A Systematic Review of Treatment-Related Adverse Events for Combination Therapy of Multiple Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor.

Background: Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This study aimed to investigate the effect of the addition of ICI to multi-TKIs on the profile of treatment-related adverse events.

Methods: An electronic database search was performed using PubMed and Web of Science to identify published clinical studies on multi-TKI monotherapy and multi-TKI plus ICI combination therapy from July 20, 2005 to July 1, 2023.

KEYNOTE-434 part B: A phase 1 study evaluating the combination of epacadostat, pembrolizumab, and chemotherapy in Japanese patients with previously untreated advanced non-small-cell lung cancer.

Background: Pembrolizumab plus epacadostat (indoleamine 2,3-dioxygenase-1 inhibitor) was well tolerated in Japanese patients with advanced solid tumors in part A of the nonrandomized, open-label, phase 1 KEYNOTE-434 study (NCT02862457). We report results from part B, which evaluated epacadostat plus pembrolizumab and chemotherapy in Japanese patients with advanced non-small-cell lung cancer (NSCLC).

Methods: Eligible patients aged ≥ 20 years had histologically or cytologically confirmed stage IIIB or IV NSCLC with no prior systemic therapy, and ECOG performance status of 0 or 1.

Migrants' access to COVID-19 vaccination in Japan: Progress and challenges.

Objectives: This study aimed to review the progress and challenges of COVID-19 vaccine roll-out for migrants in Japan and discuss the approaches to address the challenges and better prepare for future waves of COVID-19 and other pandemics.

Methods: We conducted a literature review using an assessment framework which we developed building upon existing frameworks and tools on access to health services and COVID-19 vaccination among migrants.

Results: COVID-19 vaccination coverage among foreigners might be lower than that of nationals although the data on foreigners were not widely available.

The Association of Dietary Intake, Oral Health, and Blood Pressure in Older Adults: A Cross-Sectional Observational Study.

Hypertension is related to impaired mastication that causes malnutrition, declining the general health of older adults. This study assessed the role of dietary intake in the relationship between oral health and blood pressure. Eight hundred ninety-four adults aged ≥65 years who independently lived in rural regions of Japan participated in this study.

Hepatocellular carcinoma diagnosis using a novel electrochemiluminescence immunoassay targeting serum IgM-free AIM.

Background: Recent increases in the number of patients with non-alcoholic steatohepatitis (NASH) warrant the identification of biomarkers for early detection of hepatocellular carcinoma (HCC) associated with NASH (NASH-HCC). IgM-free apoptosis inhibitor of macrophage (AIM), which generally associates with IgM in blood and exerts its biological function by dissociation from IgM, may serve as an effective biomarker for NASH-HCC. Here, we established a fully automatic and high-throughput electrochemiluminescence immunoassay (ECLIA) to measure IgM-free AIM and investigated its efficacy in diagnosing NASH-HCC and viral HCC.

The relationship between bone density and the oral function in older adults: a cross-sectional observational study.

Background: Falls among older adults with a low bone density can lead to a bedridden state. Declining bone density increases the risk of falls resulting fractures in older adults. A person's physical performance is known to be closely related to bone density, and a relationship between the physical performance and the oral function is also known to exist.

Predictability of Severe Adverse Events in Phase 3 Trials from Safety Information on Phase 1 Trials in Oncology Drug Development.

Purpose: Safety information obtained in phase 1 trials is becoming increasingly important with the recent changes in the development strategy of oncology drugs, including the skipping of phase 2 or 3 trials before regulatory approval. This study aimed to investigate the predictive factors for severe adverse events (AEs) in phase 3 trials based on phase 1 trial data.

Methods: The data on phase 1 and phase 3 trials applied for their marketing approval of the newly approved anticancer drugs in Japan were used for analysis.

Does Oral Hypofunction Promote Social Withdrawal in the Older Adults? A Longitudinal Survey of Elderly Subjects in Rural Japan.

It is often assumed that oral hypofunction is associated with social withdrawal in older adults because decreased motor function is related to decreased oral function. However, few studies have examined the relationship between social withdrawal in older adults and oral function. This longitudinal study aimed to clarify the relationship between changes in the level of social withdrawal and oral function in independent older adults.

siRNA potency enhancement via chemical modifications of nucleotide bases at the 5'-end of the siRNA guide strand.

Small interfering RNAs (siRNAs) can be utilized not only as functional biological research tools but also as therapeutic agents. For the clinical use of siRNA as drugs, various chemical modifications have been used to improve the activity of siRNA drugs, and further chemical modifications are expected to improve the utility of siRNA therapeutics. As the 5' nucleobase of the guide strand affects the interaction between an siRNA and AGO2 and target cleavage activity, structural optimization of this specific position may be a useful strategy for improving siRNA activity.

Development of Prodrug Type Circular siRNA for Knockdown by Systemic Administration.

siRNAs are being developed as a novel therapeutic modality; however, problems impeding their application in extrahepatic tissues persist, including inadequate stability in biological environments and inefficient drug delivery system to target tissues. Thus, technological improvements that enable robust silencing of target messenger RNA (mRNA) in extrahepatic tissues are necessary. We developed prodrug type covalently closed siRNA (circular siRNA) as a novel nucleic acid agent to knockdown target genes in extrahepatic tissues by systemic administration without drug delivery components.

Factors associated with access to HIV testing among international students in Japanese language schools in Tokyo.

Japan has been recognized for its excellent universal health coverage system. However, the migrant population faces many barriers in accessing health services in Japan. Japan hosts around 260,000 international students, mostly from developing countries.

Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma.

Background: The prognosis of hepatocellular carcinoma (HCC) patients remains poor despite advances in treatment modalities and diagnosis. It is important to identify useful markers for the early detection of HCC in patients. Preneoplastic antigen (PNA), originally reported in a rat carcinogenesis model, is increased in the tissues and serum of HCC patients.

Is a History of Falling Related to Oral Function? A Cross-Sectional Survey of Elderly Subjects in Rural Japan.

Background: Deteriorated physical function makes older adults prone to fall, and it is therefore known to prompt elders to require long-term care. In this regard, oral function can be related to the loss of motor function. This cross-sectional study assessed the oral factors that increase the risk of falling among older adults.

Relationship between oral environment and frailty among older adults dwelling in a rural Japanese community: a cross-sectional observational study.

Background: Oral functions are known to decline with aging. However, there is limited evidence that supports the relationship between oral health and frailty. This study aimed to clarify the relationship between oral hygiene conditions, measured by remaining teeth and mucosa, and frailty among elderly people dwelling in a Japanese rural community.

Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas.

The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated.

Expression of Carboxylesterase Isozymes and Their Role in the Behavior of a Fexofenadine Prodrug in Rat Skin.

The expression of carboxylesterase (CES) and the transdermal movement of an ester prodrug were studied in rat skin. Ethyl-fexofenadine (ethyl-FXD) was used as a model lipophilic prodrug that is slowly hydrolyzed to its parent drug, FXD (MW 502). Among the CES1 and CES2 isozymes, Hydrolase A is predominant in rat skin and this enzyme was involved in 65% of the cutaneous hydrolysis of ethyl-FXD.

Ultrastructural and immunocytochemical characterization of ameloblast-enamel adhesion at maturation stage in amelogenesis in Macaca fuscata tooth germ.

Maturation-stage ameloblasts are firmly bound to the tooth enamel by a basal lamina-like structure. The mechanism underlying this adhesion, however, remains to be fully clarified. The goal of this study was to investigate the mechanism underlying adhesion between the basal lamina-like structure and the enamel in monkey tooth germ.

Ultrastructural immunolocalization of laminin 332 (laminin 5) at dento-gingival interface in Macaca fuscata monkey.

Although laminin 332 (laminin 5), an extracellular matrix molecule involved in cell adhesion and migration, has been localized at the interface between the tooth enamel and junctional epithelium, its ultrastructural localization remains to be fully clarified. The purpose of the present study was to investigate the ultrastructural distribution of laminin 332 at the dento-gingival interface in Japanese monkey (Macaca fuscata) using pre- and post-embedding immunoelectron microscopy. Pre-embedding immunoelectron microscopy revealed a broad band of internal basal lamina together with supplementary lamina densa, and both showed immunolabeling for laminin 332.

A novel strategy for enrichment and isolation of osteoprogenitor cells from induced pluripotent stem cells based on surface marker combination.

In this study, we developed a new method to stimulate osteogenic differentiation in tissue-nonspecific alkaline phosphatase (TNAP)-positive cells liberated from human induced pluripotent stem cells (hiPSCs)-derived embryoid bodies (EBs) with 14 days long TGF-β/IGF-1/FGF-2 treatment. TNAP is a marker protein of osteolineage cells. We analyzed and isolated TNAP-positive and E-cadherin-negative nonepithelial cells by fluorescence-activated cell sorting.

Prediction of the bioconcentration factor in common carp (Cyprinus carpio L.) using data from the dietary exposure bioaccumulation fish test.

An approach to predicting the bioconcentration factor (BCFpre ) from the predicted uptake rate constant (k1 pre ) and the depuration rate constant measured in the dietary exposure bioaccumulation fish test (k2 dietary ) [BCFpre  = k1 pre /k2 dietary ] is proposed in test guideline 305 of the Organization for Economic Cooperation and Development Guidelines for Testing of Chemicals. Data were collected on the BCFs of 197 test chemicals from Japan's Chemical Substances Control Law database. To demonstrate how the BCFpre compares with experimentally derived BCF under optimum conditions, 48 of 197 test chemicals, including a number of studies that could be considered problematic, were excluded from the analysis.

Expression and localization of laminin 5, laminin 10, type IV collagen, and amelotin in adult murine gingiva.

The biochemical composition of the internal and external basal laminae in the junctional epithelium differs significantly, and the precise cellular origin of their respective molecules remains to be determined. In the present study, the expression and localization of three basement membrane-specific molecules-laminin 5 (γ2 chain), type IV collagen (α1 chain), and laminin 10 (α5 chain)-and one tooth-specific molecule, amelotin, was analyzed in adult murine gingiva by using in situ hybridization and immunohistochemistry. The results showed that the outermost cells in junctional epithelium facing the tooth enamel strongly expressed laminin 5 mRNA, supporting the immunohistochemical staining data.

[Prevalence of HIV and sexually transmitted infections and characteristics of men who have sex with men at a community-based center in Yokohama, Japan].

Objectives: To investigate the characteristics of men who have sex with men (MSM) in a sample of men who sought voluntary testing and counseling (VCT) for human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) in a community-based center in Yokohama, Japan. The prevalence of HIV/STIs and the incidence rate of HIV were also assessed.

Methods: We investigated VCT records of 449 clients who received free anonymous night VCT services between 2008 and 2011.

Enantioselective total synthesis of (+)-colletoic acid via catalytic asymmetric intramolecular cyclopropanation of an α-diazo-β-keto diphenylphosphine oxide.

The enantioselective total synthesis of (+)-colletoic acid, a potent naturally occurring 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is described. This total synthesis features a highly enantioselective catalytic asymmetric intramolecular cyclopropanation of an α-diazo-β-keto diphenylphosphine oxide and five highly stereoselective reactions (cyclopropane opening, Diels-Alder reaction, iodolactonization, alkene formation, and reduction of α,β-unsaturated carboxylic acid).