A5017900668- Chronic Myeloid Leukemia Treatments
- Phagocytosis and Immune Regulation
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Ocular Oncology and Treatments
- Epigenetics and DNA Methylation
- Mast cells and histamine
- Eosinophilic Disorders and Syndromes
- PI3K/AKT/mTOR signaling in cancer
- Nuclear Receptors and Signaling
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Ubiquitin and proteasome pathways
- Synthesis of Organic Compounds
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Kruppel-like factors research
- Cytokine Signaling Pathways and Interactions
- Hedgehog Signaling Pathway Studies
Jinan University
2016-2025
Central South University
2022-2024
Xiangya Hospital Central South University
2022-2024
Sun Yat-sen University
2009-2021
Ludong University
2020
Center for Excellence in Molecular Plant Sciences
2020
Shanghai Institutes for Biological Sciences
2020
Chinese Academy of Sciences
2020
Cedars-Sinai Medical Center
2013-2017
Zhongshan Ophthalmic Center, Sun Yat-sen University
2017
NF-kappaB may be a potential therapeutic target for acute myelogenous leukemia (AML) because activation is found in primitive human AML blast cells. In this report, we initially discovered that the potent antineoplastic effect of niclosamide, Food and Drug Administration-approved antihelminthic agent, was through inhibition pathway Niclosamide inhibited transcription DNA binding NF-kappaB. It blocked tumor necrosis factor-induced IkappaBalpha phosphorylation, translocation p65, expression...
Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous (CML). Identifying therapeutic targets eradicate CML LSCs may a strategy cure CML. In the present study, we discovered positive feedback loop between protein arginine methyltransferase 5 (PRMT5) in cells. Overexpression PRMT5 was observed human LSCs. Silencing with shRNA or blocking activity small-molecule inhibitor PJ-68 reduced...
The mesoderm- and epithelial-mesenchymal transition-associated transcription factor FOXC1 is specifically overexpressed in basal-like breast cancer (BLBC), but its biochemical function not understood. Here, we demonstrate that controls stem cell (CSC) properties enriched BLBC cells via activation of Smoothened (SMO)-independent Hedgehog (Hh) signaling. This non-canonical Hh mediated by Gli2. Furthermore, show the N-terminal domain (aa 1-68) binds directly to an internal region 898-1168)...
Abstract Purpose: Resistance to STI571 is an emerging problem for patients with chronic myelogenous leukemia (CML). Mutation in the kinase domain of Bcr-Abl predominant mechanism acquired resistance STI571. In present study, we investigated effect triptolide on cell survival or apoptosis CML cells bearing Bcr-Abl-T315I wild-type Bcr-Abl. Experimental Design: lines (KBM5 versus KBM5-T315I, BaF3-Bcr-Abl BaF3-Bcr-Abl-T315I) and primary from clinical were treated triptolide, analyzed terms...
Abstract Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial metastatic cascade. Among these, super-enhancers (SEs), emerging as new regulators, consist large clusters regulatory elements that drive high-level expression genes essential for oncogenic process, upon which cells develop a profound dependency. These SE-driven oncogenes play an important role regulating various facets...
Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I notorious point mutation that causes resistance to imatinib and second generation inhibitors, leading poor prognosis. CML blasts have constitutive p65 (RelA NF-kappaB) transcriptional activity, NF-kappaB may be a potential target for molecular therapies in also effective against cells with Bcr-Abl-T315I.In this report, we discovered pristimerin, quinonemethide triterpenoid isolated from...
Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made novel discovery that co-administration HDACIs (Trichostatin A (TSA) and others) exogenous cell-permeable short-chain ceramide (C6) results in striking increase cancer cell death apoptosis multiple cells. These events associated with perturbations diverse signaling pathways, including inactivation Akt/mTOR...
Uveal melanoma (UM) is a lethal intraocular malignancy with an average survival of only 2~8 months in patients hepatic metastasis. Currently, there no effective therapy for metastatic UM. Here, we reported that niclosamide, repellence tapeworm has been approved use approximately 50 years, exhibited strong antitumor activity UM cells vitro and vivo. We showed niclosamide potently inhibited cell proliferation, induced apoptosis reduced migration invasion. p-Niclosamide, water-soluble exerted...
Purpose: Liver metastasis is the major and direct cause of death in patients with uveal melanoma (UM). There no effective therapy for metastatic UM. Improved treatments hepatic UM were urgently needed. Inspired by readily detectable key components neddylation pathway cells, we aimed at exploring whether was a therapeutic target liver UM.Experimental Design: Expression proteins detected Western blotting, real-time quantitative RT-PCR (qRT-PCR), immunohistochemical staining. Cellular...
R2R3-MYB transcription factors (TFs) play important roles in plant growth and development, response to biotic abiotic stresses. However, their regulatory mechanisms wound-induced anthocyanin biosynthesis woody plants are largely unknown.In this work, we report that expression of genes (ABGs) were activated by PdMYB118, a MYB TF encoding gene from Populus deltoids, the activation PdMYB118 was significantly enhanced PdTT8, bHLH protein, through its direct interaction with PdMYB118. some ABGs...
Hyperglycemia during hyper-CVAD chemotherapy is associated with poor outcomes of acute lymphoblastic leukemia (ALL) (Cancer 2004; 100: 1179-85). The optimal clinical strategy to manage hyperglycemia unclear. To examine whether anti-diabetic pharmacotherapy can influence chemosensitivity ALL cells, we examined the impacts different agents on cell lines and patient samples. Pharmacologically achievable concentrations insulin, aspart glargine significantly increased number did so at lower than...
Purpose: Quiescent leukemia stem cells (LSC) are important resources of resistance and relapse in chronic myelogenous (CML). Thus, strategies eradicating CML LSCs required for cure. In this study, we discovered that AXL tyrosine kinase was selectively overexpressed primary CD34+ cells. However, the role its ligand Gas6 secreted by stromal regulation self-renewal capacity has not been well investigated.Experimental Design: The function evaluated flow cytometer, CFC/replating, long-term...
Acute lymphoblastic leukemia (ALL) is a heterogeneous group of malignant disorders derived from B- or T-cell lymphoid progenitor cells. ALL often refractory to relapses after treatment; thus, novel targeted therapy for urgently needed. In the present study, we initially found that level SIRT1, class III histone deacetylase, was higher in primary cells patients than peripheral blood mononuclear healthy individuals. But it not clear whether inhibition SIRT1 by its selective small molecule...
Abstract The development of BCR-ABL tyrosine kinase inhibitors (TKIs) has revolutionized disease management chronic myeloid leukemia (CML). However, the persistence stem cells (LSCs) remains a major barrier to curing CML, highlighting urgent need identify regulators supporting LSCs. In this study, we validated critical role histone methyltransferase SET and MYND domain containing 3 (SMYD3) in maintenance LSCs CML. SMYD3 was overexpressed CML enhanced survival self-renewal properties human...
Imatinib revolutionized the treatment of chronic myeloid leukemia (CML), but drug resistance and disease recurrence remain a challenge. In this study, we suggest novel strategy based on blocking protein neddylation to address BCR-ABL point mutations stem cells (LSC) that lie at root imatinib-resistant recurrences. On basis finding NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, hypothesized function certain neddylation-dependent substrates might be targeted therapeutic...
The pathogenesis of human basal-like breast cancer (BLBC) is not well understood and patients with BLBC have a poor prognosis. Expression the epidermal growth factor receptor (EGFR) nuclear factor-κB (NF-κB) well-known to be upregulated in BLBC. forkhead box C1 (FOXC1) transcription factor, an important prognostic biomarker specific for BLBC, has been shown induced by EGF critical effects cells. How FOXC1 transcriptionally activated clear. Luciferase reporter assays were performed show that...
Quiescent leukemia stem cells (LSCs) that are insensitive to BCR-ABL tyrosine kinase inhibitors confer resistance imatinib in chronic myelogenous (CML).Identifying proteins regulate survival and stemness of LSCs is urgently needed.Although histone deacetylase (HDACis) can eliminate quiescent CML, little known about the underlying mechanism HDACis kill LSCs.By fishing with a biotin-labeled probe, we identified HDACi JSL-1 bound protein γ-catenin.γ-Catenin expression was higher from CML...
Abstract The application of tyrosine kinase inhibitors (TKIs) has revolutionized the management chronic myeloid leukemia (CML). However, disease relapse and progression particularly due to persistent stem cells (LSCs) remain a big challenge in clinic. Therefore, validation therapeutic vulnerability LSCs is urgently needed. This study verifies critical role protein arginine methyltransferase 1 (PRMT1) maintenance CML LSCs. It found that PRMT1 promotes survival serially plating abilities human...