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Fibroblasts, an inconspicuous but essential player in colon cancer development and progression

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World Journal of Gastroenterology 2016年第23期22卷 5301-5316页

作者： Naofumi Mukaida soichiro Sasaki Division of Molecular Bioregulation Cancer Research InstituteKanazawa University

Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.

关键词： Angiogenesis Drug resistance Extracellular matrix Immune evasion Transforming growth factor-β Invasion Metastasis

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine

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World Journal of Gastroenterology 2015年第1期21卷 177-186页

作者： Toshihide Ueda Ryota Hokari Masaaki Higashiyama Yuichi Yasutake Koji Maruta Chie Kurihara Kengo Tomita Shunsuke Komoto Yoshikiyo Okada Chikako Watanabe Shingo usui Shigeaki Nagao soichiro Miura Department of Internal Medicine National Defense Medical CollegeSaitama 359-8513Japan

AIM: To investigate the effect of a fat rich diet onnon-steroidal anti-inflammatory drug(NSAID)-induced mucosal damage in the murine small ***: C57BL6 mice were fed 4 types of diets with or without *** group was fed standard laboratory *** other groups were fed a fat diet consisting of 8% w/w fat,beef tallow(rich in SFA),fish oil,(rich in omega-3 PUFA),or safflower oil(rich in omega-6 PUFA).Indomethacin(3 mg/kg) was injected intraperitoneally from day 8 to day *** day 11,intestines and adhesions to submucosal microvessels were ***: In the indomethacin-treated groups,mucosal damage was exacerbated by diets containing beef tallow and fish oil,and was accompanied by leukocyte infiltration(P < 0.05).The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet(P < 0.05).Indomethacin increased monocyte and platelet migration to the intestinal mucosa,whereas safflower oil significantly decreased monocyte and platelet recruitment(P < 0.05).CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte ***,a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

关键词： Non-steroidal anti-inflammatory drugs Small intest

Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice

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World Journal of Gastroenterology 2013年第32期19卷 5250-5260页

作者： Kazuhiro Takahashi soichiro Murata Kiyoshi Fukunaga Nobuhiro Ohkohchi Department of Surgery University of Tsukuba

AIM:To investigate the role of human platelets in liver ***:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western *** effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,*** of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using *** apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end ***,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 ***:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g

关键词： Human platelet Liver fibrosis Hepatocyte apoptosis Hepatocyte growth factor Transforming growth factor-β Matrix metallopeptidases

China ASON Network Migration Scenarios and Their Quantitative Analysis

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光学学报 2003年第S1期23卷 667-668页

作者： soichiro Araki Itaru Nishioka Yoshihiko Suemura Networking Research Laboratories NEC CorporationNetworking Research Laboratories NEC CorporationNetworking Research Laboratories NEC Corporation

This paper proposes two migration scenarios from China ring networks to ASON mesh networks. In our quantitative analysis with ASON/GMPLS simulator, a subnetwork protection scheme achieved best balanced performance in ... 详细信息

关键词： ASON it from for be In of China ASON Network Migration Scenarios and Their Quantitative Analysis LSC

Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 323-329页

作者： Masataka Amisaki Hiroaki Saito Naruo Tokuyasu Teruhisa Sakamoto soichiro Honjo Yoshiyuki Fujiwara Division of Surgical Oncology Department of SurgerySchool of MedicineTottori University Faculty of Medicine

Background: Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma(HCC).Methods: We included 145 HCC patients who underwent initial and curative resection between January2004 and December 2013. Postoperative complications of grade III or higher based on Clavien–Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase ***: Thirty-eight patients(26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration(P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications(P = 0.015). Earlyphase recurrence was observed in 20/38(53%) patients who suffered postoperative complications and36/107(34%) patients with no complications, which was statistically significant(P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level(P = 0.042),multiple tumors(P < 0.001), poor differentiation(P = 0.036) and presence of postoperative complication(P = 0.039).Conclusions: Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC.

关键词： Neoplasm metastasis Complications Risk factors Hepatocellular carcinoma

Combined preoperative platelet-to-lymphocyte ratio and serum carbohydrate antigen 19–9 level as a prognostic factor in patients with resected pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2019年第3期18卷 278-284页

作者： Teruhisa Sakamoto Hiroaki Saito Masataka Amisaki Naruo Tokuyasu soichiro Honjo Yoshiyuki Fujiwara Division of Surgical Oncology Department of Surgery School of Medicine Tottori University Faculty of Medicine

Background: Carbohydrate antigen 19–9(CA19-9) is the most frequently used tumor marker and serves as a prognostic indicator in patients with pancreatic cancer(PC). The platelet-to-lymphocyte ratio(PLR) is thought to be an inflammation-related serum marker. An elevated PLR represents increased inflammatory status and is associated with poor prognosis in patients with various cancers including PC. Methods: This study involved 103 patients with a histopathological diagnosis of pancreatic ductal adenocarcinoma who underwent pancreatectomy. The patients were assessed to determine the prognostic significance of the combination of the PLR and CA19-9 level. Results: Based on the receiver operating characteristic analysis results, the patients were divided into PLR H igh(PLR ≥ 129.1) andPLRLow(PLR < 129.1) groups and into CA19-9High(CA19-9 ≥ 74.0 U/mL) and CA19-9Low(CA19-9 < 74.0 U/mL) groups. The cumulative 5-year overall survival(OS) and disease-specific survival(DSS) rates significantly differed by both the PLR(PLR H igh group: 19.5% and 22.9%;PLRLow group: 39.1% and 45.9%) and CA19-9(CA19-9 H igh group: 19.1% and 25.6%;CA19-9Low group: 41.0% and 41.0%). We then divided the patients into Groups A(PLR L ow/CA19-9Low), B(PLR Low/CA19-9High or PLRHigh/CA19-9Low), and C(PLR H igh/CA19-9High). The cumulative 5-year OS rates in Groups A, B, and C were 44.0%, 31.9%, and 11.9%, respectively( P = 0.002). The cumulative 5-year DSS rates in Groups A, B, and C were 47.7%, 36.4%, and 16.8%, respectively( P = 0.002). Multivariate analysis revealed that the combination of the PLR and CA19-9 was an independent prognostic factor in patients with resected PC. Conclusions: The combination of the PLR and CA19-9 is useful for predicting the prognosis of patients with resected PC.

关键词： CA19-9 Pancreatic cancer Platelet-to-lymphocyte ratio Prognosis

An antioxidant resveratrol significantly enhanced replication of hepatitis C virus

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World Journal of Gastroenterology 2010年第2期16卷 184-192页

作者： Mitsuyasu Nakamura Masanori Ikeda Ryota Hokari Nobuyuki Kato Toshifumi Hibi soichiro Miura Department of Internal Medicine 2 National Defense Medical Collage3-2 NamikiTokorozawaSaitama 3598513Japan Department of Internal Medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan Department of Internal Medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan Masanori Ikeda Department of Molecular Biology Okayama University Graduate School of Medicine and Dentistry2-5-1 Shikada-choOkayama 7008558Japan Department of Internal Medicine School of MedicineKeio University35 ShinanomachiShinjuku-kuTokyo 1608582 Japan Masanori Ikeda

AIM:To elucidate the effect of antioxidants,resveratrol (RVT)and astaxanthin(AXN),on hepatitis C virus(HCV) replication. METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system *** is a strong antioxidant and a kind of polyphenol that inhibits replication of various *** is also a strong *** replication of HCV RNA was assessed by the luciferase reporter *** additive effect of antioxidants on antiviral effects of interferon(IFN)and ribavirin(RBV) was ***:This is the first report to investigate the effect of RVT and AXN on HCV *** contrast to other reported viruses,RVT significantly enhanced HCV RNA *** E also enhanced HCV RNA replication as reported previously,although AXN didnot affect *** and RBV significantly reduced HCV RNA replication,but these effects were dose-dependently hampered and attenuated by the addition of *** didnot affect antiviral effects of IFN or RBV. CONCLUSION:These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.

关键词： Replicon system Luciferase assay Ribavirin Interferon Polyphenol Astaxanthin

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

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World Journal of Gastroenterology 2017年第35期23卷 6540-6545页

作者： Shojiro Ichimata Mikiko Kobayashi Kohei Honda soichiro Shibata Akihiro Matsumoto Hiroyuki Kanno Department of Pathology Shinshu University School of Medicine Department of Medicine Shinshu University School of Medicine

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

关键词： Hepatitis C virus Acquired amegakaryocytic thrombocytopenia Anti-thrombopoietin receptor(c-Mpl) autoantibodies Idiopathic thrombocytopenic purpura Thrombocytopenia

Water-resistant organic thermoelectric generator with >10μW output

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Carbon Energy 2023年第4期5卷 55-67页

作者： Shinichi Hata Kanto Maeshiro Misaki Shiraishi soichiro Yasuda Yuta Shiozaki Koudai Kametani Yukou Du Yukihide Shiraishi Naoki Toshima Department of Applied Chemistry Faculty of EngineeringSanyo‐Onoda City UniversityYamaguchiJapan Graduate School of Engineering Sanyo‐Onoda City UniversityYamaguchiJapan College of Chemistry Chemical Engineeringand Materials ScienceSoochow UniversitySuzhouPeople's Republic of China

Flexible p–n thermoelectric generator(TEG)technology has rapidly advanced with power enhancement and size *** achieve a stable power supply and highly efficient energy conversion,absolute chemical stability of n-type materials is essential to ensuring large temperature differences between device terminals and ambient *** the aim of improving the long-term stability of the n-type operation of carbon nanotubes(CNTs)in air and water,this study uses cationic surfactants,such as octylene-1,8-bis(dimethyldodecylammonium bromide)(12-8-12),a gemini surfactant,to stabilize the nanotubes in a coating,which retains the n-doped state for more than 28 days after exposure to air and water in *** with 10 p-n units of 12-8-12/CNT(n-type)and sodium dodecylbenzene sulfonate/CNT(p-type)layers are manufactured,and their water stability is *** initial maximum output of 16.1μW(75 K temperature difference)is retained after water immersion for 40 days without using a sealant to prevent TEG module *** excellent stability of these CNT-based TEGs makes them suitable for underwater applications,such as battery-free health monitoring and information gathering systems,and facilitates the development of soft electronics.

关键词： gemini surfactant n-type carbon nanotube surfactant doping thermoelectric properties water-resistant generators water stability