Publications by authors named "Elena Wang"

3 Publications

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Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.

Pancreas 2021 Apr;50(4):524-528

From the Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Objectives: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood.

Methods: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting.

Results: The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 ≥5-fold) in AsPC-1 and 2584 genes (339 ≥5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt.

Conclusions: The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.
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April 2021

Nox4-dependent upregulation of S100A4 after peripheral nerve injury modulates neuropathic pain processing.

Free Radic Biol Med 2021 05 28;168:155-167. Epub 2021 Mar 28.

Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany. Electronic address:

Previous studies suggested that reactive oxygen species (ROS) produced by NADPH oxidase 4 (Nox4) affect the processing of neuropathic pain. However, mechanisms underlying Nox4-dependent pain signaling are incompletely understood. In this study, we aimed to identify novel Nox4 downstream interactors in the nociceptive system. Mice lacking Nox4 specifically in sensory neurons were generated by crossing Advillin-Cre mice with Nox4 mice. Tissue-specific deletion of Nox4 in sensory neurons considerably reduced mechanical hypersensitivity and neuronal action potential firing after peripheral nerve injury. Using a proteomic approach, we detected various proteins that are regulated in a Nox4-dependent manner after injury, including the small calcium-binding protein S100A4. Immunofluorescence staining and Western blot experiments confirmed that S100A4 expression is massively up-regulated in peripheral nerves and dorsal root ganglia after injury. Furthermore, mice lacking S100A4 showed increased mechanical hypersensitivity after peripheral nerve injury and after delivery of a ROS donor. Our findings suggest that S100A4 expression is up-regulated after peripheral nerve injury in a Nox4-dependent manner and that deletion of S100A4 leads to an increased neuropathic pain hypersensitivity.
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May 2021

A rapid detection method for apoptosis and necrosis measurement using the Cellometer imaging cytometry.

Apoptosis 2011 Dec;16(12):1295-303

Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA 01843, USA.

Apoptosis and necrosis play an important role in various aspects of preclinical pharmaceutical drug discovery and validation. The ability to quickly determine the cytotoxic effect of chemical compounds on cancer cells allows researchers to efficiently identify potential drug candidates for further development in the pharmaceutical discovery pipeline. Recently, a new imaging cytometry system has been developed by Nexcelom Bioscience LLC (Lawrence, MA, USA) for fluorescence-based cell population analysis. Currently, fluorescence-based cell death assays have not been demonstrated by the Cellometer system, which can potentially provide a quick, simple, and inexpensive alternative method for smaller biomedical research laboratories. In this study, we demonstrate for the first time the use of Cellometer imaging cytometry for necrosis/apoptosis detection by studying the dose-response effect of heat and drug-induced cell death in Jurkat cells labeled with annexin V-FITC (apoptotic) and propidium iodide (necrotic). The experimental results were evaluated to validate the imaging cytometric capabilities of the Cellometer system as compared to the conventional flow cytometry. Similar cell population results were obtained from the two methods. The ability of Cellometer to rapidly and cost-effectively perform fluorescent cell-based assays has the potential of improving research efficiency, especially where a flow or laser scanning cytometer is not available or in situations where a rapid analysis of data is desired.
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December 2011