Search Results 1-20 of 80

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  • Drug resistance in cancer therapy and the possible role of epigenetics

    Asano Takeshi

    … With conventional anti-cancer drugs, including alkylating drugs, anti-metabolite drugs, topoisomerase inhibitors, and microtubule inhibitors, which have been available for half a century, the drug resistance often occurs due to decreased expression of target enzymes, with increased expression of drug export pumps. …

    Journal of Nippon Medical School, 2020


  • Synthesis of artificial substrate based on inhibitor for detecting LSD1 activity

    Ohta Yuhei , Kawaguchi Mitsuyasu , Ieda Naoya , Nakagawa Hidehiko

    … <p>Lysine methylation is one of the most important modification, which is regulated by histone lysine methyltransferases and histone lysine demethylases. … Therefore, LSD1 inhibitors would be not only potential therapeutic agents for cancers but also chemical tools to research biological significance of LSD1 in physiological and pathological events. … The development of simple method in detecting LSD1 activity has been indispensable to identify useful inhibitors. …

    Journal of Clinical Biochemistry and Nutrition, 2020


  • Drug Discovery Researches on Modulators of Lysine-Modifying Enzymes Based on Strategic Chemistry Approaches

    Itoh Yukihiro

    … <p>Enzymatic and post-translational modifications (PTMs) such as ubiquitination, acetylation, and methylation occur at lysine residues. … To modulate the PTMs, we have focused on lysine-modifying enzymes and have pursued drug discovery researches on ubiquitination inducers, lysine deacetylase (KDAC) inhibitors, and lysine demethylase (KDM) inhibitors. …

    Chemical and Pharmaceutical Bulletin 68(1), 34-45, 2020


  • Improved early development of porcine cloned embryos by treatment with quisinostat, a potent histone deacetylase inhibitor

    TAWEECHAIPAISANKUL Anukul , JIN Jun-Xue , LEE Sanghoon , KIM Geon A , SUH Yoon Ho , AHN Min Seok , PARK Se Jun , LEE Byeong You , LEE Byeong Chun

    … Recently, the modification of the epigenetic status of somatic cell nuclear transfer (SCNT) embryos by treatment with histone deacetylase inhibitors (HDACis) has made it possible to alter epigenetic traits and improve the developmental competence of these embryos. …

    Journal of Reproduction and Development 65(2), 103-112, 2019


  • Discovery of Novel PRMT5 Inhibitors by Virtual Screening and Biological Evaluations

    Tao Hongrui , Yan Xue , Zhu Kongkai , Zhang Hua

    … Among all the reported PRMT5 inhibitors, two small molecules (GSK-3326595 and JNJ-64619178) are currently being assessed in clinical trial. … Alpha linked immunosorbent assay (LISA) methylation assay was performed to test their inhibitory activity against PRMT5. … The compounds discovered in this study will inspire medicinal chemists to further explore this series of PRMT5 inhibitors.</p> …

    Chemical and Pharmaceutical Bulletin 67(4), 382-388, 2019

    J-STAGE  Ichushi Web 

  • Clinicopathological features of pilocytic astrocytoma-unusual clinical features and new findings from molecular analysis

    Yoshimoto Koji

    … More recently, it has been recommended that pilocytic astrocytoma with anaplasia should be designated as anaplastic astrocytoma with piloid features according to the results of methylation-based classifications. … Clinical trials involving molecular targeted therapies using MAPK pathway inhibitors are ongoing and several promising results have been reported. …

    Progress in Neuro-Oncology 25(3), 22-26, 2019

    J-STAGE  Ichushi Web 

  • Fluorescence-based Polymerase Amplification for the Sensitive Detection of DNA Methyltransferase Activity

    ZHANG Xiao , ZHONG Xiao-Li , JIANG Wen-Wen , ZENG Si-Hao , PI Ting , ZHENG Xiang-Juan , LI Zhi-Mei

    … They come from methylation and <b>a</b> … digestion reaction of DNA S1-S1, including a 5′-GATC-3′ sequence recognized by Dam MTase and methylation sensitive restriction endonuclease Dpn I. … In human serum samples, the method has been successfully applied, and it has also been used to screen the inhibitors, which means that the developed method can be a powerful and potential tool for drug development and clinical diagnosis in the future.</p> …

    Analytical Sciences 34(8), 959-964, 2018

    J-STAGE  Ichushi Web 

  • Epigenetic aberrations in adult T-cell leukemia/lymphoma and development of a novel EZH1/2 inhibitor  [in Japanese]

    YAMAGISHI Makoto

    <p>成人T細胞白血病・リンパ腫(ATL)細胞の遺伝子発現異常の背景には,ゲノムワイドなエピジェネティック異常がある。特にEZH1およびEZH2に依存したH3K27me3の蓄積は,HTLV-1感染後の初期から悪性化の後期過程に至るまでの遺伝子制御に対して継続的に影響し,ATL細胞及びHTLV-1感染細胞の特徴を決定する。数千に及ぶ標的遺伝子にはがん抑制遺伝子のほかに,転写制御因子,mi …

    Rinsho Ketsueki 59(4), 432-438, 2018

    J-STAGE  Ichushi Web 

  • Development of therapeutic strategies based on chemical biological studies of histone methyltransferase  [in Japanese]

    Hirano Tomoya , Mori Shuichi , Kagechika Hiroyuki

    <p>ヒストンメチル化酵素(Histone methyltransferase:HMT)は、ヒストンタンパク質の特定のリシン残基をメチル化し、エピジェネティックな転写制御を担っている。近年、HMTとさまざまな疾患との関連が報告され、各々のHMTに対する阻害剤の開発が急速に進んでいる。なかでもSet7/9はヒストンタンパク質に加えて、p53、エストロゲン受容体αなどもメチル化し、その機能 …

    MEDCHEM NEWS 27(4), 208-212, 2017


  • Structural characterization and biological activities of a novel polysaccharide from <i>Phyllanthus emblica </i>

    Zeng Zihan , Lv Wenjie , Jing Yongshuai , Chen Zhiyan , Song Liyan , Liu Ting , Yu Rongmin

    … The structural features of PEPW80-1 were investigated by a combination of acid hydrolysis, periodate oxidation-Smith degradation, methylation analysis, gas chromatography-mass spectrometry, scanning electron microscope, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. … Those proposed that PEPW80-1 might be developed as a potential value-added product with the activities of immunomodulator and free-radical inhibitors.</p> …

    Drug Discoveries & Therapeutics 11(2), 54-63, 2017

    J-STAGE  Ichushi Web 

  • Cloning and expression of a novel catechol-<i>O</i>-methyltransferase in common marmosets

    UEHARA Shotaro , UNO Yasuhiro , INOUE Takashi , SASAKI Erika , YAMAZAKI Hiroshi

    … <p>Catechol-<i>O</i>-methyltransferase (COMT) catalyzes the <i>O</i>-methylation of endogenous catechol amines and estrogens and exogenous catechol-type of drugs. … Despite COMT inhibitors could potentiate the pharmacological action of levodopa on Parkinson's disease in animal models, marmoset COMT cDNA has not yet been identified and characterized. …

    Journal of Veterinary Medical Science 79(2), 267-272, 2017

    J-STAGE  Ichushi Web 

  • Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

    Mohseni Jafar , Al-Najjar Belal O , Wahab Habibah A , ZAMH Zabidi-Hussin , Sasongko Teguh Haryo

    Journal of human genetics 61(9), 823-830, 2016-09

  • Molecular Technology for Controlling Epigenetics: Regulation of Histone Acetylation and Methylation by Small Molecules  [in Japanese]

    Itoh Yukihiro , Suzuki Takayoshi

    … Histone modifications such as acetylation and methylation control gene transcription independently on DNA base sequence. … To establish this molecular technology, we have studied epigenetic inhibitors focusing on histone modification enzymes, especially on histone deacetylases (HDACs) and histone lysine demethylases (KDMs). … These inhibitors have been discovered based on organic chemistry methodology, i.e. C-H activation, click chemistry, targeted drug delivery, and structure-based drug design. …

    Journal of Synthetic Organic Chemistry, Japan 74(5), 441-452, 2016


  • Epigenetic regulation of cell adhesion-mediated drug resistance acquisition in multiple myeloma  [in Japanese]

    FURUKAWA Yusuke , KIKUCHI Jiro

    多発性骨髄腫においては骨髄間質細胞との接着によって抗がん剤耐性が誘導されるが,そのメカニズムについては不明の点が多い。本研究においては接着耐性獲得のエピジェネティク制御機構の解明を試みた。間質細胞との接着によって抗がん剤耐性が獲得される際にhistone H3-lysine 27 (H3-K27)のトリメチル化が特異的に抑制されることがわかった。そこでH3-K27メチル化酵素EZH2をsiRNAま …

    Rinsho Ketsueki 57(5), 546-555, 2016

    J-STAGE  Ichushi Web 

  • Strong Inhibition of Secretory Sphingomyelinase by Catechins, Particularly by (−)-Epicatechin 3-<i>O</i>-Gallate and (−)-3′-<i>O</i>-Methylepigallocatechin 3-<i>O</i>-Gallate

    KOBAYASHI Keiko , ISHIZAKI Yuki , KOJO Shosuke , KIKUZAKI Hiroe

    … These results suggest that sSMase inhibitors can prevent the progress of these diseases. … This effect was attenuated by methylation at the 3″- or 4″-position. …

    Journal of Nutritional Science and Vitaminology 62(2), 123-129, 2016

    J-STAGE  Ichushi Web 

  • Aberrant DNA methylation is associated with a poor outcome in Juvenile myelomonocytic leukemia

    Sakaguchi Hirotoshi , Muramatsu Hideki , Okuno Yusuke , Makishima Hideki , Xu Yinyan , Furukawa-Hibi Yoko , Wang Xinan , Narita Atsushi , Yoshida Kenichi , Shiraishi Yuichi , Doisaki Sayoko , Yoshida Nao , Hama Asahito , Takahashi Yoshiyuki , Yamada Kiyofumi , Miyano Satoru , Ogawa Seishi , Maciejewski Jaroslaw P. , Kojima Seiji

    … Epigenetic regulation of transcription, particularly by CpG methylation, plays an important role in tumor progression, mainly by repressing tumor-suppressor genes. … To clarify the clinical importance of aberrant DNA methylation, we studied the hypermethylation status of 16 target genes in the genomes of 92 patients with JMML by bisulfite conversion and the pryosequencing technique. …

    PLOS ONE 10(12), 2015-12-31



    MATSUMURA Toshiharu

    … After his remarkable contribution in nineteen sixties and seventies to modern molecular biology through his presentation of a genetic recombination model, i.e., Holliday model, and his proposal of epigenetic control mechanisms based on DNA methylation, he poured in nineteen eighties his scientific interests in the mechanisms of aging, particularly in solving the problem of in-vitro limited proliferative lifespan of cultured human diploid cells (HDCs). …


    J-STAGE  Ichushi Web 

  • Epigenetic therapy for hematologic malignancies  [in Japanese]


    造血器腫瘍のゲノム異常の解析が行われ,エピゲノム変化を司る酵素異常の発見が相次いでいる。DNAのメチル化とヒストンの修飾に関連すると考えられる酵素の遺伝子異常は,白血病・骨髄異形成症候群,悪性リンパ腫,多発性骨髄腫で発見され,これらの造血器腫瘍の少なくとも一部では遺伝子の発現調節が異常となった結果,分化の異常として腫瘍化が生じていると考えられる。DNAメチル化とヒストン修飾を標的とする酵素阻害剤の …

    Rinsho Ketsueki 56(10), 2015-2023, 2015

    J-STAGE  Ichushi Web 

  • Standardized Molecular and Genetic Diagnosis of Medulloblastoma  [in Japanese]

    Kanemura Yonehiro , Ichimura Koichi , Shofuda Tomoko , Yamasaki Mami , Shibui Soichiro , Arai Hajime , Nishikawa Ryo

     近年, 髄芽腫の分子遺伝学的診断および国際コンセンサス4分子亜群分類 (WNT, SHH, Group 3, Group 4) は, 腫瘍特性解析, 腫瘍分類, 臨床的リスク評価, 新規治療法開発に大きなブレークスルーを引き起こしている. 国内では, 日本小児分子脳腫瘍グループ (JPMNG) が組織され, 全国から試料を収集し, 国際的コンセンサスに基づく小児脳腫瘍の遺伝子診断実施体 …

    Japanese Journal of Neurosurgery 24(7), 436-444, 2015

    J-STAGE  Ichushi Web 

  • Expression of myeloperoxidase in acute myeloid leukemia blasts mirrors the distinct DNA methylation pattern involving the downregulation of DNA methyltransferase DNMT3B

    Itonaga Hidehiro , Imanishi Daisuke , Wong Yan-Fung , Sato Shinya , Ando Koji , Sawayama Yasushi , Sasaki Daisuke , Tsuruda Kazuto , Hasegawa Hiroo , Imaizumi Yoshitaka , Taguchi Jun , Tsushima Hideki , Yoshida Shinichiro , Fukushima Takuya , Hata Tomoko , Moriuchi Yukiyoshi , Yanagihara Katsunori , Miyazaki Yasushi

    … DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. … Therefore, MPO gene transcription was directly and indirectly regulated by DNA methylation. …

    Leukemia 28(7), 1459-1466, 2014-07


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