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An Engineered Protein Can Kill Cancer Cells in the Bloodstream

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Most cancer research focuses on the mechanisms of tumor development, despite the fact that tumor metastasis—the spread of tumor cells—is responsible for approximately 90 percent of cancer deaths. The team in the lab of professor Michael King at Cornell’s Meinig School of Biomedical Engineering has made a breakthrough discovery that could change the focus of cancer treatment by targeting the cells that lead to metastasis. Their study, published today in the Journal of Controlled Release, shows that a protein they engineered to fit onto nanoparticles successfully kills tumor cells in the bloodstreams of mice with prostate cancer.

King’s lab engineered tiny lipids called liposomes, which are approximately one-one-hundredth the size of white blood cells, with a protein known as TRAIL (tumor necrosis factor related apoptosis-inducing ligand) to create the nanoparticles. Once they are injected into the bloodstream, TRAIL proteins attach to white blood cells, called leukocytes, as they travel through the bloodstream and kill the cancer cells. 

“When we made these particles and introduced them to the bloodstream of the mice we were able to kill all the cancer cells in blood flow within a couple hours. This therapeutic worked so well, it was like a key fitting a lock. It solved the puzzle,” King tells mental_floss.

Mice in the control groups (“Buffer” and “ES”) showed widespread metastasis to internal organs, as indicated by the color map. In contrast, mice treated with E-selectin/TRAIL liposomes (“ES/T”) showed no spread of cancer to the other organs—as well as a reduction of the tumor burden in the prostate. Image credit: Wayne et al. in Journal of Controlled Release

King’s lab had previously been studying ways to kill cancer cells by getting the cells to adhere to a medical device, which killed them. “Our breakthrough was, instead of making medical device surfaces toxic to cancer cells, we took the adhesion TRAIL molecules and put them on the surface of nanoparticles," he says. "When we flipped the geometry like that, and injected those proteins into the bloodstream or lymphatic system, we had really astounding success.”

To test the protein’s cancer-killing abilities, cancerous cells were surgically introduced into the healthy mice, giving them prostate cancer. When the mice developed tumors in their prostates big enough for researchers to feel and see, tumor cells began to release into the blood and move throughout the body, which “is what happens in human disease as well,” says King.

Their hope was that injecting TRAIL into the bloodstream and lymphatic systems of the mice would prevent new tumors forming in distant organs. The results were even better than that. “It was a total success. It prevented metastases, and shrunk the original tumor in size, which we weren’t even expecting. That was a bonus,” King says. 

A chart showing the organization of the study. They started treatment on the mice three weeks after tumor implantation and repeated it every three days until the endpoint of the trial, at nine weeks. The mice were imaged once per week to track tumor growth. Image credit: Wayne et al. in Journal of Controlled Release

The TRAIL treatment is promising as a cancer therapeutic in humans, says King, because the protein is a natural product made by immune cells and has already been tested in humans. “We just make more of it and put it in the right place. It’s very well tolerated by human patients, with no side effects,” he says. “Dosages that we use in our system to completely prevent metastases are 1% of the dosages that have already been safely used in humans. We anticipate no adverse effects.”

They believe it has great potential as a therapy in association with cancer-removal surgeries or biopsies. “We think maybe just one dose before surgery and one or more dosages after surgery could have a noticeable and very successful suppression or prevention of metastases,” says King. “That’s something we still need to prove with animal trials. Any intervention, even needle biopsy, is a potential route for disseminating tumor cells all over the body. Scheduled surgery is a situation where you know when that event will occur so why not time it perfectly with a small number of doses.” 

Their next study will look at treating metastasis in breast cancer using a mouse model. “We would be treating the mouse exactly the way the human disease would be treated, so that would be very convincing if we are successful.”

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Medicine
Why Haven't We Cured Cancer Yet?
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Walkathons, fundraisers, and ribbon-shaped bumper stickers raise research dollars and boost spirits, but cancer—the dreaded disease that affects more than 14 million people and their families at any given time—still remains bereft of a cure.

Why? For starters, cancer isn't just one disease—it's more than 100 of them, with different causes. This makes it impossible to treat each one using a one-size-fits-all method. Secondly, scientists use lab-grown cell lines cultivated from human tumors to develop cancer therapies. Living masses are far more complex, so potential treatments that show promise in lab experiments often don't work on cancer patients. As for the tumors themselves, they're prone to tiny genetic mutations, so just one growth might contain multiple types of cancer cells, and even unique sub-clones of tumors. These distinct entities might not respond the same way, or at all, to the same drug.

These are just a few of the challenges that cancer researchers face—but the good news is that they're working to beat all of them, as this TED-Ed video explains below.

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Health
Skipping Breakfast Could Be Bad for Your Heart
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There are mountains of evidence supporting the claim that breakfast really is the most important meal of the day. Getting something in your stomach in the first hours of the morning can regulate your glucose levels, improve your cognition, and keep your hunger in check. Now new research published in the Journal of the American College of Cardiology points to another reason not to wait until lunchtime to break last night’s fast. As TIME reports, people who skip breakfast are at an increased risk for atherosclerosis, a disease caused by plaque buildup in the arteries.

Researchers surveyed over 4000 men and women between the ages of 40 and 54 living in Spain. After looking at the dietary habits of each participant, they broke them into three groups: people who consumed more than 20 percent of their daily calories in the morning; those who got 5 to 20 percent; and those who ate less than 5 percent.

The subjects who ate very little in the a.m. hours or skipped breakfast all together were 2.5 more likely to have generalized atherosclerosis. This meant that plaque was starting to collect on the walls of their arteries, hardening and narrowing them and increasing the risk for heart attack or stroke. People who fell into the 5 to 20 percent calorie category were also more likely to show early signs of the disease, while those who ate the most calories in the morning were the healthiest.

These results aren’t entirely surprising. Previous studies have shown a connection between skipping breakfast and health problems like high blood pressure, high cholesterol, diabetes, and unwanted weight gain. A possible explanation for this trend could be that waiting several hours after waking up to eat your first meal of the day could trigger hormonal imbalances. The time between getting into and out of bed is the longest most of us go without eating, and our bodies expect us to consume some calories to help kickstart our energy for the day (drinking straight coffee doesn’t cut it). Another theory is that people who don’t eat in the morning are so hungry by the time lunch rolls around that they overcompensate for those missing calories, which is why skipping breakfast doesn’t make sense as a diet strategy.

But of course there are many breakfast skippers who aren’t motivated by health reasons either way: They just don’t think they have the time or energy to feed themselves in the morning before walking out the door. If this describes you, here are some simple, protein-packed meals you can prepare the night before.

[h/t TIME]

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