A5100672935- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Multiple Myeloma Research and Treatments
- Nanoplatforms for cancer theranostics
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- Nanoparticle-Based Drug Delivery
- Autophagy in Disease and Therapy
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
- Angiogenesis and VEGF in Cancer
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
KU Leuven
2024
Takeda (United States)
2008-2023
Chinese PLA General Hospital
2015-2022
Zunyi Medical University
2022
Shanghai Ninth People's Hospital
2019-2022
Shanghai Jiao Tong University
2019-2022
First Hospital of Shanxi Medical University
2022
Shanxi Medical University
2022
Yunnan University
2022
Qingdao National Laboratory for Marine Science and Technology
2022
The proteasome was validated as an oncology target following the clinical success of VELCADE (bortezomib) for injection treatment multiple myeloma and recurring mantle cell lymphoma. Consequently, several groups are pursuing development additional small-molecule inhibitors both hematologic solid tumor indications. Here, we describe MLN9708, a selective, orally bioavailable, second-generation inhibitor that is in phase I development. MLN9708 has shorter dissociation half-life improved...
Radiotherapy is used in locally advanced pancreatic cancers which it can improve survival combination with gemcitabine. However, prognosis still poor this setting more effective therapies remain needed. MLN4924 an investigational small molecule currently phase I clinical trials. inhibits NAE (NEDD8 Activating Enzyme), a pivotal regulator of the E3 ubiquitin ligase SCF (SKP1, Cullins, and F-box protein), that has been implicated recently DNA damage repair. In study, we provide evidence be as...
Abstract The DNA methyltransferase-mediated proinflammatory activation of macrophages is causally linked to the development atherosclerosis (AS). However, role DNMT1, a methylation maintenance enzyme, in macrophage polarization and AS remains obscure. Here, we established transgenic mice with macrophage-specific overexpression DNMT1 (Tg ) or PPAR-γ investigate their effects on progression ApoE-knockout fed an atherogenic diet. Primary were extracted study DNMT1/PPAR-γ pathway regulating...
Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen evaluate the genetic determinants that confer sensitivity bortezomib (Velcade (R); PS-341). This identified 100 genes whose knockdown affected lethality and structurally diverse set of other inhibitors. A comparison three lines revealed 39 were commonly linked death. We causally bortezomib-induced death...
A next generation cancer drug candidate, a CDC7 inhibitor, TAK-931, was developed, which is being evaluated in clinical trials.
As known, radiation therapy (RT) can exacerbate the degree of hypoxia tumor cells, which induces serious resistance to RT and in turn, is greatest obstacle RT. Reoxygenation restore hypoxic state plays an important role reshaping microenviroment for achieving optimal therapeutic efficacy.Herein, we report first time that microwave (MW)-triggered IL-Quercetin-CuO-SiO2@ZrO2-PEG nanosuperparticles (IQuCS@Zr-PEG NSPs) have been used achieve outcomes by strategy upregulating reoxygenation, i.e....
The NEDD8-activating enzyme is upstream of the 20S proteasome in ubiquitin/proteasome pathway and catalyzes first step neddylation pathway. NEDD8 modification cullins required for ubiquitination cullin-ring ligases that regulate degradation a distinct subset proteins. more targeted impact on protein prompted us to study MLN4924, an investigational inhibitor, preclinical multiple myeloma models. In vitro treatment with MLN4924 led dose-dependent decrease viability (EC(50) = 25-150 nmol/L)...
Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary of intravenous (IV) ixazomib relapsed/refractory patients who had received ⩾2 prior therapies. Thirty with a range histologies 0.125−3.11 mg/m2 on days 1, 8 15 28-day cycles. Patients median two cycles (range 1−36). MTD was determined to be 2.34 mg/m2....
To explore the clinical characteristics and etiology of bacterial meningitis (BM) in Chinese children.BM cases children 28days to 18 years old were collected from January 2014-December 2016 screened according World Health Organization standards. Clinical features, pathogens, resistance patterns analyzed.Overall, 837 classified into five age groups: 28 days-2 months (17.0%), 3-11 (27.8%), 12-35 (24.0%), 3-6 (13.9%), >6years (17.3%). Major pathogens Streptococcus pneumoniae (S. pneumoniae,...
Potential combination partners of a CDC7 inhibitor TAK-931 were identified to guide its clinical development strategy.
Desmoplastic stroma, a feature of pancreatic ductal adenocarcinoma (PDAC), contains abundant activated stellate cells (PSCs). How PSCs promote PDAC progression remains incompletely understood.Effect epithelium-specific E-twenty six factor 3 (ESE3)-positive on fibrosis and chemoresistance was examined by western blot, RT-PCR, immunofluorescence, flow cytometry assay, chromatin immunoprecipitation, luciferase immunohistochemistry subcutaneous cancer mouse model.ESE3 expression increased in...
Serine/threonine kinase, cell division cycle 7 (CDC7) is critical for initiating DNA replication. TAK-931 a specific CDC7 inhibitor, which next-generation replication stress (RS) inducer. This study preclinically investigates antitumor efficacy and immunity regulation. induce RS, generating senescence-like aneuploid cells, highly expressed inflammatory cytokines chemokines (senescence-associated secretory phenotype, SASP). In vivo multilayer-omics analyses in gene expression panel, immune...
To investigate whether clinically relevant levels of epigallocatechin gallate (EGCG, a component green tea) or vitamin C (ascorbic acid) could antagonize bortezomib antitumor activity in CWR22 human prostate xenograft tumors.The pharmacokinetics (PK) EGCG and ascorbic acid were determined immunocompromised mice compared with concentrations measured PK studies dietary supplements. Antitumor combination was using several dosing regimens to evaluate different target plasma acid.Bortezomib dosed...
MLN4924 is an investigational first-in-class small molecule inhibitor of NEDD8-activating enzyme (NAE). NAE essential component the NEDD8 conjugation pathway, controlling activity a subset ubiquitin-proteasome system (UPS) E3 ligases, multiprotein complexes that transfer ubiquitin molecules to substrate proteins.MLN4924 was tested against PPTP in vitro panel using 96-hour exposure time at concentrations ranging from 1.0 nM 10 µM. It vivo dose 100 mg/kg [66 for acute lymphoblastic leukemia...
// Xin Li 1, 4 , Jie Yu 1 Malcolm V. Brock 2 Qian Tao 3 James G. Herman Ping Liang Mingzhou Guo Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China Oncology Center, Johns Hopkins University, Baltimore, Maryland, USA Clinical Oncology, The University Hong Kong, Gastroenterology & Hepatology, Correspondence to: Guo, e-mail: mzguo@hotmail.com Liang, liangping301@hotmail.com Herman, hermaji@jhmi.edu Keywords: BCL6B, DNA methylation, hepatocellular carcinoma,...
Abstract Helicobacter pylori ( H. ) infection has been the leading cause of gastric cancer development. In recent years, resistance against antibiotic treatment a great challenge for most countries worldwide. Since biofilm formation is one reasons , and phototherapy emerged as promisingly alternative antibacterial treatment, herein bacteria‐targeted near‐infrared (NIR) photosensitizer (T780T‐Gu) by combining positively‐charged guanidinium (Gu) with an efficient phototherapeutic agent T780T...