Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

Beth Israel Deaconess Medical Center

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

General-heavy army disastrous in immune battle

Immunologists have identified two big groups of T cells: “helper” CD4+ cells and “killer” CD8+ cells.* The helper cells can produce immune regulatory molecules and promote antibody responses, while the killer cells recognize and destroy virally-infected cells.

A vaccine against a virus that stimulates only helper CD4+ cells leads to uncontrolled lethal inflammation in mice once the animals are challenged with the virus, a recent paper in Science shows. Emory Vaccine Center director Rafi Ahmed is a co-author.

Senior author Dan Barouch, from Harvard/Beth Israel Deaconess Medical Center, tells The Scientist that CD4+ cells are like generals directing the battle of the immune system and “if you just have strategic generals and no soldiers, it turns out to be worse than having no army at all.” Rebalancing the system with antiviral CD8+ T cells or antibodies helps limit the problems.

The findings mesh with work by Yerkes investigators [Guido Silvestri and colleagues] suggesting that HIV vaccines that boost CD4+ cells in gateway mucosal tissues lead to higher rates of infection. In both cases, the lesson is: having more helper CD4+ T cells around actually does not help. Read more

Posted on by Quinn Eastman in Immunology Leave a comment