Publications by authors named "Steven Elliot"

4 Publications

  • Page 1 of 1

Novel Diphenylamine Analogs Induce Mesenchymal to Epithelial Transition in Triple Negative Breast Cancer.

Front Oncol 2019 30;9:672. Epub 2019 Jul 30.

Division of Medicinal Chemistry, School of Pharmacy, Duquesne University, Pittsburgh, PA, United States.

Epithelial to mesenchymal transition (EMT) is a cellular program that converts non-motile epithelial cells into invasive mesenchymal cells. EMT is implicated in cancer metastasis, chemo-resistance, cancer progression, and generation of cancer stem cells (CSCs). Inducing mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is proposed as a novel strategy to target triple negative and tamoxifen-resistant breast cancer. Triple negative breast cancer (TNBC) is characterized by the loss of hormone receptors, a highly invasive mesenchymal phenotype, and a lack of targeted therapy. Estrogen receptor-positive breast cancer can be targeted by tamoxifen, an ER antagonist. However, these cells undergo EMT over the course of treatment and develop resistance. Thus, there is an urgent need to develop therapeutic interventions to target these aggressive cancers. In this study, we examined the role of novel diphenylamine analogs in converting the mesenchymal phenotype of MDA-MB-231 TNBC cells to a lesser aggressive epithelial phenotype. Using analog-based drug design, a series of diphenylamine analogs were synthesized and initially evaluated for their effect on E-cadherin protein expression and changes incell morphology, which was quantified by measuring the spindle index (SI) value. Selected compound from this series increases the expression of E-cadherin, a primary marker for epithelial cells, and decreases the mesenchymal markers SOX2, ZEB1, Snail, and vimentin. The increase in epithelial markers and the decrease in mesenchymal markers are consistent with a phenotypic switch from spindle-like morphology to cobblestone-like morphology. Furthermore, Compound decreases spheroid viability, cell migration, and cell proliferation in triple negative BT-549 and tamoxifen-resistant MCF-7 breast cancer cells.
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http://dx.doi.org/10.3389/fonc.2019.00672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682674PMC
July 2019

Highly stretchable thermoset fibers and nonwovens using thiol-ene photopolymerization.

ACS Appl Mater Interfaces 2014 Aug 13;6(16):14259-65. Epub 2014 Aug 13.

McKetta Department of Chemical Engineering and ‡Texas Materials Institute, The University of Texas at Austin , 200 East Dean Keeton Street Stop C0400, Austin, Texas 78712, United States.

In this report, we describe the preparation and characterization of a new class of thermoset fibers with high elongation and elastic recovery. Integrating UV-activated thiol-ene photopolymerization and electrospinning, we demonstrate an environmentally friendly single step approach to convert small monomeric precursor molecules into highly elastic fibers and nonwoven mats. The fibers were derived by in situ photopolymerization of a trifunctional vinyl ether monomer and a tetrafunctional thiol. Although thermosets often offer good chemical and thermal stability, these fibers also have a high average elongation at break of 62%. The elastomeric nature of these vinyl-ether based fibers can be partly attributed to their subambient Tg and partly to the cross-link density, monomer structure, and resulting network homogeneity. Nonwoven mats of these fibers were also stretchable and exhibited a much higher elongation at break of about 85%. These thermoset stretchable fibers could have potential applications as textile, biomedical, hot chemical filtration, and composite materials.
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http://dx.doi.org/10.1021/am503563qDOI Listing
August 2014

Why do GPs with a special interest in headache investigate headache presentations with neuroradiology and what do they find?

J Headache Pain 2011 Dec 29;12(6):625-8. Epub 2011 Sep 29.

Horizon Centre, 94 Littleton Road, Salford, M7 3SE, UK.

The general practitioner with a special interest in headache offers an important contribution to the management of headache in primary care where the majority of presentations take place. A number of guidelines have been developed for neuroradiological investigation of headache, but their clinical utility and relevance is not known. Fourteen general practitioners with a special interest in headache recorded consecutive headache consultations over a 3-month period, whether patients were investigated with neuroradiology and if so the reason for investigation and outcome. Reason for investigation was compared to the guidelines published for the use in primary care. 895 patients were seen, of whom 270 (30.1%) were investigated. 47% of indications were outside the guidance framework used, the most common reason for investigation being reassurance. Of those investigated, 5.6% showed positive findings but only 1.9% of findings were felt to be of clinical significance. General practitioners with a special interest investigated with neuroradiology a greater level than general practitioners, but less than neurologists. However, yields of significant findings are broadly comparative across all groups. This report confirms other studies that suggest that even when there is a high level of clinical suspicion, yields of significant findings are very low.
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http://dx.doi.org/10.1007/s10194-011-0375-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208048PMC
December 2011

Dynamic regulation of ROCK in tumor cells controls CXCR4-driven adhesion events.

J Cell Sci 2010 Feb 5;123(Pt 3):401-12. Epub 2010 Jan 5.

Department of Oral Biology, LSU Health Sciences Center, New Orleans, LA 70112, USA.

CXCR4 is a chemokine receptor often found aberrantly expressed on metastatic tumor cells. To investigate CXCR4 signaling in tumor cell adhesion, we stably overexpressed CXCR4 in MCF7 breast tumor cells. Cell attachment assays demonstrate that stimulation of the receptor with its ligand, CXCL12, promotes adhesion of MCF7-CXCR4 cells to both extracellular matrix and endothelial ligands. To more closely mimic the conditions experienced by a circulating tumor cell, we performed the attachment assays under shear stress conditions. We found that CXCL12-induced tumor cell attachment is much more pronounced under flow. ROCK is a serine/threonine kinase associated with adhesion and metastasis, which is regulated by CXCR4 signaling. Thus, we investigated the contribution of ROCK activity during CXC12-induced adhesion events. Our results demonstrate a biphasic regulation of ROCK in response to adhesion. During the initial attachment, inhibition of ROCK activity is required. Subsequently, re-activation of ROCK activity is required for maturation of adhesion complexes and enhanced tumor cell migration. Interestingly, CXCL12 partially reduces the level of ROCK activity generated by attachment, which supports a model in which stimulation with CXCL12 regulates tumor cell adhesion events by providing an optimal level of ROCK activity for effective migration.
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http://dx.doi.org/10.1242/jcs.052167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816185PMC
February 2010
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