Knocking Out Melanoma: Does This Triple Combo Have What It Takes?

3-Way Knockout of MelanomaIt would be great if we could knock out cancer with a single punch. But the more we learn about cancer’s molecular complexities and the immune system’s response to tumors, the more it appears that we may need a precise combination of blows to defeat a patient’s cancer permanently, with no need for a later rematch. One cancer that provides us with a ringside seat on the powerful potential—and tough challenges—of targeted combination therapy is melanoma, especially the approximately 50% of advanced tumors with a specific “driver” mutation in the BRAF gene [1].

Drugs that target cells carrying BRAF mutations initially provided great hope for melanoma, with many reports of dramatic shrinkage of tumors in patients with advanced disease.  But almost invariably, the disease recurred and was no longer responsive to those same drugs.  A few years ago, researchers thought they’d come up with a solid combination to fight BRAF-mutant melanoma: a one-two punch that paired a BRAF-inhibiting drug with an agent that sensitized the immune system [2]. However, when that combo was tested in humans, the clinical trial had to be stopped early because of serious liver toxicity [3]. Now, in a mouse study published in Science Translational Medicine, NIH-funded researchers at the University of California, Los Angeles (UCLA) provide renewed hope for a safe, effective combination therapy for melanoma—with a strategy that adds a third drug to the mix [4].

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Diaper Compound Brings Change to Cell Microscopy

Traditional vs. Expansion Microscopy

Caption: Mouse brain tissue as viewed by traditional microscopy (left) and expansion microscopy (right), which makes it possible to visualize individual synapses (example in white box). In both views, green indicates neurons; blue, pre-synaptic proteins; and red, post-synaptic proteins.
Credit: Ed Boyden, Fei Chen, Paul Tillberg, MIT

Light microscopy has been a mainstay of neuroscience and many areas of biology for more than a century. But the resolution limit of light, based on immutable physical principles, has kept the fine details of many structures out of view. Scientists can’t change the laws of physics—but NIH-supported researchers recently devised a highly creative way to see images that were previously out of reach, by expanding the contents of tissue sections up to five times their normal size, while maintaining the anatomic arrangements. The new approach takes advantage of a compound used in—get this—disposable diapers!

By harnessing the super-absorbent properties of sodium polyacrylate, a polymer commonly used in diapers, a team from the Massachusetts Institute of Technology (MIT) developed a new technique that makes it possible for conventional microscopes to produce super high-resolution images of brain cells. The name of the new technique? Expansion microscopy.

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Precision Medicine: Who Benefits from Aspirin to Prevent Colorectal Cancer?

Aspirin and DNA StethoscopeIn recent years, scientific evidence has begun to accumulate that indicates taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) on a daily basis may lower the risk of developing colorectal cancer. Now, a new study provides more precise information on who might benefit from this particular prevention strategy, as well as who might not.

Published in the journal JAMA, the latest work shows that, for the majority of people studied, regular use of aspirin or NSAIDs was associated with about a one-third lower risk of developing colorectal cancer. But the international research team, partly funded by NIH, also found that not all regular users of aspirin/NSAIDs reaped such benefits—about 9 percent experienced no reduction in colorectal cancer risk and 4 percent actually appeared to have an increased risk [1]. Was this just coincidence, or might there be a biological explanation?

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LabTV: Young Scientist Curious About The Immune System

video of Heardley Moses Murdock
Welcome to LabTV! If you haven’t already, take a look at this video. I hope you will enjoy meeting the first young scientist featured in this brand new series that I’ve chosen to highlight on my blog. The inspiration for LabTV comes from Jay Walker, who is the founder of PriceLine, and curator and chairman of TEDMED, an annual conference focused on new ideas in health and medicine.

A few years ago, Walker noticed that there were many talented young people across America who are interested in science, but are uncertain about what a career in biomedical research is like. His solution was to create an online video community where anyone interested in going into research could learn from the experiences of scientists who, not so long ago, walked in their shoes. As you will see from spending a few moments in the lab with Heardley Moses Murdock, whose research involves a rare immune disorder called DOCK 8 deficiency, these video profiles put a human face on science and show its everyday stories.

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What Makes Our Brain Human? The Search for Answers

The Thinker

“The Thinker” by Auguste Rodin (photo by Brian Hillegas)

Humans’ most unique traits, such as speaking and abstract thinking, are rooted in the outer layer of our brains called the cerebral cortex. This convoluted sheet of grey matter is found in all mammals, but it is much larger and far more complex in Homo sapiens than in any other species. The cortex comprises nearly 80 percent of our brain mass, with some 16 billion neurons packed into more than 50 distinct, meticulously organized regions.

In an effort to explore the evolution of the human cortex, many researchers have looked to changes in the portion of the genome that codes for proteins. But a new paper, published in the journal Science [1], shows that protein-coding DNA provides only part of the answer. The new findings reveal that an even more critical component may be changes in the DNA sequences that regulate the activity of these genes.

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