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TAKAHASHI Satoru

    Graduate School of Medical Sciences Department of Experimental Pathology and Tumor Biology　Professor
Contact： sattakmed.nagoya-cu.ac.jp
Last Updated :2024/03/19

Researcher Information

URL

J-Global ID

Research Interests

  • 実験病理   化学予防   前立腺癌   

Research Areas

  • Life sciences / Molecular biology
  • Life sciences / Human pathology
  • Life sciences / Tumor biology
  • Life sciences / Experimental pathology

Education

  •        - 1991  Nagoya City University  Graduate School of Medical Sciences
  •        - 1987  Nagoya City University  Medical School

Association Memberships

  • アメリカ癌学会   日本がん予防学会   日本臨床細胞学会   日本毒性病理学会   日本病理学会   日本癌学会   

Published Papers

MISC

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 内木 綾; 惠谷 俊紀; 内木 拓; 高橋 智
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2019/04 -2023/03 
    Author : 高橋 智; 内木 綾; 加藤 寛之
     
    正常免疫を有するラットにおいても生着可能なラット前立腺細胞PLS10からmRNAを抽出し、作成したcDNA群をエントリーベクターに組み込みcDNAライブラリーを作成した。さらにcDNAライブラリーをレンチウイルスベクターに組み替え、cDNA発現ライブラリーを作成した。この発現ライブラリーをレンチウイルスにパッケージングし、PLS30に感染させた。セレクションマーカーであるブラストサイジン存在下で細胞を培養したところ細胞増殖がみられなかった。 PLS10、PLS20、PLS30のマイクロアレイ解析からPLS10のみ高発現がみられた遺伝子を9種類（Cd81、Ccl2、Cx3cl1、Ifi44、Pycard、Nradd、Tmem9、Ubxd8、Tmem252）見いだし、qRT-PCR法を用いて検討したところ、Cd81、Ccl2、Cx3cl1、Nradd、Tmem252の5遺伝子はmRNA量がPLS10のみ増加していることを確認した。この5遺伝子の中からCd81についてさらに検討した。PLS10、PLS30のCd81タンパク発現量を比較し、PLS10のみで高発現していることを確認した。これらを踏まえ、Cd81発現ベクターを作成し、PLS30に遺伝子導入した。PCR法によりFLAG-Cd81融合タンパク質を作成し、レンチウイルスベクターに組み込み、PLS30に導入してCd81発現安定株を樹立した。Cd81を導入したPLS30は優位に細胞増殖速度が増加していた。Cd81-PLS30および対照であるlacZ-PLS30をそれぞれ2×106個をF344ラット前立腺腹葉に移植した。20週以上経過しても前立腺内に腫瘍形成は見られず、Cd81は細胞増殖には寄与しているものの免疫回避機構には関与していないことが明らかとなった。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2019/04 -2022/03 
    Author : Naiki-Ito Aya
     
    Transgenic rats with dominant negative mutant of connexin 32, a hepatocyte gap junction protein, and dysfunction of gap-junctional intercellular communication, were treated with a high fat diet and dimethylnitrosamine to establish a model for induction of NASH, fibrosis, as well as insulin resistance. TNFα, Tgfβ1, NF-κB and JNK signaling was involved in the activation of hepatic stellate cells and NASH progression. Intake of chemicals inhibiting those signaling was found to have an inhibitory effect on NASH and fibrosis.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2020/03 
    Author : Naiki Taku
     
    Prostate cancer growth is androgen sensitive, therefore, the first-line therapy of prostate cancer is androgen deprivation therapy like castration. However, the therapeutic efficacy is limited and lead to castration resistant prostate cancer (CRPC). Previous study, we established the new CRPC model, and by analyzing them, we newly explored that oxidative stress induced mechanism was highly activated in CRPC. Therefore, in this study, we investigated the therapeutic efficacy of luteolin, which is one of natural flavonoids, in CRPC. As a result, luteolin suppressed CRPC growth both in vitro and in vivo, and the main mechanism of growth suppression was apoptosis regulated by ROS caused by the changes of molecular network. In conclusion, luteolin is promising chemotherapeutic agent for CRPC.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2019/03 
    Author : Takahashi Satoru
     
    We found that the angiotensin II receptor blocker (ARB), antihypertensive drug, exerted a suppression effects on the growth and progression of rat prostate cancer, and the clinical intervention study revealed that PSA progression was significantly prolonged in prostate cancer patients given an ARB compared with placebo control. Therefore, we examined the effect of ARB on advanced prostate cancer such as castration resistant cancer. We demonstrated that candesartan significantly attenuated both the number and incidence rate per acinus invasive carcinoma development in lateral lobe of rats. Additionally, candesartan administration tended to decrease in size of metastatic lesion in the bone of prostate cancer although there was no significant difference in the incidence of bone metastasis.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2015/04 -2018/03 
    Author : Suzuki Shugo
     
    High mobility group box 2 (HMGB2), which belongs the HMG protein families, was up-regulated in prostate adenocarcinoma compared to normal epithelium. In this study, we investigated functions of HMGB2 for progression, androgen regulation and cell proliferation of hormone naive and castration resistant prostate cancer. In prostatectomy samples, HMGB2 expression was correlated with Gleason grading and tumor stage, but was not related with overall survival. Compared to hormone naive prostate cancer, HMGB2 expression in hormone-treated prostate cancer tended to be decreased, and was reverse correlated with therapeutic effect. In prostate cancer cell lines, HMGB2 regulated androgen receptor-mediated pathway in androgen dependent cell line, LNCaP. HMGB2 also regulated cell proliferation in both androgen dependent and independent cancer cell lines.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : NAIKI-ITO Aya
     
    NASH has the potential to lead to the development of cirrhosis and hepatocellular carcinoma (HCC). To clarify the role of hepatocyte gap junction protein, Cx32 and luteolin on the progression of NASH and hepatocarcinogenesis, Cx32 dominant negative transgenic (Tg) were used. Steatohepatitis, fibrosis, inflammatory cytokine expression, reactive oxygen species and number of preneoplastic foci were greater in Tg as compared with Wt rats, and significantly suppressed by luteolin in both genotypes. Microarray analysis identified Bex1 as an up-regulated gene in Tg rat liver. in situ hybridization revealed that increased Bex1 mRNA was localized in preneoplastic foci in Tg rats. Moreover, Bex1 increased cell proliferation through activation of NF-κB signaling in rat hepatocyte and HCC cell lines. These results show that Cx32 and luteolin have suppressive roles in inflammation, fibrosis and hepatocarcinogenesis during NASH progression, suggesting a potential therapeutic application for NASH.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2016/03 
    Author : Niwa Satomi; NAIKI Taku; SASAKI Shoichi; TAKAHASHI Satoru; OHYA Susumu
     
    Ca2+-activated K+ channels (KCa) are key molecules in cancer progression and are considered to be potential targets for cancer therapy. KCa2.2 was predominantly expressed in human prostate cancer (PCa) tissues and human PCa cell lines, LNCaP and VCaP, with higher expression levels of androgen receptor (AR). A Ca2+-activated K+ channel blocker, UCL1684 suppressed the cell proliferation through the inhibition of the store-operated Ca2+ entry (SOCE) in LNCaP cells. The anti-androgenic agents and the siRNA-mediated inhibition of AR expression downregulated the expression levels of KCa2.2 in LNCaP cells. Additionally, the expression levels of KCa2.2 was upregulated with the upregulation of AR transcripts under long-term, androgen-deficient condition, whereas it was downregulated under short-term condition. These results suggest that KCa2.2 might induce a possible candidate for novel treatment target of Castration-Resistant Prostate Cancer, CRPC.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/04 -2015/03 
    Author : TAKAHASHI Satoru; SUZUKI Shugo; SATO Shinya
     
    We have established an androgen-independent (AI) subline from androgen-dependent LNCaP cells, and examined genes differentially expressed between LNCaP and LNCaP-AI by microarray analysis. We thereby found midline 1 (MID1) to be an upregulated gene in the latter. Knockdown of MID1 expression in LNCaP-AI cells resulted in significant suppression of invasion, and enforced expression of MID1 in LNCaP promoted an invasive capacity in the Matrigel chemoinvasion assay. MID1 also promoted AR transcriptional activity in gene dosage-dependent manner by luciferase reporter assay. CRYAB, one of upregulated gene in LNCaP-AI cells, promoted invasive ability and knockdown of it led to suppress invasion of prostate cancer cells in the same as MID1. However, interaction between MID1 and CRYAB did not confirmed by immunocytochemistry. These results suggest that MID1 is an AR coactivator and deeply involved in prostate cancer progression via CRYAB with an indirect manner.
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 1994 -1994 
    Author : 白井 智之; 高橋 智; 今井田 克己
     
    F344雄ラットに3,2′-dimethyl-4-aminobiphenyl(DMAB)を発がん物質として隔週に1回10回皮下投与し,そのあと種々の処置を40週間行ない60週間で終了する実験モデルを用いて下記の成果を得た。 1.DMABを投与後,20週から1-5群にそれぞれTP,TP+ethinyl estradiol(EE),DHT,DHT+EE,EEを60週まで投与し,アンドロゲンとエストロゲンの相互作用を検討した。ホルモンは何れもシリコンチューブに入れ,皮下に埋植した。TPとDHTは2cmの長さの,またEEには1cmの長さのチューブを用いた。その結果,EE投与群では下垂体腫瘍のため全例早期に死亡した。しかしTP+EEとDHT+EEでは下垂体腫瘍の発生は殆どなく長期間生存した。背側葉と前葉の浸潤がんはTPあるいはEP+EEの群にのみ見られ,その他の群には全く無かった。その発生頻度はそれぞれ18と29%,それに71と86%であった。非浸潤型である腹葉がんの発生頻度は1-4群で6,0,17,11%で,対照群の6群では33%であった。 2.DMAB投与後TPおよびEEを単独または同時に40週間投与した。TPの投与濃度を一定にし,EEの濃度を4段階に設定し,エストロゲンの濃度依存性があるかどうかを検討した。そのためTPは2cmのシリコンチューブに,EEは1cm,0.5cmのシリコンチューブで投与,あるいは飼料中に1.5ppm,0.75ppmの濃度で混じて投与した。また EEの代わりに17β-estradiol(E2)を2段階の濃度すなわち0.5cmのチューブあるいは2ppmで飲料水とともに投与する群を設けたその結果,DMAB単独群では腹葉のみにがんがみられTPの追投与により側葉,背葉,前葉および精嚢に浸潤がんが発生し,腹葉がんの発生が抑制された。低用量のEEとTPの同時投与群ではTP単独群と同様なスペクトラムのがんが発生したが,EEの濃度が上昇するに従い,側葉および背葉のがんの発生率が上昇し逆に精嚢のがんは消失した。E2もEEと類似した結果を呈した。

Social Contribution

  • 独立行政法人医薬品医療機器総合機構(PMDA)・GLP評価委員会委員
    Date (from-to) : 2014/10-Today
    Role : Investigator
  • 内閣府食品安全委員会化学物質・汚染物質専門調査会 委員
    Date (from-to) : 2013/10-Today
    Role : Investigator
  • 内閣府食品安全委員会添加物専門調査会 委員
    Date (from-to) : 2012/10-Today
    Role : Investigator
    Sponser, Organizer, Publisher  : 行政
    赤坂パークビル（東京・赤坂） 内閣府食品安全委員会添加物専門調査会の委員を務めた。
  • 一般社団法人日本医療安全調査機構・愛知地域・第17事例地域評価委員会 委員
    Date (from-to) : 2013/01-2013/03
    Sponser, Organizer, Publisher  : その他
    愛知県医師会館 一般社団法人日本医療安全調査機構・愛知地域・第17事例地域評価委員会の委員を務めた。
  • 出張講義の講師
    Date (from-to) : 2012/11/01-2012/11/01
    Sponser, Organizer, Publisher  : その他
    静岡県立浜松北高等学校 静岡県立浜松北高等学校における出張講義の講師を務めた。
  • 健康科学講座 オープンカレッジ 講師
    Date (from-to) : 2012/07/20-2012/07/20
    Sponser, Organizer, Publisher  : 大学
    名古屋市立大学桜山キャンパス 名古屋市立大学主催のオープンカレッジ「生活と毒性学の関わり－毒を知って安心・安全な生活」の講師を務めた。
  • 日本がん予防学会主催 市民公開講座 講師
    Date (from-to) : 2012/06/23-2012/06/23
    Sponser, Organizer, Publisher  : その他
    岐阜市文化産業交流センター（じゅうろくプラザ、岐阜） 日本がん予防学会主催の市民公開講座「がん予防の最前線」の講師を務めた。

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