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1.
PLoS One ; 17(1): e0263164, 2022.
Article in English | MEDLINE | ID: mdl-35100314

ABSTRACT

Infrared (IR) lasers are extensively utilized as an effective tool in many medical practices. Nevertheless, light penetration into the inspected tissue, which is highly affected by tissue optical properties, is a crucial factor for successful optical procedures. Although the optical properties are highly wavelength-dependent, they can be affected by the power of the incident laser. The present study demonstrates a considerable change in the scattering and absorption coefficients as a result of varying the incident laser power probing into biological samples at a constant laser wavelength (808 nm). The optical parameters were investigated using an integrating sphere and Kubelka-Munk model. Additionally, fluence distribution at the sample's surface was modeled using COMSOL-multiphysics software. The experimental results were validated using Receiver Operating Characteristic (ROC) curves and Monte-Carlo simulation. The results showed that tissue scattering coefficient decreases as the incident laser power increases while the absorption coefficient experienced a slight change. Moreover, the penetration depth increases with the optical parameters. The reduction in the scattering coefficients leads to wider and more diffusive fluence rate distribution at the tissue surface. The simulation results showed a good agreement with the experimental data and revealed that tissue anisotropy may be responsible for this scattering reduction. The present findings could be considered in order for the specialists to accurately specify the laser optical dose in various biomedical applications.


Subject(s)
Infrared Rays , Lasers , Optical Phenomena , Organ Specificity , Animals , Anisotropy , Computer Simulation , Finite Element Analysis , Male , Monte Carlo Method , Organ Specificity/radiation effects , ROC Curve , Rats, Wistar , Scattering, Radiation
2.
Cancer Radiother ; 26(1-2): 59-75, 2022.
Article in English | MEDLINE | ID: mdl-34953713

ABSTRACT

Dose constraints are essential for performing dosimetry, especially for intensity modulation and for radiotherapy under stereotaxic conditions. We present the update of the recommendations of the French society of oncological radiotherapy for the use of these doses in classical current practice but also for reirradiation.


Subject(s)
Organs at Risk/radiation effects , Radiation Injuries/prevention & control , Radiosurgery/methods , Radiotherapy, Intensity-Modulated/methods , Dose Fractionation, Radiation , France , Humans , Organ Specificity/radiation effects , Radiation Dosage , Radiation Oncology , Re-Irradiation/methods , Societies, Medical
3.
Dev Cell ; 56(24): 3393-3404.e7, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34879263

ABSTRACT

Deciphering gene function requires the ability to control gene expression in space and time. Binary systems such as the Gal4/UAS provide a powerful means to modulate gene expression and to induce loss or gain of function. This is best exemplified in Drosophila, where the Gal4/UAS system has been critical to discover conserved mechanisms in development, physiology, neurobiology, and metabolism, to cite a few. Here we describe a transgenic light-inducible Gal4/UAS system (ShineGal4/UAS) based on Magnet photoswitches. We show that it allows efficient, rapid, and robust activation of UAS-driven transgenes in different tissues and at various developmental stages in Drosophila. Furthermore, we illustrate how ShineGal4 enables the generation of gain and loss-of-function phenotypes at animal, organ, and cellular levels. Thanks to the large repertoire of UAS-driven transgenes, ShineGal4 enriches the Drosophila genetic toolkit by allowing in vivo control of gene expression with high temporal and spatial resolutions.


Subject(s)
Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental , Optogenetics , Animals , Body Patterning/genetics , Body Patterning/radiation effects , Drosophila melanogaster/radiation effects , Gene Expression Regulation, Developmental/radiation effects , Light , Organ Specificity/genetics , Organ Specificity/radiation effects , Pupa/genetics , Pupa/radiation effects , Time Factors
4.
Front Immunol ; 12: 680503, 2021.
Article in English | MEDLINE | ID: mdl-34079557

ABSTRACT

In the past decade, radiation therapy (RT) entered the era of personalized medicine, following the striking improvements in radiation delivery and treatment planning optimization, and in the understanding of the cancer response, including the immunological response. The next challenge is to identify the optimal radiation regimen(s) to induce a clinically relevant anti-tumor immunity response. Organs at risks and the tumor microenvironment (e.g. endothelial cells, macrophages and fibroblasts) often limit the radiation regimen effects due to adverse toxicities. Here, we reviewed how RT can modulate the immune response involved in the tumor control and side effects associated with inflammatory processes. Moreover, we discussed the versatile roles of tumor microenvironment components during RT, how the innate immune sensing of RT-induced genotoxicity, through the cGAS-STING pathway, might link the anti-tumor immune response, radiation-induced necrosis and radiation-induced fibrosis, and how a better understanding of the switch between favorable and deleterious events might help to define innovative approaches to increase RT benefits in patients with cancer.


Subject(s)
Immunity/radiation effects , Radiotherapy/adverse effects , Animals , Bystander Effect/radiation effects , Cell Survival/radiation effects , Humans , Membrane Proteins/metabolism , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/radiotherapy , Nucleotidyltransferases/metabolism , Organ Specificity/immunology , Organ Specificity/radiation effects , Radiation, Ionizing , Radiotherapy/methods , Signal Transduction/radiation effects , Tumor Microenvironment/immunology , Tumor Microenvironment/radiation effects
5.
J Radiat Res ; 62(4): 707-717, 2021 Jul 10.
Article in English | MEDLINE | ID: mdl-33993271

ABSTRACT

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider's mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 104 person-year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.


Subject(s)
Dose Fractionation, Radiation , Prostatic Neoplasms/radiotherapy , Dose-Response Relationship, Radiation , Humans , Male , Organ Specificity/radiation effects , Radiosurgery , Radiotherapy Dosage , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Risk Factors
6.
J Integr Plant Biol ; 63(8): 1537-1554, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34009694

ABSTRACT

Plants have a hierarchical circadian structure comprising multiple tissue-specific oscillators that operate at different speeds and regulate the expression of distinct sets of genes in different organs. However, the identity of the genes differentially regulated by the circadian clock in different organs, such as roots, and how their oscillations create functional specialization remain unclear. Here, we profiled the diurnal and circadian landscapes of the shoots and roots of Medicago truncatula and identified the conserved regulatory sequences contributing to transcriptome oscillations in each organ. We found that the light-dark cycles strongly affect the global transcriptome oscillation in roots, and many clock genes oscillate only in shoots. Moreover, many key genes involved in nitrogen fixation are regulated by circadian rhythms. Surprisingly, the root clock runs faster than the shoot clock, which is contrary to the hierarchical circadian structure showing a slow-paced root clock in both detached and intact Arabidopsis thaliana (L.) Heynh. roots. Our result provides important clues about the species-specific circadian regulatory mechanism, which is often overlooked, and possibly coordinates the timing between shoots and roots independent of the current prevailing model.


Subject(s)
Circadian Clocks/physiology , Circadian Rhythm/physiology , Medicago truncatula/physiology , Plant Roots/physiology , Circadian Clocks/genetics , Circadian Clocks/radiation effects , Circadian Rhythm/genetics , Circadian Rhythm/radiation effects , Gene Expression Regulation, Plant/radiation effects , Genes, Plant , Light , Medicago truncatula/genetics , Medicago truncatula/radiation effects , Nitrogen Fixation/genetics , Nitrogen Fixation/radiation effects , Organ Specificity/genetics , Organ Specificity/radiation effects , Plant Roots/genetics , Plant Roots/radiation effects , Plant Shoots/genetics , Plant Shoots/physiology , Plant Shoots/radiation effects , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Species Specificity , Transcription, Genetic/radiation effects , Transcriptome/genetics
7.
J Radiat Res ; 62(4): 600-617, 2021 Jul 10.
Article in English | MEDLINE | ID: mdl-33929015

ABSTRACT

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg-1 day-1, i.p) and exposed to γ-radiation (2.5 Gy week-1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1ß and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues' architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.


Subject(s)
Intercellular Signaling Peptides and Proteins/metabolism , Organ Specificity/radiation effects , Signal Transduction , Whole-Body Irradiation , Xanthophylls/pharmacology , Animals , Antioxidants/metabolism , Apelin Receptors/metabolism , Gamma Rays , Inflammation/pathology , Kidney/drug effects , Kidney/pathology , Kidney/radiation effects , L-Lactate Dehydrogenase/metabolism , Liver/drug effects , Liver/pathology , Liver/radiation effects , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , NF-kappa B/metabolism , Organ Specificity/drug effects , Oxidants/metabolism , Signal Transduction/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolism
8.
Int J Mol Sci ; 22(6)2021 Mar 23.
Article in English | MEDLINE | ID: mdl-33807089

ABSTRACT

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9-2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.


Subject(s)
Biomarkers , Insulin-Like Growth Factor I/metabolism , Myocardium/metabolism , Radiation Injuries/metabolism , Signal Transduction/radiation effects , Animals , Blood Cells/metabolism , Blood Cells/radiation effects , Body Weight/radiation effects , Collagen/metabolism , Disease Models, Animal , Dose-Response Relationship, Radiation , Fibrosis/etiology , Gene Expression Regulation/radiation effects , Heart Rate/radiation effects , Hematopoiesis/radiation effects , Lipid Metabolism/radiation effects , Organ Specificity/radiation effects , Radiation Injuries/genetics , Swine
9.
Nat Commun ; 12(1): 864, 2021 02 08.
Article in English | MEDLINE | ID: mdl-33558539

ABSTRACT

Circadian clocks allow organisms to synchronize their physiological processes to diurnal variations. A phase response curve allows researchers to understand clock entrainment by revealing how signals adjust clock genes differently according to the phase in which they are applied. Comprehensively investigating these curves is difficult, however, because of the cost of measuring them experimentally. Here we demonstrate that fundamental properties of the curve are recoverable from the singularity response, which is easily measured by applying a single stimulus to a cellular network in a desynchronized state (i.e. singularity). We show that the singularity response of Arabidopsis to light/dark and temperature stimuli depends on the properties of the phase response curve for these stimuli. The measured singularity responses not only allow the curves to be precisely reconstructed but also reveal organ-specific properties of the plant circadian clock. The method is not only simple and accurate, but also general and applicable to other coupled oscillator systems as long as the oscillators can be desynchronized. This simplified method may allow the entrainment properties of the circadian clock of both plants and other species in nature.


Subject(s)
Arabidopsis/physiology , Circadian Clocks/physiology , Arabidopsis/radiation effects , Circadian Clocks/radiation effects , Light , Organ Specificity/radiation effects , Temperature
10.
J Radiat Res ; 62(2): 206-216, 2021 Mar 10.
Article in English | MEDLINE | ID: mdl-33503655

ABSTRACT

Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m3 for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs.


Subject(s)
Organ Specificity/radiation effects , Radon/administration & dosage , Administration, Inhalation , Animals , Antioxidants/metabolism , Catalase/metabolism , Glutathione/metabolism , Hydrogen Peroxide/metabolism , Lipid Peroxides/metabolism , Male , Mice, Inbred BALB C , Oxidation-Reduction/radiation effects , Principal Component Analysis , Superoxide Dismutase/metabolism
11.
Anticancer Res ; 40(9): 5151-5158, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32878803

ABSTRACT

BACKGROUND/AIM: Magnetic stimulation is used in the treatment of a diversity of diseases, but a complete understanding of the underlying mechanisms of action requires further investigation. We examined the effect of static magnetic stimulation (SMS) in different cell lines. MATERIALS AND METHODS: A culture plate holder with attached NeFeB magnets was developed. Different magnetic field intensities and periods were tested in tumoral and non-tumoral cell lines. To verify the cellular responses to SMS, cell viability, cell death, cell cycle and BDNF expression were evaluated. RESULTS: Exposure of SH-SY5Y cells to SMS for 24 hours led to a decrease in cell viability. Analysis 24 h after stimulation revealed a decrease in apoptotic and double-positive cells, associated with an increase in the number of necrotic cells. CONCLUSION: The effects of SMS on cell viability are cell type-specific, inducing a decrease in cell viability in SH-SY5Y cells. This suggests that SMS may be a potential tool in the treatment of neuronal tumors.


Subject(s)
Cell Survival/radiation effects , Magnetic Phenomena , Apoptosis/radiation effects , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cell Cycle/radiation effects , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Neuroblastoma/genetics , Neuroblastoma/metabolism , Organ Specificity/radiation effects
12.
J Radiat Res ; 61(5): 747-754, 2020 Sep 08.
Article in English | MEDLINE | ID: mdl-32785596

ABSTRACT

To improve the homogeneity and conformity of the irradiation dose for postoperative breast cancer including regional lymph nodes, we planned Hybrid volumetric-modulated arc therapy (VMAT), which combines conventional tangential field mainly for the chest area and VMAT mainly for the supraclavicular area and marginal zone. In this study, we compared the dosimetric impact between traditional 3D conformal radiotherapy (3DCRT) and Hybrid VMAT and observed toxicities following Hybrid VMAT. A total of 70 patients indicated between October 2016 and December 2017 were included. The prescribed dose was 50 Gy/25 fractions. For the dosimetric impact, 3DCRT and Hybrid VMAT plans were compared in each patient with respect to the dosimetric parameters. Toxicities were followed using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up duration was 319 days. For the dosimetric impact, the homogeneity index (HI) and conformity index (CI) of PTV were significantly improved in the Hybrid VMAT plan compared with that in the 3DCRT plan (HI, 0.15 ± 0.07 in Hybrid VMAT vs 0.41 ± 0.19 in 3DCRT, P < 0.001; CI, 1.61 ± 0.44 in Hybrid VMAT vs 2.10 ± 0.56 in 3DCRT, P < 0.001). The mean irradiated ipsilateral lung dose was not significantly different in both plans (12.0 ± 2.4 Gy in Hybrid VMAT vs 11.8 ± 2.8 Gy in 3DCRT, P < 0.533). Regarding toxicity, there were no patients who developed ≥grade 3 acute toxicity and ≥grade 2 pneumonitis during the follow-up. Hybrid VMAT for postoperative breast cancer including regional lymph nodes was a reasonable technique that improved the homogeneity and conformity of the irradiation dose to the planning target volume while keeping the irradiation dose to organs at risk to a minimum.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Lymph Nodes/pathology , Postoperative Care , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Humans , Lymph Nodes/radiation effects , Middle Aged , Organ Specificity/radiation effects
13.
Mol Oncol ; 14(7): 1538-1554, 2020 07.
Article in English | MEDLINE | ID: mdl-32521079

ABSTRACT

Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients' quality of life and to escalate radiation doses to tumors when necessary. High-precision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ-specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery.


Subject(s)
Radiation Injuries/prevention & control , Radiation Injuries/therapy , Radiotherapy/adverse effects , Humans , Organ Specificity/radiation effects , Time Factors
14.
Sci Rep ; 10(1): 7902, 2020 05 13.
Article in English | MEDLINE | ID: mdl-32404910

ABSTRACT

External exposure to gamma-photon irradiation from soil contamination due to nuclear power plant (NPP) accidents has significant contribution to human radiation exposure in the proximity of the NPP. Detailed absorbed doses in human organs are rarely reported in the literature. We applied the Monte Carlo Neutron Particle (MCNP) transport code to calculate and compare the absorbed doses in different human organs. The absorbed doses by gamma-photon radiation were from cesium-137 (137Cs) in soil contaminated by the two major NPP accidents. More serious and wide-spread impacts of the Chernobyl NPP accident on soil contamination in Ukraine, Belarus, Russia and countries as far as Sweden and Greece were due to the inland location, radiative plume transport pathway and high 137Cs emission strength (9 times the Fukushima emission). Based on our MCNP calculations, the largest absorbed dose was found in skin. The maximum calculated external 137Cs annual effective dose received from the Chernobyl accident was 10 times higher relative to the Fukushima accident. Our calculated effective doses at various influenced areas were comparable to those available in the literature. The calculated annual effective doses at areas near the Fukushima and Chernobyl NPPs exceeded the ICRP recommendation of 1 mSv yr-1.


Subject(s)
Cesium Radioisotopes/adverse effects , Cesium Radioisotopes/analysis , Chernobyl Nuclear Accident , Fukushima Nuclear Accident , Radiation Dosage , Soil Pollutants, Radioactive/adverse effects , Soil Pollutants, Radioactive/analysis , Soil/chemistry , Algorithms , Environmental Exposure , Humans , Models, Theoretical , Organ Specificity/radiation effects
15.
Sci Rep ; 10(1): 6825, 2020 04 22.
Article in English | MEDLINE | ID: mdl-32321983

ABSTRACT

The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we describe the use of a promising radiation countermeasure, BBT-059, and the results of a long term mouse study (up to 12 months) in the male CD2F1 strain using 60Co gamma irradiation (~0.6 Gy/min, 7.5-12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation.


Subject(s)
Interleukin-11/pharmacology , Radiation Exposure , Whole-Body Irradiation , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Blood Cell Count , Cadherins/metabolism , Clone Cells , Colony-Forming Units Assay , Dose-Response Relationship, Radiation , Gamma Rays , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/radiation effects , Kidney/pathology , Kidney/radiation effects , Liver/pathology , Liver/radiation effects , Male , Mice , Organ Specificity/radiation effects , Survival Analysis
16.
Br J Radiol ; 93(1110): 20190869, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32242740

ABSTRACT

OBJECTIVES: To estimate risk for exposure-induced cancer death (REID), organ-specific risks of exposure-induced cancer death (REIDHT) and associated conversion coefficients (CCREID:KAP=REID/kerma-area product (KAP), CCREIDHT:KAP=REIDHT/KAP) in paediatric cardiac catheterizations using data from radiation dose structured reports (RDSR). A novel risk surveillance tool consisting of age-specific and gender-specific risk reference values (RRVs) related to population cancer risk is suggested. METHODS: The PCXMC v.2.0 code is used together with exposure-related information from RDSR from a cohort of 238 children to assess cancer risks and related conversion coefficients. The KAP corresponding to 1 in 1000 of increased REID is used to define age-specific and gender-specific KAP values to monitor risk in such patient cohorts, here denoted as RRVs. RESULTS: The REID estimates ranged from below 1 up to 300 in 100,000, and the RRVs for the different age groups and gender ranged from 0.77 Gycm2 and 2.1 Gycm2 for neonates (female, male) to 11 Gycm2 and 25 Gycm2 for 15-year-olds (female, male). The CCREID:KAP and CCREIDHT:KAP decreased biexponentially with increased age, being notably higher for female patients. CONCLUSIONS: Prominent risk contributing organs were the lungs and the (female) breast. The concept of age-specific and gender-specific RRVs related to population cancer risk is introduced and is intended to be used as a supporting tool for physicians performing such interventions. ADVANCES IN KNOWLEDGE: Age-related and gender-related conversion coefficients for radiation risk, CCREID:KAP and CCREIDHT:KAP, are introduced and a novel risk surveillance concept, the RRV, is suggested for paediatric cardiac catheterizations.


Subject(s)
Age Factors , Cardiac Catheterization/adverse effects , Heart Defects, Congenital/diagnostic imaging , Neoplasms, Radiation-Induced/mortality , Radiation Exposure/adverse effects , Sex Factors , Adolescent , Angiography , Breast Neoplasms/etiology , Breast Neoplasms/mortality , Cardiac Catheterization/methods , Child , Child, Preschool , Female , Heart Defects, Congenital/radiotherapy , Heart Defects, Congenital/surgery , Humans , Infant , Infant, Newborn , Lung Neoplasms/etiology , Lung Neoplasms/mortality , Male , Neoplasms, Radiation-Induced/etiology , Organ Specificity/radiation effects , Phantoms, Imaging , Radiation Dosage , Reference Values , Risk
17.
PLoS One ; 14(8): e0221692, 2019.
Article in English | MEDLINE | ID: mdl-31442288

ABSTRACT

Metal implants not only deteriorate image quality, but also increase radiation exposure. The purpose of this study was to evaluate the effect of metal hip prosthesis on absorbed radiation dose and assess the efficacy of organ dose modulation (ODM) and metal artifact reduction (MAR) protocols on dose reduction. An anthropomorphic phantom was scanned with and without bilateral metal hip prostheses, and surface and deep level radiation doses were measured at the abdomen and pelvis. Finally, the absorbed radiation doses at pelvic and abdominal cavities in the reference, ODM, and two MAR scans (Gemstone spectral imaging, GE) were compared. The Mann Whitney-U test and Kruskal-Wallis test were performed to compare the volume CT dose index (CTDIvol) and mean absorbed radiation doses. Unilateral and bilateral metal hip prostheses increased CTDIVOL by 14.4% and 30.5%, respectively. MAR protocols decreased absorbed radiation doses in the pelvis. MAR showed the most significant dose reduction in the deep pelvic cavity followed by ODM. However, MAR protocols increased absorbed radiation doses in the upper abdomen. ODM significantly reduced absorbed radiation in the pelvis and abdomen. In conclusion, metal hip implants increased radiation doses in abdominopelvic CT scans. MAR and ODM techniques reduced absorbed radiation dose in abdominopelvic CT scans with metal hip prostheses.


Subject(s)
Hip Prosthesis , Metals/adverse effects , Radiation Exposure , Tomography, X-Ray Computed , Absorption, Radiation , Artifacts , Humans , Organ Specificity/radiation effects , Radiation Dosage
18.
J Radiat Res ; 60(3): 401-411, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30929023

ABSTRACT

The purpose of this study was to quantify actual patient organ doses from megavoltage computed tomography (MVCT) using an MVCT beam model of a helical tomotherapy unit in a general treatment planning system (TPS). Dosimetric parameters (percentage depth dose, lateral beam profile, and longitudinal beam profile) of the MVCT beam were measured using Gafchromic EBT3 films (ISP Corporation, Wayne, NJ, USA) and used for beam modeling in a Pinnacle3 TPS (Philips, Amsterdam, Netherlands); this TPS is widely used with linear accelerators. The created beam model was adjusted and validated by assessing point doses in a cylindrical phantom in static and helical beam plans with fine, normal and coarse pitches. Maximum doses delivered to important organs from MVCT delivery for five clinical cases were calculated using the created beam model. The difference (average ± one standard deviation for all evaluation points) between calculated and measured doses was -0.69 ± 1.20% in the static beam plan. In the helical beam plan, the differences were 1.83 ± 2.65%, 1.35 ± 5.94% and -0.66 ± 8.48% for fine, normal and coarse pitches, respectively. The average maximum additional dose to important organs from MVCT in clinical cases was 0.82% of the prescribed dose. In conclusion, we investigated a method for quantifying patient organ dose from MVCT delivery on helical tomotherapy using an MVCT beam model in a general TPS. This technique enables estimation of the patient-specific organ dose from MVCT delivery, without the need for additional equipment.


Subject(s)
Organ Specificity/radiation effects , Radiotherapy Planning, Computer-Assisted , Tomography, Spiral Computed , Calibration , Dose-Response Relationship, Radiation , Humans , Radiotherapy Dosage , Reproducibility of Results , Tomography, X-Ray Computed
19.
Australas Phys Eng Sci Med ; 42(1): 211-220, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30725438

ABSTRACT

An Advanced Markus chamber on the surface of solid water phantom was used to determine surface dose reduction, with either a lead or air interface, as a function of surface-interface separation (t). The beam quality dependence of dose reduction was investigated using the 50 kV, 100 kV and 150 kV beams of an Xstrahl 150 superficial X-ray unit. For each beam the dose correction factor, DCF(t), namely the ratio of surface dose (t) to surface dose (t = 100 mm), was determined. Monte Carlo simulations of DCF(t) with a lead interface were compared with corresponding measured values. Simulated spectra were calculated at the phantom surface for full backscatter (t = 100 mm) and with either a lead or air interface at 2 mm or 8 mm depth. For each depth and beam quality lead fluorescent radiation at the surface was evident. The variation of DCF(t) for each beam and field size exhibits a minima at t ≈ 5 mm and in the range 1 mm ≤ t ≤ 40 mm surface dose reduction is larger for 100 kV than 150 kV. Monte Carlo simulated DCF(t) are consistent with corresponding measured DCF(t). From simulated spectra L-series fluorescent X-rays (≈ 15 keV) emanating from lead at t = 2 mm are evident for all beams and fluorescent K-series X-rays only occur with 100 kV and 150 kV beams.


Subject(s)
Dose-Response Relationship, Radiation , Organ Specificity/radiation effects , Computer Simulation , Fluorescence , Monte Carlo Method , Phantoms, Imaging , X-Rays
20.
Lasers Med Sci ; 34(1): 223-234, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30402798

ABSTRACT

Low power lasers have been used successfully for treatment of many diseases in soft and bone tissues. Basic and clinical researches have developed quickly being the scientific basis to therapeutic protocols based on these lasers. However, there are difficulties to compare experimental and clinical results obtained from different researchers because a complicated and intricate list of physical and biological parameters should be checked before the irradiation procedures as well as part of these parameters are omitted or inaccurately reported. This review focuses on the physical and biological parameters proposed to make experimental and clinical protocols accurate and reproducible as well as suggests dose parameters based on biological effects induced by low power lasers. A variety of parameters are reported by different authors and the number of parameter suggested could overcome three dozens. Thus, laser dose and laser dose equivalent are defined based on laser-induced biological effects and suggested as simplified dose parameters for low power lasers. These parameters could simplify and be useful to researchers and clinicians, permitting comparisons and decreasing mistakes and inaccuracies when laser-induced effects are evaluated and compared with those obtained in previous studies. The laser dose and laser dose equivalent could contribute significantly to improve accuracy, effectiveness, and safety of clinical protocols based on low power lasers.


Subject(s)
Low-Level Light Therapy , Dose-Response Relationship, Radiation , Humans , Organ Specificity/radiation effects
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