Detection of EGFR Mutations in cfDNA and CTCs, and Comparison to Tumor Tissue in Non-Small-Cell-Lung-Cancer (NSCLC) Patients.

Lung cancer is the leading cause of cancer-related mortality worldwide. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies, based on the evaluation of mutations, have shown dramatic clinical benefits. mutation assays are mainly performed on tumor biopsies, which carry risks, are not always successful and give results relevant to the timepoint of the assay.

Label-free isolation of prostate circulating tumor cells using Vortex microfluidic technology.

There has been increased interest in utilizing non-invasive "liquid biopsies" to identify biomarkers for cancer prognosis and monitoring, and to isolate genetic material that can predict response to targeted therapies. Circulating tumor cells (CTCs) have emerged as such a biomarker providing both genetic and phenotypic information about tumor evolution, potentially from both primary and metastatic sites. Currently, available CTC isolation approaches, including immunoaffinity and size-based filtration, have focused on high capture efficiency but with lower purity and often long and manual sample preparation, which limits the use of captured CTCs for downstream analyses.

Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer.

Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses.

Label-free enumeration, collection and downstream cytological and cytogenetic analysis of circulating tumor cells.

Circulating tumor cells (CTCs) have a great potential as indicators of metastatic disease that may help physicians improve cancer prognostication, treatment and patient outcomes. Heterogeneous marker expression as well as the complexity of current antibody-based isolation and analysis systems highlights the need for alternative methods. In this work, we use a microfluidic Vortex device that can selectively isolate potential tumor cells from blood independent of cell surface expression.

Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology.

Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes.

High efficiency vortex trapping of circulating tumor cells.

Circulating tumor cells (CTCs) are important biomarkers for monitoring tumor dynamics and efficacy of cancer therapy. Several technologies have been demonstrated to isolate CTCs with high efficiency but achieve a low purity from a large background of blood cells. We have previously shown the ability to enrich CTCs with high purity from large volumes of blood through selective capture in microvortices using the Vortex Chip.

Abrupt increase in rat carotid blood flow induces rapid alteration of artery mechanical properties.

Vascular remodeling is essential to proper vessel function. Dramatic changes in mechanical environment, however, may initiate pathophysiological vascular remodeling processes that lead to vascular disease. Previous work by some of our group has demonstrated a dramatic rise in matrix metalloproteinase (MMP) expression shortly following an abrupt increase in carotid blood flow.

Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist.

The blockade of aberrant hedgehog (Hh) signaling has shown promise for therapeutic intervention in cancer. A cell-based phenotypic high-throughput screen was performed, and the lead structure (1) was identified as an inhibitor of the Hh pathway via antagonism of the Smoothened receptor (Smo). Structure-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl-3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.

1-amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity.

Abnormal activation of the Hedgehog (Hh) signaling pathway has been linked to several types of human cancers, and the development of small-molecule inhibitors of this pathway represents a promising route toward novel anticancer therapeutics. A cell-based screen performed in our laboratories identified a new class of Hh pathway inhibitors, 1-amino-4-benzylphthalazines, that act via antagonism of the Smoothened receptor. A variety of analogues were synthesized and their structure-activity relationships determined.

Roles of macrophages in flow-induced outward vascular remodeling.

Sustained hemodynamic stresses, especially sustained high blood flow, result in flow-induced outward vascular remodeling. Mechanisms that link hemodynamic stresses to vascular remodeling are not well understood. Inflammatory cells, known for their release of proteinases, including matrix metalloproteinases (MMPs), are emerging as key mediators for various tissue remodeling.

Suppression of MMP-9 by doxycycline in brain arteriovenous malformations.

Background: The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs).

Methods: Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured.

Regulation of tie2 expression by angiopoietin--potential feedback system.

To study a potential feedback system in the angiopoietin (Ang)-Tie2 system, the authors examined effects of Ang1 and Ang2 on Tie2 expression on human umbilical vein endothelial cells (HUVECs) with or without stimulation by a potent inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Ang1, but not Ang2, down-regulated Tie2 expression on HUVECs without TNF-alpha stimulation. Both Ang1 and Ang2 attenuated TNF-alpha-induced Tie2 up-regulation.