A5027133464- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Phagocytosis and Immune Regulation
- Liver physiology and pathology
- Melanoma and MAPK Pathways
- Lung Cancer Treatments and Mutations
- Computational Drug Discovery Methods
- Mathematical Biology Tumor Growth
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Advanced Breast Cancer Therapies
- Fibroblast Growth Factor Research
- Synthesis and biological activity
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Environmental Chemistry and Analysis
- Enzyme function and inhibition
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
Institute of Quality Standards and Testing Technology for Agro Products
2025
Chinese Academy of Agricultural Sciences
2025
Novosibirsk Institute of Organic Chemistry
2023-2024
Mengchao Hepatobiliary Hospital
2019-2023
Fujian Medical University
2019-2023
Fuzhou University
2019-2022
Exelixis (United States)
2007-2022
Wuhan University
2016
Nanjing Agricultural University
2013
Pathways Behavioral Services
2012
The signaling pathway of the receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) is important for cell growth, survival, motility functionally linked to VEGF, which widely recognized as a key effector in angiogenesis cancer progression. Dysregulation MET/VEGF axis found number human malignancies has been associated with tumorigenesis. Cabozantinib (XL184) small-molecule inhibitor potent activity toward VEGF 2 (VEGFR2), well other kinases that have also implicated tumor...
The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a wide variety of human malignancies. Vascular endothelial (VEGF) receptors expressed on the surface vascular cells cooperate with to induce tumor invasion vascularization. EXEL-2880 (XL880, GSK1363089) is small-molecule inhibitor that targets members HGF VEGF families, additional inhibitory activity toward KIT, Flt-3, platelet-derived beta, Tie-2. Binding 2 (KDR)...
The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and constitutively activated or highly upregulated many tumor types. Mutations associated with upstream pathway components RAS Raf occur frequently contribute the oncogenic phenotype through activation of MEK then ERK. Inhibitors have been shown effectively block ERK/MAPK signaling range cell lines further demonstrated early evidence efficacy clinic for treatment cancer. Guided by structural insight, strategy...
A limited number of approved therapeutic options are available to metastatic medullary thyroid cancer (MTC) patients, and the response conventional chemotherapy and/or radiotherapy strategies is inadequate. Sporadic inherited mutations in tyrosine kinase RET result oncogenic activation that associated with pathogenesis MTC. Cabozantinib a potent inhibitor MET, RET, vascular endothelial factor receptor 2 (VEGFR2), as well other kinases have been implicated tumor development progression. The...
Abstract Semiconducting conjugated polymer nanoparticles (SPNs) represent an emerging class of phototheranostic materials with great promise for cancer treatment. In this report, low-bandgap electron donor–acceptor (D–A)-conjugated SPNs surface cloaked by red blood cell membrane (RBCM) are developed highly effective photoacoustic imaging and photothermal therapy. The resulting RBCM-coated SPN (SPN@RBCM) displays remarkable near-infrared light absorption good photostability, as well high...
GDC-0973 is a potent and selective mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) (MEK) inhibitor. Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to relate plasma tumor concentrations, pharmacodynamics antitumor efficacy establish pharmacokinetic endpoints predict active doses in the clinic.A PK-PD model characterize disposition vivo potency WM-266-4 xenograft mice. Simulations were conducted using along with human pharmacokinetics identify target...
Activation of the PI3K (phosphoinositide 3-kinase) pathway is a frequent occurrence in human tumors and thought to promote growth, survival, resistance diverse therapies. Here, we report pharmacologic characterization pyridopyrimidinone derivative XL765 (SAR245409), potent highly selective pan inhibitor class I PI3Ks (α, β, γ, δ) with activity against mTOR. Broad kinase selectivity profiling >130 protein kinases revealed that for mTOR over other kinases. In cellular assays, inhibits...
Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, prevent tumor recurrence. However, this strategy still confronts patients with many limitations, such as complex components, sophisticated construction, inadequate therapeutic efficacy. In work, small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement any other ingredients or surfactants are developed....
Growing evidence has proved that RNA editing enzyme ADAR1, responsible for detecting endogenous species, was significantly associated with poor response or resistance to immune checkpoint blockade (ICB) therapy. Here, a genetically engineered nanovesicle (siAdar1-LNP@mPD1) developed as an interference nano-tool overcome tumor ICB therapies. Small interfering against ADAR1 (siAdar1) packaged into lipid nanoparticle (LNP), which further coated plasma membrane extracted from the cells...
Agents inhibiting the epidermal growth factor receptor (EGFR) have shown clinical benefit in a subset of non-small cell lung cancer patients expressing amplified or mutationally activated EGFR. However, responsive can relapse as result selection for EGFR gene mutations that confer resistance to ATP competitive inhibitors, such erlotinib and gefitinib. We describe here activity EXEL-7647 (XL647), novel spectrum-selective kinase inhibitor with potent against EGF vascular endothelial tyrosine...
Abstract Dysregulation of PI3K/PTEN pathway components, resulting in hyperactivated PI3K signaling, is frequently observed various cancers and correlates with tumor growth survival. Resistance to a variety anticancer therapies, including receptor tyrosine kinase (RTK) inhibitors chemotherapeutic agents, has been attributed the absence or attenuation downregulating signals along pathway. Thus, have therapeutic potential as single agents combination other therapies for cancer indications....
Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, immunosuppressive microenvironment is the main bottleneck responsible for patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert into hot through overcoming hypoxia, inducing immunogenic cell death, inhibition. The BFVs present PD1 necrosis factor-related apoptosis-inducing ligand (TRAIL) on surface, whereas load...
The environmental fate of phenylurea herbicides has received considerable attention in recent decades. microbial metabolism N,N-dimethyl-substituted can generally be initiated by mono-N-demethylation. In this study, the molecular basis for process was revealed. pdmAB genes Sphingobium sp. strain YBL2 were shown to responsible initial mono-N-demethylation commonly used herbicides. PdmAB is oxygenase component a bacterial Rieske non-heme iron (RO) system. pdmAB, encoding α subunit PdmA and β...
The activation of T cells, mediated by the T-cell receptor (TCR), activates a battery specific membrane-associated, cytosolic and nuclear proteins. Identifying signaling proteins downstream TCR will help us to understand regulation immune responses contribute developing therapeutic agents that target regulation. In an effort identify novel molecules for we undertook large-scale dominant effector genetic screen using retroviral technology. We cloned characterized 33 distinct genes from over...
The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment disease. A large body evidence has PI3Kγ modulation autoimmune and inflammatory processes it intriguing target drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated further optimization studies. in vitro activity first HTS hit, designated as sulfonylpiperazine scaffold, was...
The development of nanotheranostic agents integrating diagnosis and therapy has gained tremendous attention in the past few decades, but many them are inherently hydrophobic need complicated phase-transfer tedious surface modifications. This work proposed a facile method transferring Fe3O4@Cu2-xS nanoparticles from oil to water by using red blood cell membrane create theranostic nanobeads for T2-weighted MRI second near-infrared photothermal ablation. obtained nanoplatform, namely SCS@RBCM,...
In an effort to identify novel therapeutic targets for autoimmunity and transplant rejection, we developed performed a large-scale retroviral-based functional screen select proteins that inhibit antigen receptor-mediated activation of lymphocytes. addition known regulators receptor signaling, identified adaptor protein, SLAP-2 which shares 36% sequence similarity with the Src-like SLAP. Similar SLAP, is predominantly expressed in hematopoietic cells. Overexpression B T cell lines...
The multi-receptor tyrosine kinase inhibitor XL092 has been developed to inhibit the activity of oncogenic targets, including MET, VEGFR2, and TAM family kinases TYRO3, AXL MER. Presented here is a preclinical evaluation XL092. causes significant decrease in tumor MET phosphorylation (P < 0.01) murine Hs 746T xenograft models relative vehicle, 96% inhibition VEGFR2 lungs. Dose-dependent growth with was observed various models, dose-dependent regression seen NCI-H441 model. Tumor enhanced...