北村秀光 (ContributorIL-6-STAT3とMHC クラス II αβ-dimer発現調節)中外医学社 2006
シグナル受容機構の解明が導く創薬・治療への躍進
北村秀光 (Contributorサイトカイン受容体群の構造と機能)羊土社 2006
In The Innate Immune System: Strategies for Disease Control
KITAMURA Hidemitsu (ContributorHyperactivation of gp130-mediated STAT3 signaling induces a rheumatoid arthritis-like disease that is dependent on MHC class II restricted CD4+ T cells)Elsevier 2005
Peptide Science -Present and Future-
KITAMURA Hidemitsu (ContributorUnusual collagen assembly induced by acidic biopolymers in vitro)Kluwer Academic Publishers 1999
The Crucial Roles of Neurokinin A and Neurokinin Receptor 2 Signaling in Asthma Exacerbation Induced by a Viral Component, Double-Stranded RNA [Not invited]
北海道大学遺伝子病制御研究所 一般公開2018 サイエンストーク 2018/06 Public discourse
血清マイクロRNAの免疫体質評価マーカーとしての応用 [Not invited]
北村秀光
BIOtech2018 アカデミックフォーラム 2018/06 Public discourse
The Effects of Viral Components, Single-Stranded RNA and Double-Stranded RNA, on Allergen-Induced Airway Hyperresponsiveness and Airway Inflammation [Not invited]
IL-6/STAT3 signaling impairs induction of cancer-antigen specific T cells via down-regulation of dendritic cells in tumor microenvironment [Not invited]
Helper/killer hybrid epitope long peptide (H/K-HELP) effectively induces tumor antigen-specific CD4+ T and CD8+ T cells in cancer patients [Not invited]
新規Survivinヘルパーペプチドの同定と免疫不全マウスを用いたSurvivin特異的Th1細胞による抗腫瘍効果の検討(Identification of novel helper epitopes of Survivin and antitumor effects of human Th1 cells in immunodeficient mice)
T Nishimura; M Nakui; M Sato; K Iwakabe; H Kitamura; M Sekimoto; A Ohta; T Koda; S Nishimura CANCER CHEMOTHERAPY AND PHARMACOLOGY 46- S52 -S61 2000/06 [Invited]
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2018/04 -2021/03
Author : Tanino Mishie
Malignant mesothelioma(MM) is an aggressive tumor which originates from the mesothelial cells of the serosal tissues. It has been reported to be associated with inhalation exposure to asbestos. MM caused by asbestos exposure, and it will become tumor after 30 to 40 years latency period. MM is treated by multidisciplinary treatment combined with surgical excision, chemotherapy and radiation, but it shows treatment resistance and poor prognosis. A novel treatment method has been desired. In this study, we focused on the role of OTUB1, one of the deubiquitinating enzyme. OTUB1 was highly expressed in MM tissue and cell lines. It regulated TGF-beta/SMAD pathway, followed by their motility and invasion. These findings suggest OTUB1 is one of the candidate protein for new therapy of MM.
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
Date (from‐to) : 2018/06 -2020/03
Author : Taketomi Akinobu
Diacylglycerol kinase α (DGKα), a lipid kinase family, involves in the anti-cancer drug-resistance. DGKα plays pivotal roles by anti-apoptotic action in cancer cells, and by suppression of anti-tumor immune system mainly in T cells. This study demonstrated that the expression of DGKα was increased not only in cancer cells treated by the anticancer drug, but also in chemo-resistant cancer cells. Therefore, selective inhibition of DGKα function has the potential of therapeutic effect on chemo-resistant refractory cancer as well as additional effect to the traditional anticancer drug treatment.
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Date (from‐to) : 2016/04 -2019/03
Author : Taketomi Akinobu
In this study, we investigated the precise roles of STAT1 and neuropeptide signaling through NK2R, a receptor of neurokinin A, in inflammatory bowel disease (IBD) involving with inflammation and immune responses by using a dextran sulfate sodium (DSS)-induced colitis model and in vitro experiments. We found that NK2R expression levels of macrophages and dendritic cells were augmented by type-1 IFN stimulations and involved in the inflammation and immune responses in a STAT-1-dependent manner. Next, we revealed that STAT1-mediated induction of a chemokine and its receptor were related to disease state of DSS-induced colitis model. Furthermore, we confirmed STAT1 activation and NK2R expression in lesion and inflammation areas of patients with IBD such as ulcerative colitis and Crohn’s diseases. Based on these findings we speculate that regulation of STAT1 and neuropeptide signaling and the downstream molecules may be a promising strategy in the development of effective therapy for IBD.
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2016/04 -2019/03
Author : Takahashi Norihiko
In this study, we established a liver metastasis mouse model and investigated the effect of IL-6 produced from tumor-bearing host on the tumorigenesis in the liver. We found that liver metastasis of colon cancer cells was significantly reduced in IL-6-deficient mice compared to wild-type mice. Depletion of dendritic cells and macrophages or killer T cells from the liver metastasis model mice cancelled the reduction of liver metastasis under IL-6-deficient condition. We identified IL-6-related microRNA by using serum of colorectal cancer patients and confirmed that liver metastasis and serum IL-6 levels of immunodeficient mice were augment by the IL-6-related microRNA-overexpressing human colon cancer cells compared to the mock control cells. Based on these findings we speculate that blockade of IL-6 signaling may be a promising strategy in the development of effective cancer immunotherapy for cancer patients.
In this study, we investigated the precise roles of neuropeptide signaling through NK2R, a receptor of neurokinin A, in tumorigenesis of cancer cells and inflammatory bowel disease (IBD) involving with inflammation and immune responses. We found that NK2R expression levels of murine and human dendritic cells were augmented by type-1 IFN stimulations in a STAT-1-dependent manner. Antigen-specific T cell responses were attenuated in the presence of a NK2R antagonist in vitro. Next, we revealed that in vivo administration of a NK2R antagonist reduced tumorigenesis of CT26 cancer cells and disease state of dextran sulfate sodium (DSS)-induced colitis model. Furthermore, we confirmed that NK2R was expressed in lesion and inflammation areas of patients with hepatocellular carcinoma, cervical cancer, colorectal cancers, and IBD. Based on these findings we speculate that regulation of neuropeptide signaling may be a promising tool in the development of effective therapy for cancers and IBD.
In the present research, we investigated the mechanisms of protumor immune regulation in tumor microenvironment. As a result, we found that 〓 〓T cells were predominant IL-17-producing cells in tumor-bearing host, which promoted tumorigenesis through the angiogenesis. In addition, we demonstrated that the tumor-initiating capacity of CD133^+ cells was blocked by depleting Treg, which were induced in TGF-ss-dependent manner, suggesting that CD133^+ cancer initiating cells suppress CTL-mediated immunosurveillance. In the near future, overcoming the protumor immunity caused by cancer stem cells, which induces effective tumor-antigen specific Th1 cells, would be a promising strategy for cancer immunotherapy and prevention of recurrence.
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
Date (from‐to) : 2010 -2011
Author : KITAMURA Hidemitsu
Mechanism for cross-presentation of tumor antigen was elucidated in the induction of tumor-antigen specific killer T cells by the antigen-loaded DCs in tumor bearing mice. IL-6, a major cytokine produced under tumor-bearing state, significantly reduced antigen-presenting ability by DCs. Neuropeptide signaling through Neurokinin-2 receptor(NK2R) was closely related with the function of DCs in Type 1 immune responses. In the near future, development of effective generation of tumor-antigen specific T cells by regulation of DC function would be a promising strategy for cancer immunotherapy
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
Date (from‐to) : 2008 -2009
Author : KITAMURA Hidemitsu
Uptake of tumor-antigen by dendritic cells (DCs) and generation of tumor-antigen specific killer T cells by the cross-presentation were evaluated in vitro and in vivo. Although IL-6, a major cytokine produced under tumor-bearing state, enhanced the engulfment of tumor cells, it reduced antigen-presenting ability by DCs. On the other hand, the antigen presentation by DCs were increased in the presence of TLR ligands and IFN-γ. In the near future, development of effective generation of tumor-antigen specific T cells by DCs would be a promising strategy for cancer immunotherapy.