Stage fright: don't get over it, get used to it

Many can feel empathy with the situation Banerjee describes: facing “a room full of scientists, who for whatever reason, did not look very happy that Read more

Beyond birthmarks and beta blockers, to cancer prevention

Ahead of this week’s Morningside Center conference on repurposing drugs, we wanted to highlight a recent paper in NPJ Precision Oncology by dermatologist Jack Arbiser. It may represent a new chapter in the story of the beta-blocker propranolol. Several years ago, doctors in France accidentally discovered that propranolol is effective against hemangiomas: bright red birthmarks made of extra blood vessels, which appear in infancy. Hemangiomas often don’t need treatment and regress naturally, but some can lead Read more

Drying up the HIV reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo, the brain or the Read more

NSAIDs

Anti-inflammatory approach suppresses cancer metastasis in animal models

An anti-inflammatory drug called ketorolac, given before surgery, can promote long-term survival in animal models of cancer metastasis, a team of scientists has found. The research suggests that flanking chemotherapy with ketorolac or similar drugs — an approach that is distinct from previous anti-inflammatory cancer prevention efforts — can unleash anti-tumor immunity.

The findings, published in Journal of Clinical Investigation, also provide a mechanistic explanation for the anti-metastatic effects of ketorolac, previously observed in human breast cancer surgery.

Medical writer Ralph Moss has a great summary of this background. A commentary accompanying the JCI paper concludes: ” If this can be translated from mouse models into the clinic, then it could revolutionize treatments.”

Vikas P. Sukhatme, MD, ScD, dean of Emory University School of Medicine, is senior author of the JCI paper. He was previously at Beth Israel Deaconess Medical Center and Harvard Medical School, with lead authors Dipak Panigrahy, MD and Allison Gartung, PhD.

“Collectively, our findings suggest a potential paradigm shift in our approach to resectable cancers,” says Sukhatme. “Clinical trials are now urgently needed to validate these animal studies.”

Most cancer-related deaths come from metastases, the spread of cancer cells from a primary tumor to surrounding tissues or distant organs. The cells that seed metastases are often in microscopic clusters – a surgeon can’t see them. Chemotherapy, typically given after or prior to surgery is aimed at eradicating these cancer cells in the hopes of preventing cancer recurrence.  However, chemotherapy can sometimes stir up inflammation, promoting metastasis.

“Cancer therapy is a double-edged sword,” says Panigrahy. “Surgery and chemotherapy can induce an inflammatory or immunosuppressive injury response that promotes dormant metastatic cells to start proliferating, leading to tumor recurrence.”

Ketorolac is an inexpensive NSAID (nonsteroidal anti-inflammatory drug). Because of concern over side effects, it is only approved by the FDA for short-term pain management “at the opioid level.” It differs from other NSAIDs in that it preferentially inhibits the enzyme COX-1, more than COX-2. Other studies of prevention of cancer recurrence have focused on COX-2 inhibitors. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Drug discovery: selective anti-inflammatory approach to AD

Anyone familiar with Alzheimer’s disease research can say what a challenge drug development has been. In Emory’s Department of Pharmacology, Thota Ganesh is focusing on an anti-inflammatory approach. Ganesh’s work has been supported by the Alzheimer’s Drug Discovery Foundation and more recently by a five-year, $3.6 million grant from the National Institute on Aging.

Medicinal chemist Thota Ganesh, PhD, is focusing on an anti-inflammatory approach to Alzheimer’s disease, targeting the prostaglandin receptor EP2.

An assistant professor at Emory since 2011, he is continuing research he undertook with Ray Dingledine on EP2 antagonists. In animals, they showed that this class of compounds could reduce injury to the brain after a prolonged seizure. Since then, they have shown that EP2 antagonists have similar effects in protecting against organophosphate pesticides/nerve agents.

EP2 is one of the four receptors for prostaglandin E2, a hormone involved in processes such as fever, childbirth, digestion and blood pressure regulation. Before Ganesh and colleagues from the Emory Chemical Biology Discovery Center started looking for them, chemicals that could block EP2 selectively were not available.

Their idea is: blocking EP2 is a better strategy than the more general approach of going after prostaglandins, the targets for non-steroid anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and celecoxib (Celebrex). Read more

Posted on by Quinn Eastman in Neuro Leave a comment