Interferon signaling is enhanced by ATR inhibition in glioblastoma cells irradiated with X-rays, protons or carbon ions.

Background And Purpose: Interferon (IFN) signaling plays an important role in antitumor immune responses. Inhibitors of the DNA damage response, such as ATR inhibitors, can increase IFN signaling upon conventional radiotherapy with X-rays. However, it is not known whether such inhibitors also enhance IFN signaling after irradiation with high linear energy transfer (LET) particles.

Combination of proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers.

Combining radiation therapy with immunotherapy is a strategy to improve both treatments. The purpose of this study was to compare responses for two syngeneic head and neck cancer (HNC) tumor models in mice following X-ray or proton irradiation with or without immune checkpoint inhibition (ICI). MOC1 (immunogenic) and MOC2 (less immunogenic) tumors were inoculated in the right hind leg of each mouse (C57BL/6J, n = 398).

TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model.

Purpose: Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-β) family are key players in the fibrotic response. While TGF-β1 is known to be pro-fibrotic, TGF-β3 has mainly been considered anti-fibrotic.

Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters.

Background: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models.

Methods: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013.

Cytokine Levels in Saliva Are Associated with Salivary Gland Fibrosis and Hyposalivation in Mice after Fractionated Radiotherapy of the Head and Neck.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days.

Backscatter from therapeutic doses of ionizing irradiation does not impair cell migration on titanium implants in vitro.

Objective: The influence of radiation backscatter from titanium on DNA damage and migration capacity of human osteoblasts (OBs) and mesenchymal stem cells (MSCs) may be critical for the osseointegration of dental implants placed prior to radiotherapy. In order to evaluate effects of radiation backscatter, the immediate DNA damage and migration capacity of OBs and MSCs cultured on titanium or plastic were compared after exposure to ionizing irradiation.

Materials And Methods: Human OBs and MSCs were seeded on machined titanium, moderately rough fluoride-modified titanium, or tissue culture polystyrene, and irradiated with nominal doses of 2, 6, 10, or 14 Gy.

The dose-dependent impact of γ-radiation reinforced with backscatter from titanium on primary human osteoblasts.

In head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM).

The Role of TGF-β3 in Radiation Response.

Transforming growth factor-beta 3 (TGF-β3) is a ubiquitously expressed multifunctional cytokine involved in a range of physiological and pathological conditions, including embryogenesis, cell cycle regulation, immunoregulation, and fibrogenesis. The cytotoxic effects of ionizing radiation are employed in cancer radiotherapy, but its actions also influence cellular signaling pathways, including that of TGF-β3. Furthermore, the cell cycle regulating and anti-fibrotic effects of TGF-β3 have identified it as a potential mitigator of radiation- and chemotherapy-induced toxicity in healthy tissue.

2D mapping of radiation dose and clonogenic survival for accurate assessment ofX-ray GRID irradiation effects.

Spatially fractionated radiation therapy (SFRT or GRID) is an approach to deliver high local radiation doses in an 'on-off' pattern. To better appraise the radiobiological effects from GRID, a framework to link local radiation dose to clonogenic survival needs to be developed. A549 lung cancer cells were irradiated in T25 cmflasks using 220 kV x-rays with an open field or through a tungsten GRID collimator with periodical 5 mm openings and 10 mm blockings.

Sharp dose profiles for high precision proton therapy using strongly focused proton beams.

The main objective of radiotherapy is to exploit the curative potential of ionizing radiation while inflicting minimal radiation-induced damage to healthy tissue and sensitive organs. Proton beam therapy has been developed to irradiate the tumor with higher precision and dose conformity compared to conventional X-ray irradiation. The dose conformity of this treatment modality may be further improved if narrower proton beams are used.

Low-Dose-Rate Radiation-Induced Secretion of TGF-β3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism.

Spatially fractionated radiotherapy: tumor response modelling including immunomodulation.

A mathematical tumor response model has been developed, encompassing the interplay between immune cells and cancer cells initiated by either partial or full tumor irradiation. The iterative four-compartment model employs the linear-quadratic radiation response theory for four cell types: active and inactive cytotoxic T lymphocytes (immune cells, CD8T cells in particular), viable cancer cells (undamaged and reparable cells) and doomed cells (irreparably damaged cells). The cell compartment interactions are calculated per day, with total tumor volume (TV) as the main quantity of interest.

Effects of ionizing irradiation and interface backscatter on human mesenchymal stem cells cultured on titanium surfaces.

Radiotherapy to the head and neck region negatively influences the osseointegration and survival of dental implants. The effects of cobalt 60 ( Co) ionizing radiation and the impact of backscatter rays were investigated on human mesenchymal stem cells cultured on titanium surfaces. Bone marrow-derived human mesenchymal stem cells were seeded on titanium (Ti), fluoride-modified titanium (TiF), and tissue culture plastic.

Low dose-rate irradiation with [H]-labelled valine to selectively target hypoxic cells in a human colorectal cancer xenograft model.

Background: Earlier in vitro studies show that irradiation with an ultra-low dose-rate of 15 mGy/h delivered with [H]-valine leads to loss of clonogenicity in hypoxic T-47D cells. Here, the aim was to determine if [H]-valine could be used to deliver low dose-rate irradiation in a colorectal cancer model.

Methods: Clonogenicity was measured in cultured cancer cell line HT29 irradiated with 15 mGy/h combined with intermittent hypoxia.

Low-Dose-Rate Irradiation for 1 Hour Induces Protection Against Lethal Radiation Doses but Does Not Affect Life Span of DBA/2 Mice.

Prior findings showed that serum from DBA/2 mice that had been given whole-body irradiation for 1 hour at a low dose rate (LDR) of 30 cGy/h induced protection against radiation in reporter cells by a mechanism depending on transforming growth factor β3 and inducible nitric oxide synthase activity. In the present study, the effect of the 1 hour of LDR irradiation on the response of the preirradiated mice to a subsequent lethal dose and on the life span is examined. These DBA/2 mice were prime irradiated for 1 hour at 30 cGy/h.

The role of interleukin-13 in the removal of hyper-radiosensitivity by priming irradiation.

It has previously been demonstrated that the presence of fetal bovine serum is necessary for TGF-β3 (transforming growth factor beta 3)-dependent elimination of low-dose hyper-radiosensitivity (HRS) in cells by 1 h of low-dose-rate γ-irradiation (0.2-0.3 Gy/h).

Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells.

Background: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.