A5000385663- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- Circular RNAs in diseases
- interferon and immune responses
- Cancer-related Molecular Pathways
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Hedgehog Signaling Pathway Studies
- Cancer Mechanisms and Therapy
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
Tianjin Medical University Cancer Institute and Hospital
2016-2025
National Clinical Research
2021-2025
Shandong Provincial QianFoShan Hospital
2024
Shandong University
2024
State Key Laboratory of Biotherapy
2014-2021
Sichuan University
2014-2021
National Clinical Research Center for Digestive Diseases
2021
Chinese Academy of Medical Sciences & Peking Union Medical College
2016-2020
First Affiliated Hospital of Zhengzhou University
2019-2020
Cleveland Clinic Lerner College of Medicine
2014-2018
Abstract Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate adaptive antitumor immunity. Here we show that chloroquine (CQ), proven anti-malarial drug, can function as an immune modulator switches TAMs from M2 tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca 2+ release via channel mucolipin-1 (Mcoln1), which induces activation of p38 NF-κB, thus...
A number of recent reports have demonstrated that only CD133-positive cancer cells glioblastoma multiforme (GBM) tumor-initiating potential. These findings raise an attractive hypothesis GBMs can be cured by eradicating stem (CSCs), which are a small portion GBM cells. However, as known to possess various genetic alterations, might harbor heterogeneous CSCs with different alterations. Here, we compared the clinical characteristics two patient groups divided according cell ratios. The...
Interactions with the immune system may lead tumorigenic cells into dormancy. However, underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as...
The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive hence termed "go or grow." We identified a molecular target that shuttles between disparate cellular processes-the motor KIF11. Inhibition KIF11 with highly specific small-molecule inhibitor stopped the growth more treatment-resistant glioblastoma tumor-initiating cells (TICs, cancer stem cells) as well non-TICs impeded tumor initiation...
One of the most detrimental hallmarks glioblastoma multiforme (GBM) is cellular invasiveness, which considered a potential cause tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding various mechanisms controlling its nature remains poorly understood. In this study, we established highly serial intracranial transplantation. U87R4 were invasive displayed stem cell-like...
Abstract Aberrant activation of receptor tyrosine kinases (RTK) is causally linked to the pathobiological traits glioblastoma and genesis glioma stem-like cells (GSC), but underlying mechanism still unknown. Here, we show that epidermal growth factor (EGFR) signaling regulates proliferation, angiogenesis, acquisition GSC characteristics by inducing inhibitor differentiation 3 (ID3) ID3-regulated cytokines [GRO1 interleukins (IL)-6 8] induction. We found EGFR-mediated ID3 expression was...
ACT001, which is derived from an ancient anti-inflammatory drug, has been shown to cross the blood-brain barrier in preclinical studies and demonstrated anti-glioblastoma (GBM) activity clinical trials. However, its pharmacological potential for anti-GBM immune response modulation remains unclear. The chemical structure of ACT001 indicates that it may bind STAT3 thus modulate antitumor response. Methods: Bioinformatics immunohistochemistry (IHC) were used assess PD-L1 expression gliomas....
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal stem cells (GSCs). depletes S-adenosyl methionine (SAM), generated from methionine. GSCs contained lower levels of...
Dynamic interaction with the immune system profoundly regulates tumor cell dormancy. However, it is unclear how immunological cues trigger cancer cell–intrinsic signaling pathways for entering into Here, we show that IFN-β treatment induced tumor-repopulating cells (TRC) to enter dormancy through an indolamine 2,3-dioxygenase/kynurenine/aryl hydrocarbon receptor/p27–dependent (IDO/Kyn/AhR/p27-dependent) pathway. Strategies block this metabolic circuitry did not relieve dormancy, but led...
Abstract Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating (TRC) sense mechanical signals and rapidly proliferate 90 Pa soft fibrin matrix. Here, we show stiff environment induces TRC via epigenetic program initiated by translocation Cdc42, cytosolic regulator...
Cellular origins and genetic factors governing the genesis maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role developmental regulator Id4 (inhibitor differentiation 4) in GBM. In primary murine Ink4a/Arf −/− astrocytes, human glioma cells, provide evidence that enforced can drive malignant transformation by stimulating increased cyclin E to produce hyperproliferative profile Jagged1 expression with Notch1 activation astrocytes into neural...
Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. γ-Aminobutyric acid (GABA), primary inhibitory neurotransmitter adult brain, is excitatory on neurons via its action at GABAA receptor, depolarizing membrane potential and inducing a cytosolic Ca2+ increase ([Ca2+]i), because reversed transmembrane chloride gradient. Recent experimental data from several rodent studies have demonstrated that exposure to isoflurane during an initial phase causes...
Inflammatory microenvironment signalling plays a crucial role in tumour progression (i.e. cancer cell proliferation, survival, angiogenesis and metastasis) many types of human malignancies. However, the inflammation brain pathology remains poorly understood. Here, we report that interferon regulatory factor 7 is regulator heterogeneity. Ectopic expression glioma cells promotes tumorigenicity, angiogenesis, microglia recruitment stemness vivo vitro through induction interleukin 6, C-X-C motif...
Abstract Glioma-initiating cells (GIC), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, molecular mechanisms controlling crosstalk between GICs endothelial poorly understood. Here, we report that, in both cells, platelet-derived growth factor (PDGF)–driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor differentiation 4 (ID4) expression, turn...
Inhibitor of differentiation 1 (ID1) is highly expressed in glioblastoma stem cells (GSCs). However, the regulatory mechanism responsible for its role GSCs poorly understood. Here, we report that ID1 activates GSC proliferation, self-renewal, and tumorigenicity by suppressing CULLIN3 ubiquitin ligase. induces cell proliferation through increase CYCLIN E, a target molecule CULLIN3. overexpression or knockdown confers features to murine Ink4a/Arf-deficient astrocytes. Proteomics analysis...