A5070903684- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Cell death mechanisms and regulation
- Cancer, Lipids, and Metabolism
- ATP Synthase and ATPases Research
- Hormonal and reproductive studies
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Adipose Tissue and Metabolism
- Crystallography and molecular interactions
- Proteoglycans and glycosaminoglycans research
- Cancer, Hypoxia, and Metabolism
- Medical Imaging Techniques and Applications
- Cell Adhesion Molecules Research
- Digital Radiography and Breast Imaging
- Sexual Differentiation and Disorders
- Prostate Cancer Treatment and Research
- Muscle metabolism and nutrition
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- AI in cancer detection
- Liver physiology and pathology
- Peptidase Inhibition and Analysis
- Phagocytosis and Immune Regulation
Japan Industrial Safety and Health Association
2022-2023
Takeda (Japan)
2012-2020
Outcomes Research Consortium
2017
Hokkaido University
2015-2016
Osaka Electro-Communication University
2008
The University of Tokyo
2001
Dysregulation of lysine (K)-specific demethylase 1A (LSD1), also known as KDM1A, has been implicated in the development various cancers, including leukemia. Here, we describe antileukemic activity and mechanism action T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis leukemia cell lines revealed that acute erythroid (AEL) megakaryoblastic cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation erythroid/megakaryocytic lineages...
Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated However, intratumor metabolic not investigated. Here, we used global metabolomics analysis tissue slice tracer studies to demonstrate that different portions human primary tumor possess characteristics drug sensitivity. Pyruvate levels were elevated pyruvate metabolism was...
Abstract Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities a subset of acute myeloid leukemia (AML) cell lines by inducing transdifferentiation. The NEDD8-activating enzyme pevonedistat (MLN4924, TAK-924) is investigational drug with antiproliferative AML,...
Nuclear receptors (NRs) are a class of transcription factors that closely involved in the progression certain types cancer. We aimed to study relation between bladder cancer and NRs, with special focus on orphan NRs whose ligands functions have not been identified. First, we examined expression levels 22 genes encoding clinical found hepatocyte nuclear factor 4γ (HNF4G; NR2A2) NR2F6 were upregulated most frequently tissues compared their paired normal tissues. Knockdown overexpression each...
Cancer cachexia is a syndrome that impairs the quality of life and overall survival patients, thus effectiveness anticancer agents. There are no effective therapies for cancer due to complexity syndrome, insufficient knowledge its pathogenesis results in difficulty establishing appropriate animal models. Previously, promising have been obtained clinical trials using novel agents including ghrelin receptor agonist anamorelin, selective androgen modulator (SARM) enobosarm treat patients with...
Sarcopenia and cachexia present characteristic features of a decrease in skeletal muscle mass strength, anorexia, lack motivation. Treatments for these diseases have not yet been established, although selective androgen receptor modulators (SARMs) are considered as therapeutic targets. We previously reported that novel SARM compound, SARM-2f, exhibits anabolic effect on muscles, with less stimulatory prostate weight compared testosterone, rat Hershberger assays cancer models. In this study,...
Cabozantinib is known as an inhibitor of receptor tyrosine kinases mainly targeting AXL kinase (AXL), MET proto-oncogene-encoded (MET), and vascular endothelial growth factor 2. Growth arrest-specific 6 (GAS6) hepatocyte (HGF), the natural ligands MET, respectively, are associated with induction cancer cell proliferation or metastasis. Currently, it still unclear how cabozantinib regulates migration invasion by inhibiting MET. This study was conducted to investigate mechanism underlying...
Abstract SARM‐2f a selective androgen receptor (AR) modulator, increases skeletal muscle mass and locomotor activity in rats. This study aimed to clarify its pharmacological effects monkeys. In reporter assays, the EC 50 values of for rat, monkey, human AR were 2.5, 3, 3.6 nmol/L, respectively; those testosterone 12, 3.2, 11 respectively. A single oral administration (10 mg/kg SARM‐2f) produced maximal plasma concentration 3011 ng/mL, with an area under 24 hours concentration‐time curve 8152...
Inhibitor of apoptosis proteins (IAP), which are key regulators apoptosis, inhibited by second mitochondria-derived activator caspase (SMAC). Small-molecule IAP antagonists have recently been reported as novel therapeutic treatments for cancer. In this study, we showed that the octahydro-pyrrolo[1,2-a]pyrazine derivative, T-3256336, is a and orally available small-molecule antagonist. T-3256336 selectively binds to antagonizes protein interactions involving cellular IAP-1 (cIAP-1), cIAP-2,...
Mouse colon carcinoma cell line 38 was used to investigate migratory factor for fibroblasts because marked fibrotic tissue associated with these cells growing at transplanted sites and liver metastases in vivo. Migration-inducing activity detected the serum-free culture supernatants of cells, as shown by Boyden chamber assays using NIH3T3 target cells. The active substance partially purified a combination anion-exchange, hydrophobic, gel-permeation chromatography. An approximate relative...
Mouse colon carcinoma cell line 38 was used to investigate migratory factor for fibroblasts because marked fibrotic tissue associated with these cells growing at transplanted sites and liver metastases in vivo. Migration-inducing activity detected the serum-free culture supernatants of cells, as shown by Boyden chamber assays using NIH3T3 target cells. The active substance partially purified a combination anion-exchange, hydrophobic, gel-permeation chromatography. An approximate relative...
目的．肺癌において静脈血栓塞栓症（VTE）の合併はしばしば認められ，抗凝固療法は肺癌治療とともに重要である．ワルファリン内服はVTEに対する抗凝固療法の選択肢の一つだが，内服中のVTEの再発・増悪が問題となる場合も多い．本邦でも2012年1月よりヘパリンカルシウム在宅自己注射が保険適応となり，抗凝固治療の選択肢が広がってきている．方法．2006年10月から2014年4月に，北海道大学病院内科Iで肺癌にVTEを合併した39例中，ヘパリンなどの初期治療導入後，ワルファリン単独内服治療に移行できた29例を後ろ向きに検討した．結果．29例中，VTEの再発を11例認めた．そのうち10例はヘパリンカルシウムまたはXa阻害薬であるフォンダパリヌクスナトリウムの皮下注射に変更され，全例でVTEはコントロールされた．11例中9例は原病の悪化で死亡したが，残り2例はヘパリンカルシウム在宅自己注射導入後，VTEの増悪を認めず外来治療継続中である．結論．肺癌に合併したワルファリン不応性VTE症例において，ヘパリンカルシウム在宅自己注射導入は有用な治療戦略である可能性が示唆された．
<p>PDF file - 433KB, Histopathological findings of organs on xenograft model</p>
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