A5011842932- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
- Bioactive Compounds and Antitumor Agents
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Synthesis and biological activity
- Psoriasis: Treatment and Pathogenesis
- Cancer-related molecular mechanisms research
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Inflammatory mediators and NSAID effects
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Ovarian cancer diagnosis and treatment
- Curcumin's Biomedical Applications
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Bone health and treatments
- Mesenchymal stem cell research
- Cancer-related Molecular Pathways
- Immune cells in cancer
- RNA modifications and cancer
Changzhou No.2 People's Hospital
2025
Nanjing Medical University
2015-2025
People's Hospital of Cangzhou
2025
Stomatological Hospital of Chongqing Medical University
2025
Chongqing Medical University
2025
University of Miami
2007-2024
Sylvester Comprehensive Cancer Center
2011-2024
Zoucheng People's Hospital
2019-2022
University of Pittsburgh
2020
Shenzhen Children's Hospital
2020
We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and one pyrazole is considerably more potent as an agonist on ERalpha than ERbeta subtype (Sun Endocrinology 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity greatest enhancement of potency ERalpha-selective agonist, we prepared a number analogues with defined variations at positions. Analysis...
Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERα) and beta (ERβ), we found 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) acts as agonist on both ER subtypes, but has a 70-fold higher relative binding affinity 170-fold potency in transcription assays with ERβ than ERα. To investigate affinity- potency-selective character of this DPN further, prepared series analogues which ligand core aromatic rings were modified by repositioning...
Curcumin, a selective phosphorylase kinase inhibitor, is naturally occurring phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties addition the ability decrease expression of pro-inflammatory cytokines keratinocytes. The interleukin-23 (IL-23)/IL-17A cytokine axis plays critical role pathogenesis psoriasis. Here, we report that topical use curcumin gel formulation strongly inhibited imiquimod (IMQ)-induced psoriasis-like inflammation, development...
We report on the identification of novel, nonsteroidal ligands that show pronounced subtype-selective differences in ligand binding and transcriptional potency or efficacy for two estrogen receptor (ER) subtypes, ERα ERβ. An aryl-substituted pyrazole is an potency-selective agonist, showing higher affinity 120-fold stimulation vs. ERβ transactivation assays cells. A tetrahydrochrysene (THC) has a 4-fold preferential ERβ; it agonist ERα, but complete antagonist Intriguingly, activity THC...
We have studied the two estrogen receptor (ER) subtypes, ERα and ERβ, chimeric constructs with ERβ to examine bioactivities of these receptors their responses antiestrogen ligands. Transcriptional activity is highly dependent on cell/promoter context nature ligand. activated significant levels transcription in response estrogens certain cell types, but showed only moderate compared others. Antiestrogens such as tamoxifen 2-phenylbenzofuran, which show some agonistic ERα, exhibit no ERβ....
A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity one two ER subtypes, alpha or beta. We have prepared a series heterocycle-based (furans, thiophenes, and pyrroles) assessed their behavior ligands. An aldehyde enone conjugate addition approach an enolate alkylation were developed to prepare 1,4-dione that precursors trisubstituted tetrasubstituted systems, respectively. All diones easily converted into corresponding...
To develop compounds that are antagonists on ERα, but not ERβ, we have added basic side-chains typically found in nonsteroidal antiestrogens to pyrazole bind with much higher affinity ERα than ERβ. In this way developed side-chain pyrazoles (BSC-pyrazoles) high affinity, potent, selective ERα. These BSC-pyrazoles themselves inactive and they antagonize E2 stimulation by only. We investigated seven substituents various alkyl-triaryl-substituted pyrazoles, the most ERα-selective compound was...
Ligands for the estrogen receptor (ER) that have capacity to selectively bind or activate ER subtypes ER␣ ER would be useful in elucidating biology of these two receptors and might assist development pharmaceuticals with improved tissue selectivity.In this study, we examine three compounds novel structure act as subtype-selective ligands.These are a propyl pyrazole triol (PPT), which is potent agonist on but inactive ER, pair substituted tetrahydrochrysenes (THC), one enantiomer (S,S-THC)...
We have recently reported that racemic 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC, rac-2b) acts as an agonist on estrogen receptor alpha (ERα) and a complete antagonist beta (ERβ) (Sun et al. Endocrinology 1999, 140, 800−804). To further investigate this novel ER subtype-selective estrogenic activity, we synthesized series of cis- trans-dialkyl THCs. cis-Dimethyl, -diethyl, -dipropyl THCs 2a−c were prepared in highly enantio- diastereoselective manner by the acyloin...
Background: Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able act on CD4+CD25+ Foxp3+Treg lead an improvement ALI. Methods: Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) received intrapulmonary 1×106 UCMSC 4 hours after challenge. Foxp3+Treg, survival time, body weight,...
Rational targeted therapies are needed for treatment of ovarian cancers. Signaling kinases Src and MAPK activated in high-grade serous cancer (HGSOC). Here, we tested the frequency activation both HGSOC therapeutic potential dual kinase inhibition.
Abstract Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric di-methylation of residues in histones H3 and H4, marks that are generally associated with transcriptional repression. However, we found PRMT5 inhibition or depletion led to more genes being downregulated than upregulated, indicating can also act as a activator. Indeed, global level histone H3K27me3 increases deficient cells. Although does not directly affect PRC2 enzymatic activity, methylation by abrogates its...
Estrogen drives both transcriptional activation and proteolysis of estrogen receptor alpha (ER alpha; encoded by ESR1). Here we observed variable overlapping ESR1 mRNA levels in 200 ER alpha-negative 50 alpha-positive primary breast cancers examined, which suggests important posttranscriptional regulation. Our results indicate that Src cooperates with to activate proteolysis. Inducible stimulated ligand-activated activity reduced t(1/2). were inversely correlated cancers. cell lines showed...
The estrogen receptor (ER) binds to estrogen-responsive elements (EREs) activate gene transcription. best characterized EREs are located in proximal promoters, but recent data indicate that only a minority of ER binding sites lie within promoter regions. GREB1 (gene regulated by breast cancer 1) is an target regulates estrogen-induced proliferation cells. We identified three consensus EREs, at -21.2, -9.5, and -1.6 kb upstream the closest GREB1a transcription start site appear mediate...
Many transcription factors undergo transcription-coupled proteolysis. Although ligand binding activates ubiquitin proteolysis of estrogen receptor α (ERα), mechanisms governing this and its relationship to transcriptional activation were unclear. Data presented link cross talk between the Src kinase liganded ERα with ubiquitylation. Liganded rapidly recruits Src, which phosphorylates at tyrosine 537 (Y537). This enhances ligase/ERα coactivator, E6-associated protein (E6-AP), stimulating...
Bone marrow-derived mesenchymal stem cells (BMSCs, also known as bone stromal cells) are to be a component of the tumor microenvironment. BMSCs multipotent that can differentiate into variety cell types, including osteocytes, chondrocytes, adipocytes, epithelial and endothelial cells. Stem found in niches or transplanted injured tissues constantly encounter hypoxic stress. Areas with very low no oxygen pressure exist solid tumors. The differentiation capacity under conditions remains...
More effective, less toxic treatments for recurrent ovarian cancer are needed. Although more than 60% of cancers express the estrogen receptor (ER), ER-targeted drugs have been disappointing due to drug resistance. In other estrogen-sensitive cancers, activates Src phosphorylate p27 promoting its degradation and increasing cell-cycle progression. Because is activated in most we investigated whether combined ER blockade by saracatinib fulvestrant would circumvent antiestrogen resistance.ER...
Abstract Purpose: Although 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in cancer, we investigated if regulates and MEK inhibition (MEKi) reverses resistance. Experimental Design: Effects MEKi (selumetinib), (fulvestrant), or both were assayed ER-positive HGSOC vitro xenografts. Response biomarkers by gene expression microarray reverse phase protein array (RPPA). Genes differentially...
Leukemia stem cells (LSCs) are believed to have more distinct vulnerabilities than the bulk acute myeloid leukemia (AML) cells, but their rarity and lack of universal markers for prospective isolation hamper study. We report that genetically clonal induced pluripotent (iPSCs) derived from an AML patient characterized by exceptionally high engraftment potential give rise, upon hematopoietic differentiation, a phenotypic hierarchy. Through fate-tracking experiments, xenotransplantation,...
We have identified physical and functional interactions between the epidermal growth factor (EGF) receptor phospholipid scramblase 1 (PLSCR1), an endofacial plasma membrane protein proposed to affect organization. PLSCR1, a palmitoylated protein, was found partition with EGF in lipid rafts. Cell stimulation transiently elevated Tyr-phosphorylation of peaking at 5 min. Although PLSCR1 is known substrate c-Abl [Sun, J., et al. (2001) J. Biol. Chem. 276, 28984−28990], Abl inhibitor STI571 did...
Abstract Although the two subtypes of human estrogen receptor (ER), ERα and ERβ, share only 56% amino acid sequence identity in their ligand binding domain (LBD), residues that surround are nearly identical; nevertheless, subtype-selective ligands known. To understand molecular basis by which diarylpropionitrile (DPN), an ERβ-selective ligand, is able to discriminate between ERs, we examined its activity on ER mutants chimeric constructs generated DNA shuffling. The N-terminal region ERβ LBD...
We report on the identification of novel, nonsteroidal ligands that show pronounced subtype-selective differences in ligand binding and transcriptional potency or efficacy for two estrogen receptor (ER) subtypes, ERα ERβ. An aryl-substituted pyrazole is an potency-selective agonist, showing higher affinity 120-fold stimulation vs. ERβ transactivation assays cells. A tetrahydrochrysene (THC) has a 4-fold preferential ERβ; it agonist ERα, but complete antagonist Intriguingly, activity THC...