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1,006 results on '"Taura, Kojiro"'

5. Immunotherapy-based targeting of MSLN+ activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis

Author

Nishio, Takahiro, Koyama, Yukinori, Liu, Xiao, Rosenthal, Sara B, Yamamoto, Gen, Fuji, Hiroaki, Baglieri, Jacopo, Li, Na, Brenner, Laura N, Iwaisako, Keiko, Taura, Kojiro, Hagood, James S, LaRusso, Nicholas F, Bera, Tapan K, Pastan, Ira, Brenner, David A, and Kisseleva, Tatiana

Subjects
Liver Disease, Lung, Digestive Diseases, Animals, Cholestasis, Collagen, Fibroblasts, Humans, Immunotherapy, Immunotoxins, Liver Cirrhosis, Mesothelin, Mice, Thy-1 Antigens, cholestatic fibrosis, activated portal fibroblasts, mesothelin
Abstract

We investigated the role of mesothelin (Msln) and thymocyte differentiation antigen 1 (Thy1) in the activation of fibroblasts across multiple organs and demonstrated that Msln-/- mice are protected from cholestatic fibrosis caused by Mdr2 (multidrug resistance gene 2) deficiency, bleomycin-induced lung fibrosis, and UUO (unilateral urinary obstruction)-induced kidney fibrosis. On the contrary, Thy1-/- mice are more susceptible to fibrosis, suggesting that a Msln-Thy1 signaling complex is critical for tissue fibroblast activation. A similar mechanism was observed in human activated portal fibroblasts (aPFs). Targeting of human MSLN+ aPFs with two anti-MSLN immunotoxins killed fibroblasts engineered to express human mesothelin and reduced collagen deposition in livers of bile duct ligation (BDL)-injured mice. We provide evidence that antimesothelin-based therapy may be a strategy for treatment of parenchymal organ fibrosis.

Published
2021

12. Surgical Anatomy of the Liver

Author

Yoshino, Kenji, Taura, Kojiro, Takaori, Kyoichi, Kasai, Yosuke, Hatano, Etsuro, Makuuchi, Masatoshi, editor, Kokudo, Norihiro, editor, Popescu, Irinel, editor, Belghiti, Jacques, editor, Han, Ho-Seong, editor, Takaori, Kyoichi, editor, and Duda, Dan G., editor

Published
2022
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13. Nonsuperiority of technetium-99m-galactosyl human serum albumin scintigraphy over conventional volumetry for assessing the future liver remnant in patients undergoing hepatectomy after portal vein embolization

Author

Yao, Siyuan, Taura, Kojiro, Yoh, Tomoaki, Nishio, Takahiro, Koyama, Yukinori, Ogiso, Satoshi, Okamoto, Tatsuya, Fukumitsu, Ken, Ishii, Takamichi, Seo, Satoru, Hata, Koichiro, Masui, Toshihiko, Shimizu, Hironori, Ishimori, Takayoshi, and Hatano, Etsuro

Published
2023
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17. Impact of anatomical liver resection on patient survival in KRAS-wild-type colorectal liver metastasis: A multicenter retrospective study

Author

Kawai, Takayuki, Ishii, Takamichi, Uchida, Yoichiro, Sato, Asahi, Naito, Shigetoshi, Kitaguchi, Kazuhiko, Komatsubara, Takashi, Nakamura, Ikuo, Ogiso, Satoshi, Fukumitsu, Ken, Seo, Satoru, Fujikawa, Takahisa, Yasuchika, Kentaro, Hirose, Tetsuro, Zaima, Masazumi, Taura, Kojiro, Hatano, Etsuro, and Terajima, Hiroaki

Published
2022
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18. Antibiotic pretreatment alleviates liver transplant damage in mice and humans

Author

Nakamura, Kojiro, Kageyama, Shoichi, Ito, Takahiro, Hirao, Hirofumi, Kadono, Kentaro, Aziz, Antony, Dery, Kenneth J, Everly, Matthew J, Taura, Kojiro, Uemoto, Shinji, Farmer, Douglas G, Kaldas, Fady M, Busuttil, Ronald W, and Kupiec-Weglinski, Jerzy W

Subjects
Biotechnology, Digestive Diseases, Organ Transplantation, Chronic Liver Disease and Cirrhosis, Transplantation, Liver Disease, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Oral and gastrointestinal, Adult, Animals, Anti-Bacterial Agents, Endoplasmic Reticulum Stress, Female, Hepatocytes, Humans, Liver, Liver Transplantation, Male, Mice, Mice, Inbred BALB C, Reperfusion Injury, Immunology, Innate immunity, Organ transplantation, Medical and Health Sciences
Abstract

Although modifications of gut microbiota with antibiotics (Abx) influence mouse skin and cardiac allografts, its role in orthotopic liver transplantation (OLT) remains unknown. We aimed to determine whether and how recipient Abx pretreatment may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. Mice (C57BL/6) with or without Abx treatment (10 days) were transplanted with allogeneic (BALB/c) cold-stored (18 hours) livers, followed by liver and blood sampling (6 hours). We divided 264 human OLT recipients on the basis of duration of pre-OLT Abx treatment into control (Abx-free/Abx

Published
2019

19. Nontumor related risk score: A new tool to improve prediction of prognosis after hepatectomy for colorectal liver metastases

Author

Sasaki, Kazunari, Margonis, Georgios Antonios, Moro, Amika, Wang, Jane, Wagner, Doris, Gagnière, Johan, Shin, Jung Kyong, D'Silva, Mizelle, Sahara, Kota, Miyata, Tatsunori, Kusakabe, Jiro, Beyer, Katharina, Dupré, Aurélien, Kamphues, Carsten, Imai, Katsunori, Baba, Hideo, Endo, Itaru, Taura, Kojiro, Cho, Jai Young, Aucejo, Federico, Kornprat, Peter, Kreis, Martin E., Kim, Jong Man, Burkhart, Richard, David Kwon, Choon Hyuck, and Pawlik, Timothy M.

Published
2022
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24. Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution

Author

Masui, Toshihiko, Nagai, Kazuyuki, Anazawa, Takayuki, Sato, Asahi, Uchida, Yuichiro, Nakano, Kenzo, Yogo, Akitada, Kaneda, Akihiro, Nakamura, Naoto, Yoshimura, Michio, Mizowaki, Takashi, Uza, Norimitsu, Fukuda, Akihisa, Matsumoto, Shigemi, Kanai, Masashi, Isoda, Hiroyoshi, Mizumoto, Masaki, Seo, Satoru, Hata, Koichiro, Taura, Kojiro, Kawaguchi, Yoshiya, Takaori, Kyoichi, Uemoto, Shinji, and Hatano, Etsuro

Published
2022
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25. High expression of autotaxin is associated with poor recurrence‐free survival in cholangiocarcinoma.

Author

Li, Xuefeng, Koyama, Yukinori, Taura, Kojiro, Nishio, Takahiro, Yoh, Tomoaki, Nishino, Hiroto, Uemoto, Yusuke, Kimura, Yusuke, Nakamura, Daichi, Nam, Nguyen Hai, Sato, Motohiko, Seo, Satoru, Iwaisako, Keiko, and Hatano, Etsuro

Subjects
LYSOPHOSPHOLIPIDS, AUTOTAXIN, LYMPHATIC metastasis, PLASMA cells, OVERALL survival
Abstract

Background and Aim: Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. Methods: In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. Results: High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence‐free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki‐67‐positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer‐associated fibroblasts, plasma cells, and biliary epithelial cells. Conclusions: Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Cell Transplantation

Author

Anazawa, Takayuki, primary, Ito, Takashi, additional, Hata, Koichiro, additional, Masui, Toshihiko, additional, and Taura, Kojiro, additional

Published
2022
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36. Mesothelin/mucin 16 signaling in activated portal fibroblasts regulates cholestatic liver fibrosis

Author

Koyama, Yukinori, Wang, Ping, Liang, Shuang, Iwaisako, Keiko, Liu, Xiao, Xu, Jun, Zhang, Mingjun, Sun, Mengxi, Cong, Min, Karin, Daniel, Taura, Kojiro, Benner, Chris, Heinz, Sven, Bera, Tapan, Brenner, David A, and Kisseleva, Tatiana

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Animals, CA-125 Antigen, Calcium-Binding Proteins, Extracellular Matrix Proteins, Female, Fibroblasts, GPI-Linked Proteins, Humans, Liver Cirrhosis, Biliary, Male, Membrane Proteins, Mesothelin, Mice, Mice, Knockout, Signal Transduction, Thy-1 Antigens, Transforming Growth Factor beta1, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Cholestatic liver fibrosis is caused by obstruction of the biliary tract and is associated with early activation of portal fibroblasts (PFs) that express Thy-1, fibulin 2, and the recently identified marker mesothelin (MSLN). Here, we have demonstrated that activated PFs (aPFs) and myofibroblasts play a critical role in the pathogenesis of liver fibrosis induced by bile duct ligation (BDL). Conditional ablation of MSLN+ aPFs in BDL-injured mice attenuated liver fibrosis by approximately 50%. Similar results were observed in MSLN-deficient mice (Msln-/- mice) or mice deficient in the MSLN ligand mucin 16 (Muc16-/- mice). In vitro analysis revealed that MSLN regulates TGF-β1-inducible activation of WT PFs by disrupting the formation of an inhibitory Thy-1-TGFβRI complex. MSLN also facilitated the FGF-mediated proliferation of WT aPFs. Therapeutic administration of anti-MSLN-blocking Abs attenuated BDL-induced fibrosis in WT mice. Liver specimens from patients with cholestatic liver fibrosis had increased numbers of MSLN+ aPFs/myofibroblasts, suggesting that MSLN may be a potential target for antifibrotic therapy.

Published
2017

39. A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial).

Author

Ichida, Akihiko, Arita, Junichi, Hatano, Etsuro, Eguchi, Susumu, Saiura, Akio, Nagano, Hiroaki, Shindoh, Junichi, Hashimoto, Masaji, Takemura, Nobuyuki, Taura, Kojiro, Sakamoto, Yoshihiro, Takahashi, Yu, Seyama, Yasuji, Sasaki, Yasuharu, Uemura, Kohei, Kokudo, Norihiro, and Hasegawa, Kiyoshi

Subjects
CLINICAL trials, CHEMOEMBOLIZATION, INDOCYANINE green, SURGICAL excision, OVERALL survival, PROGRESSION-free survival, HEPATOCELLULAR carcinoma
Abstract

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC. [ABSTRACT FROM AUTHOR]

Published
2024
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42. ALPlat criterion for the resection of hepatocellular carcinoma based on a predictive model of posthepatectomy liver failure

Author

Yamamoto, Gen, Taura, Kojiro, Ikai, Iwao, Fujikawa, Takahisa, Nishitai, Ryuta, Kaihara, Satoshi, Zaima, Masazumi, Terajima, Hiroaki, Yoshimura, Tsunehiro, Koyama, Yukinori, Tanabe, Kazutaka, Nishio, Takahiro, Okuda, Yukihiro, Ikeno, Yoshinobu, Yoshino, Kenji, Fukuyama, Keita, Seo, Satoru, Hatano, Etsuro, and Uemoto, Shinji

Published
2020
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44. A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Author

Ichida, Akihiko, primary, Arita, Junichi, additional, Hatano, Etsuro, additional, Eguchi, Susumu, additional, Saiura, Akio, additional, Nagano, Hiroaki, additional, Shindoh, Junichi, additional, Hashimoto, Masaji, additional, Takemura, Nobuyuki, additional, Taura, Kojiro, additional, Sakamoto, Yoshihiro, additional, Takahashi, Yu, additional, Seyama, Yasuji, additional, Sasaki, Yasuharu, additional, Uemura, Kohei, additional, Kokudo, Norihiro, additional, and Hasegawa, Kiyoshi, additional

Published
2023
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