Publications by authors named "Tsuyoshi Hirata"

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.

Methods: The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib.

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Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate with a topoisomerase I inhibitor connected by a cleavable linker, has been approved for patients with HER2-positive gastric or gastroesophageal junction tumors. This biomarker study assessed HER2 expression and immune cell infiltration in relation to the therapeutic response to T-DXd. This retrospective analysis included samples from patients treated with T-DXd in three clinical trials.

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Introduction: Previous studies reported an association between immune checkpoint inhibitor infusion timing and the treatment effect in metastatic NSCLC. The present study assessed the association between durvalumab infusion timing and survival outcomes in patients with locally advanced NSCLC.

Methods: Patients receiving durvalumab after chemoradiotherapy for locally advanced NSCLC at a single institution were retrospectively analyzed, and the association of the proportion of durvalumab infusions greater than or equal to 20% versus less than 20% after 3 PM with progression-free survival (PFS) and overall survival was assessed.

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Article Synopsis
  • An 80-year-old man showed signs of yellowing in his skin (jaundice) and had low red blood cells (hemolytic anemia) and kidney problems.
  • Doctors found out he had untreated syphilis and a specific type of anemia called autoimmune hemolytic anemia (AIHA).
  • After giving him antibiotics for syphilis, he got better, but then he experienced a different condition called paroxysmal cold hemoglobinuria (PCH) when he got cold; he improved after more treatment and staying warm.
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To facilitate the introduction of proteins, such as antibodies, into cells, a variety of delivery peptides have been engineered. These peptides are typically highly cationic and somewhat hydrophobic, enabling cytosolic protein delivery at the cost of causing cell damage by rupturing membranes. This balance between delivery effectiveness and cytotoxicity presents obstacles for their real-world use.

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Article Synopsis
  • Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients have poor treatment responses, necessitating the development of therapies that disrupt the Menin-MLL1 complex, such as the compound DS-1594a.
  • Preclinical evaluations showed that DS-1594a and its salts effectively inhibited the growth of MLL1-r or NPM1c leukemic cells, outperforming traditional chemotherapy like cytrabine in in vitro and in vivo models.
  • DS-1594a, with its potent antitumor effects, suggests potential as a new oral anticancer therapy, distinct from existing treatments, offering hope for improved outcomes in acute leukemia patients.
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Laminar shear stress generated by blood flow stimulates endothelial cells and activates signal transduction, which plays an important role in vascular homeostasis. Several lines of evidence indicate that membrane and intracellular lipids are involved in the signal transduction of biomechanical stresses. In this study, we performed global profiling of cellular lipids from human pulmonary artery endothelial cells (HPAEC) exposed to laminar shear stress.

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Aims: Inflammation and hypertension contribute to the progression of atherosclerotic aneurysm in the aorta. Vascular cell metabolism is regarded to modulate atherogenesis, but the metabolic alterations that occur in atherosclerotic aneurysm remain unknown. The present study aimed to identify metabolic pathways and metabolites in aneurysmal walls and examine their roles in atherogenesis.

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Shrinkage-reducing agents have been developed to mitigate shrinkage and to control cracks in concrete. This study aims to evaluate the impact of a newly developed shrinkage-reducing agent (N-SRA) on concrete properties and to compare its properties with a conventional shrinkage-reducing agent (C-SRA). The hydration rate, compressive strength, splitting tensile strength, shrinkage, occurrence of cracking, and freezing and thawing were investigated.

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The conformations of polycarboxylate ether (PCE) type superplasticizer polymers adsorbed on the surface of MgO in cement pore solution are simulated by molecular dynamics (MD). Three types of PCEs commonly applied to concrete are simulated, namely a methacrylate type PCE (PCEM-P), an allyl ether type PCE (PCEA-P), and an isoprenyl ether type PCE (PCEI-P) with ethylene oxide (EO) unit numbers (P) of 25, 34 and 25, respectively. It is observed that the adsorbed layer thickness is inversely proportional to the experimentally measured adsorbed amount at the initial paste flow of 26 ± 0.

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Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival.

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The NONcNZO10/LtJ mouse is a polygenic model of type-2 diabetes (T2D) that shows moderate obesity and diabetes, and is regarded as a good model reflective of the conditions of human T2D. In this study, we analyzed pathological changes of pancreases with the progress of time by using histopathology and gene expression analysis, including microRNA. A number of gene expression changes associated with decreased insulin secretion (possibly regulated by miR-29a/b) were observed, and zinc homeostasis (Slc30a8, Mt1 and Mt2) or glucose metabolism (Slc2a2) was suggested as being the candidate mechanism of pancreas failure in NONcNZO10/LtJ mice.

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Article Synopsis
  • The study introduces a new method for selecting lead substances for risk assessment of mixtures, inspired by the UN GHS classification system, aiming to improve safety in regions outside Europe.
  • Unlike existing European methods that rely on specific regulations and data, the GHS-based approach offers a more universal solution applicable in different countries.
  • The research showed that the GHS method resulted in the selection of safer substances compared to other European methods, and the authors advocate for its adoption as a standardized tool for chemical management globally.
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We found a novel protein-protein interaction between ubiquitin-specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1): USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates of the cells, where they were co-expressed; and USP15 deubiquitinated SLIM1, resulting in the increase of protein levels of SLIM1. Because SLIM1 is strongly implicated in the pathogenesis of myopathies and cardiomyopathies, we generated transgenic (TG) mice with cardiac-specific overexpression of human USP15. Heart weight to body weight ratios and mRNA levels of fetal gene markers in the heart were significantly higher in USP15-TG mice than in wild-type (WT) mice.

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Objectives: DC-159a (a novel quinolone) and sitafloxacin (DU-6859a) are structurally related quinolones, bearing a 3-aminopyrrolidyl substitution. We investigated the relationship between the target preferences of these 3-aminopyrrolidyl quinolones, in vitro potencies and emergence of quinolone-resistant mutants in Streptococcus pneumoniae, compared with other quinolones.

Methods: MICs, resistance frequencies and mutant prevention concentrations (MPCs) were determined using quinolone-susceptible strains and first-step parC mutant strains of S.

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Noroviruses are one of the major causes of viral gastroenteritis in Japan. A quantitative risk assessment was conducted to evaluate the health risk caused by this virus in drinking water. A Monte Carlo analysis was used to calculate both the probability of infection and the disease burden using disability-adjusted life years (DALYs).

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This study describes an approach for genotyping individual Cryptosporidium oocysts obtained from sewage. We isolated single immunofluorescent assay (IFA)-stained Cryptosporidium oocysts from sewage concentrate using glass capillary pipettes and inverted epifluorescence microscopy. Each isolated Cryptosporidium oocyst was analyzed by semi-nested PCR for the 18S rRNA gene and direct sequencing of the PCR products.

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To experimentally demonstrate the mirror-image recognition in protein and DNA interaction, we have designed a small DNA-binding peptide based on the zinc-finger domain of GAGA transcription factor. Circular dichroism data suggest that the conformations of peptide enantiomers as well as the DNA enantiomers have a mirror-image relationship. The gel mobility shift assay showed that the synthetic enantiomers of the peptide showed reciprocal chiral-specific interactions with the DNA; the natural L-peptide binds specifically with the natural D-DNA substrate, and the unnatural D-peptide binds specifically with the unnatural L-DNA substrate.

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To assess the possibility of multi-connection of zinc finger domains for understanding of DNA binding mechanisms and gene regulation, the longest artificial zinc finger protein, Sp1ZF15, has been constructed. This zinc finger consists of 5 units of Sp1 zinc finger peptide connected by canonical short linker sequences (TGEKP). Recognition of the 50 base pairs of DNA and potential binding to shorter targets by Sp1ZF15 were determined.

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To evaluate the effectiveness of UV irradiation in inactivating Cryptosporidium parvum oocysts, the animal infectivities and excystation abilities of oocysts that had been exposed to various UV doses were determined. Infectivity decreased exponentially as the UV dose increased, and the required dose for a 2-log(10) reduction in infectivity (99% inactivation) was approximately 1.0 mWs/cm(2) at 20 degrees C.

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A one-year monitoring of Cryptosporidium oocysts and Giardia cysts was conducted at a water purification plant. A total of 13 samples of 50 L river source water and 26 samples of 2,000 L-filtered water, treated by coagulation flocculation, sedimentation and rapid filtration, were tested. Prior to conducting a survey of a water purification plant, we developed a method for concentrating Cryptosporidium oocysts from a large volume of raw or filtered water using a hollow fiber ultrafiltration (UF) membrane, and this procedure was adapted to survey a water purification plant.

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