研究者業績
基本情報
研究キーワード
1研究分野
1経歴
2-
2014年4月 - 現在
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2012年4月 - 2014年3月
学歴
1-
2006年3月 - 2012年4月
論文
77-
Traditional & Kampo Medicine 11(1) 3-12 2023年12月7日Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology. Although various new drugs have been developed in recent years, many of them are expensive, generating a demand for inexpensive and useful therapeutic drugs. Ogikenchuto (TJ‐98), an existing Kampo medicine, has been used to treat ulcers and similar conditions for some time. The current study therefore investigated whether TJ‐98 could be a new therapeutic agent for UC, a chronic inflammatory disease. Methods This study used 6‐week‐old female C57BL/6J mice to establish a mouse model of dextran sulfate sodium (DSS)‐induced colitis. We then evaluated the therapeutic effects of tacrolimus and TJ‐98 on colitis based on body weight, intestinal length, intestinal fibrosis, and cytokines. Sirius red staining was used to evaluate intestinal fibrosis, while interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) were used to evaluate cytokines involved in inflammation. Results Neither tacrolimus nor TJ‐98 ameliorated weight loss. Although tacrolimus did not remediate intestinal shortening, intestinal fibrosis, or cytokine levels (IL‐1β, IL‐6, and TNF‐α), TJ‐98 did ameliorate intestinal shortening and intestinal fibrosis and decrease IL‐1β levels. Conclusions This study confirmed that TJ‐98 suppressed the inflammation caused by DSS‐induced enteritis and decreased the associated intestinal fibrosis, highlighting its potential as an inexpensive novel therapeutic agent for UC.
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Clinical journal of gastroenterology 16(5) 685-688 2023年10月An 11-year-old girl presented with recurrent right lower quadrant (RLQ) pain. There was no evidence of inflammation and appendiceal swelling except at the initial onset. The repeated presence of a small amount of ascites at the time of abdominal pain triggered the performance of exploratory laparoscopy. Intraoperative examination revealed a non-inflamed, unswollen appendix with a cord-like atretic segment at the middle part and an appendectomy was performed. At 46 months follow-up, she remained asymptomatic. In patients with recurrent RLQ pain of unknown cause, it is necessary to consider diagnostic laparoscopy while keeping appendiceal atresia in mind as a differential diagnosis.
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Pediatric surgery international 38(8) 1157-1163 2022年8月PURPOSE: 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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Fujita medical journal 7(2) 41-49 2021年Objectives: Proximal stoma creation in neonates results in growth failure and distal intestinal atrophy. "Recycling stool" consists of stool injection from the proximal limb to the distal limb of a stoma. Because this method may prevent distal bowel atrophy and increase body weight, we investigated the effects of recycling stool upon distal intestinal mucosa by generating an ileostomy model in rats. Methods: An ileostomy was created 5 cm proximal to the cecum in male Wistar/ST rats. Discharged stool or saline was injected into the distal limb, twice per day for 7 days. The intestinal adaptation was assessed by measuring the villus height and counting goblet cell number. Proliferation and apoptosis were analyzed by Ki67 and TUNEL immunostaining. Results: The ratios of the height of the distal villi (D) to the that of proximal villi (P) were 0.97 (median [range] of D and P length: 421 [240-729] μm and 436 [294-638] μm, P<0.05) in the stool-injected group and 0.81 in the saline-injected group (442 [315-641] μm and 548 [236-776] μm, P<0.05). Compared with the saline-injected group, the stool-injected group showed elevated numbers of goblet cells (3.6 [2.0-7.6] vs. 4.9 [2.4-7.5] cells/100-μm villus length) and Ki67-positive cells (26.8% [13.8%-35.4%] vs. 40.1% [31.2%-45.7%]), along with a reduced number of apoptotic cells (5.0 [2.0-14.0] vs. 4.0 [1.0-9.0] cells/100-μm villus length). Conclusions: Recycling stool prevented distal intestinal atrophy; this experimental design may facilitate further studies concerning alternative methods to prevent intestinal atrophy and growth failure.
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Journal of Pediatric Surgery Case Reports 45 2019年6月1日
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Pediatric surgery international 35(6) 723-728 2019年6月 査読有りPURPOSE: 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.
MISC
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Minerva pediatrica 2019年1月2日BACKGROUND: 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.
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Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 16(6) 708-713 2018年12月OBJECTIVES: In pediatric patients, renal dysfunction after living-donor liver transplant is a major issue that is difficult to evaluate. Recently, predictive equations for Japanese children have been introduced. MATERIALS AND METHODS: We conducted a retrospective study by prospectively collecting data on 26 patients under 16 years old who underwent living-donor liver transplant between June 2004 and March 2015. Serum creatinine and cystatin C levels were measured. Paired t tests and Bland-Altman plots were used to compare the following formulas for estimated glomerular filtration rate: the Schwartz formula and 3 formulas that were matched with Japanese children (polynomial, simple, and cystatin C formulas). RESULTS: Average estimated glomerular filtrations rates (in mL/min/1.73 m2) were 143.46, 122.90, 121.58, and 123.31 using the Schwartz, polynomial, simple, and cystatin C formulas, respectively. The estimated glomerular filtrations rate for biliary atresia was 141.53 ± 31.37 versus 109.95 ± 19.52 for other diseases, with significant differences only noted with the cystatin C formula. The formulas tailored for Japanese children showed significantly lower estimated glomerular filtrations rates than those obtained using the Schwartz formula (P < .01). CONCLUSIONS: The use of formulas for measuring estimated glomerular filtrations rates that are based on race may allow early detection of deteriorating renal function.