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1.
Sci Rep ; 14(1): 11253, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755333

RESUMO

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.


Assuntos
Terapia por Captura de Nêutron de Boro , Lítio , Nêutrons , Terapia por Captura de Nêutron de Boro/métodos , Lítio/química , Humanos , Aceleradores de Partículas , Dosagem Radioterapêutica
2.
J Pineal Res ; 76(3): e12952, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38587234

RESUMO

Melatonin (5-methoxy-N-acetyltryptamine) binds with high affinity and specificity to membrane receptors. Several receptor subtypes exist in different species, of which the mammalian MT1 and MT2 receptors are the best-characterized. They are members of the G protein-coupled receptor superfamily, preferentially coupling to Gi/o proteins but also to other G proteins in a cell-context-depending manner. In this review, experts on melatonin receptors will summarize the current state of the field. We briefly report on the discovery and classification of melatonin receptors, then focus on the molecular structure of human MT1 and MT2 receptors and highlight the importance of molecular simulations to identify new ligands and to understand the structural dynamics of these receptors. We then describe the state-of-the-art of the intracellular signaling pathways activated by melatonin receptors and their complexes. Brief statements on the molecular toolbox available for melatonin receptor studies and future perspectives will round-up this review.


Assuntos
Melatonina , Receptor MT1 de Melatonina , Animais , Humanos , Receptores de Melatonina , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Melatonina/metabolismo , Transdução de Sinais , Receptores Acoplados a Proteínas G , Mamíferos/metabolismo
3.
Asian J Urol ; 11(2): 286-293, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38680582

RESUMO

Objectives: Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate cancer. Methods: HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were compared. Results: The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA (p<0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively (p<0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than HS. Conclusion: The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer.

4.
Med Phys ; 51(5): 3658-3664, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38507277

RESUMO

BACKGROUND: Failure mode and effects analysis (FMEA), which is an effective tool for error prevention, has garnered considerable attention in radiotherapy. FMEA can be performed individually, by a group or committee, and online. PURPOSE: To meet the needs of FMEA for various purposes and improve its accessibility, we developed a simple, self-contained, and versatile web-based FMEA risk analysis worksheet. METHODS: We developed an FMEA worksheet using Google products, such as Google Sheets, Google Forms, and Google Apps Script. The main sheet was created in Google Sheets and contained elements necessary for performing FMEA by a single person. Automated tasks were implemented using Apps Script to facilitate multiperson FMEA; these functions were built into buttons located on the main sheet. RESULTS: The usability of the FMEA worksheet was tested in several situations. The worksheet was feasible for individual, multiperson, seminar, meeting, and online purposes. Simultaneous online editing, automated survey form creation, automatic analysis, and the ability to respond to the form from multiple devices, including mobile phones, were particularly useful for online and multiperson FMEA. Automation enabled through Google Apps Script reduced the FMEA workload. CONCLUSIONS: The FMEA worksheet is versatile and has a seamless workflow that promotes collaborative work for safety.


Assuntos
Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Japão , Humanos , Física Médica , Internet , Universidades , População do Leste Asiático
5.
J Radiat Res ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38544297

RESUMO

This study assessed the significance of hands-on-training (HoT) and questionnaire-based surveys on 3D image-guided brachytherapy (3D-IGBT) and a combination of intracavitary and interstitial brachytherapy, the so-called 'hybrid' BT (HBT), in uterine cervical cancer. In October 2023, 29 radiation oncologists, nurses, radiologic technologists and medical physicists from 10 Japanese facilities participated in an HoT on 3D-IGBT and HBT. Questionnaires were distributed to each participant before and after the HoT, and feedback was obtained through online channels. The questionnaire response rate was 83% (24/29), with at least one participant responding from each facility. 'Insertion of applicators and needles', 'human resource shortage' and 'pain relief and sedation' were the primary concerns of radiation oncologists. 'Applicator reconstruction', ' optimization of dwell positions', ' treatment planning' and ' human resource shortages ' were the primary concerns of radiological technologists and medical physicists. The HoT content was adjusted according to the results of preliminary surveys. The concerns expressed by the participants were addressed during the lectures and practical training. Significant reductions in anxiety were observed toward all items of the 10-point self-assessment after the HoT, regardless of the profession. The average score on satisfaction with the HoT (on a 10-point scale) was 9.52 (minimum of 8 and maximum of 10). In conclusion, HoT tailored in response to a pre-questionnaire-based survey effectively reduced participants' anxiety regarding the implementation of 3D-IGBT and HBT.

6.
Med Dosim ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38368182

RESUMO

Previous plan competitions have largely focused on dose metric assessments. However, whether the submitted plans were realistic and reasonable from a quality assurance (QA) perspective remains unclear. This study aimed to investigate the relationship between aperture-based plan complexity metrics (PCM) in volumetric modulated arc therapy (VMAT) competition plans and clinical treatment plans verified through patient-specific QA (PSQA). In addition, the association of PCMs with plan quality was examined. A head and neck (HN) plan competition was held for Japanese institutions from June 2019 to July 2019, in which 210 competition plans were submitted. Dose distribution quality was quantified based on dose-volume histogram (DVH) metrics by calculating the dose distribution plan score (DDPS). Differences in PCMs between the two VMAT treatment plan groups (HN plan competitions held in Japan and clinically accepted HN VMAT plans through PSQA) were investigated. The mean (± standard deviation) DDPS for the 98 HN competition plans was 158.5 ± 20.6 (maximum DDPS: 200). DDPS showed a weak correlation with PCMs with a maximum r of 0.45 for monitor unit (MU); its correlation with some PCMs was "very weak." Significant differences were found in some PCMs between plans with the highest 20% DDPSs and the remaining plans. The clinical VMAT and competition plans revealed similar distributions for some PCMs. Deviations in PCMs for the two groups were comparable, indicating considerable variability among planners regarding planning skills. The plan complexity for HN VMAT competition plans increased for high-quality plans, as shown by the dose distribution. Direct comparison of PCMs between competition plans and clinically accepted plans showed that the submitted HN VMAT competition plans were realistic and reasonable from the QA perspective. This evaluation may provide a set of criteria for evaluating plan quality in plan competitions.

7.
Nat Commun ; 15(1): 902, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326347

RESUMO

GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-Gi complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.


Assuntos
Ácidos Graxos , Lisofosfolipídeos , Humanos , Microscopia Crioeletrônica , Ácidos Graxos/metabolismo , Ligantes , Lisofosfolipídeos/metabolismo , Receptores de Lisofosfolipídeos/agonistas , Receptores de Lisofosfolipídeos/metabolismo
8.
Appl Opt ; 63(2): 305-309, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227223

RESUMO

This study uses a generative adversarial network to design multilevel optical anisotropic diffraction gratings with specific customizable characteristics. As input, this method uses the far electric field of polarization and intensity in each diffracted light through the gratings to design. Using the finite-difference time-domain method, the designed structures are numerically evaluated, confirming that they can be created with the intended parameters. Multilevel optical anisotropic diffraction gratings created this way can be used in various fields to develop improved optical elements.

9.
J Appl Clin Med Phys ; 25(1): e14220, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37994694

RESUMO

PURPOSE: This study aimed to demonstrate the potential clinical applicability of an organ-contour-driven auto-matching algorithm in image-guided radiotherapy. METHODS: This study included eleven consecutive patients with cervical cancer who underwent radiotherapy in 23 or 25 fractions. Daily and reference magnetic resonance images were converted into mesh models. A weight-based algorithm was implemented to optimize the distance between the mesh model vertices and surface of the reference model during the positioning process. Within the cost function, weight parameters were employed to prioritize specific organs for positioning. In this study, three scenarios with different weight parameters were prepared. The optimal translation and rotation values for the cervix and uterus were determined based on the calculated translations alone or in combination with rotations, with a rotation limit of ±3°. Subsequently, the coverage probabilities of the following two planning target volumes (PTV), an isotropic 5 mm and anisotropic margins derived from a previous study, were evaluated. RESULTS: The percentage of translations exceeding 10 mm varied from 9% to 18% depending on the scenario. For small PTV sizes, more than 80% of all fractions had a coverage of 80% or higher. In contrast, for large PTV sizes, more than 90% of all fractions had a coverage of 95% or higher. The difference between the median coverage with translational positioning alone and that with both translational and rotational positioning was 1% or less. CONCLUSION: This algorithm facilitates quantitative positioning by utilizing a cost function that prioritizes organs for positioning. Consequently, consistent displacement values were algorithmically generated. This study also revealed that the impact of rotational corrections, limited to ±3°, on PTV coverage was minimal.


Assuntos
Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Feminino , Humanos , Radioterapia Guiada por Imagem/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Algoritmos
10.
Med Phys ; 51(3): 1571-1582, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112216

RESUMO

BACKGROUND: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs. PURPOSE: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρe ). METHODS: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρe over the multiple points on the curve (Δρm and Δρe,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρe for the specific TEMs (ΔρTEM and Δρe,TEM , respectively) were calculated by subtracting the ρ or ρe of the TEMs from the theoretical CT-ρ or CT-ρe calibration curve. RESULTS: The mean ± standard deviation (SD) of Δρm and Δρe,m for the Gammex phantom were -1.1 ± 1.2 g/cm3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm and Δρe,m for the CIRS phantom were 0.3 ± 0.8 g/cm3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm for Tomotherapy TPSs was 2.1 ± 1.4 g/cm3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρe,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs. CONCLUSIONS: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Calibragem , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Cabeça , Osso e Ossos , Imagens de Fantasmas
11.
J Radiat Res ; 65(2): 159-167, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38151953

RESUMO

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose-length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan.


Assuntos
Encéfalo , Radiocirurgia , Tomografia Computadorizada por Raios X , Humanos , Masculino , Japão , Doses de Radiação , Valores de Referência , Inquéritos e Questionários , Tomografia Computadorizada por Raios X/métodos , Encéfalo/efeitos da radiação
12.
J Radiat Res ; 64(6): 911-925, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37816672

RESUMO

Several staffing models are used to determine the required medical physics staffing, including radiotherapy technologists, of radiation oncology departments. However, since Japanese facilities tend to be smaller in scale than foreign ones, those models might not apply to Japan. Therefore, in this study, we surveyed workloads in Japan to estimate the optimal medical physics staffing in external beam radiotherapy. A total of 837 facilities were surveyed to collect information regarding radiotherapy techniques and medical physics specialists (RTMPs). The survey covered facility information, staffing, patient volume, equipment volume, workload and quality assurance (QA) status. Full-time equivalent (FTE) factors were estimated from the workload and compared with several models. Responses were received from 579 facilities (69.2%). The median annual patient volume was 369 at designated cancer care hospitals (DCCHs) and 252 across all facilities. In addition, the median FTE of RTMPs was 4.6 at DCCHs and 3.0 at all sites, and the average QA implementation rate for radiotherapy equipment was 69.4%. Furthermore, advanced treatment technologies have increased workloads, particularly in computed tomography simulations and treatment planning tasks. Compared to published models, larger facilities (over 500 annual patients) had a shortage of medical physics staff. In very small facilities (about 140 annual patients), the medical physics staffing requirement was estimated to be 0.5 FTE, implying that employing a full-time medical physicist would be inefficient. However, ensuring the quality of radiotherapy is an important issue, given the limited number of RTMPs. Our study provides insights into optimizing staffing and resource allocation in radiotherapy departments.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Carga de Trabalho , Japão , Inquéritos e Questionários , Neoplasias/radioterapia , Física
13.
J Radiat Res ; 64(6): 967-972, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37816679

RESUMO

The uterus is known as one of the moving organs. We evaluated the movement of the uterus during irradiation and the effects of changes in the surrounding organs using a magnetic resonance (MR)-guided radiotherapy system. Seven patients with cervical cancer underwent pre- and posttreatment MR imaging to assess changes in the positioning of the uterus and cervix as well as the alterations in bladder and rectal volume. The study revealed that the movements of the uterus were greater than that of the cervix and showed a tendency to correlate with the bladder rather than the rectum. We also examined whether intrafractional motion could lead to insufficient dose coverage of the clinical target volume (CTV), specifically focusing on the D98% of the CTV in the uterine body and cervix. The impact of intrafractional motion on the D98% varied among patients, with one out of the seven patients experiencing an average dosimetric change of -2.6 Gy in the uterus, although larger planning target volume margins of 1.5 cm were applied, therefore, indicating the need for individualized optimal margins in each case. Online adaptive radiotherapy offers the advantage of modifying the treatment plan when irradiating moving organs, such as the uterus. However, it should be noted that this approach may result in longer overall treatment times compared with the traditional methods. Therefore, we must carefully consider the influence of intrafractional organ motions when opting for such a treatment.


Assuntos
Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Útero , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Radioterapia Guiada por Imagem/métodos , Movimento (Física) , Dosagem Radioterapêutica
14.
Front Oncol ; 13: 1272507, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901311

RESUMO

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.

15.
Radiol Phys Technol ; 16(4): 431-442, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37668931

RESUMO

This study aimed to investigate the educational environment of radiotherapy technology and medical physics specialists (RTMP) in Japan. We conducted a nationwide questionnaire survey in radiotherapy institutions between June and August 2022. Participants were asked questions regarding the educational system, perspectives on updating RTMP's skills and qualifications, and perspectives on higher education for RTMP at radiotherapy institutions. The results were then analyzed in detail according to three factors: whether the hospital was designed for cancer care, whether it was a Japanese Society for Radiation Oncology (JASTRO)-accredited hospital, and whether it was an intensity-modulated radiation therapy charged hospital. Responses were obtained from 579 (69%) nationwide radiation therapy institutions. For non-qualified RTMP, 10% of the institutions had their own educational systems, only 17% of institutions provided on-the-job training, and 84% of institutions encouraged participation in educational lectures and workshops in academic societies. However, for qualified RTMP, 3.0% of institutions had their own educational systems, only 8.9% of the institutions provided on-the-job training, and 83% encouraged participation in academic conferences and workshops. Less than 1% of the facilities offered salary increases for certification, whereas 8.2% offered consideration for occupational promotion. Regarding the educational environment, JASTRO-accredited hospitals were better than general hospitals. Few institutions have their own educational systems for qualified and non-qualified RTMP, but they encourage them to attend educational seminars and conferences. It is desirable to provide systematic education and training by academic and professional organizations to maintain the skills of individuals.


Assuntos
Radioterapia (Especialidade) , Humanos , Japão , Física , Tecnologia , Inquéritos e Questionários
16.
Phys Eng Sci Med ; 46(4): 1411-1426, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37603131

RESUMO

This study incorporated topology Betti number (BN) features into the prediction of primary sites of brain metastases and the construction of magnetic resonance-based imaging biopsy (MRB) models. The significant features of the MRB model were selected from those obtained from gray-scale and three-dimensional wavelet-filtered images, BN and inverted BN (iBN) maps, and clinical variables (age and gender). The primary sites were predicted as either lung cancer or other cancers using MRB models, which were built using seven machine learning methods with significant features chosen by three feature selection methods followed by a combination strategy. Our study dealt with a dataset with relatively smaller brain metastases, which included effective diameters greater than 2 mm, with metastases ranging from 2 to 9 mm accounting for 17% of the dataset. The MRB models were trained by T1-weighted contrast-enhanced images of 494 metastases chosen from 247 patients and applied to 115 metastases from 62 test patients. The most feasible model attained an area under the receiver operating characteristic curve (AUC) of 0.763 for the test patients when using a signature including features of BN and iBN maps, gray-scale and wavelet-filtered images, and clinical variables. The AUCs of the model were 0.744 for non-small cell lung cancer and 0.861 for small cell lung cancer. The results suggest that the BN signature boosted the performance of MRB for the identification of primary sites of brain metastases including small tumors.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Biópsia , Espectroscopia de Ressonância Magnética
17.
Nature ; 618(7967): 1085-1093, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37286611

RESUMO

G protein-coupled receptors (GPCRs) generally accommodate specific ligands in the orthosteric-binding pockets. Ligand binding triggers a receptor allosteric conformational change that leads to the activation of intracellular transducers, G proteins and ß-arrestins. Because these signals often induce adverse effects, the selective activation mechanism for each transducer must be elucidated. Thus, many orthosteric-biased agonists have been developed, and intracellular-biased agonists have recently attracted broad interest. These agonists bind within the receptor intracellular cavity and preferentially tune the specific signalling pathway over other signalling pathways, without allosteric rearrangement of the receptor from the extracellular side1-3. However, only antagonist-bound structures are currently available1,4-6, and there is no evidence to support that biased agonist binding occurs within the intracellular cavity. This limits the comprehension of intracellular-biased agonism and potential drug development. Here we report the cryogenic electron microscopy structure of a complex of Gs and the human parathyroid hormone type 1 receptor (PTH1R) bound to a PTH1R agonist, PCO371. PCO371 binds within an intracellular pocket of PTH1R and directly interacts with Gs. The PCO371-binding mode rearranges the intracellular region towards the active conformation without extracellularly induced allosteric signal propagation. PCO371 stabilizes the significantly outward-bent conformation of transmembrane helix 6, which facilitates binding to G proteins rather than ß-arrestins. Furthermore, PCO371 binds within the highly conserved intracellular pocket, activating 7 out of the 15 class B1 GPCRs. Our study identifies a new and conserved intracellular agonist-binding pocket and provides evidence of a biased signalling mechanism that targets the receptor-transducer interface.


Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP , Imidazolidinas , Receptores Acoplados a Proteínas G , Humanos , Regulação Alostérica , beta-Arrestinas/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , Desenvolvimento de Medicamentos , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/ultraestrutura , Imidazolidinas/química , Imidazolidinas/farmacologia , Ligantes , Modelos Moleculares , Conformação Proteica/efeitos dos fármacos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/classificação , Receptores Acoplados a Proteínas G/ultraestrutura , Transdução de Sinais
18.
J Radiat Res ; 64(4): 661-667, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37295954

RESUMO

This study aimed to quantify the relative biological effectiveness (RBE) for epithermal neutron beam contaminated with fast neutrons in the accelerator-based boron neutron capture therapy (BNCT) system coupled to a solid-state lithium target. The experiments were performed in National Cancer Center Hospital (NCCH), Tokyo, Japan. Neutron irradiation with the system provided by Cancer Intelligence Care Systems (CICS), Inc. was performed. X-ray irradiation, which was assigned as the reference group, was also performed using a medical linear accelerator (LINAC) equipped in NCCH. The four cell lines (SAS, SCCVII, U87-MG and NB1RGB) were utilized to quantify RBE value for the neutron beam. Before both of those irradiations, all cells were collected and dispensed into vials. The doses of 10% cell surviving fraction (SF) (D10) were calculated by LQ model fitting. All cell experiments were conducted in triplicate at least. Because the system provides not only neutrons, but gamma-rays, the contribution from the gamma-rays to the survival fraction were subtracted in this study. D10 value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was 4.26, 4.08, 5.81 and 2.72 Gy, respectively, while that acquired by the X-ray irradiation was 6.34, 7.21, 7.12 and 5.49 Gy, respectively. Comparison of both of the D10 values, RBE value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was calculated as 1.7, 2.2, 1.3 and 2.5, respectively, and the average RBE value was 1.9. This study investigated RBE of the epithermal neutron beam contaminated with fast neutrons in the accelerator-based BNCT system coupled to a solid-state lithium target.


Assuntos
Terapia por Captura de Nêutron de Boro , Nêutrons Rápidos , Lítio , Nêutrons , Aceleradores de Partículas , Eficiência Biológica Relativa
19.
J Appl Clin Med Phys ; 24(10): e14073, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37317937

RESUMO

PURPOSE: This study was conducted to determine the margins and timing of replanning by assessing the daily interfractional cervical and uterine motions using magnetic resonance (MR) images. METHODS: Eleven patients with cervical cancer, who underwent intensity-modulated radiotherapy (IMRT) in 23-25 fractions, were considered in this study. The daily and reference MR images were converted into three-dimensional (3D) shape models. Patient-specific anisotropic margins were calculated from the proximal 95% of vertices located outside the surface of the reference model. Population-based margins were defined as the 90th percentile values of the patient-specific margins. The expanded volume of interest (expVOI) for the cervix and uterus was generated by expanding the reference model based on the population-based margin to calculate the coverage for daily deformable mesh models. For comparison, expVOIconv was generated using conventional margins: right (R), left (L), anterior (A), posterior (P), superior (S), and inferior (I) were (5, 5, 15, 15, 10, 10) and (10, 10, 20, 20, 15, 15) mm for the cervix and uterus, respectively. Subsequently, a replanning scenario was developed based on the cervical volume change. ExpVOIini and expVOIreplan were generated before and after replanning, respectively. RESULTS: Population-based margins were (R, L, A, P, S, I) of (7, 7, 11, 6, 11, 8) and (14, 13, 27, 19, 15, 21) mm for the cervix and uterus, respectively. The timing of replanning was found to be the 16th fraction, and the volume of expVOIreplan decreased by >30% compared to that of expVOIini . However, margins cannot be reduced to ensure equivalent coverage after replanning. CONCLUSION: We determined the margins and timing of replanning through detailed daily analysis. The margins of the cervix were smaller than conventional margins in some directions, while the margins of the uterus were larger in almost all directions. A margin equivalent to that at the initial planning was required for replanning.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Útero/diagnóstico por imagem , Útero/patologia , Movimento (Física) , Imageamento por Ressonância Magnética/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica
20.
J Appl Clin Med Phys ; 24(6): e14040, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37191875

RESUMO

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Projetos Piloto , Japão , Credenciamento , Radiometria , Dosagem Radioterapêutica , Oncologia , Imagens de Fantasmas
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