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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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Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
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Medicine
Bill Gates is Spending $100 Million to Find a Cure for Alzheimer's
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation

Not everyone who's blessed with a long life will remember it. Individuals who live into their mid-80s have a nearly 50 percent chance of developing Alzheimer's, and scientists still haven't discovered any groundbreaking treatments for the neurodegenerative disease [PDF]. To pave the way for a cure, Microsoft co-founder and philanthropist Bill Gates has announced that he's donating $100 million to dementia research, according to Newsweek.

On his blog, Gates explained that Alzheimer's disease places a financial burden on both families and healthcare systems alike. "This is something that governments all over the world need to be thinking about," he wrote, "including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise."

Gates's interest in Alzheimer's is both pragmatic and personal. "This is something I know a lot about, because men in my family have suffered from Alzheimer’s," he said. "I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you're experiencing a gradual death of the person that you knew."

Experts still haven't figured out quite what causes Alzheimer's, how it progresses, and why certain people are more prone to it than others. Gates believes that important breakthroughs will occur if scientists can understand the condition's etiology (or cause), create better drugs, develop techniques for early detection and diagnosis, and make it easier for patients to enroll in clinical trials, he said.

Gates plans to donate $50 million to the Dementia Discovery Fund, a venture capital fund that supports Alzheimer's research and treatment developments. The rest will go to research startups, Reuters reports.

[h/t Newsweek]

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A New Analysis of Chopin's Heart Reveals the Cause of His Death

For years, experts and music lovers alike have speculated over what caused celebrated composer Frederic Chopin to die at the tragically young age of 39. Following a recent examination of his heart, Polish scientists have concluded that Chopin succumbed to tuberculosis, just as his death certificate states, according to The New York Times.

When Chopin died in 1849, his body was buried in Paris, where he had lived, while his heart was transported to his home city of Warsaw, Poland. Chopin—who appeared to have been ill with tuberculosis (TB)—was terrified of the prospect of being buried alive, and nostalgic for his national roots. He asked for his heart to be cut out, and his sister later smuggled it past foreign guards and into what is now Poland.

Preserved in alcohol—likely cognac—and stored in a crystal jar, Chopin's heart was laid to rest inside Holy Cross Church in Warsaw. (It was removed by the Germans in 1944 during the Warsaw Uprising, and later returned.) But rumors began to swirl, as the same doctor tasked with removing the heart had also conducted an autopsy on the composer's body, according to the BBC.

The physician's original notes have been lost, but it's said he concluded that Chopin had died not from TB but from "a disease not previously encountered." This triggered some scholars to theorize that Chopin had died from cystic fibrosis, or even a form of emphysema, as the sickly musician suffered from chronic respiratory issues. Another suspected condition was mitral stenosis, or a narrowing of the heart valves.

Adhering to the wishes of a living relative, the Polish church and government have refused to let scientists conduct genetic tests on Chopin's heart. But over the years, teams have periodically checked up on the organ to ensure it remains in good condition, including once in 1945.

In 2014, a group of Chopin enthusiasts—including Polish scientists, religious officials, and members of the Chopin Institute, which researches and promotes Chopin's legacy—were given the go-ahead to hold a clandestine evening meeting at Holy Cross Church. There, they removed Chopin's heart from its perch inside a stone pillar to inspect it for the first time in nearly 70 years.

Fearing the jar's alcohol would evaporate, the group added hot wax to its seal and took more than 1000 photos of its contents. Pictures of the surreptitious evening procedure weren't publicly released, but were shown to the AP, which described Chopin's preserved heart as "an enlarged white lump."

It's unclear what prompted a follow-up investigation on Chopin's heart, or who allowed it, but an early version of an article in the American Journal of Medicine states that experts—who did not open the jar—have newly observed that the famed organ is "massively enlarged and floppy," with lesions and a white, frosted appearance. These observations have prompted them to diagnose the musician's cause of death as pericarditis, which is an inflammation of tissue around the heart. This likely stemmed from his tuberculosis, they said.

Some scientists might still clamor at the prospect of testing tissue samples of Chopin's heart. But Michael Witt of the Polish Academy of Sciences—who was involved in this latest examination—told The Guardian that it was unnecessary to disturb what many consider to be a symbol of national pride.

"Some people still want to open it in order to take tissue samples to do DNA tests to support their ideas that Chopin had some kind of genetic condition," Witt said. "That would be absolutely wrong. It could destroy the heart, and in any case, I am quite sure we now know what killed Chopin."

[h/t The New York Times]

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