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Roczniki Panstwowego Zakladu Higieny 2023Radon is noble, monatomic, radioactive, heavier than the air gas. It is colorless, odorless, tasteless. It exists in natural environment as a result of the decay of...
Radon is noble, monatomic, radioactive, heavier than the air gas. It is colorless, odorless, tasteless. It exists in natural environment as a result of the decay of radium, and emits mainly alpha radiation and less beta radiation. Residential radon concentrations vary widely by geographic area. The higher concentration of radon is expected globally in the grounds where uranium, radium and thoron are present. Radon may gather in caves, tunnels, mines as well as in other lowestlying spaces, such as basements, and cellars. In accordance with Atomic Law (2000), the reference level for the average annual concentration of radioactive radon in rooms intended for human habitation is 300 Bq/m3. The most dangerous damages caused by ionizing radiation i.e. radon and its derivatives are changes to DNA, which may disturb the functions of cells and in the consequence lead to induction of cancer of respiratory tract, mainly of lungs and also leukaemia. So, the main consequence of exposure to high amount of radon are cancers of respiratory system. Radon enters the human organism mainly through inhaled atmospheric air. Moreover, radon significantly increased a risk of induction cancer in smokers and vice versa, smoking promotes the development of lung cancer after the exposure to radon and its derivatives. Radon may also have beneficial effect on the human body. Therefore it is used in medicine; mainly in radonbalneotherapy i.e. bath treatments, rinsing the mouth and inhalation. Beneficial effects of radon confirms the validity of the theory of radiation hormesis, which assumes that low doses of radiation may stimulate the repair of DNA damage by activation of protective mechanisms, which neutralize free radicals.
Topics: Humans; Radon; Air Pollutants, Radioactive; Radium; Smoking; Neoplasms; Radiation Monitoring
PubMed: 37010341
DOI: 10.32394/rpzh.2023.0242 -
Frontiers in Robotics and AI 2023Surveying active nuclear facilities for spread of alpha and beta contamination is currently performed by human operators. However, a skills gap of qualified workers is...
Surveying active nuclear facilities for spread of alpha and beta contamination is currently performed by human operators. However, a skills gap of qualified workers is emerging and is set to worsen in the near future due to under recruitment, retirement and increased demand. This paper presents an autonomous ground vehicle that can survey nuclear facilities for alpha, beta and gamma radiation and generate radiation heatmaps. New methods for preventing the robot from spreading radioactive contamination using a state-machine and radiation costmaps are introduced. This is the first robot that can detect alpha and beta contamination and autonomously re-plan around the contamination without the wheels passing over the contaminated area. Radiation avoidance functionality is proven experimentally to reduce alpha and beta contamination spread as well as gamma radiation dose to the robot. The robot's survey area is defined using a custom designed, graphically controlled area coverage planner. It was concluded that the robot is highly suited to certain monotonous room scale radiation surveying tasks and therefore provides the opportunity for financial savings, to mitigate a future skills gap, and provision of radiation surveys that are more granular, accurate and repeatable than those currently performed by human operators.
PubMed: 37064575
DOI: 10.3389/frobt.2023.1137750 -
Theranostics 2023The dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for...
The dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for biodistribution, functionality, proliferation, and persistence and for improving their cytotoxic potency in case of treatment failure. Here we engineered CD19 CAR-T cells ("Thor"-cells) to express a membrane-bound scFv, huC825, that binds DOTA-haptens with picomolar affinity suitable for labeling with imaging or therapeutic radionuclides. We assess its versatile utility for serial tracking studies with PET and delivery of α-radionuclides to enhance anti-tumor killing efficacy in sub-optimal adoptive cell transfer using Thor-cells in lymphoma models. We show that this reporter gene/probe platform enables repeated, sensitive, and specific assessment of the infused Thor-cells in the whole-body using PET/CT imaging with exceptionally high contrast. The uptake on PET correlates with the Thor-cells on a cellular and functional level. Furthermore, we report the ability of Thor-cells to accumulate cytotoxic alpha-emitting radionuclides preferentially at tumor sites, thus increasing therapeutic potency. Thor-cells are a new theranostic agent that may provide crucial information for better and safer clinical protocols of adoptive T cell therapies, as well as accelerated development strategies.
Topics: Radioimmunotherapy; Positron Emission Tomography Computed Tomography; Tissue Distribution; Immunotherapy, Adoptive; Radioisotopes; Antineoplastic Agents; T-Lymphocytes
PubMed: 37908719
DOI: 10.7150/thno.87489 -
International Journal of Molecular... Nov 2022Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast...
Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line, MCF-10F, to low doses of high linear energy transfer (LET) α particle radiation (150 keV/μm) and subsequent growth in the presence or absence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation after being irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles. In the present report, the profiling of differentially expressed genes associated with growth factors was analyzed in their relationship with clinical parameters. Thus, the results indicated that Fibroblast growth factor2 gene expression levels were higher in cells transformed by radiation or in the presence of ionizing radiation; whereas the fibroblast growth factor-binding protein 1gene expression was higher in the tumor cell line derived from this model. Such expressions were coincident with higher values in normal than malignant tissues and with estrogen receptor (ER) negative samples for both gene types. The results also showed that transforming growth factor alpha gene expression was higher in the tumor cell line than the tumorigenic A5 and the transformed A3 cell line, whereas the transforming growth factor beta receptor 3 gene expression was higher in A3 and A5 than in Tumor2 cell lines and the untreated controls and the E cell lines. Such gene expression was accompanied by results indicating negative and positive receptors for transforming growth factor alpha and the transforming growth factor beta receptor 3, respectively. Such expressions were low in malignant tissues when compared with benign ones. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expressions were found to be present in all BRCA patients that are BRCA-Basal, BRCA-LumA, and BRCA-LumB, except in BRCA-Her2 patients. The results also indicated that the insulin growth factor receptor gene expression was higher in the tumor cell line Tumor2 than in Alpha3 cells transformed by ionizing radiation only; then, the insulin growth factor receptor was higher in the A5 than E cell line. The insulin growth factor receptor gene expression was higher in breast cancer than in normal tissues in breast cancer patients. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expression levels were in stages 3 and 4 of breast cancer patients. It can be concluded that, by using gene technology and molecular information, it is possible to improve therapy and reduce the side effects of therapeutic radiation use. Knowing the different genes involved in breast cancer will make possible the improvement of clinical chemotherapy.
Topics: Humans; Female; Transforming Growth Factor alpha; Breast Neoplasms; Estrogens; Radiation, Ionizing; Insulin, Regular, Human; Cell Line, Tumor; Insulin; Receptors, Transforming Growth Factor beta; Fibroblast Growth Factors
PubMed: 36430763
DOI: 10.3390/ijms232214284 -
Royal Society Open Science Nov 2020α-Mangostin, the extract from pericarp of . or mangosteen fruit, has been applied in various biomedical products because of its minimal skin irritation, and prominent...
α-Mangostin, the extract from pericarp of . or mangosteen fruit, has been applied in various biomedical products because of its minimal skin irritation, and prominent anti-inflammatory, antimicrobial and immune-modulating activities. Owing to its low water solubility, the particle formulations are necessary for the applications of α-mangostin in aqueous media. The particle formulations are usually prepared using surfactants and/or polymers, usually at a larger amount of these auxiliaries than the amount of α-mangostin itself. Here, we show the self-assembly of α-mangostin molecules into water-dispersible particles without a need of any polymers/surfactants. Investigations on chemical structure, crystallinity and thermal properties of the obtained α-mangostin particles, in comparison to the conventional α-mangostin crystalline solid, confirm no formation of the new compound during the particle formation and suggest changes in intermolecular interactions among α-mangostin molecules and significantly more hydroxyl functionality positioned at the particles' surface. The ability of the water suspension of the α-mangostin to inhibit the growth of , the acne-causing bacteria, is similar to that of the solution of the conventional α-mangostin in 5% dimethyl sulfoxide. Moreover, at 12.7 ppm in an aqueous environment of RAW 264.7 cell culture, α-mangostin suspension exhibits five times higher anti-inflammatory activity than the conventional α-mangostin solution, with the same acceptable cytotoxicity of less than 20% cell death.
PubMed: 33391780
DOI: 10.1098/rsos.200543 -
Radiation Oncology (London, England) Nov 2021Boron neutron capture therapy (BNCT) was first proposed as early as 1936, and research on BNCT has progressed relatively slowly but steadily. BNCT is a potentially... (Review)
Review
Boron neutron capture therapy (BNCT) was first proposed as early as 1936, and research on BNCT has progressed relatively slowly but steadily. BNCT is a potentially useful tool for cancer treatment that selectively damages cancer cells while sparing normal tissue. BNCT is based on the nuclear reaction that occurs when B capture low-energy thermal neutrons to yield high-linear energy transfer (LET) α particles and recoiling Li nuclei. A large number of B atoms have to be localized within the tumor cells for BNCT to be effective, and an adequate number of thermal neutrons need to be absorbed by the B atoms to generate lethal B (n, α)Li reactions. Effective boron neutron capture therapy cannot be achieved without appropriate boron carriers. Improvement in boron delivery and the development of the best dosing paradigms for both boronophenylalanine (BPA) and sodium borocaptate (BSH) are of major importance, yet these still have not been optimized. Here, we present a review of this treatment modality from the perspectives of radiation oncology, biology, and physics. This manuscript provides a brief introduction of the mechanism of cancer-cell-selective killing by BNCT, radiobiological factors, and progress in the development of boron carriers and neutron sources as well as the results of clinical study.
Topics: Animals; Boron Compounds; Boron Neutron Capture Therapy; Brain Neoplasms; Humans
PubMed: 34743756
DOI: 10.1186/s13014-021-01939-7 -
Biomedicines Jun 2023The development of new methods increasing the biological effectiveness of proton therapy (PT) is of high interest in radiation oncology. The use of binary technologies,... (Review)
Review
The development of new methods increasing the biological effectiveness of proton therapy (PT) is of high interest in radiation oncology. The use of binary technologies, in which the damaging effect of proton radiation is further enhanced by the selective accumulation of the radiosensitizer in the target tissue, can significantly increase the effectiveness of radiation therapy. To increase the absorbed dose in a tumor target, proton boron capture therapy (PBCT) was proposed based on the reaction of proton capture on the B isotope with the formation of three α-particles. This review summarizes data on theoretical and experimental studies on the effectiveness and prospects of proton boron capture therapy.
PubMed: 37371822
DOI: 10.3390/biomedicines11061727 -
Biology Jun 2023Time-lapse fluorescence imaging coupled to micro-irradiation devices provides information on the kinetics of DNA repair protein accumulation, from a few seconds to...
Time-lapse fluorescence imaging coupled to micro-irradiation devices provides information on the kinetics of DNA repair protein accumulation, from a few seconds to several minutes after irradiation. Charged-particle microbeams are valuable tools for such studies since they provide a way to selectively irradiate micrometric areas within a cell nucleus, control the dose and the micro-dosimetric quantities by means of advanced detection systems and Monte Carlo simulations and monitor the early cell response by means of beamline microscopy. We used the charged-particle microbeam installed at the AIFIRA facility to perform micro-irradiation experiments and measure the recruitment kinetics of two proteins involved in DNA signaling and repair pathways following exposure to protons and α-particles. We developed and validated image acquisition and processing methods to enable a systematic study of the recruitment kinetics of GFP-XRCC1 and GFP-RNF8. We show that XRCC1 is recruited to DNA damage sites a few seconds after irradiation as a function of the total deposited energy and quite independently of the particle LET. RNF8 is recruited to DNA damage sites a few minutes after irradiation and its recruitment kinetics depends on the particle LET.
PubMed: 37508352
DOI: 10.3390/biology12070921 -
Clinical Cancer Research : An Official... May 2022The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a...
PURPOSE
The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.
PATIENTS AND METHODS
Eighteen patients (median age, 64 years; range, 45-80) with relapsed or refractory AML received a single infusion of 225Ac-lintuzumab at activities of 18.5 to 148 kBq/kg.
RESULTS
The maximum tolerated dose was 111 kBq/kg. Dose-limiting toxicities included myelosuppression lasting > 35 days in one patient receiving 148 kBq/kg and death from sepsis in two patients treated with 111 and 148 kBq/kg. Myelosuppression was the most common toxicity. Significant extramedullary toxicities were limited to transient grade 3 liver function abnormalities. Pharmacokinetics were determined by gamma counting serial whole blood, plasma, and urine samples at energy windows for the 225Ac daughters, francium-221 and bismuth-213. Two-phase elimination kinetics were seen with mean plasma t1/2 - α and t1/2 - β of 1.9 and 38 hours, respectively. Peripheral blood blasts were eliminated in 10 of 16 evaluable patients (63%) but only at doses of ≥ 37 kBq/kg. Bone marrow blasts were reduced in 10 of 15 evaluable patients (67%), including 3 patients with marrow blasts ≤ 5% and one patient with a morphologic leukemia-free state.
CONCLUSIONS
Therapy for AML with the targeted α-particle generator 225Ac-lintuzumab was feasible with an acceptable safety profile. Elimination of circulating blasts or reductions in marrow blasts were observed across all dose levels.
Topics: Actinium; Alpha Particles; Antibodies, Monoclonal, Humanized; Humans; Immunoconjugates; Leukemia, Myeloid, Acute; Middle Aged
PubMed: 35247915
DOI: 10.1158/1078-0432.CCR-21-3712 -
Frontiers in Oncology 2022Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery,...
Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ doubled the cytotoxic effect of each of the treatments alone in U87 cultured cells. A colony formation assay demonstrated that the surviving fraction of U87 cells treated by TMZ in combination with alpha irradiation was lower than was achieved by alpha- or x-ray irradiation as monotherapies, or by x-ray combined with TMZ. The treatment of U87-bearing mice with DaRT and TMZ delayed tumor development more than the monotherapies. Unlike other radiation types, alpha radiation did not increase VEGF secretion from U87 cells in culture. BEV treatment introduced several days after DaRT implantation improved tumor control, compared to BEV or DaRT as monotherapies. The combination was also shown to be superior when starting BEV administration prior to DaRT implantation in large tumors relative to the seed size. BEV induced a decrease in CD31 staining under DaRT treatment, increased the diffusive spread of Ra progeny atoms in the tumor tissue, and decreased their clearance from the tumor through the blood. Taken together, the combinations of DaRT with standard-of-care chemotherapy or antiangiogenic therapy are promising approaches, which may improve the treatment of GBM patients.
PubMed: 36237307
DOI: 10.3389/fonc.2022.888100