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Immunotherapy in gastric cancer

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World Journal of Gastroenterology 2014年第7期20卷 1657-1666页

作者： satoko Matsueda David Y Graham Cancer Vaccine Development Division Research Center for Innovative Cancer TherapyKurume UniversityKurumeFukuoka 830-0011Japan Michael E DeBakey VA Medical Center Baylor College of MedicineHoustonTX 77030United States

Gastric cancer is the second most common of cancerrelated deaths *** the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain *** immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and ***,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric *** cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric ***,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune ***,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or *** also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor *** show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T *** has greatly improved and is becoming an important factor in such fields as medical care and welfare for human *** has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

关键词： Gastric cancer Immune checkpoint Immune escape Adoptive cell therapy Cancer vaccine Antibody therapy Predictive biomarker

Fantastic Histories： The Battles of Coxinga and the Preservation of Ming in Japan

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Frontiers of Literary Studies in China-Selected Publications from Chinese Universities 2015年第1期9卷 17-53页

作者： satoko SHIMAZAKI Department of East Asian Languages and Cultures University of Southern California LosAngeles CA 90089 USA

People in Japan reacted to the bewilderment they felt at the fall of Ming by creating a bifurcated view of China, evident in encyclopedias and gazeteers： On the one hand, there was the traditional China represented by the Ming; on the other, there was the new China ruled by the Dattan or the Tatars. Such was the power of the Ming as an image that it endured in Japanese literature and theater for centuries after its fall. This article explores the preservation in popular discourse of the Ming as the most natural representation of China, focusing on Chikamatsu Monzaemon＇s hit jrruri play The Battles of Coxinga （Kokusen＇ya kassen）, first staged in 1715 and produced many times after that, showing how the political turmoil was filtered through both misunderstandings and creative fabrications. It shows that The Battles of Coxinga creates a fantastic image of China, as opposed to the barbaric Dattan, by drawing on historical memories internal to Japan and readily available images of foreignness. I argue that the preservation of the Ming in popular theater offered audiences a means of rethinking Japan＇s position as the inheritor of a ＂universal＂ Chinese essence in an age when knowledge of the world was being dramatically expanded by imported European cartography, complicating earlier views of a world centered on the Three Realms or the Sinocentric world order.

关键词： fall of the Ming Chikamatsu Monzaemon The Battles of Coxinga(Kokusen 'ya kassen) Nishikawa Joken Japanese views of China

Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells

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World Journal of Gastroenterology 2009年第42期15卷 5249-5259页

作者： Katrin Eurich Mayuko Segawa satoko Toei-Shimizu Emiko Mizoguchi Gastrointestinal Unit Department of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Center for the Study of Inflammatory Bowel Disease Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States

The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 （CHI3L1）, a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

关键词： Mammals Chitinase 3-1ike 1 Colon Epithelial cells Inflammation Colitis Colon neoplasms Inflammatory bowel disease

Edo kabuki in transition

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Edo kabuki in transition

AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier

作者： Shimazaki satoko

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Cellular & Molecular Immunology 2018年第6期15卷 563-574页

作者： Toru Miyazaki Tomoko Yamazaki Ryoichi Sugisawa M Eric Gershwin satoko Arai Laboratory of Molecular Biomedicine for Pathogenesis Center for Disease Biology and Integrative MedicineFaculty of MedicineThe University of TokyoTokyo 113-0033Japan CREST Japan Agency for Medical Research and DevelopmentTokyo 113-0033Japan Max Planck-The University of Tokyo Center for Integrative Inflammology Tokyo 113-0033Japan Division of Rheumatology Allergy and Clinical Immunology The University of California School of MedicineDavisCA 95616USA

Circulating immunoglobulin M(IgM)exists in a pentameric form,possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens;thus,it is involved in both beneficial and detrimental immune responses,including protection from infection and the progression of *** the other hand,IgM also behaves as a carrier of the apoptosis inhibitor of macrophage(AIM)protein,storing a large amount of the inactivated form of AIM in the blood through this *** different disease conditions,AIM can dissociate from IgM locally or systemically to exert its function,inducing the removal of various biological debris such as excess fat,bacteria,cancer cells or dead cell *** typically,upon induction of acute kidney injury(AKI),IgM-free AIM is filtered by the glomerulus in the kidney,which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules,thereby facilitating the repair of kidney ***,cats exhibit a deficiency in AIM release from IgM,which may increase their susceptibility to renal ***,association with AIM inhibits IgM binding to the Fcα/μreceptor on follicular dendritic cells at the splenic germinal center,thereby protecting the IgM immune complex from Fcα/μreceptor-mediated internalization,which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody *** regulation of AIM–IgM binding,resulting from the discovery of reciprocal actions between AIM and IgM,could lead to the development of novel therapies against different diseases.

关键词： apoptosis inhibitor of macrophage(AIM) immunoglobulin M(IgM) acute kidney injury(AKI) hepatocellular carcinoma(HCC) cat renal failure

Hypoxia and fatty liver

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World Journal of Gastroenterology 2014年第41期20卷 15087-15097页

作者： Tomohiro Suzuki satoko Shinjo Takatomo Arai Mai Kanai Nobuhito Goda Department of Life Science and Medical BioScience Waseda University School of Advanced Science and Engineering

The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function,even under starved *** processes require a considerable amount of oxygen,which causes a steep oxygen gradient throughout the hepatic *** consumption and/or excessive food intake can alter the hepatic metabolic balance drastically,which can precipitate fatty liver disease,a major cause of chronic liver diseases worldwide,ranging from simple steatosis,through steatohepatitis and hepatic fibrosis,to liver *** hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis,resulting in severe liver *** master regulators of adaptive responses to hypoxic stress,hypoxia-inducible factors(HIFs) modulate various cellular and organ functions,including erythropoiesis,angiogenesis,metabolic demand,and cell survival,by activating their target genes during fetal development and also in many disease conditions such as cancer,heart failure,and *** the past decade,it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver *** review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

关键词： Hypoxia Fatty liver disease Hypoxia-inducible factor Lipid metabolism Obstructive sleep apnea

Association between Diabetes Mellitus and Oral Health Status in Japanese Adults

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International Journal of Oral Science 2010年第2期2卷 82-89页

作者： Masayuki Ueno Susumu Takeuchi Akiko Oshiro Kayoko Shinada satoko Ohara Yoko Kawaguchi Department of Oral Health Promotion Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Department of Comprehensive Oral Health Care Faculty of Dentistry Tokyo Medical and Dental University

Aim The objective of this study was to analyze the oral health among Japanese adults, with and without diabetes mellitus. Methodology The subjects were 518 community residents aged 20 to 91 years in Japan, who participated in the ＂Akita health and nutrition survey＂ and the ＂Akita dental disease survey＂, conducted in 2006. The surveys comprised a self-administered questionnaire, along with medical and dental examinations. Results Using the community periodontal index （CPI）, the mean numbers of sextants presenting codes 0, 1 and 2 were significantly lower in diabetics than non-diabetics among the 59 years or younger age group. Although the mean numbers of sextants with codes 0, 1 and 2 among the 60 to 69 years age group were lower, and sextants with a code X among the 59 years or younger age group were higher in diabetics than non-diabetics, no statistically significant differences were detected. The tendency of lower mean numbers of natural teeth and functional tooth units in diabetics than non-diabetics was observed, however no differences were statistically significant. Conclusion The outcome of periodontal disease seemed to be influenced by the diabetic state to some degree, but a clear association between diabetes and oral health status was not found.

关键词： diabetes mellitus periodontal disease community periodontal index functional tooth units

Advancing precision oncology:Insights into the tumor microenvironment and immunotherapy outcomes

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The Innovation 2024年第4期5卷 21-22页

作者： Tomotaka Ugai Qian Yao satoko Ugai Shuji Ogino Department of Pathology Brigham and Women’s Hospitaland Harvard Medical SchoolBostonMA 02115USA Department of Epidemiology Harvard T.H.Chan School of Public HealthBostonMA 02115USA Cancer Epidemiology Program Dana-Farber/Harvard Cancer CenterBostonMA 02215USA Broad Institute of MIT and Harvard CambridgeMA 02142USA Cancer Immunology Program Dana-Farber/Harvard Cancer CenterBostonMA 02215USA Tokyo Medical and Dental University(Institute of Science Tokyo) BunkyoTokyo 1138510Japan

The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorganisms,immune and other stromal cells,and extracellular *** orchestration of these components intricately contributes to tumor evolution and shapes responses to cancer treatment(Figure 1).A better understanding of the tumor microenvironment is critical to elucidate the etiology of cancer and develop more efficient therapeutic strategies.

关键词： microenvironment cancer tumor

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

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Journal of Environmental Sciences 2016年第11期28卷 125-130页

作者： Masaki Fujioka Min Gi satoko Kawachi Kumiko Tatsumi Naomi Ishii Kenichiro Doi Anna Kakehashi Hideki Wanibuchi Department of Molecular Pathology Osaka City University Graduate School of Medicine

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid（DMAV） is a major urinary metabolite of sodium arsenite（i As~Ⅲ） and induces urinary bladder cancers in rats. DMAVand i As~Ⅲare negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAVand i As~Ⅲin rat urinary bladder epithelium and liver using gpt delta F344 ***-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg/L DMAV, or 87 mg/L i As~Ⅲ（each 50 mg/L As） for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection（gpt assay） and deletion mutations are identified in the red/gam genes by Spi-selection（Spi-assay）. Results of the gpt and Spi-assays showed that DMAVand i As~Ⅲhad no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand i As~Ⅲare not mutagenic in urinary bladder epithelium or liver in rats.

关键词： Dimethylarsinic acid Sodium arsenite In vivo mutagenicity Urinary bladder epithelium gpt delta rat