A5047808879- Estrogen and related hormone effects
- Kruppel-like factors research
- TGF-β signaling in diseases
- Bone Metabolism and Diseases
- HER2/EGFR in Cancer Research
- Genetic Syndromes and Imprinting
- Cancer-related cognitive impairment studies
- Cancer-related gene regulation
- Muscle Physiology and Disorders
- Cytokine Signaling Pathways and Interactions
- Advanced Breast Cancer Therapies
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- Bone health and treatments
- Tendon Structure and Treatment
- Connexins and lens biology
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Retinoids in leukemia and cellular processes
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
- Pharmacogenetics and Drug Metabolism
- Male Breast Health Studies
- Menopause: Health Impacts and Treatments
- Ovarian cancer diagnosis and treatment
Mayo Clinic
2016-2025
Mayo Clinic in Arizona
2016-2025
WinnMed
2015-2024
Mayo Clinic in Florida
2023
John Wiley & Sons (United States)
2020
University of Minnesota Rochester
2016-2019
Cancer Research UK Cambridge Center
2019
Cambridge University Hospitals NHS Foundation Trust
2017
Addenbrooke's Hospital
2017
Takeda (France)
2017
Tamoxifen has been the most important therapeutic agent for treatment of estrogen receptor (ER)-positive breast cancer past three decades. is extensively metabolized by cytochrome P450 enzymes, and recent in vivo studies have shown that women with genetically impaired 2D6 reduced production endoxifen a higher risk recurrence. Despite these observations, contribution to overall drug effectiveness tamoxifen remains uncertain. Here, we provide novel evidence potent antiestrogen functions part...
Age-related cataract, an opacity of the eye lens, is leading cause visual impairment in elderly, etiology which related to oxidative stress damage. Oxidation methionine sulfoxide a major product that reaches levels as high 60% cataract while being essentially absent from clear lenses. Methionine oxidation results loss protein function can be reversed through action reductase A (MsrA), implicated protection and essential regulator longevity species ranging Escherichia coli mice. To establish...
Background Male breast cancer (MBC) is a rare disease for which there limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to III diagnosed between 2004 2014 in the National Cancer Data Base were included. Trends modalities described using average annual percentage change (AAPC) estimated Joinpoint software analysis trends. Kaplan‐Meier curves multivariate Cox proportional hazards regression model used compare survival subgroups identify Results A...
Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17β-estradiol (17β-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related dysfunction reduced body mass, ectopic lipid deposition without decreasing lean mass. These declines were reductions energy intake due to the activation hypothalamic anorexigenic pathways direct...
Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription defined subsets genes in various systems. In this study we examined role BRD4 promoting lineage-specific show that osteoblast differentiation. Genome-wide analyses demonstrate recruited transcriptional start site differentiation-induced genes. Unexpectedly, while...
Estrogen Receptor-β (ERβ) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role progression. Much of the confusion around ERβ stems from antibodies that are inadequately validated, yet have become standard tools for deciphering role. Using an ERβ-inducible cell system we assessed commonly utilized show one most used antibodies, NCL-ER-BETA, non-specific ERβ. Other limited specificity or only specific...
Perturbations in skeletal development and bone degeneration may result reduced mass quality, leading to greater fracture risk. Bone loss is mitigated by protective therapies, but there a clinical need for new bone-anabolic agents. Previous work has demonstrated that Ezh2 (enhancer of zeste homolog 2), histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation osteogenic progenitors. Here, we investigated whether inhibition can be leveraged stimulatory applications....
Peroxisome proliferator-activated receptor gamma (PPARγ) is emerging as a major regulator in neurological diseases. However, the role of and its co-regulators cerebrovascular endothelial dysfunction after stroke unclear. Here, we have demonstrated that activation by pioglitazone significantly inhibited both oxygen–glucose deprivation-induced cerebral vascular cell death middle artery occlusion-triggered damage. Consistent with this finding, selective genetic deletion cells resulted increased...
Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, clinical Eligibility included endocrine-refractory, estrogen receptor-positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by 3+3 design expansion at 40, 80, 100 mg per day. Tumor...
N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated positively correlated with poor survival patients wild-type p53-expressing prostate cancer (PCa). RIP-seq analysis revealed knockout increased methylation a subset p53 transcriptional target genes (e.g., FAS,...
Transcriptional control of Runx2 gene expression through two alternative promoters (P1 and P2) is critical for the execution its function as an osteogenic cell fate determining factor. In all vertebrates examined to date, bone related P1 promoter contains a purine-rich region (-303 -128 bp in rat) that separates regulatory domains. The length this differs dramatically between species even within same order. Using deletion analysis, we show part (-200 -128) containing duplicated element...
We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). However, relevance ERβ mediating action has yet to be explored. Here, we characterize molecular actions and examine its effectiveness as an agent these cell lines. MCF7, Hs578T U2OS were stably transfected with full-length ERβ. protein stability, dimer formation ERα expression...
Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end T-cell leukemia 1A (TCL1A) gene were musculoskeletal pain in women on adjuvant AI for We also showed estrogen-dependent, SNP-modulated variation TCL1A expression and, preliminary experiments, could induce IL-17RA expression. present set out to...
The role and clinical value of ERβ1 expression is controversial recent data demonstrates that many ERβ antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize across all sub-types breast cancer using a validated antibody determine the roles this receptor in mediating response multiple forms endocrine therapy both presence absence ERα expression. Nuclear cytoplasmic patterns were analyzed three patient cohorts, including retrospective analysis...
Significance Triple-negative breast cancer (TNBC) is the most aggressive form of and patients exhibit high rates recurrence mortality in part due to lack treatment options beyond standard-of-care chemotherapy regimens. In subset TNBCs that express estrogen receptor beta (ERβ), ligand-mediated activation ERβ elicits potent anticancer effects. We report here elucidation cistrome transcriptome TNBC identify a mechanism whereby induces cystatin gene expression resulting inhibition canonical TGFβ...
TGFβ-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges resolving this functional dichotomy may uncover new strategies to treat advanced carcinomas. The Krüppel-like transcription factor, KLF10, is pivotal effector of TGFβ/SMAD mediates antiproliferative effects TGFβ. In study, we show how KLF10 opposes the prometastatic TGFβ by limiting its ability induce...
Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves parameters slows aging in male mice. The mechanisms elicits these benefits unresolved. Herein, we show that similar genomic binding transcriptional activation through estrogen receptor α (ERα) to 17β-estradiol. In addition, the ablation ERα...
CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of regulatory (Tregs) is critical the development insulin resistance diabetes. Although cytokine control this process well understood, transcriptional regulation not. KLF10, a member Kruppel-like transcription factor family, an emerging regulator immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice identified predisposition to obesity, resistance, fatty liver due defects Treg mobilization...
Abstract Chemotherapy-induced cognitive impairment (CICI) is often reported as a neurotoxic side effect of chemotherapy. Although CICI has emerged significant medical problem, meaningful treatments are not currently available due to lack mechanistic understanding underlying pathophysiology. Using the platinum-based chemotherapy cisplatin model for CICI, we show here that suppresses nicotinamide adenine dinucleotide (NAD+) levels in adult female mouse brain vivo and human cortical neurons...