Jakubek, Jan*
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A method has been developed for routine laboratory visualisation of small-scale soft tissue by means of transmission X-ray radioscopy and tomography. Using termites as models, imaging quality with a spatial resolution of about 3 mum was achieved and 3D tomographic reconstruction was demonstrated. A termite worker individual was visualized before and after its metamorphosis towards the soldier caste. The developed methodology represents a non-invasive and real-time way of acquiring 3D anatomic data with a high contrast so that it is a promising candidate to become a tool for routine investigations in life sciences.
BACKGROUND: FLASH radiotherapy necessitates the development of advanced Quality Assurance methods and detectors for accurate monitoring of the radiation field. This study introduces enhanced time-resolution detection systems and methods used to measure the delivered number of pulses, investigate temporal structure of individual pulses and dose-per-pulse (DPP) based on secondary radiation particles produced in the experimental room. METHODS: A 20 MeV electron beam generated from a linear accelerator (LINAC) was delivered to a water phantom. Ultra-high dose-per-pulse electron beams were used with a dose-per-pulse ranging from ̴ 1 Gy to over 7 Gy. The pulse lengths ranged from 1.18 μs to 2.88 μs at a pulse rate frequency of 5 Hz. A semiconductor pixel detector Timepix3 was used to track single secondary particles. Measurements were performed in the air, while the detector was positioned out-of-field at a lateral distance of 200 cm parallel with the LINAC exit window. The dose deposited was measured along with the pulse length and the nanostructure of the pulse. RESULTS: The time of arrival (ToA) of single particles was measured with a resolution of 1.56 ns, while the deposited energy was measured with a resolution of several keV based on the Time over Threshold (ToT) value. The pulse count measured by the Timepix3 detector corresponded with the delivered values, which were measured using an in-flange integrating current transformer (ICT). A linear response (R2 = 0.999) was established between the delivered beam current and the measured dose at the detector position (orders of nGy). The difference between the average measured and delivered pulse length was ∼0.003(30) μs. CONCLUSION: This simple non-invasive method exhibits no limitations on the delivered DPP within the range used during this investigation.
A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid. The method was validated for parameters including linearity, accuracy, precision, limit of quantitation and limit of detection, as well as robustness. The response was found linear over the range of 3-100 μg/mL as demonstrated by the acquired value of correlation coefficient R2=0.9997. The described method is applicable for determination of various pharmacokinetic aspects of ketoprofen in vitro.
Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent backing were detached and immersed in the water-phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally, at different depths, and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET(Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations up to the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses.
- MeSH
- křemík MeSH
- lineární přenos energie MeSH
- protonová terapie * metody MeSH
- protony MeSH
- radiometrie * metody MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
Most cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the migration machinery has been shown to promote metastatic dissemination, successful migrastatic therapy may reduce the need for high-dose cytotoxic therapies that are currently used to prevent the risk of metastatic dissemination. In this review we focus on anti-invasive and antimetastatic strategies that hold promise for the treatment of solid tumors. The best targets for migrastatic therapy would be those that are required by all forms of motility, such as ATP availability, mitochondrial metabolism, and cytoskeletal dynamics and cell contractility.
- MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- pohyb buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Objective.This work presents a method for enhanced detection, imaging, and measurement of the thermal neutron flux.Approach. Measurements were performed in a water tank, while the detector is positioned out-of-field of a 20 MeV ultra-high pulse dose rate electron beam. A semiconductor pixel detector Timepix3 with a silicon sensor partially covered by a6LiF neutron converter was used to measure the flux, spatial, and time characteristics of the neutron field. To provide absolute measurements of thermal neutron flux, the detection efficiency calibration of the detectors was performed in a reference thermal neutron field. Neutron signals are recognized and discriminated against other particles such as gamma rays and x-rays. This is achieved by the resolving power of the pixel detector using machine learning algorithms and high-resolution pattern recognition analysis of the high-energy tracks created by thermal neutron interactions in the converter.Main results. The resulting thermal neutrons equivalent dose was obtained using conversion factor (2.13(10) pSv·cm2) from thermal neutron fluence to thermal neutron equivalent dose obtained by Monte Carlo simulations. The calibrated detectors were used to characterize scattered radiation created by electron beams. The results at 12.0 cm depth in the beam axis inside of the water for a delivered dose per pulse of 1.85 Gy (pulse length of 2.4μs) at the reference depth, showed a contribution of flux of 4.07(8) × 103particles·cm-2·s-1and equivalent dose of 1.73(3) nSv per pulse, which is lower by ∼9 orders of magnitude than the delivered dose.Significance. The presented methodology for in-water measurements and identification of characteristic thermal neutrons tracks serves for the selective quantification of equivalent dose made by thermal neutrons in out-of-field particle therapy.
- MeSH
- algoritmy * MeSH
- elektrony * MeSH
- kalibrace MeSH
- neutrony MeSH
- záření gama MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interleukin 6 (IL-6) belongs to a broad class of cytokines involved in the regulation of various homeostatic and pathological processes. These activities range from regulating embryonic development, wound healing and ageing, inflammation, and immunity, including COVID-19. In this review, we summarise the role of IL-6 signalling pathways in cancer biology, with particular emphasis on cancer cell invasiveness and metastasis formation. Targeting principal components of IL-6 signalling (e.g., IL-6Rs, gp130, STAT3, NF-κB) is an intensively studied approach in preclinical cancer research. It is of significant translational potential; numerous studies strongly imply the remarkable potential of IL-6 signalling inhibitors, especially in metastasis suppression.
- MeSH
- interleukin-6 metabolismus MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- protinádorové látky * terapeutické užití MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ion-beam radiotherapy is an advanced cancer treatment modality offering steep dose gradients and a high biological effectiveness. These gradients make the therapy vulnerable to patient-setup and anatomical changes between treatment fractions, which may go unnoticed. Charged fragments from nuclear interactions of the ion beam with the patient tissue may carry information about the treatment quality. Currently, the fragments escape the patient undetected. Inter-fractional in-vivo treatment monitoring based on these charged nuclear fragments could make ion-beam therapy safer and more efficient. We developed an ion-beam monitoring system based on 28 hybrid silicon pixel detectors (Timepix3) to measure the distribution of fragment origins in three dimensions. The system design choices as well as the ion-beam monitoring performance measurements are presented in this manuscript. A spatial resolution of 4mm along the beam axis was achieved for the measurement of individual fragment origins. Beam-range shifts of 1.5mm were identified in a clinically realistic treatment scenario with an anthropomorphic head phantom. The monitoring system is currently being used in a prospective clinical trial at the Heidelberg Ion Beam Therapy Centre for head-and-neck as well as central nervous system cancer patients.
- MeSH
- celková dávka radioterapie MeSH
- fantomy radiodiagnostické * MeSH
- lidé MeSH
- radioterapie těžkými ionty metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.
- MeSH
- kurkumin * farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- protinádorové látky * farmakologie terapeutické užití chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
