Why cancer spreads more in middle age than in old age

 Cancer becomes more common with age and is often harder to treat in older adults. Yet most cancer studies in mice do not reflect that reality. Fewer than 10% of mouse experiments use aged animals, with researchers typically relying on mice that roughly correspond to humans in their early 20s.

That gap may help explain why many cancer therapies that perform well in laboratory studies ultimately fail in human clinical trials.

New findings from Fox Chase Cancer Center, presented at the American Association for Cancer Research annual meeting, suggest that melanoma does not behave the same way throughout the aging process. Researchers found that cancer spread was lowest in young mice, reached its highest level in middle aged mice, and then declined again in very old mice.

"The vast majority of studies are done in these very young mice that have a healthy and intact immune system," said Mitchell Fane, PhD, a cancer biologist who specializes in aging and cancer, and lead investigator of the study. "Right now, it's easy to personalize care for someone who's young and fit, who's potentially not going to experience as many toxicities; understanding how therapies affect older patients would give us more and better treatment options."

Immune Cells May Hold the Key

The researchers believe a specialized group of immune cells known as gamma delta (γδ) T cells may help explain the surprising pattern.

These cells act as an early defense system, helping prevent cancer from spreading throughout the body. Young mice and very old mice had higher levels of these protective immune cells, and their tumors were more likely to remain dormant or spread less aggressively.

Middle aged mice told a different story. They had fewer γδ T cells, and melanoma was much more likely to spread to organs such as the lungs and liver.

The team also discovered that melanoma cells can actively weaken the immune system as animals age. In middle aged mice, the cancer released molecules that suppressed or exhausted γδ T cells. As those defenses weakened, previously dormant cancer cells were able to become active and spread more aggressively.

Additional experiments reinforced the importance of these immune cells. When researchers removed γδ T cells from young and very old mice, melanoma spread increased significantly. Conversely, blocking the signals that suppress immune activity restored protection and reduced cancer spread in middle aged mice, although the same effect was not seen in the younger or older groups.

Why Researchers Need More Aged Mouse Models

One reason aging studies remain uncommon is practical. Young mice are easier and less expensive to obtain, while aged mice require long term care and breeding. Researchers must typically wait 18 to 24 months before mice reach an age suitable for aging research.

To address that challenge, Fane and colleague Yash Chabra, PhD, both Assistant Professors in the Cancer Signaling and Microenvironment Research Program, helped establish an aged mouse facility at Fox Chase Cancer Center.

The goal is to make older animal models more accessible and encourage scientists to test whether their findings hold true across different stages of life.

"Now we have a facility with established aged mouse colonies, which lowers the cost and time barriers to aging research," he said. "It allows us to tell colleagues, 'Your model is interesting, why not test it in aged mice?'"

Rethinking the Link Between Cancer and Aging

Understanding how aging affects cancer could lead to more effective treatments for older adults. Fane's laboratory is particularly interested in the observation that the relationship between age and cancer does not appear to follow a simple straight line.

Although cancer risk generally rises with age, rates unexpectedly decline among people over 80 to 85 years old.

"While risk increases steadily as people age, it abruptly decreases after ages 80-85," said Fane. "We want to explain the mechanism of why very old patients are getting less cancer, but middle-aged patients are getting more."

The new findings suggest that changes in the immune system over the course of aging may play an important role in determining when cancer is most likely to spread. They also highlight the importance of including older animals in cancer research to better reflect the patients most affected by the disease.

Source: ScienceDaily

Human organoids reveal how to reverse “irreversible” nerve damage

 Scientists at the University of Cambridge have created tiny lab-grown brain and spinal cord systems that mimic how movement signals travel through the human nervous system. Using this model, the team discovered that nerve damage once believed to be permanent may actually be reversible under certain conditions.

As the human body develops from an embryo into a fetus and eventually an infant, neurons form complex communication networks between the brain and spinal cord. These signals travel through axons, the long nerve fibers that allow neurons to send messages and control muscle movement.Over time, however, the central nervous system largely loses its ability to regrow damaged axons. As a result, injuries to the brain or spinal cord often become permanent, leading to serious disabilities such as paralysis or loss of movement. This loss of regenerative ability is also linked to neurological diseases including motor neurone disease and multiple sclerosis.

Mini Human Brain and Spinal Cord Models

In 2021, Dr. András Lakatos and his colleagues at the University of Cambridge developed miniature human brain models using stem cells taken from patients. These pea-sized "brain organoids" resembled parts of the cerebral cortex and allowed researchers to study molecular changes linked to motor neurone disease and explore ways to prevent them.

Now, in a new study published in Cell Reports, the researchers expanded on that work by building a miniature version of the connected human brain and spinal cord system.

Because the brain and spinal cord are separate but connected structures in the body, the team kept the organoids physically apart in the lab. They then observed axons from the brain tissue growing across the gap and connecting with the spinal cord tissue. The resulting neural circuit was functional enough to trigger contractions in tiny clusters of muscle cells.

Nerve Regrowth Declines During Development

The scientists maintained these miniature systems in the lab for more than a year. They discovered that until about day 150 of development, roughly corresponding to the middle stage of pregnancy, damaged axons could still regrow. After that point, the neurons showed a major decline in their ability to regenerate.

George Gibbons from the Department of Clinical Neurosciences at the University of Cambridge and first author of the study said: "Neurons taken from less mature organoids regrew long fibers after injury, but those from more mature organoids showed a sharp drop in their ability to regrow. In other words, poor regeneration is built into human neurons as they mature in the central nervous system."

Source: ScienceDaily

Vitamin B12 and folate deficiencies linked to chronic fatigue

 Chronic fatigue has become increasingly common in modern life as people juggle heavier workloads and less downtime. While exhaustion is often blamed on stress or lack of sleep, researchers say poor nutrition may also play an important role.

A research team led by Professor Hiroaki Kanouchi from Osaka Metropolitan University's Graduate School of Human Life and Ecology investigated whether deficiencies in certain vitamins could be connected to fatigue and motivation levels. The scientists focused on folate (B9) and vitamin B12, two nutrients that help regulate homocysteine (Hcy), a substance in the blood that tends to rise when these vitamins are lacking.Blood Marker Linked to Fatigue and Motivation

The study included around 600 healthy Japanese adults. Researchers measured blood levels of homocysteine, folate, and vitamin B12, then evaluated participants' fatigue and motivation using the Chalder Fatigue Scale questionnaire and a Visual Analog Scale.

The team found that participants with higher homocysteine levels generally had lower levels of folate and vitamin B12, regardless of sex.

Researchers then looked more closely at how homocysteine levels related to fatigue in men and women separately. Their analysis also accounted for factors that could influence fatigue, including age, sleep duration, workload, and eating habits.

The results showed that men with higher homocysteine levels were more likely to report greater physical fatigue. In women, elevated homocysteine levels were linked to lower motivation.

Vitamin Deficiencies May Affect Energy Levels

"This suggested relationship between vitamin B12, folate, and fatigue in healthy individuals may represent the first report of its kind," said Professor Kanouchi.

"Blood homocysteine levels have traditionally raised concerns in relation to cardiovascular disease, dementia, and fractures. However, our findings suggest that attention should also be paid to fatigue and motivation in the future. To prevent an increase in homocysteine levels, it is important to avoid deficiencies in vitamin B12 and folate. Maintaining a well-balanced diet on a daily basis is essential."

Source: ScienceDaily

Antarctica’s ice sheet hit a climate tipping point 1 million years ago

 A new study published in Nature Geoscience suggests Antarctica's ice sheet underwent a dramatic change about one million years ago, becoming much more responsive to shifts in Earth's climate.

The research, led by scientists at the IBS Center for Climate Physics (ICCP) at Pusan National University in South Korea, offers fresh insight into how massive ice sheets react to long term climate changes and what that could mean for future sea level rise.Today, Antarctica contains the largest mass of ice on the planet and plays a major role in regulating global sea levels. Around one million years ago, Earth experienced a major climate transition in which ice ages became longer, colder, and more intense. Scientists refer to this period as the Mid-Pleistocene Transition. Although researchers have known about this shift for decades, exactly how Antarctica's ice sheet responded has remained uncertain.

Simulating 3 Million Years of Climate History

One of the biggest obstacles has been the lack of realistic long term climate records needed to test ice sheet behavior under ancient conditions.

To solve this problem, the team used an advanced paleoclimate simulation recently developed at the ICCP that reconstructs global climate patterns over the past 3 million years. The simulation provided detailed temperature and precipitation data, which researchers fed into the Penn State University ice-sheet-ice-shelf model.

That model tracks changes in ice sheet movement, thickness, temperature, and elevation across Antarctica and the Northern Hemisphere. It also simulates the behavior of floating ice shelves, including those in the Ross and Weddell Seas.

Using one of South Korea's most powerful supercomputers dedicated to basic science research, the team produced a physically consistent picture of how Earth's major ice sheets evolved as climate conditions changed over time.

Antarctic Ice Reached a Critical Threshold

The simulations revealed that Antarctica entered an entirely different mode of behavior after the Mid-Pleistocene Transition.

Researchers identified a key atmospheric carbon dioxide threshold of roughly 240 parts per million. Once CO2 levels dropped below that point, Antarctic ice volume began responding much more dramatically to changes in atmospheric and ocean temperatures.

"After this transition, the Antarctic ice sheet reacts much more strongly to changes in climate forcing. This indicates that the system does not evolve gradually but instead becomes more responsive after crossing a particular threshold in the climate system," said Dr. Kyung-Sook Yun, researcher at the IBS Center for Climate Physics and lead author of the study.

Why Antarctica's Ice Expanded So Rapidly

According to the simulations, several processes worked together to accelerate Antarctic ice growth after the climate transition around one million years ago.

First, colder ocean temperatures during ice ages reduced melting beneath portions of the Antarctic ice sheet that extend below sea level. At the same time, global sea levels were approximately 50-100 meters lower than today. Lower sea levels reduced pressure on the bedrock beneath Antarctic ice shelves, allowing the land underneath to slowly rise upward. That uplift helped support additional thickening of coastal ice.

Together, these mechanisms helped create the larger and more persistent Antarctic ice sheets that later defined Earth's ice age cycles.

"Our findings suggest that the Antarctic ice sheet was more sensitive to external forcings than previously assumed. This also raises important questions about its future response to global warming," said Prof. Axel Timmermann, Director of the IBS Center for Climate Physics and co-author of the study.

What the Findings Could Mean for the Future

The study highlights that ice sheets may not always respond to climate change in a slow, predictable way. Instead, they can suddenly shift into a much more sensitive state after crossing critical climate thresholds.

Scientists say understanding these abrupt transitions is essential for improving future projections of Antarctic ice loss and global sea level rise.

Source: ScienceDaily

Twisted graphene reveals a hidden superconductivity switch

 Researchers have uncovered evidence that superconductivity can be controlled by changing a material's surrounding environment, a breakthrough that could eventually lead to more efficient electronics and powerful quantum technologies.

Superconductivity allows certain materials to carry electricity with zero energy loss when cooled below a critical temperature. Even though scientists have studied the phenomenon for decades, many of its underlying mechanisms remain poorly understood. Gaining deeper insight into how superconductivity forms could help researchers design better materials and improve future electronic and quantum devices.

Twisted Graphene Reveals Unusual Behavior

The study, led by Chun Ning (Jeanie) Lau, a physics professor at The Ohio State University, focused on a specially engineered material known as twisted bilayer graphene. The material is made by stacking two sheets of carbon and rotating one slightly relative to the other.

The research team combined the graphene structure with strontium titanate, a synthetic diamond-like material. This setup allowed scientists to observe and influence how electrons interacted inside the system.

Electron interactions play a major role in determining properties such as magnetism and chemical bonding. In superconductors, electrons pair together in a special way that enables electricity to flow without resistance. By tuning the environment around the material, the team found they could strengthen or weaken those interactions and effectively switch superconductivity on and off.

"Electrons normally repel each other, but in superconductors they form pairs; this pair formation is the key to a superconductor's ability to conduct electricity without dissipation," said Lau. "Our evidence suggests that electrons themselves, depending on their sensitivity to their nearby environment, are unexpectedly important for material changes."

Discovery Challenges Traditional Superconductor Theory

The researchers were surprised by one of their findings. As they increased certain adjustments within the material, superconductivity became weaker instead of stronger.

That behavior differs from what scientists typically observe in conventional superconductors, where reducing the repulsive forces between electrons usually strengthens superconductivity. The unexpected result highlights how unusual materials like twisted bilayer graphene may behave very differently from traditional superconductors.

"If you could transmit electricity without energy loss, that would be hugely important for technologies used in our everyday life," said Lau. "Despite the fundamental questions that still need answers, this work basically provides a path toward a new type of physics mechanism."

The discovery may also help researchers move closer to one of the field's biggest goals: developing superconductors that work at much higher temperatures, potentially even room temperature. Achieving that milestone could dramatically reshape electronics, communications systems, and power transmission technologies.

Potential for More Efficient Electronics

The findings, published in Nature Physics, suggest a simpler method for controlling the conditions needed to create superconductivity.

Many high-temperature superconductors currently face limitations that reduce their performance. The researchers believe manipulating the surrounding environment of these materials could provide a new way to improve their capabilities and increase efficiency in future electronics.

According to lead author Xueshi Gao, a PhD student in physics at Ohio State, the team expects the results to become useful for many different experiments and material systems across the field.

"The mechanism of superconductivity in the twisted bilayer graphene system we used is still not well understood," said Gao. "But our result can shed light on and help people to better understand the concept when applying it to future work."

Researchers Plan Further Experiments

The scientists caution that the work represents an early step toward understanding a much broader range of complex electronic interactions. Future research will explore other interaction types and investigate additional physics questions raised by the study.

"We're showing capabilities that we haven't shown before, so many people in the field are getting really excited about this result," said Lau.

Additional co-authors from Ohio State include Aatmaj Rajesh, Emilio Codecido, Daria Sharifi, Zheneng Zhang, Youwei Liu and Marc Bockrath. Collaborators also included Alejandro Jimeno-Pozo, Pierre Pantaleon and Paco Guinea from Imdea Nanoscience in Spain, along with Kenji Watanabe and Takashi Taniguchi from the National Institute for Materials Science in Japan.

Source: ScienceDaily

Rogue planet moons could harbor alien life for billions of years

 Liquid water is widely considered one of the key ingredients for life. But new research suggests that worlds drifting through the darkness of interstellar space could still remain habitable, even without the warmth of a nearby star.

A team of scientists from the Excellence Cluster ORIGINS at Ludwig Maximilian University of Munich (LMU) and the Max Planck Institute for Extraterrestrial Physics (MPE) found that moons orbiting free floating planets may be able to maintain liquid water oceans for up to 4.3 billion years. According to the researchers, dense hydrogen atmospheres combined with tidal heating could keep these distant moons warm enough for life to potentially develop and evolve over immense stretches of time.

Rogue planets and wandering moons

Planetary systems often form in chaotic environments. During the early stages of development, giant planets can pass dangerously close to one another and sometimes sling neighboring worlds completely out of their solar systems. These expelled worlds are known as free floating planets (FFPs), or rogue planets, because they travel through the galaxy without orbiting a star.

Previous work led by LMU physicist Dr. Giulia Roccetti showed that giant planets ejected from their systems may still retain some of their moons after being thrown into deep space.

Although the moons survive, their orbits can change dramatically. Instead of moving in nearly circular paths, they often end up traveling in highly elongated orbits around their planet.

Tidal heating could keep oceans warm

As these moons move closer to and farther from their planet during each orbit, powerful gravitational forces continuously stretch and squeeze them. This repeated flexing generates internal heat through friction, a process known as tidal heating.

Researchers found that this heat could be strong enough to keep surface oceans from freezing solid, even in the extreme cold of interstellar space where no sunlight is available.

Whether that heat remains trapped near the surface depends heavily on the atmosphere.

On Earth, carbon dioxide acts as an important greenhouse gas that helps retain heat. Earlier studies suggested carbon dioxide rich atmospheres might support habitable conditions on exomoons for up to 1.6 billion years. But in the freezing environments surrounding rogue planets, carbon dioxide would eventually condense and lose much of its warming ability.

Hydrogen atmospheres may trap heat

To solve that problem, the researchers investigated atmospheres rich in hydrogen.Hydrogen molecules normally allow infrared radiation to pass through easily. However, under extremely high pressure, collisions between hydrogen molecules create temporary molecular interactions that can absorb and trap thermal radiation. This effect is called collision induced absorption.Because hydrogen remains stable at very low temperatures, the researchers found it could act as an effective insulating blanket around these moons, helping them hold onto heat for billions of years.

Clues about the origin of life

The findings may also offer insights into how life first emerged on Earth."Our collaboration with the team of Professor Dieter Braun helped us recognize that the cradle of life does not necessarily require a sun," says David Dahlbüdding, doctoral researcher at LMU and lead author of the study. "We discovered a clear connection between these distant moons and the early Earth, where high concentrations of hydrogen through asteroid impacts could have created the conditions for life."

The researchers also suggest tidal forces may drive important chemical activity. Constant stretching and compression of a moon can create recurring wet dry cycles where water repeatedly evaporates and condenses. Scientists believe these cycles may help produce complex molecules that are essential for life.

Hidden habitable worlds across the galaxy

Astronomers believe rogue planets may be extremely common throughout the Milky Way. Some estimates suggest there could be as many free floating planets as stars in our galaxy.If many of those planets also host moons, the number of possible environments where life could exist may be far larger than previously thought. The new study suggests that habitable worlds may not need sunlight at all and that life could potentially arise and survive even in the darkest regions of space.

Source: ScienceDaily

Weight-loss medications could help reduce blood pressure, study suggests

 A meta-analysis of 32 phase 3 clinical trials, involving more than 43,000 adults with overweight or obesity, found that newer anti-obesity medications were associated with significant reductions in blood pressure.

• Participants taking the medications lost an average of 10.9% of their body weight and experienced an average 5.2 mmHg reduction in systolic blood pressure compared with placebo.
• Results suggest that every 1% reduction in body weight was linked to a 0.34 mmHg drop in systolic blood pressure, with weight loss explaining roughly 77% of the blood pressure-lowering effect.
• The findings suggest that modern obesity drugs, such as GLP-1 drugs, may provide cardiovascular benefits beyond weight loss alone, although further studies are necessary.

Obesity is a chronic conditionTrusted Source that affects more than two in fiveTrusted Source adults in the United States. The main treatment for obesity is sustained weight loss, which typically involves lifestyle modifications, and may also include certain medications.

Anti-obesity medicationsTrusted Source are drugs that can aid in weight loss, primarily by curbing appetite, increasing feelings of fullness, or altering fat absorption.

There is a growing demand for weight-loss drugs, and guidelines highlight the role of certain medications, such as glucagon-like peptide-1 (GLP-1) receptor agonistsTrusted Source, in treating obesity.

Modern obesity medications may offer an additional cardiovascular benefits beyond weight loss, such as helping to manage high blood pressure, or hypertension.

Obesity and hypertension frequently occur together and significantly increase the risk of cardiovascular disease, stroke, kidney disease, and premature death. Current medical guidelinesTrusted Source already recommend weight management as a key strategy for controlling hypertension.

Now, a study presented at the European Congress on Obesity 2026 by researchers from Leiden University Medical Center and University Health Network, in The Netherlands, suggests modern obesity medications may have a larger role in cardiovascular risk reduction than previously appreciated.

Findings from the large meta-analysis — which are yet to appear in a peer-reviewed journal — indicate that greater weight loss achieved with newer anti-obesity medications was closely associated with reductions in systolic blood pressure.

How much did blood pressure change?

Researchers analyzed data from 32 phase 3 clinical trials involving 43,618 adults with overweight or obesity. Participants had an average age of 54 years, and average body mass index (BMI) of 35.5, with nearly 60% living with hypertension and almost 10% living with type 2 diabetes.

There was an even split of male and female participants, the median treatment duration was 66 weeks, and the baseline systolic blood pressure was 128 millimeters of mercury (mm Hg).

Systolic blood pressureTrusted Source refers to the top number in a blood pressure reading and measures the pressure against the artery walls when the heart is pumping blood around the body.

The American Heart Association (AHA)Trusted Source recommends a target systolic blood pressure below 120 mm Hg, with most guidelines defining hypertension as consistent systolic readings of 130 mm Hg or higherTrusted Source.

Across all studies, participants taking obesity medications lost an average of 10.9% of their body weight compared with placebo. This was accompanied by an average reduction of 5.2 mmHg in systolic blood pressure.

Notably, the analysis found that every 1% reduction in body weight was associated with a 0.34 mmHg decrease in systolic blood pressure.

Mir Ali, MD, bariatric surgeon, bariatric medicine specialist and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, told Medical News Today he was not surprised by the association.

“These results are not surprising to me; as a bariatric surgeon, I have seen the improvement in hypertension (as well as diabetes and many other conditions) in our post-surgical weight loss patients,” said Ali.

“Any improvement in blood pressure can help reduce morbidity associated with hypertension; furthermore, many patients can have their blood pressure medications reduced with even modest improvements in blood pressure,” he noted.

Scientists find hidden pathways pancreatic cancer

 A new study from Brazil, published in the journal Molecular and Cellular Endocrinology, sheds light on how pancreatic cancer gains the ability to spread at an early stage. Researchers found that a protein called periostin, along with stellate cells in the pancreas, plays a crucial role in helping cancer cells invade nearby nerves. This early nerve invasion raises the risk of metastasis and is closely tied to how aggressive the disease becomes. The findings also highlight potential targets for more precise and personalized cancer treatments.

The research shows that pancreatic tumors do not act alone. Instead, they alter parts of the surrounding healthy tissue, effectively reprogramming it to support cancer invasion. This process helps explain why pancreatic cancer is so difficult to control once it begins to spread.

A Rare Cancer With a Deadly Impact

The most common form of pancreatic cancer is adenocarcinoma, which develops in the glandular cells that produce pancreatic juice. This type accounts for about 90% of all pancreatic cancer diagnoses. While pancreatic cancer is not among the most frequently diagnosed cancers, it is known for being especially aggressive. Its death rate nearly matches its diagnosis rate.

Worldwide, there are roughly 510,000 new pancreatic cancer cases each year, with nearly the same number of deaths reported annually.

In Brazil, estimates from the National Cancer Institute (INCA) point to about 11,000 new cases and 13,000 deaths each year. "It's an aggressive cancer that's difficult to treat. Around 10% of patients have a chance of long-term survival, such as five years after diagnosis," says Pedro Luiz Serrano Uson Junior, an oncologist and one of the study's authors.

Why Nerve Invasion Matters

One reason pancreatic cancer is so dangerous is a process known as perineural invasion. This occurs when cancer cells move into and spread along nerves. The process can cause severe pain and also helps the tumor reach other parts of the body more easily. "Perineural invasion is a marker of cancer aggressiveness," Uson explains.

Because nerves connect different regions of the body, cancer cells that enter these pathways gain new routes for expansion.

Mapping the Tumor's Hidden Support System

The research was carried out at the Center for Research on Inflammatory Diseases (CRID), one of FAPESP's Research, Innovation, and Dissemination Centers (RIDCs). The study was led by researcher Carlos Alberto de Carvalho Fraga, with Helder Nakaya serving as principal investigator. Nakaya is also a senior researcher at Einstein Israelite Hospital and a professor at the University of São Paulo's School of Pharmaceutical Sciences.

To uncover how nerve invasion occurs, the team used advanced tools that analyze the activity of thousands of genes in individual cells while mapping their exact locations within tumor tissue. "We were able to integrate data from dozens of samples with extremely powerful resolution," Nakaya says.

The researchers examined 24 pancreatic cancer samples and found that the stroma, the connective tissue that supports the tumor, plays an active role in cancer progression rather than serving as a passive structure.

The Role of Periostin and Tissue Remodeling

One of the study's most important findings involved pancreatic and stellate cells that produce large amounts of periostin. This protein is known for its ability to reshape the extracellular matrix - the structure that organizes and maintains healthy tissue.

Tumor cells rely on major changes to this matrix in order to push through tissue and reach nearby nerves. This remodeling process involves specialized enzymes and widespread tissue disruption. "Periostin participates in this remodeling, paving the way for tumor cells to invade," Nakaya explains. Once cancer cells reach a nerve, it can act like a "road" that helps them spread further.

Why Treatments Struggle to Reach the Tumor

As the tumor environment changes, it triggers a desmoplastic reaction. This involves the buildup of dense, fibrous tissue around the tumor, made up of cells and proteins that stiffen and inflame the area. The hardened tissue makes it harder for chemotherapy and immunotherapy drugs to penetrate the tumor.

This protective microenvironment allows cancer cells to survive and continue spreading. "That's why pancreatic cancer is still so difficult to treat," says Uson.

Early Spread Leads to Poor Outcomes

According to Uson, the tumor's ability to infiltrate surrounding tissue is a major reason for the poor outlook faced by many patients. "Perineural invasion is a sign that cancer cells have gained mobility. They escape the tumor mass, travel through healthy tissue, and reach nerve and lymphatic bundles, which carry them to other regions of the body, facilitating the development of metastases."

More than half of pancreatic cancer cases already show signs of perineural invasion at an early stage. However, this spread is usually discovered only after surgery. "Unfortunately, we discover this perineural invasion after it's already occurred. It's only seen in the surgical specimen when it goes for biopsy," Uson says.

Promising target

Given these challenges, the researchers believe periostin represents a promising target for future treatments. Reducing its activity or removing the stellate cells that produce it could help limit nerve invasion and slow the cancer's ability to spread. "This work points to paths that may guide future approaches to treating pancreatic cancer," Nakaya says.

Clinical trials in other types of cancer are already testing antibodies designed to block periostin. According to Nakaya, these efforts may help determine whether the same approach could work in pancreatic cancer.

Uson notes that this strategy aligns with the broader shift toward precision medicine. "If we can develop antibodies or drugs that block these stellate cells, we'll have tools to prevent the tumor from acquiring this invasive capacity so early." He adds that there is currently no treatment specifically aimed at perineural invasion and that such therapies could also benefit patients with other cancers, including intestinal and breast cancers.

Beyond identifying new treatment targets, the study also highlights the power of advanced data analysis using public databases. "We were able to ask and answer new questions that the original authors hadn't considered," Nakaya says.

The next step, according to the researchers, is turning these insights into treatments that act before invasion begins. "Precision medicine is advancing. In the future, we'll treat patients based on genomic and molecular changes rather than tumor type specifically. This is a significant advance in oncology," Uson concludes.

Source: ScienceDaily

Scientists discover sleep switch that builds muscle, burns fat, and boosts brainpower

 Deep sleep does more than help you feel rested. It actively rebuilds your body, strengthening muscles, supporting bone growth, and helping burn fat. For teenagers, it is also essential for reaching full height potential.

At the center of all this is growth hormone, which surges during sleep. But scientists have long puzzled over why poor sleep, especially the early deep stage known as non-REM sleep, leads to lower levels of this critical hormone.

Scientists Discover the Brain Circuit Behind It

Researchers at the University of California, Berkeley, have now uncovered the answer. In a study published in Cell, they mapped the brain circuits that control growth hormone release during sleep and identified a new feedback system that keeps those levels in balance.

This discovery offers a clearer understanding of how sleep and hormones work together. It may also open the door to new treatments for sleep disorders linked to metabolic diseases like diabetes, as well as neurological conditions such as Parkinson's and Alzheimer's.

"People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep," said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute. "We're actually directly recording neural activity in mice to see what's going on. We are providing a basic circuit to work on in the future to develop different treatments."

Lack of sleep does more than leave you tired. Because growth hormone helps control how the body processes sugar and fat, poor sleep can increase the risk of obesity, diabetes, and heart disease.

The Brain Regions Driving Growth Hormone

The system behind this process is buried deep in the hypothalamus, an ancient part of the brain shared by all mammals. Here, specialized neurons release signals that either trigger or suppress growth hormone.

Two key players are growth hormone releasing hormone (GHRH), which stimulates release, and somatostatin, which inhibits it. Together, they coordinate hormone activity across the sleep-wake cycle.

Once growth hormone enters the system, it activates the locus coeruleus, a brainstem region that controls alertness, attention, and cognitive function. Disruptions in this area are linked to a wide range of neurological and psychiatric disorders.

"Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance," said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. "There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn't been talked about before."

How Sleep Stages Control Hormone Release

To study this system, researchers recorded brain activity in mice by inserting electrodes and stimulating neurons with light. Because mice sleep in short bursts throughout the day and night, they provided a detailed view of how growth hormone changes across sleep stages.

The team found that GHRH and somatostatin behave differently depending on whether the brain is in REM or non-REM sleep.

During REM sleep, both hormones increase, leading to a surge in growth hormone. During non-REM sleep, somatostatin drops while GHRH rises more modestly, still boosting hormone levels but in a different pattern.

A Surprising Feedback Loop in the Brain

The researchers also uncovered a feedback loop that links growth hormone to wakefulness. As sleep continues, growth hormone gradually builds up and stimulates the locus coeruleus, nudging the brain toward waking.

But there is a twist. When this brain region becomes too active, it can actually trigger sleepiness instead, creating a delicate balance between sleep and alertness.

"This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness," Silverman said. "Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health."

Why It Matters for Brain and Body

This balance does more than affect physical growth. Because growth hormone works through brain systems that control alertness, it may also influence how clearly you think and how focused you feel.

Source: ScienceDaily

Scientists find the genetic switch that makes pancreatic cancer resist chemotherapy

 Researchers at Duke-NUS Medical School have discovered a molecular "switch" that determines whether pancreatic cancer cells respond to chemotherapy or resist it. The finding points to a way to potentially shift some of the most treatment resistant tumors into a state where existing drugs can work more effectively.

The study, published in the Journal of Clinical Investigation, explains how this switch operates at a molecular level. The results suggest that pairing targeted therapies with standard chemotherapy may improve outcomes for patients whose tumors no longer respond to treatment.

Why Pancreatic Cancer Is So Difficult to Treat

Pancreatic cancer is one of the deadliest cancers worldwide. In Singapore, it ranks as the ninth most common cancer but the fourth leading cause of cancer related death. Because symptoms often appear late and current treatments have limited impact, most patients depend on chemotherapy, which typically provides only modest benefit.

Over the past decade, scientists have identified two main molecular subtypes of pancreatic cancer, classical and basal. Tumors in the classical subtype tend to be more organized at the cellular level, and patients with this form are more likely to respond to treatment. In contrast, basal subtype tumors are more disorganized and aggressive, and they are often resistant to chemotherapy.

Importantly, pancreatic cancer cells are not fixed in one subtype. They can shift between these states, moving from a more treatable form to a more resistant one. This flexibility is known as cancer cell plasticity.

The Role of GATA6 in Tumor Behavior

The research team focused on a gene called GATA6, which helps maintain pancreatic cancer cells in the more structured and less aggressive classical state. When GATA6 levels are high, tumors tend to grow in a more organized way and are more likely to respond to chemotherapy. When GATA6 levels fall, cells lose that structure, become more aggressive, and are harder to treat.

Professor David Virshup of Duke-NUS's Programme in Cancer & Stem Cell Biology, the study's lead author, said:

"We have known that pancreatic cancer cells can switch between these two states. What we didn't understand was the mechanism driving that switch. By identifying the pathway that suppresses GATA6, we now have a clearer picture of how tumors become resistant -- and potentially how to reverse that process."

KRAS and ERK Pathway Drive the Switch

The researchers traced the switch to a chain of signals inside pancreatic cancer cells. A gene called KRAS, which is mutated in nearly all pancreatic cancers, sends constant growth signals that drive tumor development. KRAS passes these signals through a partner protein known as ERK, which relays the instructions further inside the cell.

When the ERK pathway becomes highly active, it protects another protein that interferes with the production of GATA6. As GATA6 levels drop, cancer cells lose their organized structure, shift toward the more aggressive basal state, and become much less responsive to chemotherapy.

Using genetic screening, molecular analysis in cancer cells, and drug treatments, the team demonstrated that blocking the KRAS and ERK pathway lifts this suppression. When that happens, GATA6 levels rise again. The cancer cells then shift back toward the more organized state and regain sensitivity to chemotherapy.

Combination Therapy Shows Stronger Effects

The study also found that higher levels of GATA6 on their own made pancreatic cancer cells more responsive to treatment. When drugs that inhibit the KRAS and ERK pathway were combined with standard chemotherapy, the anti cancer effects were stronger than with either approach alone. However, this enhanced benefit occurred only when GATA6 was present, highlighting its central role in determining which patients might benefit most from combination therapy.

These findings help clarify why patients with higher GATA6 levels often respond better to certain chemotherapy regimens. They also provide a scientific foundation for ongoing clinical trials that are testing new treatments aimed at KRAS and related pathways.

Professor Lok Sheemei, Duke-NUS' Interim Vice-Dean for Research, said:

"Pancreatic cancer remains one of the toughest cancers to treat. These findings provide a mechanistic explanation for why tumors respond poorly to chemotherapy and offers a rational strategy for combining targeted therapies with existing drugs."

Broader Implications for Other KRAS Driven Cancers

The implications may extend beyond pancreatic cancer. Many other cancers fueled by KRAS mutations show similar shifts in cell behavior and treatment response. Understanding how cancer cells transition between different states could help researchers address therapy resistance in additional cancer types.

Source: ScienceDaily

Hidden sugar patterns on human cells

 Every human cell is covered by a thin layer of sugars called the glycocalyx. This outer coating helps cells interact with their surroundings and may also provide important clues about what is happening inside the cell itself. Researchers at the Max Planck Institute for the Science of Light (MPL) have now created detailed maps of these sugar structures using advanced high resolution microscopy. Their findings, published in Nature Nanotechnology, suggest that changes in the arrangement of these sugars could one day help doctors detect diseases such as cancer.

The glycocalyx surrounds all human cells like a protective outer shell. Rather than remaining fixed in place, these complex sugar molecules constantly shift and reorganize. Scientists in the "Physical Glycosciences" research group, led by Prof. Leonhard Möckl at MPL, study how this sugar coating behaves and what it reveals about cell biology.

To investigate these structures, the team developed a technique called "Glycan Atlasing." Using cutting edge super resolution microscopy, they mapped the glycocalyx at the level of individual sugar molecules across many different types of cells. Their work included cell culture lines, primary human blood cells, and tissue samples.

The resulting maps showed that the glycocalyx changes its molecular arrangement depending on the condition of the cell. For example, immune cells displayed different sugar patterns after being stimulated, similar to what happens during an immune response. According to the researchers, this provides the first direct evidence that the glycocalyx functions almost like a display screen, showing information about a cell's internal state on its outer surface.

Sugar Patterns Could Help Detect Cancer

The team found that these nanoscale sugar patterns could reliably distinguish between different cellular states. Their measurements allowed them to identify separate stages of cancer development, tell the difference between activated and inactive immune cells, and distinguish cancerous regions from healthy regions in human breast tissue.

The findings suggest that the cell surface contains structured biological information that can be read using a standardized approach. "The results provide a promising foundation for the development of future diagnostic methods, as Glycan Atlasing delivers reliable results even in complex samples," explains Möckl, the study leader and corresponding author.

Future Medical Applications

The researchers now plan to expand the method by analyzing additional target structures and automating more of the process. They also hope to study much larger numbers of samples so the technique can eventually be adapted for routine medical use.

"In large-scale studies, we want to investigate which surface patterns are associated with specific disease courses or therapeutic responses and how cell states can be detected early and objectively via the surface," Möckl explains, outlining his team's future plans.

Source: ScienceDaily

New study debunks the biggest fear about yo-yo dieting

 Repeated weight loss followed by weight regain, often called "yo-yo dieting" or weight cycling, has long been viewed as unhealthy and potentially even worse than staying overweight. However, a major new review published in The Lancet Diabetes & Endocrinology argues that this belief is not backed by strong scientific evidence.

In an invited Personal View article, Professor Faidon Magkos of the University of Copenhagen and Professor Norbert Stefan of the German Center for Diabetes Research (DZD), University Hospital Tübingen, and Helmholtz Munich reviewed decades of research involving both humans and animals. After examining the evidence, they found no convincing proof that weight cycling itself causes long-term harm in people with obesity.

"Many people struggling with weight are discouraged from trying to lose weight because they fear 'yo-yo dieting' will lead to muscle loss and somehow damage their metabolism," says Prof. Magkos. "Our review indicates that these fears are largely unsupported. In most cases, the benefits of trying to lose weight clearly outweigh the theoretical risks of weight cycling."

Longstanding fears about yo-yo dieting

For years, weight cycling has been linked to a wide range of health concerns, including greater fat accumulation, faster muscle loss, slower metabolism, and increased risks of diabetes and cardiovascular disease. These concerns have influenced public opinion and even medical advice, leading some people to believe repeated dieting attempts may ultimately cause more harm than benefit.

The new analysis disputes that idea.

What researchers found

The researchers reviewed observational studies, randomized clinical trials, and animal studies focused on repeated weight loss and regain. They looked at how weight cycling affects body weight, body composition, metabolism, and blood sugar control.

"Once you properly account for pre-existing health conditions, aging, and overall exposure to obesity, the supposed harmful effects of weight cycling largely disappear," explains Prof. Stefan.

The review found no consistent evidence that weight cycling leads to excessive loss of lean (muscle) mass or causes lasting metabolic slowdown. In many cases, people who regained weight returned to a body composition similar to where they started, rather than ending up in worse condition. The researchers also found no strong evidence that weight cycling is responsible for the gradual long-term weight gain commonly seen in obesity.

Weight regain versus actual harm

The authors stress an important distinction. Regaining weight can undo many of the positive effects of weight loss, including improvements in blood sugar, blood pressure, and cholesterol levels. But losing those benefits does not necessarily mean a person becomes less healthy than they were before losing weight.

"Regaining weight brings people back toward baseline risk -- not beyond it," says Magkos. "There's a crucial difference between losing benefits and causing harm."

Several large studies also showed that when researchers account for a person's average body weight over time, weight cycling itself is no longer linked to higher risks of diabetes or cardiovascular disease. Instead, excess body fat appears to be the main factor driving metabolic risk.

Implications for obesity drugs and treatment

The findings arrive at a time when newer obesity medications, including GLP-1 and dual incretin agonists, are becoming increasingly common. These drugs can produce significant weight loss, but many patients regain weight after stopping treatment, creating a pattern similar to weight cycling.

According to the researchers, this regain should not automatically be viewed as harmful. Even temporary periods of weight reduction can still provide important health benefits and improve quality of life, even if the weight loss is not permanent.

A reassuring message for patients

Magkos and Stefan say the evidence should encourage people with overweight or obesity not to abandon efforts to lose weight simply because maintaining weight loss can be difficult.

"The idea that 'yo-yo dieting ruins your metabolism' is not supported by robust evidence," they say. "Trying -- and even failing -- to lose weight is not harmful. But giving up altogether may be."

Source: ScienceDaily