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Affiliation |
Hospital Central Laboratory Division |
Research Interests 【 display / non-display 】
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Cancer immunology
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Hematology
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Immunology
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Hematology
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Cancer immunology
Graduating School 【 display / non-display 】
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-2018.03
Akita University Graduate School, Division of Medicine Graduated
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-2010.03
Akita University Faculty of Medicine Graduated
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-2004.03
University of Tsukuba Second Cluster of College Graduated
Graduate School 【 display / non-display 】
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-2018.03
Akita University Graduate School, Division of Medicine Doctor's Course Completed
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-2006.03
University of Tsukuba Graduate School, Division of Medical Science Master's Course Completed
Campus Career 【 display / non-display 】
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2022.04-Now
Akita University Hospital Central Laboratory Division Assistant Professor
External Career 【 display / non-display 】
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2022.04
Akita University Hospital Central Laboratory Division Assistant Professor
Research Achievements 【 display / non-display 】
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Maiko Abumiya, Ayano Saito, Yuki Fujioka, Masatomo Miura, Naoto Takahashi
International journal of hematology ( International Journal of Hematology ) 2025.02
Research paper (journal)
Bosutinib is known to increase serum creatinine levels, and its mechanism of action is believed to involve a decrease in tubular creatinine excretion due to inhibition of tubular transporters and organic cation transporter 2. This study aimed to determine whether discontinuation of bosutinib could reverse bosutinib-induced elevation of serum creatinine levels. Serum creatinine levels were compared immediately before and after bosutinib administration and after bosutinib discontinuation in 11 patients with chronic myeloid leukemia. The median serum creatinine concentration significantly increased from 0.66 mg/dL before bosutinib to 0.76 mg/dL after bosutinib (P = 0.003) and decreased from 0.79 mg/dL before discontinuation of bosutinib to 0.66 mg/dL after discontinuation of bosutinib at 3 months (P = 0.005). This study revealed that bosutinib-induced elevation of serum creatinine, which was more pronounced in patients with the SLC22A2 808G/G genotype, does not indicate chronic kidney disease, but rather is simply a laboratory abnormality. If bosutinib-induced chronic kidney disease is suspected, renal function should be assessed by urinalysis and cystatin C levels to differentiate from simple elevation of serum creatinine.
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Toshinori Ezawa, Riku Otomo, Yumi Kariya, Kyoko Nozawa, Sonosuke Kyoya, Chikako Furutani, Keiichi Noguchi, Masafumi Yohda, Masafumi Odaka, Hirotoshi Matsumura, Ayano Saito, Masaya Saito, Fumito Abe, Yuki Fujioka, Akihiro Kitadate, Hideki Wakui, Naoto Takahashi
FASEB journal : official publication of the Federation of American Societies for Experimental Biology ( FASEB Journal ) 39 ( 1 ) e70296 2025.01
Research paper (journal)
Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease-causing LCs contributing to the onset of MM-associated tubular diseases remain unclear. We herein report a rare case of MM-associated combined tubulopathies: non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN). The patient's urinary κ-LC (Bence-Jones proteins, BJP-κ PT-CN) was detected through immunofixation. Renal biopsy revealed cytoplasmic vacuoles in swollen proximal tubular cells and distal tubular casts. Immunohistochemistry showed proximal tubular reabsorption granules and distal tubular casts positively stained with an anti-κ-LC antibody. Electron microscopy identified vacuolation and an increased number of lysosomes in proximal tubular epithelial cells without crystalline structures. Distal tubular casts comprised numerous crystals with both rod-shaped and needle-like configurations and tube-shaped materials. To elucidate the molecular mechanisms underlying tubular toxicity, we performed the following physicochemical analyses of BJP-κ PT-CN: N-terminal amino acid sequencing, cDNA cloning, size-exclusion chromatography, thermal shift assays, and X-ray crystallography. The variable segment of BJP-κ PT-CN was derived from the IGKV1-39 gene. The characteristic features of BJP-κ PT-CN were a positively charged surface patch, concentration-dependent monomer-dimer equilibrium, and the R61G mutation. This is the first biochemical and structural characterization of disease-causing BJPs in MM-associated LCPT and crystalline LCCN. The results obtained suggest that these characteristic features enhance protein binding to negatively charged sites on brush-border membranes in proximal tubules and promote the formation of organized casts in distal tubular lumens.
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Eline Zwiers, Daphne Montizaan, Annemarie Kip, Kelsy Waaijenberg, Paul S Fichtinger, Sameer K Mathur, Yuki Fujioka, Shigeharu Ueki, Helmuth van Es, Renato G S Chirivi, Eric Meldrum, Maarten van der Linden
Frontiers in immunology ( Frontiers in Immunology ) 16 1533407 - 1533407 2025
Research paper (journal)
Eosinophils are a subset of granulocytes that protect the host against fungal and parasitic infection through secretion of their granular contents. In response to specific stimuli, eosinophils also undergo a type of lytic cell death, referred to as eosinophil extracellular trap (EET)-associated cell death (EETosis), where histone citrullination facilitates chromatin decondensation, cell rupture and release of pro-inflammatory, decondensed chromatin into the extracellular environment as EETs. In this study, we show the abundant presence of eosinophils and citrullinated histones in nasal polyp tissue of patients with eosinophilic chronic rhinosinusitis (ECRS). Using live imaging microscopy on purified human eosinophils, we demonstrate that physiologically relevant stimuli induce release of citrullinated EETs and the marker of eosinophil activation galectin-10. While the kinetics of release of EETs and galectin-10 are similar, inhibitors of citrullination block EETosis in a dose dependent manner but fail to inhibit galectin-10 release. The importance of citrullination is further exemplified with CIT-013, a monoclonal antibody specific for citrullinated histones H2A and H4. CIT-013 potently inhibits release of EETs (half-maximal inhibitory concentration of 2.5 nM) without inhibiting other eosinophil functions such as degranulation, adhesion, superoxide production and induction of chemokine expression. Together, this study provides new insights into the requirement of protein arginine deiminase 4 (PAD4) for EETosis, differentiates requirements of EETosis from galectin-10 release, and identifies a novel therapeutic approach for EETosis inhibition by targeting citrullinated histones in eosinophil-driven diseases such as ECRS.
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Comparison of Transient and Persistent Adverse Events After COVID-19 Vaccination: A Retrospective Analysis.
Haruka Hikichi, Yuki Fujioka, Akiko Saga, Ken Watanabe, Ryo Hasegawa, Yuki Moritoki, Shigeharu Ueki
Cureus 16 ( 6 ) e63410 2024.06
Research paper (journal)
OBJECTIVE: Most reported adverse events following COVID-19 vaccination have been transient. However, persistent adverse events may occur with some frequency. This study aimed to analyze patient background characteristics and trends, with a focus on whether adverse events following COVID-19 vaccination were transient or persistent. METHODS: A retrospective study was performed at a single institution in Japan. PATIENTS: The study cohort included 47 patients who presented with symptoms after COVID-19 vaccination between May 2021 and September 2023. The patients were classified into two groups based on the duration of symptoms: transient group, less than four weeks; persistent group, greater than or equal to four weeks. Data on age, sex, body mass index, smoking history, underlying conditions, type of COVID-19 vaccination, number of doses, onset, symptoms, and treatments were collected retrospectively. RESULTS: The median age was 51.0 years and 74.5% were females, with a particularly high proportion of women in their 40s. The use of the bivalent omicron-containing booster vaccine (BA.1) was significantly more common in the persistent group than in the transient group (p = 0.0267). Onset in the transient group was more common after the first vaccination, whereas onset in the persistent group was more common after the second and subsequent vaccinations (p = 0.003). Regarding symptoms, pain was more frequent in the persistent group than in the transient group (60% vs. 13.6%; p = 0.001). CONCLUSIONS: This study investigated the presence of persistent symptoms, especially pain, after COVID-19 vaccination. Persistent symptoms were frequently reported after the second vaccination. It should be noted that the study does not negate the usefulness of COVID-19 vaccines.
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Ponatinib Improved the Prognosis of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Japanese Single-Center Cohort Study.
Nagi Tozawa, Takaya Yamashita, Miho Nara, Yuki Fujioka, Sho Ikeda, Takahiro Kobayashi, Isuzu Kobayashi, Akihiro Kitadate, Yoshihiro Kameoka, Naoto Takahashi
Cureus 15 ( 12 ) e50416 2023.12
Research paper (journal)
Introduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data. Methods We performed a single-center retrospective analysis utilizing Akita University Hospital data (Akita, Japan) from November 2000 to June 2023 to evaluate the outcomes of TKI with intensive chemotherapy for Ph+ALL. Results Twenty-three patients with Ph+ALL were treated with intensive chemotherapy combined with TKI, including six imatinib, four dasatinib, and 13 ponatinib. The median patient age was 53 years (range; 28-67). Eighteen patients (78%) achieved complete molecular remission (CMR) within three months. HSCT was performed in 16 patients (70%), all of whom did not receive post-transplant TKI maintenance therapy. Six of the seven patients who did not undergo HSCT received maintenance therapy with ponatinib after intensive chemotherapy. The three-year OS was 81%. Ponatinib treatment resulted in a much higher OS rate than imatinib/dasatinib (100% vs. 60%; P=0.011). CMR within three months was identified as a prognostic factor for molecular relapse-free survival (hazard ratio (HR)=0.22; P=0.027). CD20 positivity was identified as a risk factor for hematological relapse (HR=5.2, P=0.032). Conclusion Even in a single-center cohort study, ponatinib, as a combination TKI with intensive chemotherapy or maintenance therapy, may improve the prognosis of Ph+ALL. Patients with CMR within three months might not necessarily need to receive HSCT, but a subsequent treatment-free status could have been achieved only by HSCT. Furthermore, CD20 positivity may be a useful biomarker for future treatment decisions in patients with Ph+ALL.
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TFR後の晩期再発は免疫の調節不全を背景にしている
藤岡 優樹, 植木 重治, 高橋 直人
日本血液学会学術集会 ( (一社)日本血液学会 ) 86回 O1 - 5 2024.10
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Endovascular Retrieval of a Fractured Tunneled Hemodialysis Central Venous Catheter Using the Loop Snare Technique.
Tomoko Sasaki, Yuki Fujioka, Haruka Hikichi, Daisuke Yokota, Shigeharu Ueki
Cureus 15 ( 2 ) e35617 2023.02
The tunneled cuffed hemodialysis catheter is a valuable vascular access option for patients with end-stage renal disease (ESRD). Healthcare providers have become more familiar with the insertion of medical devices, including central venous catheters, in their daily practice. The occurrence of foreign body fragmentation is rare with these catheters. This article presents a case in which a fracture of the distal portion of the hemodialysis catheter was inadvertently identified during a coronary angiography. Percutaneous removal of the fractured venous catheter was performed successfully using a loop snare catheter, which prevented the patient from experiencing further complications.
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免疫プロファイリングによる、濾胞性リンパ腫の予後予測(Immune profiling analysis for prediction of outcome in patients with folliclular lymphoma)
山内 寛彦, 湯田 淳一朗, 藤岡 優樹, 長崎 譲慈, 山崎 美貴, 冨樫 庸介, 南 陽介, 西川 博嘉
臨床血液 ( (一社)日本血液学会-東京事務局 ) 59 ( 9 ) 1503 - 1503 2018.09 [Refereed]
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Presentations 【 display / non-display 】
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Kinetics of Treg after TKI discontinuation as a TFR biomarker
2023.10 - 2023.10
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Immune analyses of each TKI discontinuation trials leads the difference of immune induction ability
Yuki Fujioka, Naoto Takahashi, Hiroyoshi Nishikawa, Shigeki Ohtake, Yosuke Minami, Hitoshi Kiyoi, Yasushi Miyazaki, Itaru Matsumura
2022.10 - 2022.10