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医学部 附属病院 消化器内科 |
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Ozono Y., Shide K., Kameda T., Kamiunten A., Tahira Y., Sekine M., Akizuki K., Nakamura K., Iwakiri H., Sueta M., Hidaka T., Kubuki Y., Yamamoto S., Hasuike S., Sawaguchi A., Nagata K., Shimoda K.
Leukemia 35 ( 2 ) 454 - 467 2021年2月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
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Ozono Y., Nagata K., Hasuike S., Iwakiri H., Nakamura K., Tsuchimochi M., Yamada Y., Takaishi Y., Sueta M., Miike T., Tahara Y., Yamamoto S., Shide K., Hidaka T., Kubuki Y., Kusumoto K., Ochiai T., Kato J., Komada N., Hirono S., Kuroki K., Shigehira M., Shimoda K.
World Journal of Hepatology 9 ( 36 ) 1340 - 1345 2017年12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） 出版者・発行元：World Journal of Hepatology
AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir (SOF) and ledipasvir (LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1. METHODS This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects (AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger (aged < 75 years) and elderly (aged ≥ 75 years). Virological data and AEs were analyzed by age group. RESULTS The sustained virological response (SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.
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Ozono Y., Kawakami H., Hatada H., Uchiyama N., Ogawa S., Uchida K., Tamura H., Komaki Y., Nakamura K., Iwakiri H., Hasuike S., Nagata K.
BMC Gastroenterology 26 ( 1 ) 108 2026年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Gastroenterology
Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease with increasing global prevalence. Although diabetes is a major factor in NAFLD progression, up to 75% of the patients with NAFLD do not have diabetes. Tofogliflozin (Tofo), a sodium-glucose cotransporter type-2 inhibitor, is widely used in patients with type 2 diabetes. Several clinical trials with Tofo have shown its beneficial effects in NAFLD patients with diabetes; however, currently, there are limited data on NAFLD patients without diabetes. Methods: C57Bl/6J mice were fed a choline-deficient, L-amino acid–defined, high-fat diet (CDAHFD) as a model of non-diabetic non-alcoholic steatohepatitis (NASH). The mice were fed either a normal diet or CDAHFD for 12 weeks, and received either vehicle or Tofo based on their assigned group for 12 weeks. Results: Tofo treatment attenuated CDAHFD-induced liver steatosis and fibrosis. The percentage of monocyte-derived macrophages in the liver, which was significantly increased in the CDAHFD-fed mice, was reduced by Tofo treatment. Furthermore, Tofo treatment increased the hepatic protein and mRNA expression levels related to fatty acid oxidation, which was decreased in CDAHFD-fed mice. Additionally, Tofo treatment decreased the hepatic protein and mRNA expression levels related to fatty acid synthesis, which was increased in CDAHFD-fed mice. Conclusion: Tofo may be a potential candidate for inhibiting liver steatosis and fibrosis via an alternative pathway, unlike glucose metabolism, in NAFLD patients without diabetes.
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Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia. 査読あり
Uchida T, Shide K, Kameda T, Ozono Y, Kubuki Y, Tahira Y, Kamiunten A, Marutsuka K, Akizuki K, Karasawa M, Uehira Y, Ueno H, Yamaguchi H, Shimoda K
Blood 2026年7月
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Hepatic focal nodular hyperplasia after liver transplantation: case report and review of literature 査読あり
Nakamura K., Ozono Y., Hasuike S., Hatada H., Uchiyama N., Komaki Y., Iwakiri H., Nagata K., Umekita Y., Aishima S., Kawakami H.
Clinical Journal of Gastroenterology 18 ( 5 ) 910 - 917 2025年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Journal of Gastroenterology
Patients with decompensated cirrhosis complicated by hepatocellular carcinoma (HCC) or those who have undergone liver transplantation following liver failure after HCC treatment should continue to receive post-transplant surveillance. Any new liver tumor must be carefully evaluated to determine whether it is a recurrence of HCC. Focal nodular hyperplasia (FNH), the second most common benign hepatic tumor, is believed to result from the hyperplastic response of hepatocytes to pre-existing vascular malformation. Here, we report a case of hepatic FNH two years after living-donor liver transplantation in a patient who experienced liver failure following treatment for HCC. Given the rarity of hepatic FNH after liver transplantation, we present this case along with a review of the literature.
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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MASHの線維化におけるfibrocyteの役割解明とfibrocyteを標的とした新規治療薬の探索
研究課題/領域番号：25K19303 2025年04月 - 2028年03月
独立行政法人日本学術振興会 科学研究費基金 若手研究
担当区分：研究代表者
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肝硬変、NASH発症・進展に果たす造血細胞の関与の解明と新たな治療標的の確立
研究課題/領域番号：19K17404 2019年04月 - 2022年03月
科学研究費補助金 若手研究
担当区分：研究代表者