A5100390917- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Neuroendocrine Tumor Research Advances
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Erythrocyte Function and Pathophysiology
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Circular RNAs in diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Extracellular vesicles in disease
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Advanced Glycation End Products research
- Escherichia coli research studies
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
- Cancer Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Viral gastroenteritis research and epidemiology
- Cancer Mechanisms and Therapy
- Pancreatic function and diabetes
- Renal Diseases and Glomerulopathies
Nanjing Drum Tower Hospital
2025
Nanjing University
2008-2024
State Key Laboratory of Pharmaceutical Biotechnology
2009-2024
Emory University
2001-2024
Pharmaceutical Biotechnology (Czechia)
2024
GlaxoSmithKline (United States)
2023
Georgia State University
2013-2022
Hebei Medical University
2022
South China Normal University
2015
Biomark (United States)
2009
Abstract HER2-directed therapies, such as trastuzumab and lapatinib, are important treatments for breast cancer. However, some tumors do not respond or develop resistance to these agents. We isolated characterized multiple lapatinib-resistant, HER2-positive, estrogen receptor (ER)–positive cancer clones derived from lapatinib-sensitive BT474 cells by chronic exposure lapatinib. show overexpression of AXL a novel mechanism acquired HER2-targeted agents in models. GSK1363089 (foretinib),...
Here we report on the existence and functionality of immune checkpoint signal regulatory protein α (SIRPα) in NK cells describe how it can be modulated for cell therapy. SIRPα is up-regulated upon IL-2 stimulation, interacts with target CD47 a threshold-dependent manner, counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression protected K562 tumor mouse human MHC class I–deficient against SIRPα+ primary cells, but not SIRPα− NKL NK92 cells. deficiency antibody...
Recent studies have demonstrated that CD47 plays an important role in regulating human neutrophil (PMN) chemotaxis. Two ligands for CD47, thrombospondin and SIRPα, been described. However, it is not known if SIRP-CD47 interactions play a PMN migration. In this study, we show SIRPα1 directly binds to the immunoglobulin variable domain loop of purified such regulate transmigration. Specifically, migration across both epithelial monolayers collagen-coated filters was partially inhibited by...
Cell-secreted miRNAs are highly stable and can serve as biomarkers for various diseases signaling molecules in intercellular communication. The mechanism underlying the stability of circulating miRNAs, however, remains incompletely understood. Here we show that Argonaute 2 (Ago2) complexes microvesicles (MVs) provide specific non-specific protection miRNA cell-secreted MVs, respectively. First, resistance MV-encapsulated to RNaseA was both depended on intact vesicular structure MVs...
CD47, a cell surface glycoprotein, plays an important role in modulating neutrophil (PMN) migration across endothelial and epithelial monolayers. Here we show that anti-CD47 monoclonal antibodies (mAbs) delay PMN collagen-coated filters or T84 monolayers toward the chemoattractant formylmethionylleucylphenylalanine (fMLP). Despite delayed transmigration by mAbs, numbers of migrating either condition were same as presence control non-inhibitory mAbs. Cell labeling immunoprecipitation...
Neutrophil (polymorphonuclear leukocytes [PMN]) transepithelial migration during inflammatory episodes involves a complex series of adhesive interactions and signaling events. Previous studies have shown that key between leukocyte CD11b/CD18 basally expressed fucosylated glycoproteins followed by binding to desmosomal-associated JAM-C are elements the transmigration response. Here we provide first evidence PMN-expressed junctional adhesion molecule-like protein (JAML) regulates via with...
Significance The present study reveals that macrophage phagocytosis toward healthy self-cells is controlled by a two-tier mechanism: forefront activation mechanism requiring the inflammatory cytokine-stimulated protein kinase C (PKC)-spleen tyrosine (Syk) pathway, to which IL-10 conversely regulates, and subsequent self-target discrimination CD47-signal regulatory α (SIRPα)–mediated inhibition. findings significantly expand our understanding of phagocytic plasticity behavior under different...
Abstract CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis healthy host cells. Previous studies suggested cells may lose CD47 during aging or apoptosis enable phagocytic clearance. In current study, we demonstrate level cell is not decreased, but distribution pattern altered, apoptosis. On nonapoptotic molecules are clustered in lipid rafts forming...
Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism not fully elucidated. Here we identify hepatic miR-122 as a mediator of induced various liver injuries. Analyses acute chronic mouse models confirm that dysfunction can cause damage. Injured livers release large amounts in an exosome-independent manner into circulation compared with normal livers. Circulating then preferentially transported to lungs taken up alveolar macrophages,...
Abstract Radiotherapy (RT)-induced tumoricidal immunity is severely limited when tumors are well-established. Here, we report that depleting SIRPα on intratumoral macrophages augments efficacy of RT to eliminate otherwise large, treatment-resistant colorectal (MC38) and pancreatic (Pan02 KPC) tumors, inducing complete abscopal remission long-lasting humoral cellular prevent recurrence. -deficient activated by irradiated tumor-released DAMPs exhibit robust orchestrate an anti-tumor response...
Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for its transendothelial migration remain unknown.By assessing of various across TNF-alpha pre-activated human umbilical vein (HUVECs), we found that migrated HUVEC differentially transmigration was dependent. Cell surface labeling with extracellular domain/Fc chimera...
Abstract Neutrophil (polymorphonuclear leukocytes [PMN]) infiltration plays a central role in inflammation and is also major cause of tissue damage. Thus, PMN must be tightly controlled. Using zymosan-induced peritonitis as an vivo model, we show this study that response were significantly enhanced mice experiencing various types systemic inflammation, including colitis diabetes. Adoptive transfer from with into healthy recipients or inflammatory followed by inducing demonstrated both...
Abstract Advanced glycation end products (AGEs) delay spontaneous apoptosis of monocytes and contribute to the development inflammatory responses. However, mechanism by which AGEs affect monocyte is unclear. We studied role microRNA-214 (miR-214) its target gene in AGE-induced monocytic delay. Using microRNA (miRNA) microarray stem-loop, quantitative RT-PCR assay, we genome-wide miRNA expression THP-1 cells treated with or without AGEs. Significant upregulation miR-214 was consistently...
Hepatic miR-122 can serve as a pro-apoptotic factor to suppress tumorigenesis. The underlying mechanism, however, remains incompletely understood. Here we present the first evidence that promotes hepatocellular carcinoma cell apoptosis through directly silencing biogenesis of survival oncomiR miR-21 at posttranscriptional level. We find is strongly expressed in primary liver nucleus but its nuclear localization markedly decreased transformed cells particularly chemoresistant tumor cells....
It is generally regarded that E-cadherin downregulated during tumorigenesis via Snail/Slug-mediated transcriptional reduction. However, this suppressive mechanism cannot explain the failure of producing protein in metastatic breast cancer cells after overexpressing mRNA. Here we reveal a novel post-transcriptionally regulated by Slug-promoted miR-221, which serves as an additional blocker for expression tumor cells. Profiling predicted E-cadherin-targeting miRNAs tissues and showed miR-221...
Methylation of miRNAs at the 2'-hydroxyl group on ribose 3'-end (2'-O-methylation, 2'Ome) is critical for miRNA function in plants and Drosophila. Whether this methylation phenomenon exists mammalian remains unknown. Through LC-MS/MS analysis, we discover that majority miR-21-5p isolated from human non-small cell lung cancer (NSCLC) tissue possesses 3'-terminal 2'Ome. Predominant 2'Ome confirmed by qRT-PCR northern blot after oxidation/β-elimination procedure. Cancerous paired non-cancerous...
This study presents, attenuated total reflection Fourier transforms infrared spectroscopy of dried serum samples in an effort to assess biochemical changes induced by non-Hodgkin's lymphoma and subcutaneous melanoma. An EL4 mouse model non-Hodgkin a B16 melanoma are used extract snapshot tumor-associated alteration the serum. The both cancer-bearing models wild types their corresponding control types, emphasizes diagnostic potential this approach as screening technique for skin cancer....
Abstract Neutrophils infiltration/activation following wound induction marks the early inflammatory response in repair. However, role of infiltrated/activated neutrophils tissue regeneration/proliferation during repair is not well understood. Here, we report that at site release pyruvate kinase M2 (PKM2) by its secretive mechanisms stages The released extracellular PKM2 facilitates healing promoting angiogenesis site. Our studies reveal a new and important molecular linker between...
Abstract Trimethylamine oxide (TMAO) is a newly found intestinal microbiota metabolite. Here, we aimed to explore the effects of TMAO on calcium homeostasis and its implication in cardiac hypertrophy, especially focusing regulatory mechanism key transporter SERCA2a. Echocardiography histological assessment showed that mice fed with or Choline for 8 weeks exhibited significant pathological changes which accompanied by increased plasma levels TMAO. The results indicated could increase...
Abstract Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated inflammatory responses. In this study, we provide evidence demonstrating RAGE involved in responses the intestines. We showed expressed intestinal epithelial cells, primarily concentrated at lateral membranes close to apical junction complexes. Although expression was low epithelium under normal conditions, protein up-regulated after...