Publications by authors named "Hiroto Kishi"

Article Synopsis
  • * Researchers analyzed RNA-seq data from 465 blood samples, uncovering 1169 expression quantitative trait loci (eQTLs) and 1549 splice QTLs (sQTLs) linked to COVID-19 severity, including immune-related expressions.
  • * The study highlights the impact of disease severity on gene expression, identifying specific eQTLs that interact with COVID-19 phenotypes, and provides an extensive resource for understanding gene regulation in response to the virus.
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Article Synopsis
  • Researchers conducted a genome-wide association study (GWAS) with 2,393 COVID-19 patients and 3,289 controls in Japan, identifying a specific genetic variant (rs60200309-A) on chromosome 5 linked to severe cases in individuals under 65.
  • The variant is more common in East Asians and associated with reduced expression of the DOCK2 gene, which was found to be lower in severe COVID-19 cases, particularly in non-classical monocytes.
  • Additionally, inhibiting DOCK2 in hamsters worsened pneumonia symptoms, indicating its potential as a biomarker and therapeutic target for severe COVID-19.
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Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-spike mAbs from two convalescent COVID-19 patients infected with prototypic SARS-CoV-2 by single-cell sorting of immunoglobulin-G-positive (IgG) memory B cells.

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Background: In December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients.

Methods: Data of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed.

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The Consultation Support and Information Providing Committee, which is a subsidiary organization of the Kumamoto Cancer Medical Cooperation Council, created a critical path called"my medical chart,"which is used in Kumamoto prefecture jointly. The path was implemented in 2009 at designated cancer hospitals. For promoting cancer consultation support centers and nurturing cancer counselors, the Cancer Special Counselor Working Group was formed, and activities were initiated.

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Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model.

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Objectives: We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100mg/m(2)) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR).

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Objectives: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed.

Methods: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry.

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Aims: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer.

Materials & Methods: After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan(®) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC.

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Preparation of a system of community cooperation clinical pathway is called for by The Basic Act on Anti-Cancer Measures and The Basic Plans for National Cancer Strategy. Designated cancer care hospitals should play a very important role in constructing a local communication system among hospitals, clinics and nursing homes. In order to cooperate for seamless care of cancer, a notebook for patients with cancer has been made in Kumamoto by launching the Kumamoto Prefecture Regional Cooperation Conference of cancer management with the assistance of Kumamoto Prefectural government and the designated cancer care hospitals.

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Amrubicin, a synthetic 9-aminoanthracycline agent, was recently approved in Japan for treatment of small-cell lung cancer and non-small-cell lung cancer. Amrubicin is converted enzymatically to the C-13 hydroxy metabolite amrubicinol, which is active and possesses a cytotoxicity 10 to 100 times that of the parent drug. The purpose of this study was to characterize the pharmacokinetics of amrubicin and its active metabolite amrubicinol.

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Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses.

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Article Synopsis
  • More than 30% of non-small cell lung cancer (NSCLC) cases occur in patients aged 70 and older, prompting a study to evaluate the efficacy and safety of carboplatin-paclitaxel chemotherapy in this demographic.
  • The phase II trial involved 25 elderly patients (average age 76) who were treated with a specific chemotherapy regimen, resulting in a 28% objective response rate and a median survival time of 12.3 months.
  • The treatment showed manageable toxicity, with similar outcomes in patients aged 75 and older, indicating that this chemotherapy combination is a viable option for fit elderly patients with advanced NSCLC.
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The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or deltaEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumor-specific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor.

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