安 健博 (アン ジェンボウ)

AN Jianbo



大学院医学系研究科(医学専攻等)  医学専攻  病態制御医学系  分子機能学・代謝機能学講座

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  • がん微小環境

  • マクロファージ

  • 動脈硬化

  • 転移

  • MRTF-A

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    北京大学   医学部   卒業

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    東京医科歯科大学  生命情報科学教育部  バイオ情報学  博士課程  修了

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  • 東京医科歯科大学 -  博士(理学)

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  • 2019年04月

    秋田大学   大学院医学系研究科(医学専攻等)   医学専攻   病態制御医学系   助教  

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  • 2015年12月

      東京医科歯科大学難治疾患研究所   分子病態分野   助教

  • 2014年10月

      東京大学生産技術研究所   炎症・免疫制御学社会連携研究部門   日本学術振興会特別研究員

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  • ライフサイエンス / 病態医化学


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  • IkBL is a new clue involved in the regulation of alternative splicing in human and viral genes

    Jianbo An

      2013年09月  [査読有り]

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  • Squamous cell carcinoma‐derived <scp>G‐CSF</scp> promotes tumor growth and metastasis in mice through neutrophil recruitment and tumor cell proliferation, associated with poor prognosis of the patients

    Kohei Kemuriyama, Jianbo An, Satoru Motoyama, Yushi Nagaki, Tomokazu Yamaguchi, Yusuke Sato, Akiyuki Wakita, Yoshihiro Minamiya, Keiji Kuba

    Genes to Cells ( Wiley )  28 ( 8 ) 573 - 584   2023年05月



    Tumor‐derived G‐CSF is a well‐known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G‐CSF in squamous cell carcinoma (SCC). High expression of G‐CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR‐S1M cells produce considerable amount of G‐CSF, which expression is correlated with its metastatic potentials. Deletion of G‐CSF in NR‐S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR‐S1M tumors in the mice. Mechanistically, G‐CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR‐S1M tumor‐bearing mice, accumulation of plasma G‐CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8<sup>+</sup> T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G‐CSF produced by NR‐S1M cells facilitates tumor progression in mice through bi‐functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G‐CSF expression.


  • Identification of Galectin-7 as a crucial metastatic enhancer of squamous cell carcinoma associated with immunosuppression.

    Jianbo An, Yushi Nagaki, Satoru Motoyama, Yuta Kuze, Midori Hoshizaki, Kohei Kemuriyama, Tomokazu Yamaguchi, Takashi Ebihara, Yoshihiro Minamiya, Yutaka Suzuki, Yumiko Imai, Keiji Kuba

    Oncogene   41 ( 50 ) 5319 - 5330   2022年12月


    Metastasis predicts poor prognosis in cancer patients. It has been recognized that specific tumor microenvironment defines cancer cell metastasis, whereas the underlying mechanisms remain elusive. Here we show that Galectin-7 is a crucial mediator of metastasis associated with immunosuppression. In a syngeneic mouse squamous cell carcinoma (SCC) model of NR-S1M cells, we isolated metastasized NR-S1M cells from lymph nodes in tumor-bearing mice and established metastatic NR-S1M cells in in vitro culture. RNA-seq analysis revealed that interferon gene signature was markedly downregulated in metastatic NR-S1M cells compared with parental cells, and in vivo NR-S1M tumors heterogeneously developed focal immunosuppressive areas featured by deficiency of anti-tumor immune cells. Spatial transcriptome analysis (Visium) for the NR-S1M tumors revealed that various pro-metastatic genes were significantly upregulated in immunosuppressive areas when compared to immunocompetent areas. Notably, Galectin-7 was identified as a novel metastasis-driving factor. Galectin-7 expression was induced during tumorigenesis particularly in the microenvironment of immunosuppression, and extracellularly released at later stage of tumor progression. Deletion of Galectin-7 in NR-S1M cells significantly suppressed lymph node and lung metastasis without affecting primary tumor growth. Therefore, Galectin-7 is a crucial mediator of tumor metastasis of SCC, which is educated in the immune-suppressed tumor areas, and may be a potential target of cancer immunotherapy.

    DOI PubMed

  • ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury.

    Takafumi Minato, Tomokazu Yamaguchi, Midori Hoshizaki, Satoru Nirasawa, Jianbo An, Saori Takahashi, Josef M Penninger, Yumiko Imai, Keiji Kuba

    PloS one   17 ( 7 ) e0270920   2022年07月


    Angiotensin-converting enzyme 2 (ACE2) is the carboxypeptidase to degrade angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and improves the pathologies of cardiovascular disease and acute respiratory distress syndrome (ARDS)/acute lung injury. B38-CAP is a bacteria-derived ACE2-like carboxypeptidase as potent as human ACE2 and ameliorates hypertension, heart failure and SARS-CoV-2-induced lung injury in mice. Recombinant B38-CAP is prepared with E. coli protein expression system more efficiently than recombinant soluble human ACE2. Here we show therapeutic effects of B38-CAP on abdominal sepsis- or acid aspiration-induced acute lung injury. ACE2 expression was downregulated in the lungs of mice with cecal ligation puncture (CLP)-induced sepsis or acid-induced lung injury thereby leading to upregulation of Ang II levels. Intraperitoneal injection of B38-CAP significantly decreased Ang II levels while upregulated angiotensin 1-7 levels. B38-CAP improved survival rate of the mice under sepsis. B38-CAP suppressed the pathologies of lung inflammation, improved lung dysfunction and downregulated elevated cytokine mRNA levels in the mice with acute lung injury. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for the patients with severe sepsis or ARDS.

    DOI PubMed

  • Peritumoral CD16b positive-neutrophil accumulation strongly correlates with regional lymph node metastasis in thoracic esophageal squamous cell cancer.

    Hiromu Fujita, Satoru Motoyama, Jianbo An, Yushi Nagakai, Tomokazu Yamaguchi, Souichi Koyota, Yusuke Sato, Akiyuki Wakita, Kazuhiro Imai, Keiji Kuba, Yoshihiro Minamiya

    Surgery   171 ( 6 ) 1535 - 1542   2022年06月


    BACKGROUND: The mechanism underlying cancer cell metastasis from the tumor to regional lymph nodes is not yet fully understood. We hypothesized that peritumoral neutrophil accumulation promotes regional lymph node metastasis in thoracic esophageal squamous cell cancer. METHODS: Between 2010 and 2019, 126 thoracic esophageal squamous cell cancer patients received curative (R0) esophagectomy without preoperative treatment in our hospital. Using paraffin-embedded resected tumors, we performed immunohistochemical analysis of CD16b-positive neutrophil accumulation in the peritumoral area, which was defined as a 1-mm region centered on the border separating the malignant cell nests from the host tissue. The relationship between the density of peritumoral CD16b staining and pathological lymph node metastasis or 5-year overall survival was evaluated. RESULTS: Although the clinicopathological characteristics of CD16b-high and CD16b-low patients did not differ, greater pathological lymph node metastasis (P < .001) and lymphatic invasion by the tumor (P = .024) and a poorer 5-year survival (P = .010) were seen in CD16b-high patients. Moreover, CD16b-positive neutrophil density was generally higher in the peritumoral area than within the tumor itself. Univariate and multivariate analyses showed that CD16b-positive neutrophil accumulation was an independent factor for lymph node metastasis with an odds ratio >25 (P < .001). On the other hand, blood neutrophil counts did not correlate with lymph node metastasis. CONCLUSION: Peritumoral accumulation of CD16b-positive neutrophils is an independent factor strongly correlated with lymph node metastasis in thoracic esophageal squamous cell cancer.

    DOI PubMed

  • ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury.

    Tomokazu Yamaguchi, Midori Hoshizaki, Takafumi Minato, Satoru Nirasawa, Masamitsu N Asaka, Mayumi Niiyama, Masaki Imai, Akihiko Uda, Jasper Fuk-Woo Chan, Saori Takahashi, Jianbo An, Akari Saku, Ryota Nukiwa, Daichi Utsumi, Maki Kiso, Atsuhiro Yasuhara, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Yuji Fujino, Satoru Motoyama, Satoshi Nagata, Josef M Penninger, Haruhiko Kamada, Kwok-Yung Yuen, Wataru Kamitani, Ken Maeda, Yoshihiro Kawaoka, Yasuhiro Yasutomi, Yumiko Imai, Keiji Kuba

    Nature communications   12 ( 1 ) 6791 - 6791   2021年11月


    Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS-CoV-2-infected hamsters, leading to elevation of angiotensin II levels. Recombinant Spike also downregulates ACE2 expression and worsens the symptoms of acid-induced lung injury. B38-CAP does not neutralize cell entry of SARS-CoV-2. However, B38-CAP treatment improves the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients.

    DOI PubMed

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