Strategies for Preclinical Studies Evaluating the Biological Effects of an Accelerator-based BNCT System

This review discusses the strategies of preclinical studies intended for accelerator-based (AB)-boron neutron capture therapy (BNCT) clinical trials, which were presented at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy held from April 20 to 22, 2022. Clinical studies of BNCT have been conducted worldwide using reactor neutron sources, with most targeting malignant brain tumors, melanoma, or head and neck cancer. Recently, small accelerator-based neutron sources that can be installed in hospitals have been developed. AB-BNCT clinical trials for recurrent malignant glioma, head and neck cancers, high-grade meningioma, melanoma, and angiosarcoma have all been conducted in Japan. The necessary methods, equipment, and facilities for preclinical studies to evaluate the biological effects of AB-BNCT systems in terms of safety and efficacy are described, with reference to two examples from Japan. The first is the National Cancer Center, which is equipped with a vertical downward neutron beam, and the other is the University of Tsukuba, which has a horizontal neutron beam. The preclinical studies discussed include cell-based assays to evaluate cytotoxicity and genotoxicity, in vivo cytotoxicity and efficacy of BNCT, and radioactivation measurements

Evaluation of Fatigue Properties under Four-point Bending and Fatigue Crack Propagation in Austenitic Stainless Steel with a Bimodal Harmonic Structure

Austenitic stainless steel (JIS-SUS304L) with a bimodal harmonic structure, which is defined as a coarse-grained structure surrounded by a network of fine grains, was fabricated using powder metallurgy to improve both the strength and ductility. Four-point bending fatigue tests and K-decreasing tests were conducted in air at room temperature under a stress ratio R of 0.1 to investigate fatigue crack propagation in SUS304L. The fatigue limit of this harmonic-structured material was higher than that of the material with a homogeneous coarse-grained structure. This is attributable to the formation of fine grains by mechanical milling and to the suppression of pore formation. In contrast, the threshold stress intensity range, DKth, for the harmonic-structured material was lower than that for the homogeneous coarse-grained material, while the crack growth rates, da/dN, were higher at comparable DK. These results can be attributed to a reduction in the effective threshold stress intensity range, DKeff,th, due to the presence of fine grains in the harmonic structure

Evaluation of fatigue properties under four-point bending and fatigue crack propagation in austenitic stainless steel with a bimodal harmonic structure

Austenitic stainless steel (JIS-SUS304L) with a bimodal harmonic structure, which is defined as a coarse-grained structure surrounded by a network of fine grains, was fabricated using powder metallurgy to improve both the strength and ductility. Four-point bending fatigue tests and K-decreasing tests were conducted in air at room temperature under a stress ratio R of 0.1 to investigate fatigue crack propagation in SUS304L. The fatigue limit of this harmonic-structured material is higher than that of the material with a homogeneous coarse-grained structure. This is attributable to the formation of fine grains by mechanical milling and to the suppression of pore formation. In contrast, the threshold stress intensity range, ?Kth, for the harmonic-structured material is lower than that for the homogeneous coarse-grained material, while the crack growth rates, da/dN, are higher at comparable ?K. These results can be attributed to a reduction in the effective threshold stress intensity range, ?Keff,th, due to the presence of fine grains in the harmonic structure

Broad Spectrum Antiangiogenic Treatment for Ocular Neovascular Diseases

Pathological neovascularization is a hallmark of late stage neovascular (wet) age-related macular degeneration (AMD) and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV), while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF) exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD

Prediction of Boron Concentrations in Blood from Patients on Boron Neutron Capture Therapy

Background: In boron neutron capture therapy, blood boron concentration is the key factor to calculate radiation dose, however, blood sampling is difficult during neutron irradiation. Materials and Methods: The prediction of blood boron concentrations for BNCT treatment planning has been prospectively investigated using patient data obtained at first craniotomy after the infusion of a low dose of sodium undecahydroclosododecaborate. Results: The boron biodistribution data showed a biexponential pharmacokinetic profile. If the final boron concentration at 6 or 9 hours after the end of the infusion is within the 95% confidence interval of the prediction, direct prediction from biexponential fit will reduce the error of blood boron concentrations during irradiation to around 6%. Conclusion: Actual boron concentrations during BNCT were reasonably and accurately predictable from the test data

Antarctic micrometeorites collected at the Dome Fuji Station

Antarctic micrometeorites (AMMs) were found among the precipitated fine particles recovered from a water tank in the Dome Fuji Station. These AMMs had been contained in the recent fallen snow around the station. Initial processing of the precipitated particles revealed that they were dominated by natural and artificial terrestrial materials, thus a series of processes were developed to separate AMMs from terrestrial particles. The recovery rate of AMMs by the processes was approximately 45% in weight, which was determined from a weight ratio of recovered/accreted AMMs. The micro-morphology and major-element concentration of the recovered AMMs were characterized. They appear to have been heated upon atmospheric entry to varying temperatures and can be classified into two major types based on the degree of heating : (1) fine-grained, irregular-shaped, partial-melted micrometeorites with chondritic composition, and (2) total-melted spherical micrometeorites with chondritic composition except for volatile elements. A digital catalog for the AMMs identified in this study was established on the web site [URL : http : //dust. cc. gakushuin. ac. jp/], in which optical characteristics, high-resolution images, and chemical compositions of individual AMMs are presented. The AMMs listed in the catalog are the first Japanese collection of extraterrestrial dust. The criterion and techniques developed for the selection and initial analysis of AMMs are applicable for the dust samples that are being collected by the 39th Japanese Antarctic Research Expedition team

Aortic Dissection in a Patient with Human Immunodeficiency Virus Infection That was Diagnosed at Autopsy : A Case Report.

A 43-year-old homosexual man was referred to our hospital for chest pain and loss of consciousness. He was hypertensive, and had an uncontrolled viral load. Serum creatinine revealed acute renal failure, and he died 3 days later. On autopsy, aortic dissection (TypeB) was found. No obvious inflammatory change, granulation, bacterial or fungal infection, or medionecrosis were seen at the dissection site. To our knowledge, this was the first case with HIV in whom aortic dissection was diagnosed at autopsy. Aortic dissection is a potential differential diagnosis even in young patients presenting with hypertension and chest pain