The bone is a complex organ that is dependent on a tight regulation between bone formation by osteoblasts (OBs) and bone resorption by osteoclasts (OCs). These processes can be influenced by ...environmental factors such as ionizing radiation (IR). In cancer therapy, IR is applied in high doses, leading to detrimental effects on bone, whereas radiation therapy with low doses of IR is applied for chronic degenerative and inflammatory diseases, with a positive impact especially on bone homeostasis. Moreover, the effects of IR are of particular interest in space travel, as astronauts suffer from bone loss due to space radiation and microgravity. This review summarizes the current state of knowledge on the effects of IR on bone with a special focus on the influence on OCs and OBs, as these cells are essential in bone remodeling. In addition, the influence of IR on the bone microenvironment is discussed. In summary, the effects of IR on bone and bone remodeling cells strongly depend on the applied radiation dose, as differential results are provided from in vivo as well as in vitro studies with varying doses of IR. Furthermore, the isolated effects of IR on a single cell type are difficult to determine, as the bone cells and bone microenvironment are building a tightly regulated network, influencing on one another. Therefore, future research is necessary in order to elucidate the influence of different bone cells on the overall radiation-induced effects on bone.
Immunotherapy approaches currently make their way into the clinics to improve the outcome of standard radiochemotherapy (RCT). The programed cell death receptor ligand 1 (PD-L1) is one possible ...target that, upon blockade, allows T cell-dependent antitumor immune responses to be executed. To date, it is unclear which RCT protocol and which fractionation scheme leads to increased PD-L1 expression and thereby renders blockade of this immune suppressive pathway reasonable. We therefore investigated the impact of radiotherapy (RT), chemotherapy (CT), and RCT on PD-L1 surface expression on tumor cells of tumor entities with differing somatic mutation prevalence. Murine melanoma (B16-F10), glioblastoma (GL261-luc2), and colorectal (CT26) tumor cells were treated with dacarbazine, temozolomide, and a combination of irinotecan, oxaliplatin, and fluorouracil, respectively. Additionally, they were irradiated with a single dose 10 Gray (Gy) or hypo-fractionated (2 × 5 Gy), respectively, norm-fractionated (5 × 2 Gy) radiation protocols were used. PD-L1 surface and intracellular interferon (IFN)-gamma expression was measured by flow cytometry, and IL-6 release was determined by ELISA. Furthermore, tumor cell death was monitored by AnnexinV-FITC/7-AAD staining. For first
analyses, the B16-F10 mouse melanoma model was chosen. In B16-F10 and GL261-luc2 cells, particularly norm-fractionated and hypo-fractionated radiation led to a significant increase of surface PD-L1, which could not be observed in CT26 cells. Furthermore, PD-L1 expression is more pronounced on vital tumor cells and goes along with increased levels of IFN-gamma in the tumor cells. In melanoma cells CT was the main trigger for IL-6 release, while in glioblastoma cells it was norm-fractionated RT.
, fractionated RT only in combination with dacarbazine induced PD-L1 expression on melanoma cells. Our results suggest a tumor cell-mediated upregulation of PD-L1 expression following in particular chemoradiation that is not only dependent on the somatic mutation prevalence of the tumor entity.
The understanding and the application of radiation-induced immune modulation has become more and more relevant in the therapy of malignant, but also benign diseases ...
Direct analysis of whole blood on bloodstained textiles is achieved with thread spray mass spectrometry (MS). This capability satisfies investigators' first priority in crime scene investigations, ...which is determining if a stain is blood. This thread spray method explores the use of evidentiary fabric threads for rapid determination of hemoglobin directly from whole blood within textiles without prior extraction steps. The multiplicity of information that can be derived from the thread spray MS method distinguishes it from the current presumptive Bluestar® method, by enabling the detection of hemoglobin (both α- and β-chains), the heme co-factor and lipids all from a single blood sample. Lipid composition was found to differ for blood samples originating from human, canine, and horse species. The robustness of the thread spray MS method as a forensic analytical platform was evaluated in three ways: (1) its successful applicability to samples previously tested by the Bluestar® presumptive method, offering a confirmatory test without prior sample pre-treatment, (2) successful detection of heme from previously washed fabrics, which demonstrated the unprecedented sensitivity of the thread spray method, and (3) the ability to analyze samples stored under ambient conditions for up to 30 days. These results attest to the potential capabilities of the thread spray MS platform in forensic serology, and its application for direct analysis of evidentiary garments, which confer the advantages of rapid analysis and the reduction of the false positive and negative identification rates for blood on textiles.
In cancer treatments, especially high-dose radiotherapy (HDRT) is applied. Patients suffering from chronic inflammatory diseases benefit from low-dose radiation therapy (LDRT), but exposure to very ...low radiation doses can still steadily increase for diagnostic purposes. Yet, little is known about how radiation impacts on forms of cell death in human immune cells. In this study, the radiosensitivity of human immune cells of the peripheral blood was examined in a dose range from 0.01 to 60 Gy with regard to induction of apoptosis, primary necrosis, and secondary necrosis. Results showed that immune cells differed in their radiosensitivity, with monocytes being the most radioresistant. T cells mainly died by necrosis and were moderately radiosensitive. This was followed by B and natural killer (NK) cells, which died mainly by apoptosis. X-radiation had no impact on cell death in immune cells at very low doses (≤0.1 Gy). Radiation doses of LDRT (0.3⁻0.7 Gy) impacted on the more radiosensitive NK and B cells, which might contribute to attenuation of inflammation. Even single doses applied during RT of tumors did not erase the immune cells completely. These in vitro studies can be considered as the basis to optimize individual radiation therapy schemes in multimodal settings and to define suited time points for further inclusion of immunotherapies.
Radon Exposure-Therapeutic Effect and Cancer Risk Maier, Andreas; Wiedemann, Julia; Rapp, Felicitas ...
International journal of molecular sciences,
12/2020, Letnik:
22, Številka:
1
Journal Article
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Largely unnoticed, all life on earth is constantly exposed to low levels of ionizing radiation. Radon, an imperceptible natural occurring radioactive noble gas, contributes as the largest single ...fraction to radiation exposure from natural sources. For that reason, radon represents a major issue for radiation protection. Nevertheless, radon is also applied for the therapy of inflammatory and degenerative diseases in galleries and spas to many thousand patients a year. In either case, chronic environmental exposure or therapy, the effect of radon on the organism exposed is still under investigation at all levels of interaction. This includes the physical stage of diffusion and energy deposition by radioactive decay of radon and its progeny and the biological stage of initiating and propagating a physiologic response or inducing cancer after chronic exposure. The purpose of this manuscript is to comprehensively review the current knowledge of radon and its progeny on physical background, associated cancer risk and potential therapeutic effects.
Despite continuous advances in therapy, malignant melanoma is still among the deadliest types of cancer. At the same time, owing to its high plasticity and immunogenicity, melanoma is regarded as a ...model tumor entity when testing new treatment approaches. Cold physical plasma is a novel anticancer tool that utilizes a plethora of reactive oxygen species (ROS) being deposited on the target cells and tissues. To test whether plasma treatment would enhance the toxicity of an established antitumor therapy, ionizing radiation, we combined both physical treatment modalities targeting B16F10 murine melanoma cell in vitro. Repeated rather than single radiotherapy, in combination with gas plasma-introduced ROS, induced apoptosis and cell cycle arrest in an additive fashion. In tendency, gas plasma treatment sensitized the cells to subsequent radiotherapy rather than the other way around. This was concomitant with increased levels of TNFα, IL6, and GM-CSF in supernatants. Murine JAWS dendritic cells cultured in these supernatants showed an increased expression of cell surface activation markers, such as MHCII and CD83. For PD-L1 and PD-L2, increased expression was observed. Our results are the first to suggest an additive therapeutic effect of gas plasma and radiotherapy, and translational tumor models are needed to develop this concept further.
Three-dimensional (3D) dried blood spheroids form when whole blood is deposited onto hydrophobic paper and allowed to dry in ambient air. The adsorbed 3D dried blood spheroid present at the surface ...of the hydrophobic paper is observed to offer enhanced stability for labile analytes that would otherwise degrade if stored in the traditional two-dimensional (2D) dried blood spot method. The protective mechanism for the dried blood spheroid microsampling platform was studied using scanning electron microscopy (SEM), which revealed the presence of a passivation thin film at the surface of the spheroid that serves to stabilize the interior of the spheroid against environmental stressors. Through time-course experiments based on sequential SEM analyses, we discovered that the surface protective thin film forms through the self-assembly of red blood cells following the evaporation of water from the blood sample. The bridging mechanism of red blood cell aggregation is evident in our experiments, which leads to the distinct rouleau conformation of stacked red blood cells in less than 60 min after creating the blood spheroid. The stack of self-assembled red blood cells at the exterior of the spheroid subsequently lyse to afford the surface protective layer detected to be approximately 30 μm in thickness after three weeks of storage in ambient air. We applied this mechanistic insight to plasma and serum to enhance stability when stored under ambient conditions. In addition to physical characterization of these thin biofilms, we also used paper spray (PS) mass spectrometry (MS) to examine chemical changes that occur in the stored biofluid. For example, we present stability data for cocaine spiked in whole blood, plasma, and serum when stored under ambient conditions on hydrophilic and hydrophobic paper substrates.
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