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医学部 附属病院 肝胆膵外科 |
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SETDB1-Mediated Chromatin Regulation in Intestinal Epithelial Cells During Intestinal Ischemia-Reperfusion Injury. 査読あり
Higuchi K, Ikenoue M, Ishizuka T, Kai K, Takahashi N, Kubota T, Shirouzu S, Lkham-Erdene B, Aung KM, Nakai M, Sawaguchi A, Nanashima A, Hishikawa Y
Acta histochemica et cytochemica 58 ( 1 ) 9 - 18 2025年2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）
SET domain bifurcated 1 (SETDB1), a histone H3K9-specific methyltransferase, is crucial for heterochromatin formation and intestinal homeostasis, but its role in intestinal ischemia-reperfusion injury (IRI) remains unclear. This study investigated changes in SETDB1-mediated nuclear chromatin regulation in intestinal epithelial cells (IECs) using an IRI mouse model. Jejunal samples were collected after 75 min of ischemia followed by 24 hr of reperfusion. Sinefungin was administered as a histone methyltransferase inhibitor. Morphologic changes were evaluated using hematoxylin-eosin staining and electron microscopy, and cell-adhesion molecule expression, including ZO-1, E-cadherin, integrin-β4, and laminin, was evaluated using immunohistochemistry. Super-resolution microscopy analyzed intranuclear SETDB1 localization and heterochromatin formation in IECs. IRI-affected jejunum exhibited massive IEC detachment, dilated intercellular spaces, basement membrane damage, and decreased expression of E-cadherin and integrin-β4. Sinefungin prevented these changes, however. The proportion of IECs expressing nuclear SETDB1 throughout the euchromatin was significantly higher in IRI-affected jejunum (77.8%) than sham-treated (3.0%) or sinefungin-treated, IRI-affected jejunum (2.7%). The proportion of IECs with decreased heterochromatin was significantly higher in sinefungin-treated, IRI-affected jejunum (84.3%) than untreated IRI-affected jejunum (15.6%). These findings suggest that SETDB1-mediated chromatin regulation is pivotal in intestinal IRI and represents a potential therapeutic target.
DOI： 10.1267/ahc.24-00061
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河野 文彰, 千代反田 顕, 中目 和彦, 明利 聡瑠, 福島 剛, 佐藤 勇一郎, 山口 秀樹, 池ノ上 実, 宗像 駿, 樋口 和宏, 武野 慎祐, 七島 篤志
Endocrinology Diabetes and Metabolism Case Reports 2025 ( 2 ) e250014 2025年5月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Bioscientifica
Summary
Spindle epithelial tumor with thymic-like elements (SETTLE) is an extremely rare tumor that occurs primarily in the thyroid gland. Histologically, SETTLE is characterized by the presence of spindle-shaped epithelial cells and glandular structures. However, it is known that diagnosis via fine-needle aspiration cytology can be challenging. SETTLE predominantly occurs in younger individuals and has a less favorable prognosis compared to differentiated thyroid carcinoma. Therefore, ensuring accurate diagnosis and appropriate treatment is crucial. We encountered a case of spindle epithelial tumor with thymus-like differentiation in a 10-year-old patient for whom the preoperative diagnosis was successfully established through fine-needle aspiration cytology, which facilitated appropriate surgical resection. Comprehensive histopathological examination and immunohistochemical analysis are essential to ensure appropriate management and surveillance of SETTLE.
Learning points
A rare thyroid tumor, spindle epithelial tumor with thymic-like elements (SETTLE), was diagnosed preoperatively and treated surgically.
SETTLE presents with characteristic histological features that must be recognized for accurate diagnosis. In addition, diagnosis through cytology is often challenging.
The primary treatment for SETTLE is surgical intervention as radiotherapy and pharmacological treatments are generally not expected to be highly effective.
Radical resection is the only effective treatment, making the selection of the surgical procedure according to the stage of the disease essential. -
Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27. 査読あり
Kai K, Ishizuka T, Matsumoto J, Shimamawari K, Mori R, Fidya, Lkham-Erdene B, Kubota T, Ikenoue M, Higuchi K, Nanashima A, Hishikawa Y
Acta histochemica et cytochemica 58 ( 2 ) 69 - 79 2025年4月
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Relationship between survival outcomes in patients with colorectal liver metastasis undergoing hepatectomy and significance of fibrotic markers for liver injury assessment. 査読あり 国際誌
Nanashima A, Hiyoshi M, Imamura N, Hamada T, Tsuchimochi Y, Shimizu I, Ochiai T, Ichihara A, Hamada K, Ichiki N, Kai K, Higuchi K
Translational cancer research 14 ( 1 ) 461 - 472 2025年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Progression of chronic liver dysfunction influenced by long-term chemotherapy or repeated hepatectomy might be related to patient overall survival as well as tumor factors in colorectal liver metastasis (CLM) patients. Our aim of this study was to clarify the relationship between fibrotic liver damage and malignant behaviors of CLM malignancy or its long-term survivals by the retrospective cohort study. METHODS: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), The fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative patient survival in the 45 consecutive patients with CLM who underwent radical hepatectomy. RESULTS: Fibrotic parameters were platelet count of 23.0±8.5 ×104/µL, HA level of 68.9±82.3 ng/mL, M2BPGi of 0.87±0.48 ng/mL, and type IV collagen level of 5.74±3.76 ng/mL. Platelet count was significantly correlated with HA level (P<0.05) and tended to be correlated with M2BPGi levels (P=0.056). HA level was significantly associated with albumin level (P<0.05). Overall survival in this series showed five-year overall survivors after hepatectomy in 44 patients (98%), but cancer-related deaths were observed in only one patient. Patients with higher grades and increased bilirubin levels demonstrated significantly lower cancer-free survival (P<0.05), but fibrotic parameters were not associated with prognostic factors. CONCLUSIONS: Fibrotic markers indicating chemotherapy or repeated surgical liver injury were not significant predictive factors reflecting cancer malignant behaviors or patient overall survival, contrary to our hypothesis. The current overall survival status using various modalities for cancer recurrence is satisfactory under our present perioperative management.
DOI： 10.21037/tcr-24-1138
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Effect of Hepatic Lipid Overload on Accelerated Hepatocyte Proliferation Promoted by HGF Expression via the SphK1/S1PR2 Pathway in MCD-diet Mouse Partial Hepatectomy. 査読あり
Lkham-Erdene B, Choijookhuu N, Kubota T, Uto T, Mitoma S, Shirouzu S, Ishizuka T, Kai K, Higuchi K, Mo Aung K, Batmunkh JE, Sato K, Hishikawa Y
Acta histochemica et cytochemica 57 ( 5 ) 175 - 188 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine- and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow- and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytometry and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation.
DOI： 10.1267/ahc.24-00046
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現状と理想からブレイクスルーする地方外科医の働き方改革 大学病院の立場から 査読あり
樋口 和宏, 濱田 聖暁, 市来 伸彦, 原 大介, 市原 明子, 内勢 由佳子, 落合 貴裕, 野村 信介, 池ノ上 実, 田代 耕盛, 河野 文彰, 武野 慎祐, 七島 篤志
日本臨床外科学会雑誌 84 ( 増刊 ) S60 - S60 2023年10月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：日本臨床外科学会
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繰り返す吻合部狭窄により発症した胃切除術後の盲係蹄症候群の1例 査読あり
樋口 和宏, 池ノ上 実, 落合 貴裕, 野村 信介, 田代 耕盛, 河野 文彰, 武野 慎祐, 七島 篤志, 安倍 弘生, 河上 洋
日本消化器病学会九州支部例会・日本消化器内視鏡学会九州支部例会プログラム・抄録集 120回・114回 211 - 211 2022年12月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：日本消化器病学会-九州支部
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内視鏡・腹腔鏡下合同手術の現状 十二指腸腫瘍に対するDLECSの導入と実際 査読あり
樋口 和宏, 河野 文彰, 田代 耕盛, 池ノ上 実, 野村 信介, 落合 貴裕, 猪俣 麻佑, 山田 隆盛, 武野 慎祐, 七島 篤志
日本臨床外科学会雑誌 83 ( 増刊 ) S159 - S159 2022年10月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：日本臨床外科学会
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経肛門的直腸異物の3例 査読あり
樋口 和宏, 河野 文彰, 田代 耕盛, 野村 信介, 池ノ上 実, 落合 貴裕, 猪俣 麻佑, 山田 隆盛, 佐野 浩一郎, 末田 秀人, 武野 慎祐, 七島 篤志
Japanese Journal of Acute Care Surgery 12 ( Suppl. ) 154 - 154 2022年9月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本Acute Care Surgery学会
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S状結腸癌による通過障害により発症した魚骨S状結腸穿孔の1例 査読あり
樋口 和宏, 末田 秀人, 佐野 浩一郎, 真方 寿人, 千代反田 顕, 坂元 里彩, 七島 篤志
日本大腸肛門病学会雑誌 75 ( 6 ) 312 - 313 2022年6月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本大腸肛門病学会
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最優秀演題賞
2019年2月 第113回日本血管外科学会九州地方会若手優秀演題セッション 極めてまれな先天性腹部大動脈瘤の１例
樋口和宏
受賞区分：国内外の国際的学術賞