Curriculum Vitaes
Profile Information
- Affiliation
- School of Medicine Faculty of Medicine, Fujita Health University
- Degree
- 博士（医学）(藤田医科大学)
- J-GLOBAL ID
- 201501009281932970
- researchmap Member ID
- 7000012895
Research Areas
1Research History
1-
2013 - Present
Papers
85-
Pediatric surgery international, 39(1) 196-196, May 9, 2023BACKGROUND: We previously reported that polyphyllin D, the main component of the traditional herbal medicinal Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine in vivo antitumor effects of polyphyllin D. METHODS: Subcutaneous tumors were established in immune-deficient BALB/c nude mice using human neuroblastoma cell lines IMR-32 and LA-N-2. To evaluate the polyphyllin D activity, we used a mouse model of IMR-32 or LA-N-2 cell lines and analyzed subcutaneous tumors. RESULTS: Subcutaneous tumor models were successfully established in mice using two human neuroblastoma cell lines. In the subcutaneous tumor model, porphyrin D was found to suppress tumor volume. We found that polyphyllin D suppressed the number of foci by Ki-67 staining (IMR-32 and LA-N-2; p < 0.01, 0.02, respectively). We found that polyphyllin D induces the RIPK3 expression, while polyphyllin D phosphorylates Ser358 in IMR-32 and Ser358 and Tyr376 in LA-N-2. CONCLUSION: We developed a mouse model of subcutaneous tumors of neuroblastoma and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma. Polyphyllin D can cause necroptosis depending on the cell type. The new drug can be expected by investigating a method to selectively induce cell death through the analysis of necroptosis.
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Pediatric surgery international, 38(8) 1157-1163, Aug, 2022PURPOSE: We previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aims of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D were to establish a liver metastasis model of neuroblastoma and to evaluate the anti-metastasis effects of polyphyllin D. METHODS: Subcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA-N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of liver metastasis with the IMR-32 cells line injected through the tail vein. We analyzed the livers number and area of liver tumors in of the phosphate buffer solution- and polyphyllin D-treated groups. RESULTS: Liver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis, the model of IMR-32 cells, we found that polyphyllin D suppressed both the number and total area of metastatic foci the average number of metastatic foci, average focus areas, and number of cleaved caspase-3-positive cells were significantly lower in the polyphyllin D group (p = 0.016, 0.020, 0.043, respectively). CONCLUSIONS: We developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.
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Asian journal of surgery, 45(3) 849-853, Mar, 2022BACKGROUND: Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). METHODS: Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P < 0.05). RESULTS: Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). CONCLUSIONS: We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.
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The Japanese Journal of Pediatric Hematology/Oncology, 57(1) 24-27, 2020 Peer-reviewedLead author
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日本小児外科学会雑誌, 55(7) 1164-1169, Dec, 2019【目的】胆道閉鎖症(以下、BA)スクリーニングのために便色カラーカードが2012年に母子健康手帳へ導入され5年が経過した。しかしながら未だに3ヵ月を越えて紹介されてくる患児も多く、便カラーカードの意義や本症に対して医療従事者らがBAおよびカードをどのように認識しているかを評価し、知識を深めることを目的にアンケート調査と啓蒙活動を行った。【方法】当院に勤務する小児科医、産婦人科医、小児もしくは産科病棟の看護師および准看護師、助産師ら172名を対象に便色カードに関するアンケートテストと本症に関するプレゼンテーションを行い、結果と効果を確認する。【結果】109名(63.3%)の回答を得られた。カラーカードを知らないと回答したのは13名(11.9%)であった。カラーカードを用いずに便色を判定していただき39名(35.7%)がわからないと回答した。一方でBAを知っていると回答したのは105名(96.3%)で、59名(54.1%)が生後1ヵ月以内で発見されると回答した。BAが完治すると回答したのは45名(41.2%)であった。BAに関するプレゼンテーションについて「ものすごく勉強になった」と回答したのは92名(84.4%)であった。【結論】今回のアンケートから、小児外科医以外の医師や看護師のBAに対する認識は低いものと考えられた。カラーカードは導入されたが、その意義やBAに対する認識を患者両親に正しく伝えるためにも、今後さらなる啓蒙活動の推進が必要である。(著者抄録)
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日本小児外科学会雑誌, 55(7) 1164-1169, Dec, 2019 Peer-reviewed【目的】胆道閉鎖症(以下、BA)スクリーニングのために便色カラーカードが2012年に母子健康手帳へ導入され5年が経過した。しかしながら未だに3ヵ月を越えて紹介されてくる患児も多く、便カラーカードの意義や本症に対して医療従事者らがBAおよびカードをどのように認識しているかを評価し、知識を深めることを目的にアンケート調査と啓蒙活動を行った。【方法】当院に勤務する小児科医、産婦人科医、小児もしくは産科病棟の看護師および准看護師、助産師ら172名を対象に便色カードに関するアンケートテストと本症に関するプレゼンテーションを行い、結果と効果を確認する。【結果】109名(63.3%)の回答を得られた。カラーカードを知らないと回答したのは13名(11.9%)であった。カラーカードを用いずに便色を判定していただき39名(35.7%)がわからないと回答した。一方でBAを知っていると回答したのは105名(96.3%)で、59名(54.1%)が生後1ヵ月以内で発見されると回答した。BAが完治すると回答したのは45名(41.2%)であった。BAに関するプレゼンテーションについて「ものすごく勉強になった」と回答したのは92名(84.4%)であった。【結論】今回のアンケートから、小児外科医以外の医師や看護師のBAに対する認識は低いものと考えられた。カラーカードは導入されたが、その意義やBAに対する認識を患者両親に正しく伝えるためにも、今後さらなる啓蒙活動の推進が必要である。(著者抄録)
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日本小児外科学会雑誌, 55(5) 1010-1010, Aug, 2019 Peer-reviewed
Major Misc.
6-
Pediatric surgery international, 35(6) 723-728, Jun, 2019PURPOSE: Arctigenin has been shown to have anti-tumor effects in various types of cancers. This study was conducted to verify these effects in the human-derived hepatoblastoma cell line, HUH-6 clone 5 (hereinafter, HUH-6). METHODS: Arctigenin was added to cultured HUH-6 cells, and cellular activity was evaluated by MTS assay. To determine the relationship between reduced cellular activity and apoptosis, we measured the activities of caspase 3/7, 8, and 9 and conducted flow cytometry with Annexin V/PI staining. RESULTS: The MTS assay revealed that cellular activity decreased after arctigenin treatment in a concentration-dependent manner (IC50 = 4 µM). To investigate apoptosis induction, activity assays of caspase 3/7, 8, and 9 were performed. While caspase 3/7 and 8 exhibited high activity, caspase 9 showed no activity. Thus, apoptosis induction may have involved the action of tumor necrosis factor receptor 1 (TNFR1). Flow cytometry conducted with Annexin V/PI staining revealed the occurrence of early apoptosis. CONCLUSION: We found that arctigenin has anti-tumor effects in HUH-6 cells in a concentration-dependent manner. Arctigenin may have exerted its anti-tumor effect by inducing apoptosis via TNFR1, which recruits Complex IIa to activate caspase 8 and 3/7. These results may be useful for developing therapeutic agents for hepatoblastoma.
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Minerva pediatrica, Jan 2, 2019BACKGROUND: Neuroblastoma (NB) is a pediatric malignant solid tumor characterized as refractory cancer with poor prognosis. Mitosis-karyorrhexis index (MKI) is a prognostic factor but is prone to observer bias. The usefulness of MKI with Ki-67, as a marker of malignancy, was investigated. The efficacy of molecular-targeted therapeutic agents with fewer side effects in tumors has been studied. Molecular-targeted therapy targets include vascular endothelial growth factor (VEGF), involved in tumor angiogenesis; c-Kit, receptor of Kit/stem cells involved in tumor growth, vasculature, and lymphangiogenesis; platelet-derived growth factor receptor (PDGFR); and B-Raf proto-oncogene, serine/threonine kinase (BRAF), involved in the RAS protein-mediated mitogen-activated protein kinase pathway. Therefore, expression profiles of these factors and growth inhibitory effects of molecular-targeted drugs against NB were investigated. METHODS: Ten frozen NB tissue samples collected during January 1993-December 2017 were evaluated immunohistochemically for Ki-67 and VEGF. c-Kit, PDGFR, and BRAF expression levels were evaluated using enzyme-linked immunosorbent assays; relationships between these factors and clinicopathological parameters of NB were analyzed. RESULTS: Eight patients with NB showed no amplification of MYCN (MYCN proto- oncogene, bHLH transcription factor). There were two cases of ganglioneuroblastoma (GNB). More NB cells were positive for Ki-67 than for GNB cells. VEGF expression was observed in all NB specimens and was stronger in stage IIB and higher. No BRAF or c-Kit activity was observed; PDGFR activity was greater in NB than in GNB (p = 0.02). CONCLUSIONS: Thus, Ki-67 may help evaluate NB malignancy. As the first therapy for NB prevents amplification of MYCN, agents targeting PDGFR as well as VGFG can inhibit NB cell proliferation.
Presentations
9-
51st Annual Scientific Meeting of the Pacific Association of Pediatric Surgeons, 2018, May, 2018
Teaching Experience
4Professional Memberships
5Research Projects
1-
Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2021 - Mar, 2023