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Research Roundup

Posted by Kathy Whitney on Friday, March 19, 2021 in Around the Medical Center, Spring 2021 .

Polymer protection for heart muscle

Following an ischemic event that disrupts oxygen supply to the heart, such as myocardial infarction or cardiac arrest, the return of blood flow can result in additional cellular injury, known as reperfusion injury.

Studies have suggested that Poloxamer 188 (P188), a polymer with hydrophobic and hydrophilic chemical properties, can stabilize cell membranes and protect cardiac muscle when given before or during the ischemic event.

Matthias Riess, MD, PhD, and colleagues studied the effects of P188 delivered at the beginning of reperfusion, a clinically important time frame for preserving cell function. They used hypoxia/reoxygenation of an in vitro cardiomyocyte system to simulate ischemia/reperfusion. They showed that reoxygenation potentiated injury caused by hypoxia; P188 dose-dependently protected cardiac muscle cells from reoxygenation injury; and the hydrophobic portion of the P188 polymer is necessary.

The findings, reported in Pharmacology Research & Perspectives, support continued study of P188 as a potential therapy to prevent reperfusion injury.


New therapeutic target for lung cancer

Continuous activation of cell surface receptors increases signaling that can promote oncogenic transformation. One receptor, EphA2, has been identified as a driver of lung cancer, but its interacting partners are not well characterized.

Reporting in Molecular Cancer Research, Jin Chen, MD, PhD, Dana Brantley-Sieders, PhD, and colleagues have identified a novel interactor of EphA2 that promotes growth of non-small cell lung cancer.

Using a yeast-two-hybrid screen where EphA2 acts as a bait protein and a library of potential interactors from lung cancer cells acts as prey, the researchers found that the enzyme PLCgamma1 strongly interacts with EphA2. In human lung cancer cells, genetic or pharmacologic inhibition of EphA2 kinase activity decreased the phosphorylation (activation) of PLCgamma1 and the loss of PLCgamma1 inhibited tumor cell growth in vitro. Knockout of PLCgamma1 by CRISPR- mediated genome editing also impaired tumor growth in a mouse lung cancer model.

The EphA2-PLCgamma1 signaling axis thus is a potential therapeutic target for the treatment of EphA2-driven lung cancers.


MRI view of brain tumor prognosis

Clinical investigations in neuro-oncology have focused mostly on brain tumors, with less exploration of the surrounding normal brain tissue and cerebrospinal fluid (CSF) — the supporting environment for brain tumors.

Akshitkumar Mistry, MD, and colleagues analyzed total volumes of tumor- and brain-related features on pre-operative magnetic resonance images (MRIs) of 210 adult glioblastoma patients from a single institution. They used a fully automated tool to analyze the MRIs.

The investigators found that higher edema levels (tumor-related) and higher CSF volume (brain-related) detected at diagnosis were independently associated with decreased survival in glioblastoma patients. They confirmed the findings in a second dataset of 96 glioblastoma patients from The Cancer Imaging Archive.

The findings, reported in the Journal of Clinical Neuroscience, highlight the importance of broader quantitative imaging analyses of brain tumors and invite efforts to understand the tumor-related causes of increased edema and CSF volume.