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International Journal of Particle... Jun 2024It is known that radiation to dentofacial structures during childhood can lead to developmental disturbances. However, this appears to be a relatively subordinated... (Review)
Review
PURPOSE
It is known that radiation to dentofacial structures during childhood can lead to developmental disturbances. However, this appears to be a relatively subordinated research subject. For this reason, this review aims to establish the current evidence base on the effect of PBT on dentofacial development in paediatric patients treated for cancer in the head and neck region.
MATERIALS AND METHODS
A comprehensive search was undertaken to identify both published and unpublished studies or reports. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was then conducted.
RESULTS
82 records were screened in total, resulting in 11 included articles. These articles varied in terms of study design and reporting quality. Owing to both poor study reporting and limited patient numbers, it is not possible to determine the effect of cancer diagnosis, chronological age at treatment, radiation dose or treatment modality on the incidence of facial deformation or dental development anomalies.
CONCLUSION
Disturbances in dentofacial development are an under-reported toxicity in paediatric cancer survivors treated with PBT to the head and neck. There is a need for more research on dentofacial toxicity reporting, focused on the impact of treatment age, radiation dose, concurrent therapies, and the subsequent impact on quality of life.
PubMed: 38952615
DOI: 10.1016/j.ijpt.2024.100107 -
Journal of Leukocyte Biology Jul 2024The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation...
The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation post-cancer treatment, which influences treatment outcomes. Understanding these biomarker variations and leukocyte subpopulation interplay is crucial for optimizing radiotherapy. Herein, leukocyte subpopulations (T-CD4+, T-CD8+, B-cells, NK-cells, neutrophils, monocytes) during and after brain irradiation (using X-rays or Protons) in tumor-free mice were used to compute ALC, LMR, and NLR, on which radiation parameter influence was assessed by principal component analysis (PCA). NLR kinetics were further examined using modeling. Leukocyte subpopulations interplays and their response to radiation parameters were examined using PCA and correlation analysis. Under X-rays, ALC and LMR decreased, with ALC recovered to baseline after irradiation, but not LMR. Both X-rays and protons increased the NLR during irradiation, recovering in protons but not X-rays. Both irradiation volume and dose rate had a pronounced effect on the NLR. Leukocyte subpopulation interplay was observed under X-rays and protons, normalizing in the proton group by day 28. Lymphopenia was observed in all lymphocyte subpopulations under X-ray irradiation but not protons. The recovery patterns varied among the subpopulations. Neutrophil counts increased during irradiation, with the recovery of protons, but not X-rays, by day 28. Interplays between NK-cells and myeloid subpopulations were evident under X-rays but not protons. Importantly, no interplay was detected between myeloid cells and T/B-cells, indicating that LMR and NLR variations were primarily due to independent responses to brain irradiation. A tumor-free experimental mouse model was used to study the effects of brain radiotherapy on systemic immunity. When administering fractionated irradiation with a total dose of 20 Gy using a vertical beam to either the whole brain or hemi-brain, proton irradiation had fewer adverse impacts on the immune system compared to X-rays in tumor-free rodents.
PubMed: 38952292
DOI: 10.1093/jleuko/qiae156 -
Journal of Nanobiotechnology Jul 2024Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently,...
BACKGROUND
Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear.
RESULTS
Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs.
CONCLUSIONS
These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.
Topics: Animals; Extracellular Vesicles; Mice; Myocardial Reperfusion Injury; Myocytes, Cardiac; Male; Mice, Inbred C57BL; Mitochondrial Proton-Translocating ATPases; Mitochondria; Myocardium; Reactive Oxygen Species; Ferroptosis; Disease Models, Animal
PubMed: 38951822
DOI: 10.1186/s12951-024-02618-x -
Supportive Care in Cancer : Official... Jun 2024This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise compliance, and self-efficacy in patients receiving proton and heavy ion therapy for head and neck cancer.
METHODS
This open-label, parallel-group, randomized, superiority trial involved a self-developed "Health Enjoy System" intervention. We assessed maximal mouth opening, exercise compliance, and self-efficacy at baseline (T), post-treatment (T), and at 1 month (T) and 3 months (T) after radiotherapy. Generalized estimating equations were used to analyze differences between the groups over time, with results reported as P values and 95% confidence intervals (CIs).
RESULTS
The study included 44 participants. At T, the intervention group showed a 6 mm greater increase in maximal interincisal opening than the control group (mean difference = 6.0, 95% CI = 2.4 to 9.5, P = 0.001). There was also a significant difference in exercise compliance between the groups (mean difference = 31.7, 95% CI = 4.6 to 58.8, P = 0.022). However, no significant difference in self-efficacy was found between the groups.
CONCLUSION
This study demonstrated that an mHealth intervention incorporating behavior change theory could effectively enhance or maintain maximal mouth opening in patients undergoing proton and heavy ion therapy for head and neck cancer in China. This approach provides valuable support during and after treatment.
TRIAL REGISTRATION
ChiCTR: ChiCTR2300067550. Registered 11 Jan 2023.
Topics: Humans; Head and Neck Neoplasms; Male; Middle Aged; Female; Proton Therapy; Self Efficacy; Telemedicine; Trismus; Heavy Ion Radiotherapy; Exercise Therapy; Aged; Patient Compliance; Adult
PubMed: 38951291
DOI: 10.1007/s00520-024-08679-w -
Medical Physics Jul 2024MR-integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an...
BACKGROUND
MR-integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross-talk during beam delivery and image acquisition.
PURPOSE
To create and benchmark a self-consistent proton PBS nozzle model for empowering the next stages of MR-integrated proton therapy development, namely exploring and de-risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle.
MATERIALS AND METHODS
Magnetic field (COMSOL ) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL simulations. In total 315 spots were simulated which consisted of a scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self-consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of 20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off-axis positions were measured at 22 cm downstream of isocenter ( 50, 100, and 150 cm from CAX).
RESULTS
The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0-2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9 1.2 -9.4 1.2 changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point.
CONCLUSIONS
For the first time a robust, accurate and self-consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR-integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de-risk and realize the full potential of MR-integrated proton therapy.
PubMed: 38949569
DOI: 10.1002/mp.17279 -
JPMA. the Journal of the Pakistan... Jun 2024To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
OBJECTIVES
To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
METHODS
The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25.
RESULTS
Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia.
CONCLUSIONS
Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.
Topics: Humans; Proton Pump Inhibitors; Female; Cross-Sectional Studies; Male; Hyperprolactinemia; Prolactin; Adult; Middle Aged; Pakistan; Prevalence
PubMed: 38948973
DOI: 10.47391/JPMA.9541 -
Food Research International (Ottawa,... Aug 2024There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung...
There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 (Divalent metal transporter 1), Fpn 1 (Ferroportin 1), and Dcytb (Duodenal cytochrome b) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.
Topics: Animals; Vigna; Anemia, Iron-Deficiency; Biological Availability; Mice; Ferrous Compounds; Peptides; Iron; Male; Iron Chelating Agents; Hemoglobins; Dietary Supplements; Cation Transport Proteins; Disease Models, Animal; Glycine
PubMed: 38945571
DOI: 10.1016/j.foodres.2024.114602 -
Radiotherapy and Oncology : Journal of... Jun 2024Sacrococcygeal chordomas have high recurrence rates and are challenging to treat.
INTRODUCTION
Sacrococcygeal chordomas have high recurrence rates and are challenging to treat.
METHODS
In this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3-5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS).
RESULTS
The study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5-6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade IV wound healing disorders (6 %).
CONCLUSION
The initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma.
PubMed: 38944346
DOI: 10.1016/j.radonc.2024.110418 -
Japanese Journal of Clinical Oncology Jun 2024Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison...
BACKGROUND
Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison with traditional proton beam therapy, scanning proton beam therapy is effective in delivering proton beams to irregularly shaped tumors, reducing excessive radiation exposure to the alimentary tract during the treatment of liver cancer.
METHODS
In this study, we utilized positron emission tomography/computed tomography (PET/CT) imaging to assess the total amount of radiation to the alimentary tract during liver cancer treatment with proton beam therapy, involving the administration of complex irradiation in 13 patients.
RESULTS
This approach resulted in the prevention of excess radiation. The planned radiation restraint doses for the colon exhibited a significant correlation with the PET values of the colon (correlation coefficient 0.8384, P = .0003). Likewise, the scheduled radiation restraint doses for the gastroduodenum were correlated with the PET values of the gastroduodenum (correlation coefficient 0.5397, P = .0569).
CONCLUSIONS
PET/CT conducted after proton beam therapy is useful for evaluating excess radiation in the alimentary tract. Proton beam therapy in liver cancer, assessed via PET/CT, effectively reduced alimentary tract radiation, which is vital for optimizing treatments and preventing excess exposure.
PubMed: 38943456
DOI: 10.1093/jjco/hyae085 -
Radiotherapy and Oncology : Journal of... Jun 2024To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor...
PURPOSE
To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber.
METHODS AND MATERIALS
227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector.
RESULTS
Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ± 3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ± 0.8 Gy/s and mean local average dose rate of 160.6 ± 3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose.
CONCLUSION
In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.
PubMed: 38942121
DOI: 10.1016/j.radonc.2024.110404