Search results for "Estro."
showing 10 items of 770 documents
Abstract PD3-06: Neratinib + fulvestrant for HER2-mutant, HR-positive, metastatic breast cancer: Updated results from the phase 2 SUMMIT trial
2019
Abstract Background: HER2 mutations define a rare subset of metastatic breast cancer (MBC) with a unique mechanism of oncogenic addiction to HER2 signaling. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated single-agent clinical activity in HER2-mutant MBC. In HER2-mutant, HR+ MBC, neratinib + fulvestrant (N+F) appears synergistic vs single-agent neratinib, possibly due to more complete inhibition of bi-directional signaling between HER2 and estrogen receptors. Here we describe interim efficacy results of the expanded HER2-mutant, HR+ MBC cohort treated with N+F from SUMMIT (NCT01953926). Methods: HR+ MBC patients (pts) with HER2 mutations documented by local te…
The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial
2021
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evalu…
Epidemiology and biological characteristics of male breast cancer in Italy.
2020
Aim: To evaluate the epidemiology of male breast cancer (MBC) in Italy and to describe incidence and survival data in relation to age, morphology, year of incidence, geographic area, and possible association with other cancers compared with female BC. Methods: Cases were extracted from 40 Italian Cancer Registries. Standardized incidence rates (SIR), age-specific rates, and 5-year survival were calculated. The association with second tumors was also evaluated. All data were compared with data from female BCs. Results: In the 2000–2014 period, 2175 new cases of MBC were registered, with an SIR of 1.7 × 100,000. The incidence showed a slight upward trend and increased with increasing age. The…
Design and protocol of Estrogenic Regulation of Muscle Apoptosis (ERMA) study with 47 to 55-year-old women's cohort : novel results show menopause-re…
2018
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Palbociclib - from Bench to Bedside and Beyond.
2016
Endocrine therapy is the cornerstone in the treatment of hormone receptor-positive breast cancer. During the last decades, much has been learned about the subtle regulation of the cell cycle. In this tightly regulated network, cyclin-dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key regulator of the G1-S transition. Realizing its importance, specific inhibitors of CDK4/6 were developed. The drug most advanced in clinical development in this class is palbociclib (PD 0332991). This review highlights preclinical data and brings into focus early clinical trials that led to an accelerated approval by the US Food and Drug Administration (FDA) as first-line treatment in co…
Is Danggui Safe to be Taken by Breast Cancer Patients?-A Skepticism Finally Answered by Comprehensive Preclinical Evidence.
2019
Angelica sinensis (AS, Danggui) has long been regarded to stimulate breast cancer growth; hence, the use of AS in breast cancer patients remains a major concern for both patients and practitioners. Since safety studies of herbs would be unethical to carry out in patients, the present study aimed to investigate the potential unsafe effects of AS in a systematic pre-clinical approach. Human breast cancer cells, breast orthotopic tumor-bearing mouse models, as well as primary breast cancer cells from patients’ tumors were used to evaluate the effect of AS hot water extract on the progression of breast tumors and/or growth of breast cancer cells. We showed that AS is not that stimulatory in bre…
Estrogen Receptor Signaling and the PI3K/Akt Pathway Are Involved in Betulinic Acid-Induced eNOS Activation
2016
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antiviral and anti-cancer properties. Beneficial cardiovascular effects such as increased nitric oxide (NO) production through enhancement of endothelial NO synthase (eNOS) activity and upregulation of eNOS expression have been demonstrated for this compound. In the present study, immortalized human EA.hy 926 endothelial cells were incubated for up to 1 h with 1–100 µM BA and with the phosphatidylinositol-3-kinase (PI3K) inhibitors LY294002 and wortmannin, or the estrogen receptor (ER) antagonist ICI 182,780. Phosphorylation status of eNOS and total eNOS protein were analyzed by Western blotting us…
MicroRNA as crucial regulators of gene expression in estradiol-treated human endothelial cells.
2018
Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cel…
Neurotoxicity of zearalenone’s metabolites and beauvericin mycotoxins via apoptosis and cell cycle disruption
2021
Cell cycle progression and programmed cell death are imposed by pathological stimuli of extrinsic or intrinsic including the exposure to neurotoxins, oxidative stress and DNA damage. All can cause abrupt or delayed cell death, inactivate normal cell survival or cell death networks. Nevertheless, the mechanisms of the neuronal cell death are unresolved. One of the cell deaths triggers which have been wildly studied, correspond to mycotoxins produced by Fusarium species, which have been demonstrated cytotoxicity and neurotoxicity through impairing cell proliferation, gene expression and induction of oxidative stress. The aim of present study was to analyze the cell cycle progression and cell …
Regulatory network analysis in estradiol-treated human endothelial cells.
2021
Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a com-prehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miR-NA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17ß- Estradiol (E2) (1 nmol/lL, 24 h). miRNA--mRNA pairings and their associated canonical pat…