辻川　華子 (ツジカワ　ハナコ)

Tsujikawa, Hanako

写真a

所属（所属キャンパス）

医学部 病理診断部 （信濃町）

職名

専任講師（有期）
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経歴 【 表示 ／ 非表示 】

  • 2008年08月
    -
    2009年03月

    医学部総合医科学研究センター, 非常勤大学研究員(有期・文部科学省グローバルCOEプログラム「幹細胞医学のための研究拠点」)

  • 2008年09月
    -
    2009年03月

    東京都清瀬小児病院, 非常勤職員

  • 2008年10月
    -
    2009年03月

    永寿総合病院, 非常勤職員

  • 2010年05月
    -
    2010年08月

    さいたま市立病院, 病理診断科, 非常勤職員

  • 2010年09月
    -
    継続中

    日野市立病院, 検査科, 非常勤職員

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学歴 【 表示 ／ 非表示 】

  • 2008年04月
    -
    2012年03月

    慶應義塾, 医学部, 医学科病理専攻

    大学院, 卒業, 博士

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免許・資格 【 表示 ／ 非表示 】

  • 医師免許, 2006年04月

  • 死体解剖資格, 2012年03月

  • 病理専門医, 2013年07月

  • 細胞診専門医, 2013年12月

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論文 【 表示 ／ 非表示 】

  • Plasmacytoid dendritic cells protect against immune-mediated acute liver injury via IL-35

    Koda Y., Nakamoto N., Chu P., Ugamura A., Mikami Y., Teratani T., Tsujikawa H., Shiba S., Taniki N., Sujino T., Miyamoto K., Suzuki T., Yamaguchi A., Morikawa R., Sato K., Sakamoto M., Yoshimoto T., Kanai T.

    Journal of Clinical Investigation （Journal of Clinical Investigation)  129 （ 8 ） 3201 - 3213 2019年08月

    ISSN  00219738

    　概要を見る

    © 2019, American Society for Clinical Investigation. Acute liver failure (ALF) is a life-threatening condition, and liver transplantation is the only therapeutic option. Although immune dysregulation is central to its pathogenesis, the precise mechanism remains unclear. Here, we show that the number of peripheral and hepatic plasmacytoid DCs (pDCs) decrease during acute liver injury in both humans and mice. Selective depletion of pDCs in Siglechdtr/+ mice exacerbated concanavalin A–induced acute liver injury. In contrast, adoptively transferred BM-derived pDCs preferentially accumulated in the inflamed liver and protected against liver injury. This protective effect was independent of TLR7 and TLR9 signaling, since a similar effect occurred following transfer of MyD88-deficient pDCs. Alternatively, we found an unexpected immunosuppressive role of pDCs in an IL-35–dependent manner. Both Il12a and Ebi3, heterodimeric components of IL-35, were highly expressed in transferred pDCs and CD4+CD25+ Tregs. However, the protective effect of pDC transfer was completely lost in mice depleted of Tregs by anti-CD25 antibody. Moreover, pDCs derived from IL-35–deficient mice had less of a protective effect both in vivo and in vitro even in the presence of Tregs. These results highlight a unique aspect of pDCs in association with Tregs, serving as a guide for immunotherapeutic options in ALF.

  • Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features

    Hatano M., Ojima H., Masugi Y., Tsujikawa H., Hiraoka N., Kanai Y., Shimada K., Shinoda M., Sakamoto M.

    Human Pathology （Human Pathology)  86   222 - 232 2019年04月

    ISSN  00468177

    　概要を見る

    © 2018 Elsevier Inc. We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

  • Diffuse and canalicular patterns of glypican-3 expression reflect malignancy of hepatocellular carcinoma

    Kawaida M., Yamazaki K., Tsujikawa H., Fukuma M., Abe Y., Kitago M., Shinoda M., Kitagawa Y., Sakamoto M.

    Pathology International （Pathology International)  69 （ 3 ） 125 - 134 2019年03月

    ISSN  13205463

    　概要を見る

    © 2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Glypican-3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki-67 indices, high serum α-fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT-activated HCCs. Induction of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5-induced cells formed tumors with canaliculus-like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.

  • A Pre-Clinical Large Animal Model of Sustained Liver Injury and Regeneration Stimulus

    Inomata K., Tajima K., Yagi H., Higashi H., Shimoda H., Matsubara K., Hibi T., Abe Y., Tsujikawa H., Kitago M., Shinoda M., Obara H., Itano O., Soto-Gutierrez A., Kitagawa Y.

    Scientific Reports （Scientific Reports)  8 （ 1 ）  2018年12月

    　概要を見る

    © 2018, The Author(s). A feasible large animal model to evaluate regenerative medicine techniques is vital for developing clinical applications. One such appropriate model could be to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have developed the first porcine model using RS and PH. RS or saline control was administered intraperitoneally to Göttingen miniature pigs twice, two weeks apart. Four weeks after the second dose, animals underwent PH. Initially, we tested different doses of RS and resection of different amounts of liver, and selected 50 mg/kg RS with 60% hepatectomy as our model for further testing. Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and resected liver were collected. Serum and liver RS content was determined by Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17 days after PH in RS-treated animals, to the extent of 20%. Histological examination indicated hepatic injury and regenerative responses after PH. Immunohistochemical staining demonstrated accumulation of Cyclin D1 and suppression of Ki-67 and PCNA in RS-treated animals. We report the development of the first large animal model of sustained liver injury with suppression of hepatic regeneration.

  • Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification

    Kurebayashi Y., Ojima H., Tsujikawa H., Kubota N., Maehara J., Abe Y., Kitago M., Shinoda M., Kitagawa Y., Sakamoto M.

    Hepatology （Hepatology)  68 （ 3 ） 1025 - 1041 2018年09月

    ISSN  02709139

    　概要を見る

    © 2018 by the American Association for the Study of Liver Diseases. Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations of immune cells forming the immune microenvironment and their association with histological findings remain largely unknown. Moreover, it is unclear which immune cells or immune microenvironments are the most prognostically significant. Here, we comprehensively analyzed the immune microenvironment and its intratumor heterogeneity in 919 regions of 158 hepatocellular carcinomas (HCCs), and the results were compared with the corresponding histological and prognostic data. Consequently, we classified the immune microenvironment of HCC into three distinct immunosubtypes: Immune-high, Immune-mid, and Immune-low. The Immune-high subtype was characterized by increased B-/plasma-cell and T cell infiltration, and the Immune-high subtype and B-cell infiltration were identified as independent positive prognostic factors. Varying degrees of intratumor heterogeneity of the immune microenvironment were observed, some of which reflected the multistep nature of HCC carcinogenesis. However, the predominant pattern of immunosubtype and immune cell infiltration of each tumor was prognostically important. Of note, the Immune-high subtype was associated with poorly differentiated HCC, cytokeratin 19 (CK19)+, and/or Sal-like protein 4 (SALL4)+ high-grade HCC, and Hoshida's S1/Boyault's G2 subclasses. Furthermore, patients with high-grade HCC of the predominant Immune-high subtype had significantly better prognosis. These results provide a rationale for evaluating the immune microenvironment in addition to the usual histological/molecular classification of HCC. Conclusion: The immune microenvironment of HCC can be classified into three immunosubtypes (Immune-high, Immune-mid, and Immune-low) with additional prognostic impact on histological and molecular classification of HCC. (Hepatology 2018).

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

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総説・解説等 【 表示 ／ 非表示 】

  • 【NAFLD/NASH診療の現況と展望】NAFLD/NASHの病理所見(解説/特集)

    辻川　華子,　坂元　亨宇

    Pharma Medica 37 ( 9 ) 19 - 22 2019年09月

    総説・解説（学術雑誌）, 共著

  • 【NAFLDとNASHの現況と展望-国民病となったNAFLD/NASHの疾患概念の変遷と問題点】NASHにおける組織学的所見(解説/特集)

    辻川　華子,　坂元　亨宇

    カレントテラピー 37 ( 1 ) 54 - 59 2019年01月

    総説・解説（学術雑誌）

  • 【肝臓II:肝病理診断のポイント-結節性肝病変-】早期肝細胞癌(解説/特集)

    辻川　華子,　上野　彰久,　坂元　亨宇

    病理と臨床 35 ( 4 ) 321 - 325 2017年04月

  • 肝細胞癌の分子病理と悪性度(総説)

    川井田　みほ,　辻川　華子,坂元　亨宇

    日本消化器病学会雑誌 113 ( 5 ) 761 - 766 2016年05月

  • 【NASHを知る!診る!】NASH病理診断のポイント(解説/特集)

    辻川　華子,　坂元　亨宇

    (Mebio)  33 ( 1 ) 15 - 19 2016年01月

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研究発表 【 表示 ／ 非表示 】

  • 肝細胞癌におけるインテグリンβ4発現の意義

    辻川　華子，山﨑　剣，真杉　洋平，坂元　亨宇

    第108回病理学会 (東京) , 2019年05月

  • 肝細胞癌の免疫組織学的サブクラス分類

    辻川　華子，尾島　英知，坂元　亨宇

    第54回　肝癌研究会 (久留米) , 2018年06月

  • 肝細胞癌の免疫組織学的サブクラス分類

    辻川　華子，真杉　洋平，坂元　亨宇

    第106回日本病理学会総会, 2017年04月

  • 肝細胞癌の亜分類と個別化医療 免疫組織化学染色による肝細胞癌亜分類の試み

    辻川 華子尾島英典、坂元亨宇

    第51回肝臓学会 (熊本県) , 2015年05月, シンポジウム・ワークショップ パネル（公募）, 日本肝臓学会

  • 肝細胞癌におけるbiliary/stem cell markerの発現

    辻川 華子真杉洋平、Kathryn effendi、山崎剣、坂元亨宇

    第102回　日本病理学会総会 (北海道札幌市) , 2013年06月, ポスター（一般）, 日本病理学会

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競争的資金等の研究課題 【 表示 ／ 非表示 】

  • 肝細胞癌サブクラス分類が悪性度を反映する機序の解明と診断への応用

    2017年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 辻川　華子, 若手研究(B), 補助金,  代表

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担当授業科目 【 表示 ／ 非表示 】

  • 病理学総論

    2020年度

  • 病理学総論

    2019年度

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