Updated on 2025/08/22

写真a

 
TANAKA Shingo
 
Organization
School of Medicine Department of Clinical Laboratory Medicine Lecturer
Title
Lecturer
External link

Research Areas

  • Life Science / Gastroenterology

Papers

  • Analytical and Clinical Validation of a Plasma Fibroblast Growth Factor 21 ELISA Kit Using an Automated Platform in Steatotic Liver Disease

    Makito Tanaka, Shingo Tanaka, Ryo Kobayashi, Ryosei Murai, Satoshi Takahashi

    Biomolecules   15 ( 6 )   877 - 877   2025.6

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Steatotic liver disease is a global health challenge that requires reliable and noninvasive diagnostic biomarkers. This research aimed to validate the analytical and clinical performance of a fibroblast growth factor 21 (FGF21) enzyme-linked immunosorbent assay (ELISA) kit using an automated immunoassay analyzer. Plasma FGF21 levels were measured using a commercial ELISA kit on an automated immunoassay analyzer. Validation included intra- and inter-assay precision, dilution linearity, spike recovery, lower limit of quantification (LLOQ), interference testing, and sample stability analysis. Clinical evaluation involved 97 patients who underwent abdominal ultrasound-based attenuation imaging for the diagnosis of hepatic steatosis. The assay demonstrated high analytical precision, with intra- and inter-assay coefficients of variation <15% and an LLOQ of 3.260 pg/mL. Dilution linearity, spike recovery, and interference tests confirmed the reliability of the assay, whereas stability tests highlighted the minimal effect of freeze-thaw cycles and storage conditions. Clinically, FGF21 levels correlated with attenuation coefficient (r = 0.44). Diagnostic performance indicated 84% sensitivity and 81% specificity at defined FGF21 thresholds for the diagnosis of hepatic steatosis. This research confirmed the reliable analytical and clinical performance of the FGF21 ELISA kit, reinforcing its potential as a diagnostic biomarker of hepatic steatosis.

    DOI： 10.3390/biom15060877

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  • Clinical utility of in-hospital qPCR for cytomegalovirus detection: a single-center analysis

    Mai Oikawa, Shingo Tanaka, Takashi Kondo, Makito Tanaka, Ryo Kobayashi, Ryosei Murai, Satoshi Iyama, Satoshi Takahashi

    Journal of Infection and Chemotherapy   31 ( 6 )   102715 - 102715   2025.6

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jiac.2025.102715

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  • Efficient implementation of hepatitis B surface antigen confirmatory neutralization tests. International journal

    Hitoshi Yonezawa, Shingo Tanaka, Makito Tanaka, Ryo Kobayashi, Satoshi Takahashi

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   30 ( 1 )   29 - 33   2024.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    INTRODUCTION: To prevent misreporting of false positives in the hepatitis B surface antigen (HBsAg) assay, it is recommended to confirm the low-positive cases with neutralization tests. However, currently not many facilities are implementing this due to the additional cost. The aim of this study was to clarify the risk factors for false positives in the high-sensitivity HBsAg quantitative tests to reduce the neutralization tests. METHODS: In this retrospective cohort study, we analyzed 47,305 patients who had their HBsAg value measured at Sapporo Medical University Hospital between November 2016 and March 2022. The patients eligible for the neutralization tests were those with HBsAg values between 0.005 and 1.000, even after reexamination by high-speed centrifugation. RESULTS: HBsAg quantitative tests were performed in 71,475 tests. Of these, 817 tests and 376 patients were subjected to neutralization tests. Of the patients who met the criteria, 329 were included in this study. Fifty-seven cases (17%) had negative results in the neutralization tests, suggesting false positives for the HBsAg assay. Multivariate analysis showed that younger age (adjusted odds ratio [aOR] 6.57), female sex (aOR 2.32), lower HBsAg values (aOR 59.6), and reagent improvement (aOR 2.06) were independent risk factors for false positives. The false-positive rate was actually high at 33.1% in the HBsAg range of 0.005-0.049 IU/mL and at 1.2% in the range above 0.050 IU/mL. CONCLUSIONS: Confirmatory neutralization tests should be performed at least in the range of 0.005-0.049 IU/mL where quantification is possible with a higher-sensitivity assay.

    DOI： 10.1016/j.jiac.2023.09.007

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  • Investigation of the Scope of Patients and Repeat Reports in Reporting Critical Values of Platelet Counts

    田中信悟, 米澤仁, 村井良精, 井山諭, 高橋聡

    日本臨床検査医学会誌   72 ( 6 )   2024

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  • Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma. International journal

    Ryo Ito, Koji Miyanishi, Tomohiro Kubo, Kota Hamaguchi, Takahiro Osuga, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato

    Hepatology international   17 ( 3 )   735 - 744   2023.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

    DOI： 10.1007/s12072-023-10484-2

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  • Effect of albumin measurement methods on the albumin-bilirubin grade. International journal

    Makito Tanaka, Shingo Tanaka, Ema Suzuki, Ryo Kobayashi, Satoshi Takahashi

    Annals of clinical biochemistry   60 ( 2 )   100 - 108   2023.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Albumin-bilirubin (ALBI) grade is an index of liver function based on total bilirubin (T-BIL) and albumin levels, and its usefulness has been widely reported. This study aimed to investigate the effect of different methods of measuring T-BIL and albumin levels on the ALBI grade in patients with liver disease. METHODS: In total, 170 patients from our hospital were included in this study. Correlations between T-BIL levels measured using the vanadate oxidation and enzymatic methods were analysed. Similarly, a correlation analysis of albumin levels between the bromocresol green (BCG) and modified bromocresol purple (BCP) methods was performed. Additionally, the ALBI grade was calculated for patients with liver disease, and the differences between each method of albumin measurement were compared. RESULTS: No differences were observed in the measured T-BIL values between the two methods. Contrastingly, the albumin levels of 100 random samples and 70 liver disease patients obtained using the modified BCP method were significantly lower than those measured using the BCG method. The rate of change in the modified ALBI grade between the BCG and BCP methods was 25.7%. CONCLUSIONS: Caution should be taken when comparing ALBI grades with those measured by other facilities because the method of albumin measurement can affect the ALBI grade. Standardization of albumin measurement is needed worldwide.

    DOI： 10.1177/00045632221143685

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  • Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/β-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma. International journal

    Kota Hamaguchi, Koji Miyanishi, Takahiro Osuga, Shingo Tanaka, Ryo Ito, Hiroki Sakamoto, Tomohiro Kubo, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato

    Cancers   14 ( 9 )   2022.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/β-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/β-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/β-catenin signaling and trigger carcinogenesis.

    DOI： 10.3390/cancers14092066

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  • A case of acute exacerbation of chronic hepatitis C during the course of adrenal Cushing's syndrome International journal

    Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Junji Kato

    Clinical Case Reports   10 ( 2 )   e05337   2022.2

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    A 50-year-old woman with adrenal Cushing's syndrome and chronic hepatitis C developed an acute exacerbation of chronic hepatitis C before adrenectomy. After administration of glecaprevir/pibrentasvir was started, her transaminase levels normalized promptly and a rapid virological response also was achieved. Laparoscopic left adrenectomy was then performed safely.

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.5337

    DOI： 10.1002/ccr3.5337

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  • A Case of Unresectable Combined Hepatocellular-Cholangiocarcinoma Successfully Treated with Lenvatinib. International journal

    Takahiro Osuga, Koji Miyanishi, Ryo Ito, Shingo Tanaka, Kota Hamaguchi, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Taro Sugawara, Shintaro Sugita, Ichiro Takemasa, Tadashi Hasegawa, Junji Kato

    Case reports in oncology   15 ( 1 )   318 - 325   2022

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    Language：English  

    A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

    DOI： 10.1159/000523895

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  • 当院におけるアルブミン製剤の適正使用について

    田中 信悟, 村井 良精, 田中 真輝人, 北山 育実, 片山 雄貴, 木次谷 玲那, 盛合 美加子, 遠藤 明美, 淺沼 康一, 遠藤 輝夫, 高橋 聡, 加藤 淳二

    日本臨床検査医学会誌   69 ( 12 )   903 - 908   2021.12

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  • MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model International journal

    Hiroki Sakamoto, Koji Miyanishi, Shingo Tanaka, Ryo Ito, Kota Hamaguchi, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Takahiro Osuga, Kazuyuki Murase, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

    Scientific Reports   11 ( 1 )   3599 - 3599   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    <title>Abstract</title>Non-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (<italic>Mutyh</italic><sup>+/+</sup>), heterozygous (<italic>Mutyh</italic><sup>+/−</sup>), and MUTYH-null (<italic>Mutyh</italic><sup>−/−</sup>) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 <italic>Mutyh</italic><sup>−/−</sup> mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh<sup>+/+</sup> fed an HFHC diet, <italic>P</italic> = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of <italic>c-Myc</italic> in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.

    Other Link： http://www.nature.com/articles/s41598-021-83138-8

    DOI： 10.1038/s41598-021-83138-8

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  • Combination of psoas muscle mass index and neutrophil/lymphocyte ratio as a prognostic predictor for patients undergoing nonsurgical hepatocellular carcinoma therapy International journal

    Yusuke Sugama, Koji Miyanishi, Takahiro Osuga, Shingo Tanaka, Kota Hamaguchi, Ryo Ito, Hiroki Sakamoto, Tomohiro Kubo, Hiroyuki Ohnuma, Kazuyuki Murase, Kohich Takada, Masayoshi Kobune, Junji Kato

    JGH Open   5 ( 12 )   1335 - 1343   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    BACKGROUND AND AIM: Reliable predictors for hepatocellular carcinoma (HCC) are urgently needed. The psoas muscle index (PMI) is a simple and rapid method for evaluating muscle atrophy. Furthermore, the neutrophil/lymphocyte ratio (NLR) is a prognostic factor that is easy to calculate in everyday clinical practice. We aimed to investigate the value of the PMI and NLR as prognostic factors for patients receiving nonsurgical HCC therapy, hepatic arterial infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), or molecular targeted drugs such as sorafenib (SOR) and lenvatinib (LEN). METHODS: We enrolled 87 patients with HCC who were treated with HAIC, TACE, SOR, or LEN. The primary endpoint was overall survival (OS) with variable PMI or NLR status. For Barcelona Clinic Liver Cancer (BCLC)-B patients, useful prognostic factors were examined by comparing the OS between stratified groups. Prognostic factors including PMI and NLR were evaluated by univariate and multivariate analysis. RESULTS: Analysis of HAIC or TACE (HAIC/TACE) and SOR or LEN (SOR/LEN) patients showed significant differences in OS between low and high PMI. In patients treated with TACE, there was a significant difference in OS between low and high NLR. For BCLC-B and low PMI, the prognosis was significantly worse for SOR/LEN than for TACE, although there was no difference for high PMI, suggesting that PMI may be useful for treatment selection. In addition, the prognostic formula composed of PMI, NLR, and up-to-seven criteria developed in the present study may be useful. CONCLUSION: PMI and NLR are considered to be independent prognostic factors for HCC.

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jgh3.12676

    DOI： 10.1002/jgh3.12676

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  • 他の施設から得られた不規則抗体情報の有用性に関する検討

    村井 良精, 遠藤 輝夫, 盛合 美加子, 片山 雄貴, 遠藤 明美, 淺沼 康一, 田中 信悟, 高橋 聡

    医学検査   70 ( 4 )   773 - 777   2021.10

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  • Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study. International journal

    Hitoshi Yonezawa, Shingo Tanaka, Momoko Furuya, Koji Yamada, Koichi Asanuma, Yoshihiro Fujiya, Koji Miyanishi, Satoshi Takahashi, Junji Kato

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 10 )   1454 - 1458   2021.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    INTRODUCTION: In quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases. METHODS: In this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation. RESULTS: In total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010). CONCLUSIONS: Patients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.

    DOI： 10.1016/j.jiac.2021.06.009

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  • Programmed cell death ligand 1 expression in a case of poorly differentiated lymphocyte‐rich hepatocellular carcinoma International journal

    Ginji Omori, Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Yasuhiro Kikuchi, Toshihiko Torigoe, Junji Kato

    Clinical Case Reports   9 ( 9 )   e04764   2021.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Our pathological study of a case of poorly differentiated lymphocyte-rich hepatocellular carcinoma suggested that immune checkpoint inhibitor may be an effective therapy. The histological type is an important factor in determining treatment choices.

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.4764

    DOI： 10.1002/ccr3.4764

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  • 進行性腎細胞癌に対するスニチニブ治療に伴う左室壁運動異常の出現様式

    安井 謙司, 湯田 聡, 大井 由紀子, 橋本 浩平, 市原 浩司, 柳原 希美, 田中 信悟, 永原 大五, 高橋 聡

    臨床泌尿器科   75 ( 2 )   151 - 156   2021.2

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  • A case of hypervascular tumors in the liver and pancreas: synchronous hepatocellular carcinoma and pancreatic metastasis from renal cell carcinoma 36 years after nephrectomy International journal

    Hajime Nakamura, Shingo Tanaka, Koji Miyanishi, Yutaka Kawano, Takahiro Osuga, Kazuma Ishikawa, Makoto Yoshida, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Hiroshi Yamaguchi, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Junji Kato

    Clinical Case Reports   9 ( 2 )   932 - 937   2020.12

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    It is sometimes difficult to distinguish between multiple cancers and metastases using only diagnostic imaging, particularly when multiple hypervascular tumors are found in multiple organs. We present a case in which the preoperative histological evaluation was essential to determine the management of a hypervascular pancreatic tumor and liver tumor.

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.3691

    DOI： 10.1002/ccr3.3691

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  • 高感度HBsAg測定試薬の改良による偽陽性抑制効果の検討 Reviewed

    米澤 仁, 田中 信悟, 八鍬 佑貴, 高橋 聡

    感染症学雑誌   94 ( 1 )   97 - 101   2020.1

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  • 小型混合型肝癌の1例 Reviewed

    大須賀 崇裕, 宮西 浩嗣, 田中 信悟, 中村 元, 坂本 拡基, 大沼 啓之, 村瀬 和幸, 高田 弘一, 小船 雅義, 加藤 淳二, 永山 稔, 木村 康利, 竹政 伊知朗, 辻脇 光洋, 長谷川 匡

    肝臓   60 ( 8 )   294 - 301   2019.8

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  • 新規ガストリン放出ペプチド前駆体測定系における測定値安定性についての検討 Reviewed

    小林 亮, 高橋 祐輔, 田中 信悟, 柳原 希美, 淺沼 康一, 高橋 聡

    臨床化学   48 ( 3 )   232 - 238   2019.7

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    Language：Japanese   Publisher：(一社)日本臨床化学会  

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  • Changes of tight junction and interleukin-8 expression using a human gastroid monolayer model of Helicobacter pylori infection. Reviewed International journal

    Takahiro Uotani, Kosuke Murakami, Tomohisa Uchida, Shingo Tanaka, Hiroyuki Nagashima, Xi-Lei Zeng, Junko Akada, Mary K Estes, David Y Graham, Yoshio Yamaoka

    Helicobacter   24 ( 3 )   e12583   2019.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Lack of a model that mirrors Helicobacter pylori-induced gastric mucosal inflammation has hampered investigation of early host-bacterial interactions. We used an ex vivo model of human stomach, gastric epithelial organoid monolayers (gastroid monolayers) to investigate interactions of H pylori infection and the apical junctional complex and interleukin-8 (IL-8) expression. METHOD: Morphology of human antral mucosal gastroid monolayers was evaluated using histology, immunohistochemical (IHC) staining, and transmission electron microscopy (TEM). Functional and gross changes in the apical junctional complexes were assessed using transepithelial electrical resistance (TEER), cytotoxicity assays, and confocal laser scanning microscopy. IL-8 expression was evaluated by real-time quantitative PCR and ELISA. RESULTS: When evaluated by IHC and TEM, the morphology of gastroid monolayers closely resembled in vivo human stomach. Following inoculation of H pylori, TEER transiently declined (up to 51%) in an H pylori density-dependent manner. TEER recovered by 48 hours post-infection and remained normal despite continued presence and replication of H pylori. Confocal scanning microscopy showed minimal disruption of zonula occludens-1 or E-cadherin structure. IL-8 production was unchanged by infection with either CagA-positive or CagA-negative H pylori and JNK and MEK inhibitors did not suppress IL-8 production, whereas p38 and IKK inhibitor significantly did. CONCLUSION: Human gastroid monolayers provide a model for experimental H pylori infection more consistent with in vivo human infections than seen with typical gastric epithelial cell lines. This ex vivo system should lead to better understanding of H pylori host-pathogen interactions.

    DOI： 10.1111/hel.12583

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  • Successful Treatment of Hepatocellular Carcinoma with Transcatheter Arterial Chemoembolization followed by Radical Liver Transplantation in a Patient with Severe Liver Damage Reviewed International journal

    Hajime Nakamura, Yutaka Kawano, Koji Miyanishi, Kazuma Ishikawa, Tomohiro Kubo, Shingo Tanaka, Kohichi Takada, Masayoshi Kobune, Kohei Harada, Norio Kawamura, Tsuyoshi Shimamura, Hiromi Kanno-Okada, Junji Kato

    Case Reports in Oncology   12 ( 1 )   289 - 296   2019.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

    Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage.

    DOI： 10.1159/000499703

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  • The role of iron in hepatic inflammation and hepatocellular carcinoma Reviewed International journal

    Koji Miyanishi, Shingo Tanaka, Hiroki Sakamoto, Junji Kato

    Free Radical Biology and Medicine   133   200 - 205   2019.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    Iron is an essential for organisms and the liver plays a major role in its storage. In pathologic conditions, where iron absorption from the intestine or iron uptake into the hepatocytes is increased, excess iron accumulates in the hepatocytes, leading to hepatocyte injury through the production of free radicals. Iron exerts its toxicity by catalyzing the generation of reactive oxygen species (ROS). ROS causes cell injury by inducing damage to the lysosomal, cytoplasmic, nuclear and mitochondrial membranes, apoptosis through activation of the caspase cascade, and hyperoxidation of fatty chains. In this manuscript, we reviewed the articles regarding role of iron in hepatic inflammation and hepatocellular carcinoma.

    DOI： 10.1016/j.freeradbiomed.2018.07.006

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  • ルミパルスプレストPIVKAII-Nエーザイにおける基本性能の評価 Reviewed

    古谷 桃子, 山田 浩司, 菅原 清美, 淺沼 康一, 田中 信悟, 永原 大五, 柳原 希美, 高橋 聡

    医学検査   68 ( 1 )   56 - 60   2019.1

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  • A case of small combined hepatocellular-cholangiocellular carcinoma

    Takahiro Osuga, Koji Miyanishi, Shingo Tanaka, Hajime Nakamura, Hiroki Sakamoto, Hiroyuki Onuma, Kazuyuki Murase, Koichi Takada, Masayoshi Kobune, Junji Kato, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Mitsuhiro Tsujiwaki, Tadashi Hasegawa

    Acta Hepatologica Japonica   60 ( 8 )   294 - 301   2019

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    DOI： 10.2957/kanzo.60.294

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  • An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma. Reviewed International journal

    Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

    Free radical biology & medicine   129   88 - 96   2018.12

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    DOI： 10.1016/j.freeradbiomed.2018.09.010

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  • Clostridium difficile肝膿瘍の1例

    松野 鉄平, 田中 信悟, 宮西 浩嗣, 河野 豊, 中村 元, 坂本 拡基, 早坂 尚貴, 石川 和真, 村瀬 和幸, 高田 弘一, 高梨 訓博, 勝木 伸一, 小船 雅義, 加藤 淳二

    肝臓   59 ( 3 )   180 - 186   2018.3

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  • Increased Duodenal Iron Absorption through Upregulation of Ferroportin 1 due to the Decrement in Serum Hepcidin in Patients with Chronic Hepatitis C. Reviewed

    Sato M, Miyanishi K, Tanaka S, Sakurada A, Sakamoto H, Kawano Y, Takada K, Kobune M, Kato J

    Canadian journal of gastroenterology & hepatology   2018   2154361   2018

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  • Interleukin-17C in Human Helicobacter pylori Gastritis Reviewed

    Shingo Tanaka, Hiroyuki Nagashima, Modesto Cruz, Tomohisa Uchida, Takahiro Uotani, Jose A. Jimenez Abreu, Varocha Mahachai, Ratha-korn Vilaichone, Thawee Ratanachu-ek, Lotay Tshering, David Y. Graham, Yoshio Yamaoka

    INFECTION AND IMMUNITY   85 ( 10 )   2017.10

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    DOI： 10.1128/IAI.00389-17

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  • Autophagy-related genes in Helicobacter pylori infection Reviewed

    Shingo Tanaka, Hiroyuki Nagashima, Takahiro Uotani, David Y. Graham, Yoshio Yamaoka

    HELICOBACTER   22 ( 3 )   2017.6

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    DOI： 10.1111/hel.12376

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  • 集学的治療により救命し得たClostridium perfringensによる肝膿瘍の2例

    久保 智洋, 河野 豊, 宮西 浩嗣, 石川 和真, 桜田 晃, 佐藤 昌則, 保木 寿文, 田村 文人, 田中 信悟, 高田 弘一, 小船 雅義, 加藤 淳二

    肝臓   58 ( 2 )   105 - 114   2017.2

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    DOI： 10.2957/kanzo.58.105

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  • Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection Reviewed

    Takahiro Uotani, Mitsushige Sugimoto, Hitomi Ichikawa, Shingo Tanaka, Hiroyuki Nagashima, Tomohisa Uchida, David Y. Graham, Yoshio Yamaoka

    JOURNAL OF DIGESTIVE DISEASES   17 ( 1 )   20 - 27   2016.1

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    DOI： 10.1111/1751-2980.12309

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  • Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis Reviewed International journal

    Toshifumi Hoki, Koji Miyanishi, Shingo Tanaka, Kohichi Takada, Yutaka Kawano, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

    HEPATOLOGY   62 ( 3 )   751 - 761   2015.9

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    DOI： 10.1002/hep.27774

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  • Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy Reviewed International journal

    Koji Miyanishi, Toshifumi Hoki, Shingo Tanaka, Junji Kato

    World Journal of Hepatology   7 ( 3 )   593 - 599   2015

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    DOI： 10.4254/wjh.v7.i3.593

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  • Clinical Significance of Adjuvant Surgical Resection for Initially Unresectable Pancreatic Cancer Responsive to Arterial Infusion Chemotherapy Reviewed

    Tadashi Doi, Hisato Homma, Takehide Akiyama, Shinichi Mezawa, Minoru Takahashi, Motoo Ohi, Shingo Tanaka, Kazuhiro Morii, Katsuhisa Kogawa, Motoya Takeuchi, Kenichirou Hirata, Satoshi Hirano

    HEPATO-GASTROENTEROLOGY   61 ( 131 )   828 - 833   2014.5

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    DOI： 10.5754/hge13857

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  • アデホビル長期投与中にFanconi症候群による低リン血性骨軟化症を発症したB型慢性肝炎の1例

    石川 和真, 宮西 浩嗣, 保木 寿文, 田村 文人, 河野 豊, 高田 弘一, 田中 信悟, 櫻田 晃, 佐藤 康史, 佐藤 勉, 林 毅, 瀧本 理修, 小船 雅義, 加藤 淳二

    肝臓   55 ( 3 )   162 - 169   2014.3

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    DOI： 10.2957/kanzo.55.162

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  • Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Reviewed

    Shingo Tanaka, Koji Miyanishi, Masayoshi Kobune, Yutaka Kawano, Toshifumi Hoki, Tomohiro Kubo, Tsuyoshi Hayashi, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Junji Kato

    Journal of gastroenterology   48 ( 11 )   1249 - 58   2013.11

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    BACKGROUND: The rate of onset of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) has been reported recently to be comparable to that of patients with chronic hepatitis C. However, the precise mechanism contributing to carcinogenesis in the former remains unclear. Although increased oxidative stress is presumed to play a role in carcinogenesis in patients with NASH, this relationship remains to be directly proven. In this study, we investigated the involvement of oxidative DNA damage in hepatocarcinogenesis in patients with NASH. METHODS: Patients with nonalcoholic fatty liver disease who were treated at our university hospital were eligible for enrolment in the study(n = 49). The study cohort included 30 patients with NASH without HCC (NASH without HCC), six HCC patients with NASH (NASH-HCC), and 13 patients with simple steatosis. Quantitative immunohistochemistry with a KS-400 image analyzing system was used for 8-hydroxy-2'-deoxyguanosine (8-OHdG) detection. RESULTS: The 8-OHdG content in the liver tissue of NASH-HCC patients was significantly different from that in the other patients. The median immunostaining intensity was 8.605 in the NASH-HCC cases, which was significantly higher than that in the cases of NASH without HCC (4.845; P = 0.003). Multivariate analysis using hepatic 8-OHdG content as a factor in addition to age and fasting blood sugar revealed a significant difference in clinicopathological factors between NASH-HCC and NASH without HCC cases. Old age (P = 0.015) and high relative immunostaining intensity for intrahepatic 8-OHdG (P = 0.037) were identified as independent factors. CONCLUSIONS: 8-OHdG content in liver tissue may serve a marker of oxidative stress and could be a particularly useful predictor of hepatocarcinogenesis.

    DOI： 10.1007/s00535-012-0739-0

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  • Safety and effectiveness of low-dose lenalidomide therapy for multiple myeloma complicated with bortezomib-associated interstitial pneumonia. Reviewed

    Nagamachi Y, Yamauchi N, Muramatsu H, Okamoto T, Inomata H, Nozawa E, Koyama R, Ihara K, Nishisato T, Yamada H, Yano T, Tanaka S, Ono K, Kikuchi S, Kato J

    [Rinsho ketsueki] The Japanese journal of clinical hematology   54 ( 5 )   451 - 456   2013.5

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    A 78-year-old woman was diagnosed with multiple myeloma (MM: IgG κ type, stage IIIA, ISS III) at a nearby hospital in August 2010. High-dose dexamethasone therapy was ineffective, and she was treated with 2 courses of bortezomib. She was referred to our hospital with back pain and dyspnea in November. She was diagnosed with interstitial pneumonia (IP) and improved rapidly with steroid pulse therapy. Because the involvement of bortezomib was suspected in IP, lenalidomide therapy was selected for MM. Lenalidomide (15 mg) was administered for 2 courses. The patient achieved a PR and the treatment is still ongoing with a good response. According to the interim report on PMS (post-marketing surveillance), 3 of the 1,177 patients treated with lenalidomide developed IP. The dose level was 25 mg in 2 cases and 10 mg in 1 case. The outcomes of these patients were death in 1 case, not recovered in 1 case, and unknown in 1 case. When lenalidomide is used to treat bortezomib-induced IP, there are no rules or regulations about its dose level. In the present case, the dose of lenalidomide (15 mg) was based on the retreatment dose after bone marrow suppression. Low-dose lenalidomide therapy was effective and safe against MM with a bortezomib-associated lung disorder.

    Other Link： https://jlc.jst.go.jp/DN/JALC/10019534809?from=CiNii

    DOI： 10.11406/rinketsu.54.451

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  • A case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy Reviewed

    Tadashi Doi, Toshinori Okuda, Shinya Minami, Shingo Tanaka, Masahiro Hirakawa, Tomohiro Kubo, Yuki Ikeda, Natsumi Yamauchi, Naoki Uemura, Akihito Fujimi, Yuji Kanisawa

    Journal of Japanese Society of Gastroenterology   110 ( 2 )   248 - 254   2013.2

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    DOI： 10.11405/nisshoshi.110.248

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  • A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine Reviewed

    Sho Takahashi, Yasushi Sato, Tamotsu Sagawa, Shingo Tanaka, Kazuyuki Murase, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Tetsuro Okamoto, Junji Kato

    Journal of Japanese Society of Gastroenterology   108 ( 8 )   1405 - 1412   2011.8

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    DOI： 10.11405/nisshoshi.108.1405

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  • Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis Reviewed International journal

    Tsutomu Sato, Masayoshi Kobune, Kazuyuki Murase, Yukari Kado, Tetsuro Okamoto, Shingo Tanaka, Shohei Kikuchi, Hiroyuki Nagashima, Yutaka Kawano, Kohichi Takada, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Junji Kato

    HEPATOLOGY RESEARCH   41 ( 7 )   660 - 667   2011.7

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    DOI： 10.1111/j.1872-034X.2011.00821.x

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  • 女性は女性医師による大腸内視鏡検査を望んでいるか

    大浦 佳永, 黒瀬 加奈, 牧野 聖子, 住吉 徹哉, 田中 信悟, 田村 文人, 對馬 隆浩, 水島 健, 千葉 大樹, 辻 靖, 由崎 直人, 近藤 仁

    Gastroenterological Endoscopy   52 ( 12 )   3347 - 3352   2010.12

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    DOI： 10.11280/gee.52.3347

    Ichushi

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  • Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer Reviewed International journal

    Yasushi Sato, Tetsuji Takayama, Tamotsu Sagawa, Yasuo Takahashi, Hiroyuki Ohnuma, Syunichi Okubo, Naoaki Shintani, Shingo Tanaka, Masaya Kida, Yasuhiro Sato, Hidetoshi Ohta, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Koji Yamaguchi, Koichi Hirata, Yoshiro Niitsu, Junji Kato

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   66 ( 4 )   721 - 728   2010.9

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    DOI： 10.1007/s00280-009-1215-2

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  • Effect of alcohol consumption on the prevalence of fatty liver disease

    Tadashi Doi, Shingo Tanaka, Yasuhiro Sato, Hidetoshi Ohta, Shinya Minami, Akihito Fujimi, Yuji Kanisawa, Fumihito Tamura, Masahiro Hirakawa, Kaoru Ono

    Acta Hepatologica Japonica   51 ( 9 )   501 - 507   2010

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    DOI： 10.2957/kanzo.51.501

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  • Adenocarcinoma of Meckel's diverticulum diagnosed by capsule endoscopy and single-balloon enteroscopy Reviewed

    Yasuhiro Sato, Shingo Tanaka, Yutaku Ko, Toshinori Okuda, Fumito Tamura, Akihito Fujimi, Tadashi Doi, Yuji Kanisawa, Hidetoshi Ohta

    Clinical Journal of Gastroenterology   2 ( 6 )   388 - 393   2009.12

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    DOI： 10.1007/s12328-009-0111-y

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  • A case of early esophageal adenocarcinoma arising from esophageal cardiac glands Reviewed

    Yutaku Ko, Yasuhiro Sato, Shingo Tanaka, Toshinori Okuda, Akihito Fujimi, Tadashi Doi, Yuji Kanisawa, Kazuhiro Iwai, Hidetoshi Ohta

    Journal of Japanese Society of Gastroenterology   106 ( 9 )   1327 - 1333   2009.9

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    DOI： 10.11405/nisshoshi.106.1327

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  • [Spontaneous pneumothorax, an unusual manifestation of imatinib-resistant chronic eosinophilic leukemia: an autopsy study]. Reviewed

    Fujimi A, Kanisawa Y, Tanaka S, Okuda T, Sato Y, Doi T, Ohta H, Iwasaki S, Ishizu A, Huang Y

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   98 ( 4 )   862 - 865   2009.4

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    Language：Japanese   Publisher：The Japanese Society of Internal Medicine  

    Other Link： https://jlc.jst.go.jp/DN/JALC/00330166346?from=CiNii

    DOI： 10.2169/naika.98.862

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  • ダブルバルーン小腸内視鏡にて除去しえた小腸内異物の3例

    佐川 保, 高山 哲治, 佐藤 康史, 高橋 祥, 田中 信悟, 小笹 里砂, 井山 諭, 黒田 裕行, 加藤 淳二, 新津 洋司郎

    Gastroenterological Endoscopy   50 ( 10 )   2684 - 2690   2008.10

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    DOI： 10.11280/gee1973b.50.2684

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  • [Two cases of advanced gastric cancer in which paclitaxel proved effective after resistance to docetaxel]. Reviewed

    Tsushima T, Tsuji Y, Abe S, Tanaka S, Tamura F, Mizushima T, Makino K, Oura K, Honda K, Sumiyoshi T, Yoshizaki N, Kondo H

    Gan to kagaku ryoho. Cancer & chemotherapy   34 ( 10 )   1647 - 1650   2007.10

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    Docetaxel and paclitaxel are demonstrated to be effective for use as salvage therapy for advanced gastric cancer. Both drugs are taxane derivatives but there is only partial cross-resistance between them. For breast cancer and ovarian cancer, there have been several reports that showed docetaxel is effective for paclitaxel-resistant cancer, and vice versa. We experienced two cases of advanced gastric cancer effectively treated by sequential therapy of docetaxel and paclitaxel. One patient was a 43-year-old woman with a type 4 gastric carcinoma, and the other a 51-year-old woman who had suffered a recurrence of the gastric cancer after a total gastrectomy. At first, chemotherapy failed, so we chose docetaxel/high-dose 5-FU (HDFU) for the second-line therapy. After resistance to Docetaxel/HDFU, paclitaxel was effective for third-line treatment of both patients.

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  • [Feasibility of modified FOLFIRI regimen for patients with refractory advanced or recurrent colorectal cancer]. Reviewed

    Takahari D, Tsuji Y, Tanaka S, Tsushima T, Ohura K, Honda K, Sumiyoshi T, Yoshizaki N, Kondo H

    Gan to kagaku ryoho. Cancer & chemotherapy   34 ( 2 )   207 - 211   2007.2

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  • [Gastric relapse of stage I ocular adnexal mucosa-associated lymphoid tissue lymphoma]. Reviewed

    Sato T, Takimoto R, Iyama S, Ono K, Tanaka S, Araki N, Nishiie K, Murase K, Sato Y, Kobune M, Matsunaga T, Kato J, Niitsu Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   48 ( 1 )   56 - 60   2007.1

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    A 57-year-old male with right ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) was successfully treated with local radiation therapy. The gastroendoscopic examination revealed a slight inflammatory change of the gastric mucosa, and the urease test was positive. Eradication therapy against <i>Helicobacter pylori</i> was successfully done, however, the patient developed gastric MALT lymphoma two years after the initial treatment. Southern blot analysis of the immunoglobulin heavy chain gene rearrangement revealed that the lymphoma cells from the ocular adnexal and gastric MALT lymphomas were identical, indicating that the gastric MALT lymphoma was not the primary but the metastatic region from the ocular adnexal MALT lymphoma. Further, immunohistochemical staining demonstrated the expression of integrin &alpha;4&beta;7 on ocular adnexal MALT lymphoma cells, which is essential for the adhesion of lymphocytes to gastrointestinal mucosa. These results indicate that ocular adnexal MALT lymphoma cells can metastasize to the stomach, depending on the adhesional function of integrin &alpha;4&beta;7.

    Other Link： http://search.jamas.or.jp/link/ui/2007162208

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  • [Present status of home therapy cancer patients using an infusor]. Reviewed

    Tsuji Y, Tsushima T, Tanaka S, Mizushima T, Tamura F, Chiba H, Honda K, Makino K, Ohura K, Sumiyoshi T, Yoshizaki N, Kondo H

    Gan to kagaku ryoho. Cancer & chemotherapy   33 Suppl 2   260 - 263   2006.12

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    We started a department of medical oncology and the risk management system of cancer chemotherapy since April in 2004. After that, chemotherapy administration increased steadily in numbers, especially on an outpatient basis. For reliable venous access, we made active use of a central venous Port (more than 60% of cases) as a rout of administration. Fifty five patients with advanced colorectal cancer were treated by FOLFIRI or FOLFOX regimen from April 2005 to June 2006. Two hundred sixty four cycles of FOLFIRI and 276 cycles of FOLFOX were administered. One hundred sixteen cycles (44%) and 117 cycles (42%) were performed through home therapy, respectively. Twenty five out of 55 patients could shift to home therapy using an infusor. Nine out of 30 patients wanted to continue on an inpatient basis, because their private insurance for medical care did not support the outpatient chemotherapy.

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  • [Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells]. Reviewed

    Matsunaga T, Sato T, Iyama S, Tanaka S, Murase K, Sato Y, Kobune M, Takimoto R, Kato J, Kuroda H, Niitsu Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   47 ( 11 )   1457 - 1462   2006.11

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    A 72-year-old male was admitted to our hospital to determine the cause of neck lymphadenopathies. He was diagnosed pathologically by a lymph node biopsy as having peripheral T-cell lymphoma (PTCL). He also had developed eosinophilia and his serum concentration of Interleukin-5 (IL-5) was extremely high. Immunostaining of a resected lymph node revealed that there were lymphoma cells which were stained with anti-IL-5 antibody. After 2 courses of CHOP therapy, the lymphadenopathies and eosinophilia disappeared and the concentration of serum IL-5 was normalized. It was suggested that IL-5 produced by lymphoma cells had induced his eosinophilia.

    Other Link： https://jlc.jst.go.jp/DN/JALC/00288263616?from=CiNii

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Research Projects

  • Novel strategies for the treatment of solid tumors with CAR and CIML NK cells

    Grant number：21H02789  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）

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  • 酸化的DNA傷害修復酵素欠損マウス由来肝腫瘍オルガノイドを用いた新規治療法の探索

    Grant number：21K08011  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    田中 信悟, 加藤 淳二, 宮西 浩嗣

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    肝細胞癌は依然予後不良の疾患であり，分子標的薬導入後の平均生存期間は1年程度である．肝細胞癌の背景肝疾患は多岐にわたり，遺伝子変異も多様かつ低頻度に生じることが報告されている．このことが分子標的薬開発の進まない原因とされ，前臨床段階からの背景肝疾患別アプローチが必要と考えられている．また，分子標的薬の開発において，腫瘍の状態を忠実に反映した新規in vitroスクリーニング試験の開発が強く求められている．申請者らはこれまでに酸化的DNA傷害修復酵素MUTYH欠損マウスに高脂質・高糖質・鉄過剰食を給餌して肝発癌モデルマウス(HCV，NASHモデル)を作成した．本研究の目的は同マウス肝腫瘍由来オルガノイドを作成し，新規肝細胞癌治療薬を探索することである．
    研究計画としては，1. MUTYH欠損マウス由来肝腫瘍(HCV，NASHモデル)とヒト肝細胞癌との類似性の評価 (令和3年度)，2. MUTYH欠損マウス由来肝腫瘍からのオルガノイド作成 (令和3,4年度)，3. 肝腫瘍オルガノイドを用いた抗腫瘍薬スクリーニング (令和4,5年度)と設定し，まず令和3年度は上記1,2に取り組んだ．
    上記1についはNASHモデルの肝腫瘍についてデータを取得し，現在比較対象となるヒト肝細胞癌のsomatic mutationデータ（International Cancer Genome Consortium，The Cancer Genome Atlas，Cancer Gene Census)との相同性について解析中である．上記2については，培養法の確立に取り組んでいる．

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  • Elucidation of NASH hepatocarcinogenesis mechanism and therapeutic application using oxidative DNA damage repair enzyme-deficient mice

    Grant number：19K17405  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Tanaka Shingo

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    The applicants established a new NASH model mouse created by loading high-calorie and high-oxidative stress on oxidative DNA injury repair enzyme (MUTYH)-deficient mice. The purpose of this study was to evaluate this mice and to develop a novel antioxidant therapy.
    Increased levels of 4-HNE and 8-OHdG, which are indicators of oxidative stress, were observed in the liver tissue of mice fed a high-fat, cholesterol and iron-rich diet(HFHC+Fe). When MUTYH-null mice were fed with HFHC+Fe, 25% of the mice showed liver tumors. Comparison of gene expression revealed that Wnt/β catenin signaling, which is relatively frequent in human hepatocellular carcinoma, is involved.

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  • Development of novel treatment for liver cancer with class-selective HDAC inhibitors

    Grant number：18K07914  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Miyanishi Koji

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    Histone deacetylase (HDAC) is expressed in various cancers and is involved in cancer treatment resistance. HDAC class IIa is found in hepatocellular carcinoma cells. In this study, we found that the combined use of HDAC class IIa inhibitors with lenvatinib induces a synergistic antitumor effect. Lenvatinib is thought to exert an antitumor effect by inhibition of fibroblast growth factor receptor 4 (FGFR4) . It is considered that the induction of apoptosis by the combined use of both drugs depends on the expression of FGFR4. Furthermore, the decreased expression of FGFR4 was considered to induce a synergistic effect.

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  • Elucidation of induction mechanism of iron oxidative stress in NASH and application to treatment

    Grant number：17K15955  2017.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    TANAKA Shingo, KATO junji, MIYANISHI koji, SAKAMOTO hiroki

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    Caco-2/TC7 cells were cultured on a porous filter in order to form monolayers having the morphology and function of small intestinal epithelial cells as in vitro experiments. It was possible to measure DMT1 mRNA expression level and IRP activity.
    In vivo experiment, a steatohepatitis model mouse was prepared. It was reared in Surwit diet, iron content was added 450 mg/kg diet in iron excess group. After liver tissue was collected and fixed specimens were prepared, liver injury, fibrosis, iron deposition, degree of oxidative stress using 8-OHdG antibody, and carcinogenesis could be analyzed.

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  • Analysis of relation between oxidative DNA repair genes,MUTYH and hepatocarcinogenesis

    Grant number：24590985  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MIYANISHI Koji, JUNJI Kato

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    Grant amount：\5460000 （ Direct Cost: \4200000 、 Indirect Cost：\1260000 ）

    In one of MutYH SNPs (s3219487), the frequency of minor homo or hetero allele carrier in the HCC group significantly higher than that in HCC group. In addition, the expression of MUTYH mRNA in minor homo allele tended to be lower than that in major homo allele. Multivariate Cox regression analysis indicated that Age and the minor allele of this SNP in MUTYH factors were significantly associated with hepatocarcinogenesis independently. These results indicated that the minor hetero allele of this SNP in MUTYH could be a significant risk factor of liver carcinogenesis from CHC and could be a predictive marker of HCC development in CHC patients.

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