Formation of hepatocyte cytoplasmic inclusions and their contribution to methylcarbamate-induced hepatocarcinogenesis in F344 rats.

Methylcarbamate (MC), a reaction product between dimethyl dicarbonate and ammonia or ammonium ion, is a potent hepatocarcinogen in F344 rats. Various genotoxicity tests have shown negative results for MC. Although previous studies have described the effects of MC on the liver, including the formation of characteristic basophilic cytoplasmic inclusions (CIs) in hepatocytes, the toxicological significance of CIs and their involvement in hepatocarcinogenesis remain unclear.

Site-specific genotoxicity of rubiadin: localization and histopathological changes in the kidneys of rats.

Rubiadin (Rub) is a genotoxic component of madder color (MC) that is extracted from the root of Rubia tinctorum L. MC induces renal tumors and preneoplastic lesions that are found in the proximal tubule of the outer stripe of the outer medulla (OSOM), suggesting that the renal carcinogenicity of MC is site specific. To clarify the involvement of Rub in renal carcinogenesis of MC, we examined the distribution of Rub in the kidney of male gpt delta rats that were treated with Rub for 28 days.

Experimentally determined relative biological effectiveness of cyclotron-based epithermal neutrons designed for clinical BNCT: in vitro study.

A neutron beam for boron neutron capture therapy (BNCT) of deep-seated tumours is designed to maintain a high flux of epithermal neutrons, while keeping the thermal and fast neutron component as low as possible. These neutrons (thermal and fast) have a high relative biological effectiveness in comparison with high energy photon beams used for conventional X-ray radiotherapy. In the past, neutrons for the purpose of BNCT were generated using nuclear reactors.

Hepatocyte proliferation activity in untreated rats, measured by immunohistochemical detection of Ki-67: The effect of age on the repeated-dose liver micronucleus assay.

The repeated-dose liver micronucleus (RDLMN) assay is a widely accepted method for detecting genotoxic substances. We investigated the effect of animal age on this assay. Proliferation activity in the liver tissue of untreated rats at age = 3.

Comprehensive analysis of the general toxicity, genotoxicity, and carcinogenicity of 3-acetyl-2,5-dimethylfuran in male gpt delta rats.

The safety of flavoring agents has been evaluated according to classification by chemical structure and using a decision tree approach. The genotoxic potential found in some flavoring agents has highlighted the importance of efficient toxicity studies. We performed a comprehensive toxicity analysis using reporter gene transgenic rats to assess the safety of 3-acetyl-2,5-dimethylfuran (ADF), a flavoring agent exhibiting genotoxic potential in silico and in vitro assays.

Lack of hepatocarcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane, 3-hydroxy-2-naphthoic acid, and acetoacetanilide in a medium-term rat liver bioassay.

The carcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane (ethylene glycol diglycidyl ether; EGDE), 3-hydroxy-2-naphthoic acid (HNA), and acetoacetanilide (AAA) was investigated using a medium-term rat liver bioassay for an occupational safety assessment. F344 male rats were administered a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body weight (bw)/day) and then starting 2 weeks later, they received EGDE at 6, 20, and 60 mg/kg bw/day, HNA at 20, 60, and 200 mg/kg bw/day, or AAA at 60, 200, and 600 mg/kg bw/day by oral gavage for 6 weeks. The animals in the positive control group received phenobarbital sodium solution (PB, 25 mg/kg bw/day) by oral gavage and those in the negative control group received a vehicle (water/corn oil) during the administration period of test substances in this model.

The effect of aging on the repeated-dose liver micronucleus assay using diethylnitrosamine.

Background: The repeated-dose liver micronucleus (RDLMN) assay has been well-developed and applied because of its simplicity and the ease of integration into general toxicity studies which is the preferred method from the 3R's point of view. In this assay, we observed micronucleated hepatocytes which accumulated during a rather long-term dosing period. When considering integration into general toxicity studies, the effects of age of the animals used in the micronucleus assay becomes a major issue.

[PET Research in Clinical Oncology].

Positron emission tomography (PET) in nuclear medicine is especially used for diagnosis in clinical oncology, and PET/CT examination using F-FDG is very useful for staging and therapy evaluation of cancer. The excellent property of PET diagnosis is that the functional information of cells can be evaluated quantitatively, but it also has the problem that its quantitative value fluctuates depending on image reconstruction conditions and body movements/respiratory movements. In this paper, we summarize the PET research that has been conducted so far in clinical oncology, and also introduce our researches for improve the quantitativeness.

Visualization of the distribution of anthraquinone components from madder roots in rat kidneys by desorption electrospray ionization-time-of-flight mass spectrometry imaging.

Madder color (MC), a natural dye isolated from Rubia tinctorum, is a potent carcinogen that targets the outer stripe of outer medulla (OSOM) in the kidneys of rats. To clarify the role of MC components in renal carcinogenesis, we examined distributions of MC components and metabolites in the kidneys of rats treated with MC using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Alizarin, lucidin, munjistin, nordamnacanthal, purpurin, pseudopurpurin, rubiadin, and some other metabolites detected and identified by liquid chromatography time-of-flight MS analysis of rat serum 1 h after MC administration were subjected to DESI-MSI.

Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies.

Background: Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals.

Development of an irradiation method for superficial tumours using a hydrogel bolus in an accelerator-based BNCT.

The aim of this study is the development of an irradiation method for the treatment of superficial tumours using a hydrogel bolus to produce thermal neutrons in accelerator-based Boron Neutron Capture Therapy (BNCT).To evaluate the neutron moderating ability of a hydrogel bolus, a water phantom with a hydrogel bolus was irradiated with an epithermal neutron beam from a cyclotron-based epithermal neutron source. Phantom simulating irradiation to the plantar position was manufactured using three-dimensional printing technology to perform an irradiation test of a hydrogel bolus.

A 90-day subchronic toxicity study of Myrrh in F344 rats.

Myrrh is a flavoring agent and food additive. Here, we performed a subchronic toxicity study of Myrrh in male and female F344 rats by feeding at 5,000, 15,000 and 50,000 ppm for 90 days. No deaths or clinical signs were observed.

Design and construction of an accelerator-based boron neutron capture therapy (AB-BNCT) facility with multiple treatment rooms at the Southern Tohoku BNCT Research Center.

Installation of an accelerator-based boron neutron capture therapy (AB-BNCT) system was started in April 2014 at the Southern Tohoku BNCT Research Center (STBRC), and clinical trials began in January 2016. There are two treatment rooms, which have same specifications, and the beam quality equivalency was confirmed both rooms. Here, we describe the design and construction of the first hospital-based AB-BNCT facility in the world with multiple treatment rooms.

The clinical utility of phase-based respiratory gated PET imaging based on visual feedback with a head-mounted display system.

Objective: We developed a new respiratory-gated positron emission tomography (PET) imaging method (RGV-PET) that phase-based respiratory gated PET imaging (RG-PET) combine with head-mounted display (HMD)-guided "visual feedback." The purpose of this study was to investigate whether RGV-PET is effective at improving the quantitative measurement of tracer uptake in tumors using the phase-based respiratory gating method.

Methods: Of the 41 enrolled patients with hepatobiliary or pancreatic cancer, 20 patients underwent RGV-PET and the remaining 21 patients underwent RG-PET.

Verification of the tumor volume delineation method using a fixed threshold of peak standardized uptake value.

We aimed to determine the difference in tumor volume associated with the reconstruction model in positron-emission tomography (PET). To reduce the influence of the reconstruction model, we suggested a method to measure the tumor volume using the relative threshold method with a fixed threshold based on peak standardized uptake value (SUV). The efficacy of our method was verified using F-2-fluoro-2-deoxy-D-glucose PET/computed tomography images of 20 patients with lung cancer.

High current DC negative ion source for cyclotron.

A filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In Cs-free operation, continuous H(-) beam of 10 mA and D(-) beam of 3.3 mA were obtained stably at an arc-discharge power of 3 kW and 2.

[Application of the PET for Radiation Therapy].

Because radiotherapy is local treatment, it is very important to define target volume and critical organs based on accurate lesion area. The PET using an index such as the SUV is quantifiable noninvasively with information of the molecular biology for individual case/lesion. In particular, PET with 18F-fluorodeoxyglucose (FDG-PET) has been used for the diagnosis and treatment evaluation of various tumors.

Evaluation of a new motion correction algorithm in PET/CT: combining the entire acquired PET data to create a single three-dimensional motion-corrected PET/CT image.

Purpose: This study evaluated the potential of Q.Freeze algorithm for reducing motion artifacts, in comparison with ungated imaging (UG) and respiratory-gated imaging (RG).

Patients And Methods: Twenty-nine patients with 53 lesions who had undergone RG F-FDG PET/CT were included in this study.

Development of a high current H(-) ion source for cyclotrons.

A multi-cusp DC H(-) ion source has been designed and fabricated for medical applications of cyclotrons. Optimization of the ion source is in progress, such as the improvement of the filament configuration, magnetic filter strength, extraction electrode's shape, configuration of electron suppression magnets, and plasma electrode material. A small quantity of Cs has been introduced into the ion source to enhance the negative ion beam current.

Evaluation of thermal neutron irradiation field using a cyclotron-based neutron source for alpha autoradiography.

It is important to measure the microdistribution of (10)B in a cell to predict the cell-killing effect of new boron compounds in the field of boron neutron capture therapy. Alpha autoradiography has generally been used to detect the microdistribution of (10)B in a cell. Although it has been performed using a reactor-based neutron source, the realization of an accelerator-based thermal neutron irradiation field is anticipated because of its easy installation at any location and stable operation.

Amyloid imaging mismatch.

An 82-year-old man with suspected systemic amyloidosis and complete atrioventricular block underwent vascular biopsy during his pacemaker implantation with pathology showing amyloid deposits. 99mTc-aprotinin SPECT revealed increased radiotracer uptake along the left ventricular wall, consistent with cardiac amyloidosis. 11C-PiB PET/CT performed for the evaluation of amyloid deposits in the brain showed findings suggestive of Alzheimer disease without abnormal radiotracer concentration in the myocardium to match the 99mTc-aprotinin SPECT findings.

Reevaluation of FDG-PET/CT in patients with hoarseness caused by vocal cord palsy.

Objective: Vocal cord palsy (VCP) is a potential cause of hoarseness that results in decreasing mobility of the vocal cord. VCP can arise from a variety of causes; so, systematic screening is warranted for the management of patients with VCP. Asymmetrical fluorodeoxyglucose (FDG) uptake in vocal cords is a well-known feature in patients with VCP, but no detailed analysis has been performed.