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医学部 医学科 機能制御学講座薬理学分野 |
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Preβ1-HDL binds to TG-rich lipoproteins and its release is impaired in the postprandial state among patients with poorly controlled type 2 diabetes. 査読あり 国際誌
Yuna Horiuchi, Satoshi Hirayama, Atsushi Hori, Yuri Ichikawa, Satoshi Soda, Utako Seino, Kazumasa Sekihara, Tsuyoshi Ueno, Yoshifumi Fukushima, Katsuo Kubono, Takashi Miida
Annals of clinical biochemistry 45632251328154 - 45632251328154 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Although preβ1-high-density lipoprotein (preβ1-HDL) promotes cholesterol efflux, high fasting preβ1-HDL levels after breakfast are reduced in patients with poorly controlled type 2 diabetes. OBJECTIVE: This study investigated whether preβ1-HDL binds to triglyceride (TG)-rich lipoproteins (TGRLs) in the postprandial state and is released during lipolysis. METHODS: We measured preβ1-HDL concentrations, lecithin-cholesterol acyltransferase (LCAT) activity, and LCAT-dependent preβ1-HDL conversion before and after breakfast in patients with diabetes. We also performed in vitro studies using TGRLs. Preβ1-HDL was quantified by enzyme-linked immunosorbent assay and native two-dimensional gradient gel (N-2D-gel) electrophoresis. RESULTS: Before breakfast, the diabetes group had higher preβ1-HDL concentrations than the healthy controls; after breakfast, levels in the two groups were similar. Neither LCAT mass nor the LCAT-dependent preβ1-HDL conversion rate changed after breakfast. Mixing of fasting plasma with chylomicrons or very-low-density lipoprotein (VLDL) reduced the preβ1-HDL level by 15% ± 4% and 45% ± 10%, respectively. N-2D-gel electrophoresis showed that preβ1-HDL was generated by bacteria-derived TG lipase only from postprandial VLDL of patients with type 2 diabetes. CONCLUSION: Preβ1-HDL binds to TGRLs in the postprandial state and is released during lipolysis, implying that postprandial hyperlipidemia impairs reverse cholesterol transport in patients with poorly controlled type 2 diabetes.
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Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer. 査読あり 国際誌
Kazumasa Sekihara, Hidetomo Himuro, Soji Toda, Nao Saito, Ryoichi Hirayama, Nobuyasu Suganuma, Tetsuro Sasada, Daisuke Hoshino
Biomedicines 12 ( 6 ) 2024年6月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy characterized by advanced disease at diagnosis and a poor prognosis. Despite multimodal therapeutic approaches that include surgery, radiotherapy, and chemotherapy, an optimal treatment strategy remains elusive. Current developments in targeted therapies and immunotherapy offer promising avenues for improved outcomes, particularly for BRAF-mutant patients. However, challenges remain regarding overcoming drug resistance and developing effective treatments for BRAF-wild-type tumors. This comprehensive review examines the clinical and biological features of ATC, outlines the current standards of care, and discusses recent developments with a focus on the evolving role of radiotherapy. Moreover, it emphasizes the necessity of a multidisciplinary approach and highlights the urgent need for further research to better understand ATC pathogenesis and identify new therapeutic targets. Collaborative efforts, including large-scale clinical trials, are essential for translating these findings into improved patient outcomes.
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Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy. 査読あり 国際誌
Yutaro Kobori, Satoshi Hirayama, Yoshifumi Fukushima, Tsuyoshi Ueno, Kazumasa Sekihara, Atsushi Hori, Yuna Horiuchi, Shintaro Makino, Emiko Nishioka, Takashi Miida
Annals of clinical biochemistry 45632241239806 - 45632241239806 2024年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. OBJECTIVE: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. METHODS: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. RESULTS: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (p < 0.001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (p < 0.001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.830 ± 0.074 vs. 0.788 ± 0.098, respectively; p < 0.05), whereas the urine FCA/TCA ratio was similar between the groups. CONCLUSION: Low carnitine level is associated with increased renal excretion during late pregnancy.
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SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection. 査読あり 国際誌
Xiaofang Li, Kenji Nakashima, Masahiko Ito, Mami Matsuda, Takeshi Chida, Kazumasa Sekihara, Hirotaka Takahashi, Takanobu Kato, Tatsuya Sawasaki, Tetsuro Suzuki
Antiviral research 220 105756 - 105756 2023年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the C-terminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection.
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Validation of EZH2 Inhibitor Efficiency in Anaplastic Thyroid Carcinoma Cell Lines. 査読あり 国際誌
Hirotaka Nakayama, Nao Saito, Rika Kasajima, Nobuyasu Suganuma, Yasushi Rino, Katsuhiko Masudo, Haruhiko Yamazaki, Soji Toda, Kazumasa Sekihara, Hiroyuki Iwasaki, Daisuke Hoshino
Anticancer research 43 ( 3 ) 1073 - 1077 2023年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND/AIM: The prognosis of anaplastic thyroid carcinoma (ATC) is poor, and there is currently no established treatment to improve its outcome. We previously reported that enhancer of zeste homolog 2 (EZH2) was highly expressed in ATC, and may be a therapeutic target; however, the effects of EZH2 on ATC growth currently remain unknown. MATERIALS AND METHODS: We investigated the effects of an EZH2 inhibitor (DZNep) on four ATC cell lines (8305C, KTA1, TTA1 and TTA2). We performed a gene panel analysis of all ATC cell lines to identify differences in DZNep sensitivity between the cell lines. To investigate the effects of DZNep on the recovery of differentiation, we assessed changes in thyroid differentiation markers (TDMs) before and after the DZNep treatment using PCR. RESULTS: EZH2 was expressed in all ATC cell lines. The cell-reducing effects of DZNep were detected in all ATC cell lines, and were the strongest in KTA1 cells followed by TTA2 cells. The TTA1 and 8305C cell lines, which showed weak cell-reducing effects, had TP53 mutations. No changes in TDMs were observed in any ATC cell line. CONCLUSION: DZNep, an EZH2 inhibitor, exerted suppressive effects on the growth of ATC cell lines and has potential as a therapeutic strategy; however, its effects may be attenuated in ATC with TP53 mutations.
講演・口頭発表等 【 表示 ／ 非表示 】
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ヒト末梢血単核細胞に対する重粒子線とX線の及ぼす影響の比較検討
氷室秀知, 関原和正, 紅露拓, 魏菲菲, 辻嘉代子, 駒橋充, 星野大輔, 笹田哲朗
日本放射線腫瘍学会第37回学術大会
開催年月日： 2024年11月21日 - 2024年11月23日
会議種別：ポスター発表
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放射線単独および分子標的薬との併用療法は甲状腺未分化がん細胞を効果的に殺傷する
関原和正, 氷室秀知, 笹田哲朗, 星野大輔
第83回日本癌学会学術総会
開催年月日： 2024年9月19日 - 2024年9月21日
会議種別：口頭発表（一般）
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A Novel Therapeutic Strategy for ATC: Carbon Ion Radiation Therapy Combined with Targeted Agents.
Kazumasa Sekihara, Hidetomo Himuro, Ryoichi Hirayama, Tetsuro Sasada, Daisuke Hoshino
48th European Radiation Research Society Annual Meeting
開催年月日： 2024年9月10日 - 2024年9月13日
会議種別：ポスター発表
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重粒子線照射は甲状腺未分化がん細胞の増殖および遊走を抑制する
関原和正, 氷室秀知, 平山亮一, 笹田哲朗, 星野大輔
第33回日本がん転移学会学術集会・総会
開催年月日： 2024年6月27日 - 2024年6月28日
会議種別：ポスター発表
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悪性腫瘍（放射線、抗がん剤に抵抗性を示す難治がん含む）に対する重粒子線の有用性および分子機構の解明
関原和正, 氷室秀知, 平山亮一, 笹田哲朗, 星野大輔
2023年度重粒子線がん治療装置等共同利用研究成果報告会（録画発表）
開催年月日： 2024年6月3日 - 2024年6月5日
会議種別：口頭発表（一般）
受賞 【 表示 ／ 非表示 】
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2024年度日本放射線影響学会奨励賞
2024年9月 日本放射線影響学会
関原和正
受賞区分：国内学会・会議・シンポジウム等の賞
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ICRR2023 Travel Award
2023年8月 日本放射線影響学会
関原和正
受賞区分：国内学会・会議・シンポジウム等の賞
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ACRR2017 Travel Award
2017年8月 日本放射線影響学会
関原和正
受賞区分：国内学会・会議・シンポジウム等の賞
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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従来法とオルガノイド培養法の重粒子線による生物効果解析
研究課題/領域番号：23K07100 2023年04月 - 2026年03月
日本学術振興会 科学研究費基金 基盤研究(C)
関原和正、平山亮一、氷室秀知
担当区分：研究代表者
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放射線耐性を導く口腔がん幹細胞におけるSIRT6の役割
研究課題/領域番号：19K19206 2019年04月 - 2022年03月
日本学術振興会 科学研究費補助金 若手研究
関原和正
担当区分：研究代表者
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がん放射線治療の基礎となるPLDR阻害と修復不能なDNA二重鎖切断の関わり
研究課題/領域番号：16K19855 2016年04月 - 2020年03月
日本学術振興会 科学研究費補助金 若手研究(B)
関原和正
担当区分：研究代表者
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CXCL2依存性の腸脳相関を介した放射線治療効果増感についての検討
研究課題/領域番号：23K07125 2023年04月 - 2026年03月
日本学術振興会 科学研究費補助金 基盤研究(C)
氷室秀知、関原和正、平山亮一
担当区分：研究分担者
その他競争的資金獲得実績 【 表示 ／ 非表示 】
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重粒子線照射後に分泌される細胞外小胞による細胞死および免疫リプログラミング分子機構の解明
2024年04月 - 2026年03月
公益財団法人 放射線影響協会 令和5年度放射線影響研究奨励助成
関原和正
担当区分：研究代表者
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重粒子照射が細胞外小胞分泌に与える影響と治療効果予測マーカーの探索
2023年04月 - 2024年03月
公益財団法人 横浜学術教育振興財団 研究助成（医学）
関原和正
担当区分：研究代表者
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M2マクロファージおよび骨髄由来免疫抑制細胞の口腔がん予後予測マーカーとしての可能性
2019年07月 - 2020年08月
一般財団法人 横浜総合医学振興財団 わかば研究助成
関原和正
担当区分：研究代表者