Health

What You Should Know Today

Published

5 months ago

April 2, 2024

In 1996, Doug Olson learned he had chronic lymphocytic leukemia (CLL), a type of cancer that starts in white blood cells. This cancer often grows slowly, so his doctor decided to watch it and wait to treat him.

But when Olson’s cancer started to grow a few years later, he had several rounds of chemotherapy. Then, in 2009, the tumor changed. Chemo no longer helped. Olson’s doctor, David Porter, MD, recommended a bone marrow transplant. But none of Olson’s siblings was a good match.

“It seemed like the news kept getting worse,” Olson says.

Then Olson’s doctor suggested a clinical trial for a new kind of cancer treatment. Specifically, it was a type of immunotherapy called CAR T-cell therapy. The aim: Re-engineer Olson’s immune cells in the lab to turn them into weapons to hunt down cancer cells.

CAR T-cell therapy may work when other treatments haven’t. And unlike chemo and radiation, which kill healthy cells as well as cancerous ones, immunotherapy targets the tumors with more precision.

CAR T-cell therapy, or CAR T, is one of a few types of immunotherapy. Each one works in a different way.

Doctors may turn to CAR T when T cells, which normally patrol the bloodstream to spot germs and other invaders, can’t recognize cancer as a foreign cell. That happens if the T cells lack the specific proteins that can bind to the tumor in order to attack.

It’s as if “the cancer cell has a piece of Velcro, but the patient’s T cells don’t have the corresponding piece of Velcro to make it stick,” says Porter, who is director of the Cell Therapy and Transplant Program at the University of Pennsylvania.

During CAR T-cell therapy, doctors first remove T cells from your body. Then they add a gene that makes the T cells produce special proteins called CARs (chimeric antigen receptors) on their surface, which can stick to the cancer cells. After the CAR T cells multiply in the lab, doctors put them back into your body.

The reengineered T cells “have been educated to recognize and kill the tumor cells,” says Renier Brentjens, MD, PhD, professor of medicine and director of the Cell Therapy Service at Memorial Sloan Kettering Cancer Center.

Not only that, the T cells “expand by 1,000- to 10,000-fold in the body. And every one of those cells can go on to kill more cancer cells,” Porter says.

Olson received three doses of CAR T cells. After a couple of weeks, almost 20% of his white blood cells were CAR T. When he returned to Porter for tests, “he told me they couldn’t find a single cancer cell in my body,” Olson recalls.

The FDA approved the first CAR T-cell therapy in 2017. To date, the agency has approved two CAR T-cell therapies for cancer.

Axicabtagene ciloleucel (Yescarta). This is approved for B-cell lymphoma in adults that hasn’t responded to other treatments or has come back after treatment.

Tisagenlecleucel (Kymriah). This has the same approval as axicabtagene ciloleucel, but it also can be used to treat children and young adults with acute lymphoblastic leukemia.

In studies, 9 out of 10 people with acute lymphoblastic leukemia whose cancer didn’t respond to other treatments or whose cancer came back had full remission with CAR T-cell therapy. Remission means the cancer can’t be found in tests.

Complete remission rates for chronic lymphocytic leukemia and non-Hodgkin’s lymphoma are lower — 35% to 70%. Of that number, about a third have long-lasting remissions. “For those people it absolutely lives up to the promise,” Porter says.

But the catch is that remissions aren’t always permanent, Brentjens says. In many cases, doctors don’t know why the cancer returns. It could be that CAR T cells may not last long in the body. Or they may eventually get overtaken by a group of T cells that don’t have the protein that can chase down the cancer.

You won’t have hair loss that commonly follows chemotherapy. Instead, CAR T-cell therapy can lead to a short-lived but severe reaction called cytokine release syndrome, or CRS.

“It is similar to having a horrible case of the flu,” says Terry Fry, MD, a cancer researcher and professor at Children’s Hospital Colorado.

Cytokines are proteins that immune cells release when they attack an infection. Symptoms include a high fever, nausea, chills, headache, rash, and trouble breathing. CRS can be deadly, but it’s treatable in a hospital.

CAR T-cell therapy also can affect the brain, causing confusion, trouble speaking, and sometimes seizures. Usually, Fry says, those symptoms happen within in a couple of weeks after the infusion and get better in about a month.

It’s been less than a decade since the first person received CAR T-cell therapy. So doctors still don’t know about any long-term risks.

CAR T-cell therapy works for blood cancers. But so far, it hasn’t been able to treat solid tumors like breast or lung cancer.

Leukemia and lymphoma cells are easier to hunt down because the targeted protein is on the surface, and because they’re not on healthy cells.

Fry says “solid tumors are a tougher nut to crack” because it’s harder to distinguish between targeted proteins that are on cancer tumors and those on healthy tissue.

Brentjens is one of the researchers who is looking at ways to get around this and other hurdles.

“I’m an optimist, so I would say in the next 5 to 10 years we might have some CAR T cells that might be able to target some solid tumors,” he says. “But this is still very much a work in progress.”

Although there is still work to be done, CAR T-cell therapy has been a lifesaving treatment for many of the people who’ve received it. “A significant proportion of patients treated with these CAR T cells will be long-term survivors. And the patients we’re treating are the ones whose survival expectation was slim to none,” Brentjens says.

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Health

Walmart Is Selling a $300 Power Tower for Just $128, and Shoppers Say It's 'Surprisingly Sturdy'

Published

18 hours ago

September 7, 2024

Michael Charboneau

Men’s Journal aims to feature only the best products and services. If you buy something via one of our links, we may earn a commission.

When building a home gym, it’s easy to get overwhelmed by all the equipment options, especially when you’re working with limited space and a tight budget. But when you focus on versatile gear and hunt for deals, creating a useful setup is easily doable. Thankfully, Walmart has been slashing prices on a ton of fitness equipment, including its bestselling adjustable dumbbells and even a complete home gym system. Now, it’s reduced the price of a popular power tower by over $170, and it even ships for free.

The Pooboo Body Champ Multifunction Power Tower is on sale for $128, a 57% discount on its normal price of $300. This incredibly versatile workout station has earned nearly 250 five-star ratings from Walmart shoppers who’ve praised its “strong and sturdy” build and “quality fit and finish,” and it’s currently one of the top 5 bestselling models on the site.

Pooboo Body Champ Multifunction Power Tower, $128 (was $300) at Walmart

Don’t let the brand’s bizarre name fool you—this power tower is a well-made piece of gym equipment. It features steel construction and is rated to hold up to 480 pounds (the tower itself weighs 66 pounds). A nearly 42-inch H-shaped base gives it excellent stability, so it won’t wobble or shake when you’re exercising, and anti-slip feet on the bottom keep it securely planted on the floor. It’s also adjustable (from 71.4 inches to 94 inches) to accommodate users of varying heights. And, once it’s set up, you can use it for a huge range of exercises, including dips, pull-ups, chin-ups, push-ups, vertical leg raises, knee raises, and more.

According to Walmart reviewers, the Pooboo Body Champ stands out for its solid build and usefulness. “It’s a surprisingly sturdy piece of equipment,” a shopper said. “Everything about this fitness tower is perfect. I originally purchased this with the intention of only doing pull-ups on it, but after quickly assembling the power tower, I came to realize just how versatile it is. It has cushions for knee and leg raises, it’s sturdy, and the perfect width for dips.” Another shopper agreed, saying, “This was a much-needed addition to my home gym.”

“This thing is amazing and worth every penny,” said another, who added that it’s “easy to install and can hold a lot of weight.”

At just $128, this Pooboo power tower is a screaming deal, and it’s sure to get lots of use during your workouts. But this discount won’t last long, so grab one today before the price pumps back up.

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Health

Alzheimer’s Drug May Save Lives Through ‘Suspended Animation’

Published

1 day ago

September 7, 2024

Harvard Gazette

By Lindsay Brownell | Wyss Institute Communications | Harvard Gazette

Could buy patients more time to survive critical injuries and diseases, even when disaster strikes far from a hospital

Donepezil, an FDA-approved drug to treat Alzheimer’s, has the potential to be repurposed for use in emergency situations to prevent irreversible organ injury, according to researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Using Donepezil (DPN), researchers report that they were able to put tadpoles of Xenopus laevis frogs into a hibernation-like torpor.

“Cooling a patient’s body down to slow its metabolic processes has long been used in medical settings to reduce injuries and long-term problems from severe conditions, but it can only currently be done in a well-resourced hospital,” said co-author Michael Super, director of immuno-materials at the Wyss Institute. “Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.”

This research, published Thursday in ACS Nano, was supported as part of the DARPA Biostasis Program, which funds projects that aim to extend the time for lifesaving medical treatment, often referred to as “the Golden Hour,” following traumatic injury or acute infection. The Wyss Institute has been a participant in the Biostasis Program since 2018, and has achieved several important milestones over the last few years.

Using a combination of predictive machine learning algorithms and animal models, the Wyss’ Biostasis team previously identified and tested existing drug compounds that had the potential to put living tissues into a state of suspended animation. Their first successful candidate, SNC80, significantly reduced oxygen consumption (a proxy for metabolism) in both a beating pig heart and in human organ chips, but is known to cause seizures when injected systemically.

In the new study, they once again turned to their algorithm to identify other compounds whose structures are similar to SNC80. Their top candidate was DNP, which has been approved since 1996 to treat Alzheimer’s.

Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.

–Michael Super

“Interestingly, clinical overdoses of DNP in patients suffering from Alzheimer’s disease have been associated with drowsiness and a reduced heart rate — symptoms that are torpor-like. However, this is the first study, to our knowledge, that focuses on leveraging those effects as the main clinical response, and not as side effects,” said the study’s first author, María Plaza Oliver, who was a postdoctoral fellow at the Wyss Institute when the work was conducted.

The team used X. laevis tadpoles to evaluate DNP’s effects on a whole living organism, and found that it successfully induced a torpor-like state that could be reversed when the drug was removed. The drug, however, did seem to cause some toxicity, and accumulated in all of the animals’ tissues. To solve that problem, the researchers encapsulated DNP inside lipid nanocarriers, and found that this both reduced toxicity and caused the drug to accumulate in the animals’ brain tissues. This is a promising result, as the central nervous system is known to mediate hibernation and torpor in other animals as well.

Although DNP has been shown to protect neurons from metabolic stress in models of Alzheimer’s disease, the team cautions that more work is needed to understand exactly how it causes torpor, as well as scale up production of the encapsulated DNP for use in larger animals and, potentially, humans.

“Donepezil has been used worldwide by patients for decades, so its properties and manufacturing methods are well-established. Lipid nanocarriers similar to the ones we used are also now approved for clinical use in other applications. This study demonstrates that an encapsulated version of the drug could potentially be used in the future to buy patients critical time to survive devastating injuries and diseases, and it could be easily formulated and produced at scale on a much shorter time scale than a new drug,” said senior author Donald Ingber, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences.

This research was supported by DARPA under Cooperative Agreement Number W911NF-19-2-0027, the Margarita Salas postdoctoral grant co-funded by the Spanish Ministry of Universities, and the University of Castilla-La Mancha (NextGeneration EU UNI/551/2021).

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This story is reprinted with permission from The Harvard Gazette.

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Health

Can Stuff in Rosemary Extract Fight Cocaine Addiction?

Published

2 days ago

September 5, 2024

Futurity

Researchers have discovered that an antioxidant found in rosemary extract can reduce intakes of cocaine by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.

September 5, 2024 by Futurity Leave a Comment

By Pat Harriman-UC Irvine

The study in the journal Neuron describes researchers’ focus on a region of the brain called the globus pallidus externus, which acts as a gatekeeper that regulates how we react to cocaine.

They discovered that within the GPe, parvalbumin-positive neurons are crucial in controlling the response to cocaine by changing the activity neurons releasing the pleasure molecule dopamine.

“There are currently no effective therapeutics for dependence on psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” says corresponding author Kevin Beier, an associate professor of physiology and biophysics at the University of California, Irvine.

“Our study deepens our understanding of the basic brain mechanisms that increase vulnerability to substance use disorder-related outcomes and provides a foundation for the development of new interventions.”

Findings in mice revealed that globus pallidus externus parvalbumin-positive cells, which indirectly influence the release of dopamine, become more excitable after being exposed to cocaine. This caused a drop in the expression of certain proteins that encode membrane channels that usually help keep the globus pallidus cell activity in check. The researchers found that carnosic acid, an isolate of rosemary extract, selectively binds to the affected channels, providing an avenue to reduce response to the drug in a relatively specific fashion.

“Only a subset of individuals are vulnerable to developing a substance use disorder, but we cannot yet identify who they are. If globus pallidus cell activity can effectively predict response to cocaine, it could be used to measure likely responses and thus serve as a biomarker for the most vulnerable,” Beier says. “Furthermore, it’s possible that carnosic acid could be given to those at high risk to reduce the response to cocaine.”

The next steps in this research include thoroughly assessing negative side effects of carnosic acid and determining the ideal dosage and timing. The team is also interested in testing its efficacy in reducing the desire for other drugs and in developing more potent and targeted variants.

Scientists from the University of West Virginia and the University of Colorado participated in the study.

Support for this work came from the National Institutes of Health, One Mind, the Alzheimer’s Association, New Vision Research, BrightFocus Foundation, and the Brain & Behavior Research Foundation.

Source: UC Irvine

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Previously Published on futurity.org with Creative Commons License

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