More NMDA but less excitotoxicity? Now possible

Many researchers have wanted to enhance NMDA receptor signals to treat disorders such as schizophrenia. But at the same time, they need to avoid killing neurons with “excitotoxicity”, which comes from excess calcium entering the Read more

Update on pancreatic cancer: images and clinical trial

In 2018, Winship magazine had a feature story on pancreatic cancer. Our team developed an illustration that we hoped could convey the tumors’ complex structure, which contributes to making them difficult to treat. Oncologist Bassel El-Rayes described how the tumors recruit other cells to form a protective shell. "If you look at a tumor from the pancreas, you will see small nests of cells embedded in scar tissue," he says. "The cancer uses this scar Read more

New animal model for elimination of latent TB

An animal model could help researchers develop shorter courses of treatment for latent Read more

cancer prevention

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.

Infantile hemangioma (stock photo)

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 to complications because they compromise other organs. Infants receiving propranolol require close monitoring to ensure that they do not suffer from side effects related to propranolol’s beta blocker activity, such as slower heart rate or low blood sugar.

Arbiser’s lab showed that only one of two mirror-image forms of propranolol is active against endothelial or hemangioma cells, but it is the inactive one, as far as being a beta-blocker. Many researchers were already looking at repurposing propranolol based on its anti-cancer properties. The insight could be a way to avoid beta-blocker side effects, even beyond hemangiomas to malignant tumors. Check out the Office of Technology Transfer’s feature on this topic. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

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