On eight scaffolds encompassing 3.65 Mbp, 122 MHC genes were found of which 110 genes were annotated.