The current status and novel advances of boron neutron capture therapy clinical trials.

Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors.

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

Aims/introduction: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state.

Materials And Methods: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques.

Fulminant Type 1 Diabetes-East and West.

Fulminant type 1 diabetes is a subtype of type 1 diabetes in which beta cells are destroyed within days or a few weeks. The first criterion indicates a rise in blood glucose levels shown in the patient's history. The second suggests that the increase occurs suddenly within a very short period, as shown by the laboratory findings of the discrepancy between the glycated hemoglobin concentration and plasma glucose level.

Prevalence of Sapovirus and Astrovirus in Pediatric Infectious Gastroenteritis Surveillance in Kobe City, Japan, 2016-2019.

Sapovirus (SaV) and astrovirus (AstV) are important viral causes of acute gastroenteritis. From 2016 to 2019, 172 stool samples were collected from children with gastroenteritis in Kobe, Japan for sentinel surveillance of infectious gastroenteritis. In this study, we tested 53 of the 172 stool samples that tested negative for other enteric viruses to determine the prevalence of SaV and AstV.

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes.

Aim/introduction: To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes.

Methods: A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined.

Comparing the clinical significance and antigen specificity of insulinoma-associated antigen-2 autoantibodies between radioimmunoassay and enzyme-linked immunosorbent assay in Japanese patients with type 1 diabetes.

Aims/introduction: This study aimed to investigate the clinical significance and antigen specificity of autoantibodies to insulinoma-associated antigen-2 (IA-2A) by radioimmunoassay (RIA; IA-2A-RIA) and enzyme-linked immunosorbent assay (ELISA; IA-2A-ELISA) in Japanese patients with type 1 diabetes.

Materials And Methods: A total of 338 type 1 diabetic patients were enrolled, including 38 fulminant type 1 diabetes, 168 acute-onset type 1 diabetes and 137 slowly-progressive type 1 diabetes (SPIDDM). The concordance, correlation of autoantibody titer, and the relationship between IA-2A and progression to the insulin-deficient state were examined.

Japanese Type 1 Diabetes Database Study (TIDE-J): rationale and study design.

Type 1 diabetes (T1D) is classified into three subtypes: acute-onset, slowly progressive, and fulminant T1D, according to the heterogeneity of clinical course in Japan. Although several cross-sectional databases of T1D have been reported, prospective longitudinal databases to investigate clinical outcomes are lacking in our country. Therefore, we herein construct multi-center prospective longitudinal database of the three subtypes of T1D, accompanied with genetic information and biobanking, which is named Japanese Type 1 Diabetes Database Study (TIDE-J).

Fulminant type 1 diabetes patients display high frequencies of IGRP-specific type 1 CD8 T cells.

The role of cellular autoimmunity in the pathogenesis of fulminant type 1 diabetes (FT1D) remains largely unknown. In this study, we performed an integrated assay using peripheral blood mononuclear cells to determine the islet antigen-specific CD8 T cell responses in FT1D and compare the responses among acute-onset T1D (AT1D) and slowly progressive T1D (SP1D). IGRP- and ZnT8-specific IL-6, G-CSF, and TNF-α responses were significantly upregulated in patients with FT1D, while IGRP- and ZnT8-specific IP-10 responses were significantly upregulated in patients with AT1D than in non-diabetics (ND).

Benefit of Early Add-on of Linagliptin to Insulin in Japanese Patients With Type 2 Diabetes Mellitus: Randomized-Controlled Open-Label Trial (TRUST2).

Introduction: This trial was conducted to assess the long-term safety, efficacy, and benefit of early add-on of linagliptin to insulin in patients with type 2 diabetes mellitus (T2DM).

Methods: This trial enrolled 246 subjects. The subjects were randomized to the linagliptin group or the control group and were observed for 156 weeks.

Fulminant type 1 diabetes: 20 years of discovery and development.

Twenty years have passed since the first article on fulminant type 1 diabetes (FT1D) was published. FT1D is characterized by an extremely rapid onset of ketoacidosis, high plasma glucose and, conversely, a near-normal glycosylated hemoglobin level. Digestive or flu-like symptoms frequently precede the onset of ketoacidosis.

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer.

The accelerator-based boron neutron capture reaction evaluation system for head and neck cancer.

The purpose of this study is to assess accelerator-based boron neutron capture reaction (BNCR) in human tumor cell lines by colony formation assay and modified high density survival assay (HDS assay). The results of post irradiation survival rate in human oral squamous cell carcinoma and osteosarcoma using both assays were similar. Therefore, HDS assay would be efficient to evaluate BNCR in not only tumor cells but also in normal cells as BNCT screening.

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8.

Aims/introduction: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes.

Methods: Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.

Distinct Phenotypes of Islet Antigen-Specific CD4+ T Cells Among the 3 Subtypes of Type 1 Diabetes.

Context: Type 1 diabetes (T1D) is classified into 3 subtypes: acute-onset (AT1D), slowly progressive (SP1D), and fulminant (FT1D). The differences in the type of cellular autoimmunity within each subtype remain largely undetermined.

Objective: To determine the type and frequency of islet antigen-specific CD4+ T cells in each subtype of T1D.

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma-associated antigen-2 autoantibodies in the identification and characterization of Japanese type 1 diabetes.

Aims/introduction: This study aimed to investigate the significance of zinc transporter 8 autoantibody (ZnT8A) in identifying and characterizing autoimmune-mediated type 1 diabetes in Japanese individuals.

Methods: ZnT8A were determined in 324 patients with type 1 diabetes, 191 phenotypic type 2 diabetes and 288 healthy control individuals using bridging-type enzyme-linked immunosorbent assay in addition to autoantibodies to glutamic acid decarboxylase and insulinoma-associated antigen-2.

Results: We set a cut-off value of 10.

Pathogenesis of fulminant type 1 diabetes: Genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research.

We reviewed fulminant type 1 diabetes, a recently established subtype of type 1 diabetes, from the aspects of genes, viruses, immune mechanism and usefulness of patient-derived induced pluripotent stem cells (iPSCs). In an analysis of the pancreas of patients with fulminant type 1 diabetes, viral antigens and viral receptors were expressed in β-cells, as well as macrophages and T lymphocytes surrounding the β-cells. These findings suggest that the β-cells of patients with fulminant type 1 diabetes are destroyed during an immune response against viral infection of the pancreas.

Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy.

Aims: We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy.

Methods: We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search.

Results: Among the 22 patients, 11 (50.

Diffusion-weighted magnetic resonance imaging in the pancreas of fulminant type 1 diabetes.

Abrupt disease onset and severe metabolic disorders are main characteristics of fulminant type 1 diabetes. Diffusion-weighted magnetic resonance imaging (DWI) is an imaging technique that reflects restricted diffusion in organs and can detect mononuclear cell infiltration into the pancreas at the onset of the disease. Fourteen patients with fulminant type 1 diabetes who underwent abdominal magnetic resonance imaging were recruited for the measurement of apparent diffusion coefficient (ADC) values of the pancreas that were compared with those of 21 non-diabetic controls.

Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice.

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion.

Genome-Wide Association Study Confirming a Strong Effect of HLA and Identifying Variants in on Chromosome 12q13.13 Associated With Susceptibility to Fulminant Type 1 Diabetes.

The first genome-wide association study of fulminant type 1 diabetes was performed in Japanese individuals. As previously reported using a candidate gene approach, a strong association was observed with multiple single nucleotide polymorphisms (SNPs) in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region ( = 1.56 × 10, odds ratio [OR] 3.

"Benifuuki" Extract Reduces Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B: A Double-Blind Placebo-Controlled Randomized Trial.

(1) Background: Arteriosclerosis is associated with high levels of low-density lipoprotein (LDL) cholesterol. -methylated catechins in "Benifuuki" green tea are expected to reduce cholesterol levels, although there is limited research regarding this topic; (2) Methods: This trial evaluated 159 healthy volunteers who were randomized to receive ice cream containing a high-dose of "Benifuuki" extract including 676 mg of catechins (group H), a low-dose of "Benifuuki" extract including 322 mg of catechins (group L), or no "Benifuuki" extract (group C). Each group consumed ice cream (with or without extract) daily for 12 weeks, and their lipid-related parameters were compared; (3) Results: A significant reduction in the level of lectin-like oxidized LDL receptor-1 ligand containing ApoB (LAB) was detected in group H, compared to groups L and C.

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4-week, double-blind, randomized, placebo-controlled phase 2 trial.

Aims: This phase 2, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin.

Materials And Methods: Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.