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Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine

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World Journal of Gastroenterology 2014年第39期20卷 14420-14429页

作者： Shigeo Koido Toshifumi Ohkusa Shin Kan Kazuki Takakura Keisuke Saito Hideo Komita zensho ito Hiroko Kobayashi Shinichiro Takami Kan Uchiyama Hiroshi Arakawa Masaki ito Masato Okamoto Mikio Kajihara Sadamu Homma Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal Medicine The Jikei University School of Medicine Chiba 277-8567 Japan Department of Oncology The Jikei University School of Medicine Tokyo 105-8461 Japan Department of Advanced Immunotherapeutics Kitasato University School of Pharmacy Tokyo 108-8641 Japan

AIM: To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.

关键词： Commensal bacteria Corticotropin-releasing factor Dendritic cell Irritable bowel syndrome Inflammatory bowel disease Urocortin

Advances in inducing adaptive immunity using cell-based cancer vaccines: clinical applications in pancreatic cancer

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World Journal of Gastroenterology 2016年第18期22卷 4446-4458页

作者： Mikio Kajihara Kazuki Takakura Tomoya Kanai zensho ito Yoshihiro Matsumoto Shigetaka Shimodaira Masato Okamoto Toshifumi Ohkusa Shigeo Koido Division of Gastroenterology and Hepatology Department of Internal Medicine the Jikei University School of Medicine (Kashiwa Hospital) Cell Processing Center Shinshu University Hospital Department of Advanced Immunotherapeutics Kitasato University School of Pharmacy Institute of Clinical Medicine and Research The Jikei University School of Medicine

The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

关键词： Pancreatic cancer Dendritic cell whole tumor cell Cancer vaccine Cytotoxic T lymphocyte

The Efficacy of the Consumption of n-3 Polyunsaturated Fatty Acids for the Maintenance of Remission in Patients with Inflammatory Bowel Disease

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Food and Nutrition Sciences 2018年第2期9卷 105-118页

作者： Kan Uchiyama Hiroko Aiki Aki Matsumura Kanako Saruta Ai Yuasa zensho ito Shinichiro Takami Keisuke Saito Yuichiro Ohtaki Shizuka Suzuki Susumu Hayashi Shigeo Koido Hiroshi Yoshida Toshifumi Ohkusa Masayuki Saruta Department of Internal Medicine Division of Gastroenterology and Hepatology The Jikei University Kashiwa Hospital Kashiwa Japan Department of Nutrition The Jikei University Kashiwa Hospital Kashiwa Japan Department of Laboratory Medicine The Jikei University Kashiwa Hospital Kashiwa Japan Department of Internal Medicine Division of Gastroenterology and Hepatology The Jikei University Hospital Tokyo Japan

The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalization (Q1) was completed by 24 patients with IBD (10 ulcerative colitis (UC) subjects and 14 Crohn’s disease (CD) subjects) treated at our hospital. We educated the study subjects about an n-3 PUFA diet, and a follow-up survey (Q2) was conducted 6 to 12 months after discharge. Disease activity was evaluated using the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and/or the Crohn’s Disease Activity Index (CDAI) score for CD and the partial UCDAI score without endoscopic evaluation for UC. Q1 showed that the average n-3 and n-6 PUFA intakes were 1673 ± 1651 mg and 9146 ± 5217 mg, respectively, and the average n-3/n-6 ratio was 0.27 ± 0.31. In Q2, the intake of n-3 PUFA was significantly higher (3671 ± 1684 mg, p < 0.001), whereas the n-6 PUFA intake decreased significantly (5217 ± 1973 mg, p < 0.001) compared to those in Q1. As a consequence, the dietary n-3/ n-6 ratio was significantly increased (0.87 ± 0.60, p < 0.001). Maintenance of the remission rate was significantly higher in IBD patients who complied with the n-3 diet, and these patients maintained a dietary n-3/n-6 ratio of 0.432 or higher (17 of 23 cases;70.8%, p < 0.03) compared to that observed for IBD patients who did not comply with the diet. These results emphasize the importance of adjusting dietary PUFA and suggest that the n-3 diet may be effective in maintaining the remission of IBD.

关键词： Crohn’s Disease Inflammatory Bowel Disease N-3 Diet Polyunsaturated Fatty Acid Ulcerative Colitis

Immunotherapy for colorectal cancer

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World Journal of Gastroenterology 2013年第46期19卷 8531-8542页

作者： Shigeo Koido Toshifumi Ohkusa Sadamu Homma Yoshihisa Namiki Kazuki Takakura Keisuke Saito zensho ito Hiroko Kobayashi Mikio Kajihara Kan Uchiyama Seiji Arihiro Hiroshi Arakawa Masato Okamoto Jianlin Gong Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal Medicine The Jikei University School of Medicine Department of Oncology Institute of DNA Medicine The Jikei University School of Medicine Institute of Clinical Medicine and Research The Jikei University School of Medicine Department of Endoscopy The Jikei University School of Medicine Division of Cellular Signaling Institute for Advanced Medical Research Keio University School of Medicine Department of Medicine Boston University School of Medicine Boston

The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely *** chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced *** this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine *** possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.

关键词： Colorectal cancer Cytotoxic T lymphocyte Dendritic cell Immunotherapy vaccine

Prognostic significance of plasma interleukin-6/-8 in pancreatic cancer patients receiving chemoimmunotherapy

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World Journal of Gastroenterology 2015年第39期21卷 11168-11178页

作者： Shintaro Tsukinaga Mikio Kajihara Kazuki Takakura zensho ito Tomoya Kanai Keisuke Saito Shinichiro Takami Hiroko Kobayashi Yoshihiro Matsumoto Shunichi Odahara Kan Uchiyama Hiroshi Arakawa Masato Okamoto Haruo Sugiyama Kazuki Sumiyama Toshifumi Ohkusa Shigeo Koido Division of Gastroenterology and Hepatology Department of Internal Medicine The Jikei University School of Medicine Department of Endoscopy The Jikei University School of Medicine Department of Advanced Immunotherapeutics Kitasato University School of Pharmacy Department of Functional Diagnostic Science Graduate School of Medicine Osaka University Institute of Clinical Medicine and Research The Jikei University School of Medicine

AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with ***: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) ***: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term ***: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.

关键词： Chemoimmunotherapy Dendritic cell Delayed-type hyp

Challenging situation of coronary artery anomaly associated with ischemia and/or risk of sudden death

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World Journal of Cardiology 2024年第4期16卷 173-176页

作者： Shigenori ito Division of Cardiology Sankuro HospitalToyota 471-0035Japan

Coronary artery anomaly is known as one of the causes of angina pectoris and sudden death and is an important clinical entity that cannot be *** incidence of coronary artery anomalies is as low as 1%-2%of the general population,even when the various types are *** anomalies are practically challenging when the left and right coronary ostium are not found around their normal positions during coronary angiography with a *** there is atherosclerotic stenosis of the coronary artery with an anomaly and percutaneous coronary intervention(PCI)is required,the suitability of the guiding catheter at the entrance and the adequate back up force of the guiding catheter are *** level of PCI risk itself should also be considered on a caseby-case *** this case,emission computed tomography in the R-1 subtype single coronary artery proved that ischemia occurred in an area where the coronary artery was not visible to the naked *** follow-up would be crucial,because sudden death may occur in single coronary *** prevent atherosclerosis with full efforts is also important,as the authors indicated admirably.

关键词： Coronary artery anomaly Single coronary artery Ischemia Sudden death Percutaneous coronary intervention Coronary vessel anomalies Myocardial ischemia Sudden cardiac death

Bicuspidization Using the Open-Sleeve Technique for Congenital Aortic Stenosis during Infancy

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Congenital Heart Disease 2024年第2期19卷 177-183页

作者： Toshi Maeda Hiroki ito Keiichi Hirose Kisaburo Sakamoto Departments of Cardiovascular Surgery Mt.Fuji Shizuoka Children’s HospitalShizuoka420-8660Japan

Congenital aortic stenosis(cAS)frequently requires intervention during the neonatal or infantile ***,surgical repair is challenging because of the narrow surgical *** performed bicuspidization using the open-sleeve technique for cAS with a unicuspid aortic valve in two ***,the patients were doing well without reintervention for the aortic valve for 8 and 6 years,*** aortic annular diameter increased along with somatic *** for neonates or infancy can be performed safely using the open-sleeve technique as its midterm results have been satisfactory.

关键词： Aortic valve repair infant bicuspidization open-sleeve technique

1,3-Dipolar Cycloaddition of Polycyclic Aromatic Azomethine Ylides and Alkynylbenziodoxoles for Synthesis of Functional Dibenzoullazines

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Chinese Journal of Chemistry 2024年第10期42卷 1079-1083页

作者： Hui Han Glen Wee Zhuan Goh Yongxin Li Naohiko Yoshikai Shingo ito Schoolof Chemistry ChemicalEngineering and BiotechnologyNanyang Technoogical University21 Nanyang LinkSingapore 637371Singapore Graduate School of Pharmaceutical Sciences Tohoku UniversitySendai 980-8578Japan

A new family of dibenzoullazine derivatives was synthesized through 1,3-dipolar cycloaddition of polycyclic aromatic azomethine ylides with alkynylbenziodoxoles followed by *** benziodoxole moiety in the resulting products was used as a versatile linchpin for the synthesis of structurally diverse functional dibenzoullazines that are difficult to access by other synthetic methods.

关键词： Cycloaddition Nitrogen heterocycles Azomethine ylides Hypervalent compounds Dibenzoullazine

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

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Neural Regeneration Research 2025年第1期20卷 188-190页

作者： Shiho ito Takeshi Kawauchi Department of Adaptive and Maladaptive Responses in Health and Disease Graduate School of MedicineKyoto UniversityKyotoJapan Department of Physiology Keio University School of MedicineTokyoJapan

Cell adhesion plays pivotal roles in the morphogenesis of multicellular *** cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

关键词： cerebral skeletal cooperation