Tag Archives: progression

New Insights into How Exercise Can Help Slow Cancer Progression.

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Exercise reduces cancer cell size in mice—possibly applicable to humans

Alfredas Pliadis/Xinhua News Agency/Alamy

Exercise has the potential to slow tumor development in mice by altering metabolic pathways, enabling muscle cells to absorb glucose instead of cancer cells for growth. This may also occur in humans.

While it’s established that exercise lowers cancer risk and healthier individuals generally have better cancer survival rates, the underlying mechanisms are still being explored. Notably, some benefits of exercise appear linked to changes in gut microbiota and the immune system.

To examine another possible pathway, Rachel Perry and her colleagues at Yale University School of Medicine conducted an experiment on 18 mice injected with breast cancer cells. Twelve of these mice were given an obesity-inducing diet, known to accelerate various cancers. Half of the group was also equipped with a running wheel to exercise as desired.

After four weeks, tumors in the exercising obese mice were found to be 60% smaller compared to their non-exercising counterparts, and were slightly smaller than tumors in sedentary mice fed a standard diet. The study revealed that just 30 minutes of exercise led to an increase in oxygen and glucose uptake in skeletal and cardiac muscles, with a corresponding decrease in glucose assimilation by tumors.

“This research demonstrates that aerobic fitness significantly alters the metabolic rivalry between muscle and tumor,” states Perry. “Crucially, the exercise was voluntary—these mice weren’t being forced to run like marathon athletes; they exercised as per their preference.”

The scientists evaluated gene expression and identified changes in 417 genes associated with vital metabolic pathways in mice due to exercise. This indicates that muscle tissue utilizes more glucose while tumor tissue absorbs less.

Specifically, a reduction in mTOR, a protein pivotal for cancer cell proliferation, shows potential for limiting tumor expansion, according to the researchers.

Perry anticipates that these metabolic patterns, which are similar across mammals, may extend to humans, even those without obesity. In fact, analogous gene activity shifts during exercise have been documented in cancer patients.

“This points to another mechanism illustrating how exercise fosters a cancer-suppressive environment,” mentions Rob Newton from Edith Cowan University in Perth, Australia. “We need to conduct clinical trials in humans, as there’s no clear reason to suspect it wouldn’t produce similar outcomes.”

Perry emphasizes that metabolism encompasses all tissues and is influenced by both the microbiome and immune responses. “These metabolic adaptations may bridge the connections between exercise, the microbiome, the immune system, and tumor progression,” she explains. “However, I’d be surprised if the positive implications of exercise stemmed from a single mechanism.”

This discussion also sheds light on why lower muscle mass heightens cancer mortality risk, as observed by Newton. “If your muscles preferentially absorb glucose, increasing muscle mass and regularly activating your muscles could yield significant advantages.”

He believes it’s crucial to view exercise not just as a lifestyle change but as an adjunctive anti-cancer intervention alongside other treatments. “Identifying primary environmental contributors to cancer is key, and we must formulate specific strategies to address them,” Newton concludes. “While enhancing cardiorespiratory fitness is beneficial, if a patient presents with notably low muscle mass, that should be prioritized with strength training.”

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Source: www.newscientist.com

Y Chromosome Loss: A Possible Factor in Lung Cancer Progression and Outcomes

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Insights into the impact of Y chromosome loss on lung cancer treatment outcomes may guide therapeutic choices.

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Research indicates that men diagnosed with the predominant type of lung cancer are more likely to lose the Y chromosome in their cells. This phenomenon has both pros and cons; while it can prevent the immune system from combating tumors, it also enhances the effectiveness of standard anti-cancer therapies.

As men grow older, their cells frequently undergo mutations, leading to the loss of the Y chromosome. In immune cells, this loss is believed to correlate with heart disease and decreased life expectancy. Additionally, there is growing evidence that cancer cells that lose the Y chromosome may influence symptom progression, with bladder cancer being the most thoroughly researched case.

The loss of the Y chromosome is a binary occurrence—it either happens or it doesn’t. However, the health implications seem to depend significantly on the proportion of specific cells that lack the Y chromosome.

The recent study initiated by Dawn DeMeo and her team at Brigham and Women’s Hospital in Boston, Massachusetts, investigated how Y-chromosome genes are expressed in a publicly available dataset of lung adenocarcinoma samples. Lung adenocarcinoma, the most common form of lung cancer, originates from the mucus-producing cells lining the airways. Enhanced understanding of the relationship between Y loss and various health issues has motivated researchers to delve deeper into gene expression studies, according to DeMeo.

The team discovered that cancer cells, in contrast to healthy lung and immune cells, often lack the Y chromosome. This occurrence is independent of whether the tissue donor is a smoker—despite smoking being linked to lung cancer and Y chromosome loss.

The loss of Y chromosomes appears to accumulate over time. “Certain groups demonstrate a higher rate of Y chromosome loss across a greater number of cells, and we observe significant Y chromosome loss in a large fraction of tumors,” stated John Quackenbush from Harvard University.

To comprehend the reasons behind this accumulation, researchers examined other genetic alterations in Y-negative cells. They found that the loss of a common set of antigens produced by cancer cells correlates with diminished expression levels. These antigens usually notify immune T cells that cancer cells are abnormal and should be targeted. The decreased expression allows Y-negative cancer cells to proliferate unchecked.

“This implies that as tumor cells lose their Y chromosome, they become increasingly adept at evading immune surveillance, suggesting a selection of tumor cells that escape immune detection,” Quackenbush explained. T cell counts were consistently lower in samples with Y loss compared to those retaining the Y chromosome.

Positive findings emerged when researchers analyzed data from 832 lung adenocarcinoma patients treated with the immune checkpoint inhibitor pembrolizumab, a medication designed to restore the body’s immune response against tumors by reversing T-cell suppression. The analysis confirmed that Y chromosome loss was linked to improved treatment outcomes.

“Patients experiencing LOY [loss of Y] are more responsive to checkpoint inhibitors,” noted Dan Theodorescu from the University of Arizona, who found similar results in bladder cancer, establishing validation against an entirely different dataset.

However, while loss of the Y chromosome is linked to shorter life expectancies for men compared to women, existing data suggests it does not impact survival in patients with lung adenocarcinoma. Further research is needed to explore how the effects of such mutations influence survival across different cancer types, according to Theodorescu. As our understanding advances, he believes that loss of Y could eventually serve as a biomarker for clinical decision-making.

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Source: www.newscientist.com

Slowing Alzheimer’s Disease Progression: How Light and Sound Can Remove Toxins from the Brain

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Cross-section of a mouse brain highlighting neurons that appear to release molecules that increase toxin clearance

Tsai Laboratory/MIT Picower Laboratory

A new explanation has emerged for why an experimental treatment for Alzheimer’s disease that involves flickering sounds and lights may help slow cognitive decline. This frequency appears to strengthen the brain’s waste processing network, helping to remove beta-amyloid and other toxic proteins that contribute to memory and concentration issues.

“Once we understand the mechanism, we can probably understand how to further optimize this whole concept and improve its effectiveness,” he says. Cai Li Hui at Massachusetts Institute of Technology.

The treatment involves exposure to light that flashes at a frequency of 40 times per second, or 40 hertz, and to a bass sound, also at 40 hertz. Typically, stimulation is given for one hour per day.

The key to this new approach is that large networks of brain cells naturally fire in sync with each other at different frequencies, known as brain waves. Brain waves around 40 Hz are common when people are concentrating and forming or accessing memories.

In 2016, Tsai’s team wondered if 40Hz stimulation could enhance cognitive performance in Alzheimer’s patients, since visual or auditory stimulation at a certain frequency is known to enhance brain waves at that same frequency. I decided to investigate.

Their group and other researchers have shown that this reduces amyloid accumulation in mice with Alzheimer’s disease and has cognitive benefits. Small trial in people with this condition, an even larger trial is underway. However, it is unclear how this treatment works, and another idea is that it boosts the function of immune cells in the brain.

Well, the special light and sound appears to work by enhancing the function of the brain’s drainage system, also known as the glymphatic system.

In the latest study, Tsai’s team conducted a series of experiments to study the mechanism of treatment in mice that were genetically modified to have amyloid buildup that normally occurs with age and to have worse memory than typical mice. carried out.

As expected, when the animals were exposed to light and sound, the amount of amyloid decreased. The new findings were that during treatment, the amount of cerebrospinal fluid entering the brain increased, and the amount of waste fluid leaving the brain through the glymphatic vessels increased.

This appears to occur because nearby blood vessels pulsate more, which may help glymph fluid flow through the blood vessels, allowing more water to flow into the glymph system.

The research team also found that the activity of a particular type of brain cell known as an interneuron appears to cause an increase in glymph flow by releasing a molecule called vasoactive intestinal peptide. When the research team chemically blocked the production of this molecule, the treatment no longer accelerated amyloid clearance.

Miken Nedergaard A professor at the University of Rochester in New York who helped discover the glymphatic system says the discovery is consistent with what we already know about it. “The brain, blood, and cerebrospinal fluid are all contained within the skull. When the blood volume expands, the brain tissue cannot be compressed, so the cerebrospinal fluid volume must also move.”

In the accompanying article natural medicineDr. Nedergaard says that a better understanding of the mechanisms of toxin removal in the brain “could be the key to unlocking that.” [their] Treatment Possibilities.”

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Source: www.newscientist.com