Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel effective targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family of transcriptional regulators, commonly mutated in TNBC, in determining the phenotypic response to the AurA inhibitor alisertib (MLN8237). Alisertib exhibited potent antiproliferative and proapoptotic activity in a subset of TNBC models. The induction of apoptosis in response to alisertib exposure was dependent on p53 and p73 activity. In the absence of functional p53 or p73, there was a shift in the phenotypic response following alisertib exposure from apoptosis to cellular senescence. In addition, senescence was observed in patient-derived tumor xenografts with acquired resistance to alisertib treatment. AurA inhibitors are a promising class of novel therapeutics in TNBC. The role of p53 and p73 in mediating the phenotypic response to antimitotic agents in TNBC may be harnessed to develop an effective biomarker selection strategy in this difficult to target disease.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425647 | PMC |
| http://dx.doi.org/10.1158/1535-7163.MCT-14-0538-T | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mapping quantitative trait loci regions associated with Marek's disease on chicken autosomes by means of selective DNA pooling.
Sci Rep
December 2024
Hy-Line International, 2583 240th St, PO Box 310, Dallas Center, 50063, IA, USA.
Marek's Disease (MD), which can result in neurological damage and tumour formation, has large effects on the economy and animal welfare of the poultry industry worldwide. Previously, we mapped autosomal MD QTL regions (QTLRs) by individual genotyping of an F population from a full-sib advanced intercross line. We further mapped MD QTLRs on the chicken Z chromosome (GGZ) using the same F population, and by selective DNA pooling (SDP) of 8 elite egg production lines.
View Article and Find Full Text PDFPeripheral contributions to resting state brain dynamics.
Nat Commun
December 2024
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, US.
The correlational structure of brain activity dynamics in the absence of stimuli or behavior is often taken to reveal intrinsic properties of neural function. To test the limits of this assumption, we analyzed peripheral contributions to resting state activity measured by fMRI in unanesthetized, chemically immobilized male rats that emulate human neuroimaging conditions. We find that perturbation of somatosensory input channels modifies correlation strengths that relate somatosensory areas both to one another and to higher-order brain regions, despite the absence of ostensible stimuli or movements.
View Article and Find Full Text PDFMolecular epidemiology of invasive group B Streptococcus in South Africa, 2019-2020.
J Infect Dis
December 2024
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa.
Background: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development.
Methods: Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020.
JAK inhibition decreases the autoimmune burden in Down syndrome.
Elife
December 2024
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States.
Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.
Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.
Enhancing human ACE2 expression in mouse models to improve COVID-19 research.
FEBS Open Bio
December 2024
Guangzhou National Laboratory, Guangzhou, China.
Mice are one of the most common biological models for laboratory use. However, wild-type mice are not susceptible to COVID-19 infection due to the low affinity of mouse ACE2, the entry protein for SARS-CoV-2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID-19 manifestations and their utility in viral studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!