A5070013569- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Heat shock proteins research
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Immune cells in cancer
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Circular RNAs in diseases
- Cancer Research and Treatments
- Retinoids in leukemia and cellular processes
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Advanced Breast Cancer Therapies
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Endoplasmic Reticulum Stress and Disease
Wenzhou Medical University
2025
Qilu Hospital of Shandong University
2010-2025
Affiliated Zhongshan Hospital of Dalian University
2025
Zhejiang Taizhou Hospital
2025
China Medical University
2020-2024
Second Affiliated Hospital of Dalian Medical University
2023
Shanxi Academy of Medical Sciences
2020-2022
Sanofi (United States)
2014-2021
Sanofi (Mexico)
2020
Ningbo University
2018
By incorporating histone deacetylase (HDAC) inhibitory functionality into the pharmacophore of epidermal growth factor receptor (EGFR) and human 2 (HER2) inhibitors, we synthesized a novel series compounds with potent, multiacting HDAC, EGFR, HER2 inhibition identified 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as drug candidate, which is now in clinical development. displays potent vitro activity against an IC(50) 4.4, 2.4, 15.7 nM,...
Abstract Purpose: Given that histone deacetylase (HDAC) inhibitors are known to induce multiple epigenetic modifications affecting signaling networks and act synergistically with phosphatidylinositol 3-kinase (PI3K) inhibitors, we developed a strategy simultaneously inhibit HDACs PI3K in cancer cells. Experimental Design: We constructed dual-acting by incorporating HDAC inhibitory functionality into inhibitor pharmacophore. CUDC-907, development candidate selected from these dual was...
Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is importance to immunization against tumor-associated antigens. In this study, we have investigated induction immunity human MUC1 carcinoma-associated antigen in transgenic mice unresponsive antigen. Immunization adult with irradiated MUC1-positive tumor cells was unsuccessful reversing MUC1. By contrast, fusions dendritic induced cellular and humoral cell that express resulted...
Receptor tyrosine kinase inhibitors have recently become important therapeutics for a variety of cancers. However, due to the heterogeneous and dynamic nature tumors, effectiveness these agents is often hindered by poor response rates acquired drug resistance. To overcome limitations, we created novel small molecule, CUDC-101, which simultaneously inhibits histone deacetylase receptor kinases epidermal growth factor (EGFR) human 2 (HER2) in cancer cells. Because its integrated inhibition,...
Abstract Purpose: We designed and synthesized CUDC-305, an HSP90 inhibitor of the novel imidazopyridine class. Here, we report its unique pharmacologic properties antitumor activities in a variety tumor types. Experimental Design: The potency compound was analyzed by fluorescence polarization competition binding assay. Its antiproliferative were assessed 40 human cancer cell lines. evaluated xenograft models. Results: CUDC-305 shows high affinity for HSP90α/β (IC50, ∼100 nmol/L) complex...
TGFβ is a pleiotropic cytokine that may have both tumor inhibiting and promoting properties, depending on tissue cellular context. Emerging data support role for in suppression of antitumor immunity. Here we show SAR439459, pan-TGFβ neutralizing antibody, inhibits all active isoforms human murine TGFβ, blocks TGFβ-mediated pSMAD signaling, T cells NK cells. In vitro, SAR439459 synergized with anti-PD1 to enhance cell responsiveness. syngeneic models, treatment impaired growth, while the...
Immune checkpoint blockade elicits durable anti-cancer responses in the clinic, however a large proportion of patients do not benefit from treatment. Several mechanisms innate and acquired resistance to have been defined include mutations MHC I IFNγ signaling pathways. However, such occur low frequency additional yet be elucidated. In an effort better understand blockade, we generated mouse tumor model exhibiting vivo anti-PD-1 antibody MC38 tumors PD-1 following serial passaging. Lack...
Abstract Oxaliplatin is the main chemotherapy drug for gastric cancer (GC), but quite a few patients are resistant to oxaliplatin, which contributes poor prognosis of GC patients. There therefore an urgent need identify potential targets reversing resistance in In this study, we analyzed tumor samples who received neoadjuvant based on oxaliplatin through quantitative proteomics and identified chemoresistance-related protein cellular retinoic acid binding 2 (CRABP2). CRABP2 was significantly...
Abstract CUDC-305 is a heat shock protein 90 (HSP90) inhibitor of the novel imidazopyridine class. Here, we report its activities in non–small cell lung cancer (NSCLC) lines with gene deregulations conferring primary or secondary resistance to epidermal growth factor receptor (EGFR) inhibitors. We show that binds strongly HSP90 extracted from erlotinib-resistant NSCLC cells (IC50 70 nmol/L). This result correlates well potent antiproliferative activity 120–700 nmol/L) reported previously....
Mechanisms of unassisted delivery RNA therapeutics, including inhibitors microRNAs, remain poorly understood. We observed that the hepatocellular carcinoma cell line SKHEP1 retains productive free uptake a miR-21 inhibitor (anti-miR-21). Uptake anti-miR-21, but not mismatch (MM) control, induces expression known targets (DDAH1, ANKRD46) and leads to dose-dependent inhibition growth. To elucidate mechanisms sensitivity we conducted an unbiased shRNA screen revealed tumor susceptibility gene...
Abstract Colorectal cancer (CRC) is a common malignant tumor with poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for overall survival. Circular RNA (circRNA) class of noncoding RNAs discovered many years ago. Only recently have they re-evaluated their important roles in the regulation gene expression. Studies confirmed that circRNAs biological functions variety tumors. This study aimed to characterize one circRNA derived from MBOAT2 and termed it...
Cholestatic liver diseases are characterized by excessive bile acid accumulation in the liver. Endothelial cells (ECs) shape local microenvironment both normal conditions and injury, yet their role cholestasis is unclear. Through a comparative analysis of single-cell RNA sequencing data from various murine models we identify distinctive Myc activation within ECs during obstructive resulting duct ligation (BDL). overexpression significantly upregulates P-selectin, increasing neutrophil...
Acute liver failure (ALF) is a fatal syndrome associated with massive hepatocyte death. Previous studies have found that Farnesyltransferase (FTase) inhibitors improve disease progression in mouse models of endotoxemia, sepsis, and autoimmune hepatitis. PANoptosis novel type programmed cell death (PCD), including pyroptosis, apoptosis, necrosis, plays an important role ALF. This study was designed investigated whether the FTase inhibitor PD083176 (d2,d3,d5) could attenuate ALF by modulating...
To measure the expression profile of circular RNA (circRNA) in hepatic tissues a liver fibrosis model and to explore their function using molecular biology bioinformatic techniques.The classic CCl4 mouse was established alongside normal control group. The circRNA tissue from two groups compared high-throughput microarray. differentially expressed circRNAs were identified, real-time quantitative polymerase chain reaction (RT-qPCR) used verify subset (target genes). At same time, oxidative...
Abstract Hepatic ischemia–reperfusion (IR) injury remains a common issue lacking effective strategy and validated pharmacological targets. Here, using an unbiased metabolomics screen, this study finds that following murine hepatic IR, liver 3‐hydroxyanthranilic acid (3‐HAA) quinolinic (QA) decline while kynurenine kynurenic (KYNA) increase. Kynurenine aminotransferases 2, functioning at the key branching point of pathway (KP), is markedly upregulated in hepatocytes during ischemia, shifting...
Retinoic acid induced 14 (RAI14), also known as NORPEG, is reported being deregulated in non-small-cell lung cancer, together with having involvement its cell proliferation a super enhancer related gene.The objective of this study was to investigate the role RAI14 progression and metastasis gastric cancer explore associated mechanism.GEPIA database used analyze expression cancer. MNK45 AGS cells were transfected siRNA-RAI14 block RAI14. Cell Counting Kit 8 colony formation assays performed...
Abstract As documented, the expression, biological roles, and prognostic significance of FKBP10 in stomach adenocarcinoma (STAD) have not been investigated till now. This drives us to detect roles clinical STAD. The expression level was measured based on data obtained from TCGA, ONCOMINE, GEPIA databases, STAD cell lines. Through vitro experiments, behaviors were evaluate effects Moreover, PI3K‐AKT signaling pathway measured. Relying cancer lines, up‐regulated when compared with normals....
The ETS family modulates immune response and drug efficiency to targeted therapies, but their role in melanoma is largely unclear. In this study, the was systematically analyzed multiple public data sets. Bioinformatics tools were used characterize function of ETV7 melanoma. A prognostic model constructed using LASSO Cox regression method. We found that only differentially expressed gene with significant relevance Enrichment analysis seven independent sets indicated participation various...
Abstract Background Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development metastasis. m6 A (N6—methyladenosine) is one of the most common RNA modifications eukaryotes. The aim our research was to investigate potential prognostic value m6A-related lncRNAs ovarian cancer (OC). Methods data we need for downloaded from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database. Pearson correlation analysis...
Hepatocellular carcinoma (HCC) represents a serious public health challenge with few therapeutic options available to cancer patients.Wnt/β-catenin pathway is thought play significant role in HCC pathogenesis. In this study, we confirmed high frequency of CTNNB1 (β-catenin) mutations two independent cohorts patients and demonstrated upregulation β-catenin protein the overwhelming majority patient samples, patient-derived xenografts (PDX) established cell lines. Using genetic tools validated...