A5103040643- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- HIV/AIDS drug development and treatment
- Melanoma and MAPK Pathways
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Synthesis and biological activity
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Endoplasmic Reticulum Stress and Disease
- Cancer therapeutics and mechanisms
- Cancer, Hypoxia, and Metabolism
- Click Chemistry and Applications
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Sphingolipid Metabolism and Signaling
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Lung Cancer Treatments and Mutations
- Microtubule and mitosis dynamics
Sungkyunkwan University
2020-2025
Hanmi Pharmaceutical (South Korea)
2015-2024
Hanyang University
2008-2022
Gyeonggi Research Institute
2021
Inha University
2020
CHA University
2009
Ajou University
2009
To prevent the development of malignancies, mammalian cells activate disposal programs, such as programmed cell death, in response to deregulated oncogene expression. However, molecular basis for regulation cellular machinery activated oncogenes is unclear at present. In this study, we show that upregulation autophagy-related protein, Atg5, critically required oncogenic H-ras-induced autophagic death and Rac1/mitogen-activated kinase (MKK) 7/c-Jun N-terminal (JNK) signals Atg5....
Naturally occurring triterpenoid compounds have long been used as anti-inflammatory, antimalarial, and insecticidal agents. It has become evident that some of the natural or synthetic triterpenoids promising clinical potential both a therapeutic chemopreventive agent for cancer. However, molecular basis antitumor activity yet to be defined. In this study, we show pristimerin, triterpenoid, induces mitochondrial cell death in human cervical cancer cells reactive oxygen species (ROS)-dependent...
<p>Relative effects of TUS and gilteritinib on phosphorylation FLT3 downstream kinases in (<b>A</b>) MOLM-14 (<b>B</b>) KG-1a cells. A representative Western blot from two independent experiments is shown. <b>A</b> was assembled several separate blocks.</p>
<div>Abstract<p>Tuspetinib (TUS) is a well-tolerated, once daily, oral kinase inhibitor in clinical development for treatment of acute myeloid leukemia (AML). Nonclinical studies show that TUS targets key prosurvival kinases with IC<sub>50</sub> values the low nmol/L range, including SYK, wild-type (WT) and mutant forms FLT3, but not WT KIT, RSK2, TAK1–TAB1 kinases, indirectly suppresses expression MCL1. Oral markedly extended survival subcutaneously orthotopically...
<p>Supplementary Figure 1</p>
<p>Resistance to TUS creates a synthetic lethal hypersensitivity VEN. Growth inhibition curves documenting the effect of VEN on parental MOLM-14 and four sublines selected for growth in 75 nmol/L TUS. Data are presented as mean ± SEM from three-independent experiments; <i>P</i> < 0.001 vs. cells all 4 TUS/R lines.</p>
<p>Characterization of TUS/R MOLM-14 cell lines. <b>A,</b> Effect TUS on the growth rate parental cells and four sublines selected for in 75 nmol/L (<i>P</i> < 0.01 vs. all lines). <b>B,</b> Change IC<sub>50</sub> resistant when grown TUS-free media. Data are presented as mean ± SEM from three-independent experiments. Western blot analysis documenting levels kinases (<b>C</b>) TUS-resistant lines 3 4 (<b>D</b>)...
<p>Supplementary Figure 4</p>
<p>Supplementary Figure 6</p>
<p>Supplementary Figure 7</p>
<p>Supplementary Figure 3</p>
<p>Structure of TUS and pattern kinase inhibition. <b>A,</b> Structure TUS. <b>B,</b> Principal kinases inhibited by as determined from broad screens.</p>
<p>Effect of NRAS<sup>G12D</sup> expression in MV-4-11 clones on sensitivity to (<b>A</b>) TUS and (<b>B</b>) VEN (data are mean ± SEM from three-independent experiments). <b>C,</b> Antitumor activity TUS, belvarafenib, the combination both mice bearing subcutaneous tumors (drugs were given once daily for 15 days via oral gavage; data presented as SEM).</p>
<p>Effect of TUS alone on survival mice orthotopically inoculated with FLT3-ITD-mutant AML cell lines; (<b>A</b>) MV-4-11; (<b>B</b>) MOLM-13; and, (<b>C</b>) MOLM-14. Efficacy in combination VEN or AZA subcutaneously (<b>D</b>) MV-4-11 tumors treated either (orally, every day), VEX the combination; (<b>E</b>) MOLM-14 FLT3-ITD/F691L TUS, (3 mg/kg i.v. days 0–4), combination. Data are presented as mean ± SEM.</p>
<p>Information on antibody RRID and Other catalog numbers</p>
<p>Supplementary Figure 2</p>
<p>Supplementary Figure 5</p>
<p>Supplementary Figure 8</p>
Systemic lupus erythematosus (SLE) is associated with B cell hyperactivity, and nephritis (LN), in particular, promoted by the production of autoantibodies immune complex deposition. Bruton's tyrosine kinase (BTK) plays critical roles receptor-related Fc signaling. We aimed to investigate impact therapeutic intervention HM71224 (LY3337641), a selective BTK inhibitor, on development murine SLE-like disease features.We examined effects features MRL/lpr NZB/W F1 mice. The disease-related skin...
Abstract The Akt and mitogen-activated protein kinase (MAPK) pathways have been implicated in tumor cell survival contribute to radiation resistance. However, the molecular basis for link between MAPK response is unclear. Here, we show that c-Src-Rac1-p38 pathway signals activation radiation. Ionizing triggered Thr308 Ser473 phosphorylation of Akt. Exposure cells also induced p38 c-Jun NH2-terminal activations. Inhibition suppressed radiation-induced death, whereas inhibition effectively...
Sphingosine induces activation of multiple signaling pathways that play critical roles in controlling cell death. However, the precise molecular mechanism death induced by sphingosine remains to be clarified. In this study, we show receptor-independent caspase-8 and apoptotic via p38 mitogen-activated protein kinase (MAPK) suppression MAPK/extracellular signal-regulated (ERK) kinase/ERK pathway phosphatase 2A (PP2A) is required for MAPK activation. Treatment cells with ERK MAPK. Inhibition...