scholarly journals Comparison of Proton and Photon Beam Irradiation in Radiation-Induced Intestinal Injury Using a Mouse Model

2019 ◽  
Vol 20 (8) ◽  
pp. 1894 ◽  
Author(s):  
Changhoon Choi ◽  
Chansu Lee ◽  
Sung-Won Shin ◽  
Shin-Yeong Kim ◽  
Sung Noh Hong ◽  
...  
Keyword(s):  
Proton Beam ◽  
Mouse Models ◽  
Proton Irradiation ◽  
Apoptotic Cell ◽  
Proton Beam Therapy ◽  
Tunel Assay ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Limiting Factor ◽  
X Rays ◽  
X Ray

When radiotherapy is applied to the abdomen or pelvis, normal tissue toxicity in the gastrointestinal (GI) tract is considered a major dose-limiting factor. Proton beam therapy has a specific advantage in terms of reduced doses to normal tissues. This study investigated the fundamental differences between proton- and X-ray-induced intestinal injuries in mouse models. C57BL/6J mice were irradiated with 6-MV X-rays or 230-MeV protons and were sacrificed after 84 h. The number of surviving crypts per circumference of the jejunum was identified using Hematoxylin and Eosin staining. Diverse intestinal stem cell (ISC) populations and apoptotic cells were analyzed using immunohistochemistry (IHC) and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay, respectively. The crypt microcolony assay revealed a radiation-dose-dependent decrease in the number of regenerative crypts in the mouse jejunum; proton irradiation was more effective than X-ray irradiation with a relative biological effectiveness of 1.14. The jejunum is the most sensitive to radiations, followed by the ileum and the colon. Both types of radiation therapy decreased the number of radiosensitive, active cycling ISC populations. However, a higher number of radioresistant, reserve ISC populations and Paneth cells were eradicated by proton irradiation than X-ray irradiation, as shown in the IHC analyses. The TUNEL assay revealed that proton irradiation was more effective in enhancing apoptotic cell death than X-ray irradiation. This study conducted a detailed analysis on the effects of proton irradiation versus X-ray irradiation on intestinal crypt regeneration in mouse models. Our findings revealed that proton irradiation has a direct effect on ISC populations, which may result in an increase in the risk of GI toxicity during proton beam therapy.

scholarly journals Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 554
Author(s):  
Changhoon Choi ◽  
Ga Haeng Lee ◽  
Arang Son ◽  
Gyu Sang Yoo ◽  
Jeong Il Yu ◽  
...  
Keyword(s):  
Proton Beam ◽  
Proton Irradiation ◽  
Apoptotic Cell ◽  
Relative Effectiveness ◽  
Hdac Inhibitors ◽  
Proton Beam Therapy ◽  
Clonogenic Survival ◽  
X Rays ◽  
Histone H4 ◽  
X Ray

Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Panobinostat increased G2/M arrest and production of intracellular reactive oxygen species, which was further enhanced by proton irradiation. Immunofluorescence staining of γH2AX showed that panobinostat enhanced proton-induced DNA damage. Panobinostat dose-dependently decreased expression of an anti-apoptotic protein, Mcl-1, concomitant with increasing acetylation of histone H4. The combination of panobinostat with proton irradiation enhanced apoptotic cell death to a greater extent than that with X-ray irradiation. Depletion of Mcl-1 by RNA interference enhanced proton-induced apoptosis and proton radiosensitization, suggesting a potential role of Mcl-1 in determining proton sensitivity. Together, our findings suggest that panobinostat may be a promising combination agent for proton beam therapy in HCC treatment.

scholarly journals A novel range telescope concept for proton CT

2022 ◽  
Author(s):  
Marc Granado-González ◽  
César Jesús-Valls ◽  
Thorsten Lux ◽  
Tony Price ◽  
Federico Sánchez
Keyword(s):  
Computed Tomography ◽  
Proton Beam ◽  
Energy Resolution ◽  
Plastic Scintillator ◽  
Proton Beam Therapy ◽  
Stopping Power ◽  
High Quality ◽  
X Ray ◽  
Proton Computed Tomography ◽  
Clinical Conditions

Abstract Proton beam therapy can potentially offer improved treatment for cancers of the head and neck and in paediatric patients. There has been asharp uptake of proton beam therapy in recent years as improved delivery techniques and patient benefits are observed. However, treatments are currently planned using conventional x-ray CT images due to the absence of devices able to perform high quality proton computed tomography(pCT) under realistic clinical conditions. A new plastic-scintillator-based range telescope concept, named ASTRA, is proposed here to measure the proton’s energy loss in a pCT system. Simulations conducted using GEANT4 yield an expected energy resolution of 0.7%. If calorimetric information is used the energy resolution could be further improved to about 0.5%. In addition, the ability of ASTRA to track multiple protons simultaneously is presented. Due to its fast components, ASTRA is expected to reach unprecedented data collection rates, similar to 10^8 protons/s.The performance of ASTRA has also been tested by simulating the imaging of phantoms. The results show excellent image contrast and relative stopping power reconstruction.

scholarly journals Micrometer-resolution imaging using MÖNCH: towards G2-less grating interferometry

2016 ◽  
Vol 23 (6) ◽  
pp. 1462-1473 ◽  
Author(s):  
Sebastian Cartier ◽  
Matias Kagias ◽  
Anna Bergamaschi ◽  
Zhentian Wang ◽  
Roberto Dinapoli ◽  
...  
Keyword(s):  
High Resolution ◽  
Silicon Detector ◽  
Limiting Factor ◽  
X Rays ◽  
X Ray ◽  
Charge Cloud ◽  
High Resolution Images ◽  
Resolution Imaging ◽  
Hybrid Silicon ◽  
Small Pixel

MÖNCH is a 25 µm-pitch charge-integrating detector aimed at exploring the limits of current hybrid silicon detector technology. The small pixel size makes it ideal for high-resolution imaging. With an electronic noise of about 110 eV r.m.s., it opens new perspectives for many synchrotron applications where currently the detector is the limiting factor,e.g.inelastic X-ray scattering, Laue diffraction and soft X-ray or high-resolution color imaging. Due to the small pixel pitch, the charge cloud generated by absorbed X-rays is shared between neighboring pixels for most of the photons. Therefore, at low photon fluxes, interpolation algorithms can be applied to determine the absorption position of each photon with a resolution of the order of 1 µm. In this work, the characterization results of one of the MÖNCH prototypes are presented under low-flux conditions. A custom interpolation algorithm is described and applied to the data to obtain high-resolution images. Images obtained in grating interferometry experiments without the use of the absorption grating G2are shown and discussed. Perspectives for the future developments of the MÖNCH detector are also presented.

Computational evaluation of dose distribution for BNCT treatment combined with X-ray therapy or proton beam therapy

2020 ◽  
Vol 165 ◽  
pp. 109295
Author(s):  
Kenta Takada ◽  
Hiroaki Kumada ◽  
Akira Matsumura ◽  
Hideyuki Sakurai ◽  
Takeji Sakae
Keyword(s):  
Proton Beam ◽  
Dose Distribution ◽  
Proton Beam Therapy ◽  
X Ray ◽  
Computational Evaluation

scholarly journals Proton beam therapy: perspectives on the National Health Service England clinical service and research programme

2020 ◽  
Vol 93 (1107) ◽  
pp. 20190873 ◽  
Author(s):  
Neil G Burnet ◽  
Ranald I Mackay ◽  
Ed Smith ◽  
Amy L Chadwick ◽  
Gillian A Whitfield ◽  
...  
Keyword(s):  
Dna Damage ◽  
National Health Service ◽  
Health Service ◽  
Proton Beam ◽  
National Health ◽  
Proton Beam Therapy ◽  
Systematic Evaluation ◽  
High Dose ◽  
X Rays ◽  
The Uk

The UK has an important role in the evaluation of proton beam therapy (PBT) and takes its place on the world stage with the opening of the first National Health Service (NHS) PBT centre in Manchester in 2018, and the second in London coming in 2020. Systematic evaluation of the role of PBT is a key objective. By September 2019, 108 patients had started treatment, 60 paediatric, 19 teenagers and young adults and 29 adults. Obtaining robust outcome data is vital, if we are to understand the strengths and weaknesses of current treatment approaches. This is important in demonstrating when PBT will provide an advantage and when it will not, and in quantifying the magnitude of benefit. The UK also has an important part to play in translational PBT research, and building a research capability has always been the vision. We are perfectly placed to perform translational pre-clinical biological and physical experiments in the dedicated research room in Manchester. The nature of DNA damage from proton irradiation is considerably different from X-rays and this needs to be more fully explored. A better understanding is needed of the relative biological effectiveness (RBE) of protons, especially at the end of the Bragg peak, and of the effects on tumour and normal tissue of PBT combined with conventional chemotherapy, targeted drugs and immunomodulatory agents. These experiments can be enhanced by deterministic mathematical models of the molecular and cellular processes of DNA damage response. The fashion of ultra-high dose rate FLASH irradiation also needs to be explored.

scholarly journals Checkpoint Kinase 1 (CHK1) Inhibition Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Proton Irradiation via Rad51 Downregulation

2020 ◽  
Vol 21 (8) ◽  
pp. 2691 ◽  
Author(s):  
Changhoon Choi ◽  
Won Kyung Cho ◽  
Sohee Park ◽  
Sung-Won Shin ◽  
Won Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Proton Irradiation ◽  
Treatment Options ◽  
Annexin V ◽  
Proton Beam Therapy ◽  
X Rays ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC.

PIXE STUDIES ON GOLD STANDARDS BY PROTONS OF ENERGY 3.3 MeV

2004 ◽  
Vol 14 (03n04) ◽  
pp. 141-146 ◽  
Author(s):  
DAISY JOSEPH ◽  
A. SAXENA ◽  
S. K. GUPTA ◽  
S. KAILAS
Keyword(s):  
Proton Beam ◽  
Energy Dispersive ◽  
X Rays ◽  
X Ray ◽  
Ion Accelerator ◽  
Folded Tandem Ion Accelerator ◽  
Certified Values ◽  
A Current ◽  
Gold Standards

Proton Induced X-ray Emission Technique (PIXE) has been used in analyzing Gold standards of 22, 20, 18, and 14 karats with a proton beam of Energy 3.3 MeV at the newly commissioned Folded Tandem Ion Accelerator (FOTIA) at B.A.R.C, Trombay. Well resolved Au and Ag X-rays were detected at a current of 3 nA . Percentage values of gold and silver were calculated and were checked with those obtained by Energy Dispersive X-ray Fluorescence (EDXRF) Method and were found to be in agreement with the certified values as well as those obtained by XRF.

Heavy Ion-Induced Characteristic X-Ray Generation as an Analytical Probe

1970 ◽  
Vol 14 ◽  
pp. 173-183 ◽  
Author(s):  
J. A. Cairns ◽  
D. F. Holloway ◽  
R. S. Nelson
Keyword(s):  
Cross Sections ◽  
Heavy Ions ◽  
Proton Irradiation ◽  
Heavy Ion ◽  
X Rays ◽  
X Ray ◽  
The Past ◽  
Tracer Techniques ◽  
New Type ◽  
Gas Volume

AbstractIncreasing attention is currently focused on the generation of characteristic x-ray by proton irradiation. This has the advantage of yielding “clean” x-ray- i. e. free from background brerasstrahlung radiation, from even the lightest elements. The disadvantage is that the yields are naturally much lower than those produced by electrons of the same energy. A recent study has extended characteristic x-ray production to a variety of heavy ions and has shown that the cross- sections for the production of clean x-rays are often higher , by as much as several orders of magnitude, than those produced by protons of the same energy. In addition, there has emerged a further advantage, viz. the ability of specially chosen heavy ions to excite characteristic x-ray from a particular element in a selective manner. Since heavy ions penetrate only a few hundred Angstroms in to most solids, the phenomenon can be used as the basis of a technique for the examination of surface deposits, or to measure depth distributions of impurities. For example, Kr ions can be used t o determine the range distribution of antimony which had been implanted in to silicon at 100 keV. The antimony concentration was determined as a function of ∼ 150 Å steps, and was found to exhibit a maximum concentration of ∼ 1 part in 103 of silicon at 450 Å below the surface, falling to zero concentration at ∼2000 Å a depth. In the past, in order to obtain the required degree of sensitivity, such range determinations have relied on radio active tracer techniques.An entirely new type of proportional counter has been developed during the course of these studies. This instrument, because of its special construction, can be positioned very close to targets in non-dispersive studies, so as to collect the highest possible fraction of emitted x-ray. It incorporates a replaceable anode unit, together with a built- in miniature head amplifier, and exhibits extremely good performance, particularly for ultra-soft x-ray. In addition, rotation of a dial on the end of the counter body allows alteration of the active gas volume during operation, and so permits tuning into x-rays of a particular energy.

PLATINUM GROUP ELEMENT HIGH-ENERGY PIXE

1990 ◽  
Vol 01 (02) ◽  
pp. 147-156 ◽  
Author(s):  
NORMAN M. HALDEN ◽  
FRANK C. HAWTHORNE ◽  
J.J. GUY DUROCHER ◽  
JASPER S.C. McKEE ◽  
ALI MIRZAI
Keyword(s):  
Quantitative Analysis ◽  
Proton Beam ◽  
Cross Section ◽  
Platinum Group Element ◽  
High Energy ◽  
Group Element ◽  
X Rays ◽  
Proton Bombardment ◽  
X Ray ◽  
Platinum Group

K X-ray spectra have been obtained from Platinum-Group Element (PGE) minerals using 40 MeV Proton-Induced X-ray Emission. It is possible to resolve all four component X-ray lines for the PGEs. In cases where there is more than one PGE present, some K X-ray lines may overlap, but in all cases, there were single lines available for quantitative analysis. The spectrum obtained from the sperrylite during exposure to the proton beam beam contained Au X-rays. The presence of the Au can be attributed to (p,xn) reactions with Pt, induced by proton bombardment of the sample. The intensity of Au X-ray lines in the spectrum is proportional to the amount of Pt in the sample and the cross-section for (p,xn) reactions between Pt and Au at 40 MeV.

INVESTIGATION OF TUMOR CELL TOXICITY FROM PARTICLE INDUCED X-RAY EMISSION FROM A 45-MeV PROTON BEAM IRRADIATED FERRITE NANOPARTICLE

2009 ◽  
Vol 19 (03n04) ◽  
pp. 143-155 ◽  
Author(s):  
KI-HONG KIM ◽  
HONG-TAE KIM ◽  
JONG-HEE KIM ◽  
SEUNG-JUN SEO ◽  
DUCK-SOO CHUNG ◽  
...  
Keyword(s):  
Proton Beam ◽  
Proton Beam Therapy ◽  
Ferrite Nanoparticles ◽  
Cancer Center ◽  
Control Group ◽  
X Ray ◽  
Nanoparticle Distribution ◽  
Acridine Orange Staining ◽  
Horizontal Beam ◽  
Center Hospital

In order to investigate the potential cytotoxic effects of particle-induced x-ray emission (PIXE) on tumor cells, 45 MeV proton beam was irradiated on C6 glioma cell lines that had taken up alginate-coated ferrite nanoparticles (Alg-SNP). Cells were anchored in vertical 96-well dishes facing a horizontal beam where the Bragg peak was placed on the upper part of the 96-well dish. Experimental groups included cells without SNP as a control (No-SNP), and cells incubated with SNP for 6 hours (6hr-SNP) or overnight (ON-SNP). A 0 to 200 Gy proton beam from an MC50 cyclotron (Scanditronix, Sweden) at the Korea Cancer Center Hospital (Seoul, Korea) was used to irradiate each experimental group. Perinuclear Alg-SNP nanoparticle distribution was observed in glioma cells. The test groups (6hr-SNP or ON-SNP) showed an estimated 20-28% (ANOVA, P < 0.05) less cell survival compared to the control group based on MTT assay. Nuclear damage, indicating apoptosis, was present at a higher frequency in the 6hr-SNP and ON-SNP groups up to relatively low radiation dose of 100 Gy by fluorescence microscopy upon Hoechst 33342 and Acridine Orange staining. Ferrite nanoparticles alone were not cytotoxic at the experimental concentration of 0.15 mg/ml. Therefore ferrite nanoparticles may induce additional cytotoxicity from X-ray emission from potential PIXE effects. PIXE and metal nanoparticles may be developed as a therapeutic factor and prodrug for localized proton beam therapy without side effects of solid or disseminate tumors on the surrounding normal tissue.

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