総合医科学研究所 遺伝子発見機構学
Profile Information
- Affiliation
- 教授, 医学部 医学科 小児外科学, 藤田医科大学
- Degree
- 博士(医学)
- J-GLOBAL ID
- 200901042339226272
- researchmap Member ID
- 5000030080
Research Areas
1Papers
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Clinical and experimental hepatology, 10(2) 98-103, Mar, 2024AIM OF THE STUDY: This study aimed to establish an objective, simple, and minimally invasive screening method to detect patients with biliary atresia during neonatal checkups by using indocyanine green (ICG) fluorescence in the stool. MATERIAL AND METHODS: We produced a rat model of extrahepatic biliary obstruction (group O, n = 9) and compared the stools from these rats with those of control group rats (group C, n = 6) by a fluorescence technique. ICG was administered (0.5 mg/kg) through the caudal vein; group O received ICG at the end of surgery. RESULTS: In group C, we collected stools at 3, 6, 12, 24, 48, and 72 hours, and fluorescence disappeared at 48 hours. In group O, stools were collected at 24, 48, 72, 96, and 120 hours after surgery, and fluorescence continued at 120 hours without the loss of fluorescence. Quantitative assessment of lightness showed significant differences between the groups at 48 and 72 hours (p = 0.0016 and p = 0.0004, respectively). CONCLUSIONS: This study shows that ICG is excreted into the gastrointestinal tract via a route other than the bile duct in a rat model of extrahepatic biliary obstruction. Our findings also suggest that ICG has the potential for initial screening of biliary congestive disease in the neonatal period, which could be followed up by detailed testing.
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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.
Misc.
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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.
Books and Other Publications
7Presentations
26Professional Memberships
3Research Projects
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 2003 - 2004
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 2001 - 2002
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 1999 - 2000
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科学研究費助成事業, 日本学術振興会, 1998 - 1999