A5017068879- Estrogen and related hormone effects
- Chemokine receptors and signaling
- Advanced Breast Cancer Therapies
- Cancer Cells and Metastasis
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Synthesis and biological activity
- MicroRNA in disease regulation
- Cancer Treatment and Pharmacology
- FOXO transcription factor regulation
- Retinoids in leukemia and cellular processes
- Photosynthetic Processes and Mechanisms
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Lipids, and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Tissue Engineering and Regenerative Medicine
- bioluminescence and chemiluminescence research
- Breast Cancer Treatment Studies
- Genomics, phytochemicals, and oxidative stress
- Glycosylation and Glycoproteins Research
- Cancer Risks and Factors
Ochsner Health System
2024
Xavier University of Louisiana
2014-2023
Louisiana Cancer Research Center
2020-2022
Xavier University
2019
Office of Minority Health
2013
Tulane University
2007-2012
University of New Orleans
2012
Louisiana State University Health Sciences Center New Orleans
2010
Vanderbilt University
2010
Research Institute for Bioscience and Biotechnology
2006-2008
Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1-CXCR4 axis. Thus, development estrogen endocrine therapy patients may be driven by signaling. Here we report that CXCR4 overexpression is indeed correlated worse prognosis decreased patient survival irrespective status receptor (ER). Constitutive activation poorly MCF-7 cells led...
Background Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The DDT BPA are ubiquitously present in environment, levels human blood adipose tissue detectable most if not all women men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) more recently non-coding (ncRNAs). Of ncRNAs, microRNAs emerged as a target signaling. Given...
Abstract Introduction Acquired tamoxifen resistance involves complex signaling events that are not yet fully understood. Successful therapeutic intervention to delay the onset of hormone depends critically on mechanistic elucidation viable molecular targets associated with resistance. This study was undertaken investigate global proteomic alterations in a resistant MCF-7 breast cancer cell line obtained by long term treatment wild type 4-hydroxytamoxifen (4-OH Tam). Methods We cultured cells...
Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC50 = 4.1 nM) effectively downregulates in both tamoxifen-sensitive tamoxifen-resistant cancer cells. Furthermore, It has superior oral bioavailability (AUC 2547.1 ng·h/mL) mice,...
The purpose of this study was to investigate the effects glyceollins on suppression tumorigenesis in triple-negative breast carcinoma cell lines. We further explored microRNA and protein expression MDA-MB-231 cells. Triple-negative (ER-, PgR- Her2/neu-) cells were used test vivo. Following procedure, unbiased microarray analysis performed. Additionally, we examined changes proteome induced by Tumorigenesis studies revealed a modest MDA-MB-468 tumor growth In response observed distinct change...
Aromatase inhibitors, such as letrozole, have become the first-line treatment for postmenopausal women with estrogen-dependent breast cancer. However, acquired resistance remains a major clinical obstacle. Previous studies demonstrated constitutive activation of MAPK signaling, overexpression HER2, and down-regulation aromatase ERα in letrozole-resistant cancer cells. Given complex signaling network involved letrozole-refractory lack effective hormone resistance, further investigation...
Recently, crosstalk between sphingolipid signaling pathways and steroid hormones has been illuminated as a possible therapeutic target. Sphingosine kinase (SK), the key enzyme metabolizing pro-apoptotic ceramide to pro-survival sphingosine-1-phosphate (S1P), is promising target for solid tumor cancers. In this study, we examined ability of pharmacological inhibition S1P formation block estrogen targeted breast cancer therapy. We found that Sphk1/2 selective inhibitor (SK (SKI))-II, blocked...
Decellularized human adipose tissue has potential clinical utility as a processed biological scaffold for soft cosmesis, grafting, and reconstruction. Adipose decellularization been accomplished using enzymatic-, detergent-, and/or solvent-based methods. To examine the hypothesis that distinct processes may yield scaffolds with differing compositions, current study employed mass spectrometry to compare proteomes of adipose-derived matrices generated through three independent methods...
The catalytic core of cytochrome c oxidase is composed three subunits: I, II, and III. Subunit III a highly hydrophobic membrane protein that contains no redox centers; its role in function not obvious. Here, subunit has been removed from the three-subunit mitochondrial-like Rhodobacter sphaeroides by detergent washing. resulting two-subunit oxidase, (−), active. Ligand-binding analyses resonance Raman spectroscopy show heme a3−CuB active site normal. However, (−) spontaneously irreversibly...
The organochlorine dichlorodiphenyltrichloroethane (DDT), a known estrogen mimic and endocrine disruptor, has been linked to animal human disorders. However, the detailed mechanism(s) by which DDT affects cellular physiology remains incompletely defined.We others have shown that activates cell-signaling cascades, culminating in activation of receptor-dependent -independent gene expression. Here, we identify mechanism alters signaling expression, independent receptor.We performed quantitative...
Development of orally bioavailable nonsteroidal selective estrogen receptor downregulators (SERDs) provides clinical opportunities for the long-term treatment and adjuvant therapy breast cancer at all stages. We describe design, synthesis, identification a boron-modified GW7604 derivative (GLL398, 9), SERD candidate, in which boronic acid functional group replaces phenolic hydroxyl GW7604. Compound 9 strongly binds to ERα fluorescence resonance energy transfer binding assay (IC50 = 1.14 nM)...
Advances in oral SERDs development so far have been confined to nonsteroidal molecules such as those containing a cinnamic acid moiety, which are earlystage clinical evaluation. ZB716 was previously reported an orally bioavailable SERD structurally analogous fulvestrant. In this study, we examined the binding details of estrogen receptor alpha (ERα) by computer modeling reveal its interactions with ligand domain steroidal molecule. We also found that modulates ERα-coregulator nearly...
In humans, cytochrome P450 1A2 is the major enzyme metabolizing environmental arylamines or heterocyclic amines into carcinogens. Since evidence shows that planar triangle-shaped molecules are capable of selectively inhibiting 1A2, 16 triangular flavone, and coumarin derivatives were designed synthesized for these studies. Among compounds, 7,8-furanoflavone time-dependently inhibits with a KI value 0.44 μM. With 5 min preincubation in presence NADPH, 0.01 μM completely inactivates but does...
Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) aromatase, enhances bioavailability signaling positive (ER⁺) breast cancer (BC) growth metastasis. In this study, we evaluate the effect on ER⁺BC outside ERα axis using models with constitutively active resulting from clinically relevant...
Growth factor activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been shown to activate estrogen receptor (ER) alpha and mediate tamoxifen resistance in breast cancer. Here, we investigated regulation transcriptional activity newer ER beta by PI3K-AKT signaling. Tissue arrays cancer specimens showed a positive association between expressions AKT clinical setting. Reporter gene assays using pharmacologic molecular inhibitors constitutively active revealed for first time...
The activity of nuclear transcription factors is often regulated by specific kinase-signaling pathways. We have previously shown that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) stimulates activator protein-1 through p38 mitogen-activated protein kinase (MAPK). Here, we show DDT and its metabolites also stimulate transcriptional cyclic adenosine monophosphate response element-binding Elk1 potentiate gene expression hypoxia elements. Because various hence multiple...
Abstract While decellularized adipose tissue (DAT) has potential as an “off‐the‐shelf” biomaterial product for regenerative medicine, it remains to be determined if donor‐source body mass index (BMI) impacts the functionality of DAT. This study set out comparatively characterize lean versus overweight/obese‐donor derived DAT hydrogel based on proteome and analyze their respective effects stromal/stem cell (ASC) viability, differentiation in vitro. Decellularized from (lDAT) overweight/obese...
In breast carcinomas, increased levels of insulin-like growth factor 1 (IGF-1) can act as a mitogen to augment tumorigenesis through the regulation MAPK and AKT signaling pathways. Signaling these two pathways allows IGF-1 employ mechanisms that favor proliferation cellular survival. Here we demonstrate subset previously described tumor suppressor oncogenic microRNAs (miRNAs) are under direct signaling. Additionally, show selective inhibition either or prior stimulation prevents expression...
The estrogen receptor α (ERα) is a transcription factor that mediates the biological effects of 17β-estradiol (E 2 ). ERα transcriptional activity also regulated by cytoplasmic signaling cascades. Here, several Gα protein subunits were tested for their ability to regulate activity. Reporter assays revealed overexpression constitutively active o subunit potentiated in absence and presence E . Transient transfection human breast cancer cell line MCF-7 showed augments ERα-regulated genes....
The p38 mitogen activated protein kinase pathway (MAPK) is known to promote cell survival, endocrine therapy resistance and hormone independent breast cancer proliferation. Therefore, we utilized the novel inhibitor RWJ67657 investigate relevance of targeting this in ER (+) line MCF-7. Our results show that inhibits both basal estrogen stimulated phosphorylation p38α, resulting decreased activation downstream p38α targets hsp27 MAPAPK. Furthermore, inhibition by blocks clonogenic survival...
Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 cancer biology is not fully understood. Triple-negative breast (TNBC) presents a clinical challenge due to aggressive nature disease lack targeted therapies. signaling contributes drug resistance metastatic progression through distinct mechanisms, including activation epithelial-to-mesenchymal transition (EMT). More...