Pancreatic cancer has a poor prognosis, with only about 10% of patients living longer than five years after diagnosis. However, doctors believe survival could improve significantly if the disease is caught earlier, when treatment is more effective. Despite this, there are currently no reliable screening tools available to detect pancreatic cancer in its early stages.

Testing Existing and New Blood Biomarkers

To address this gap, scientists from the University of Pennsylvania Perelman School of Medicine, Philadelphia, and Mayo Clinic, Rochester, Minnesota, analyzed blood samples from individuals with and without pancreatic cancer. They evaluated several biomarkers, including carbohydrate antigen 19-9 (CA19-9), commonly used to monitor treatment response, and thrombospondin 2 (THBS2), another previously studied marker.

Individually, these markers have limitations. CA19-9 levels can rise in non-cancerous conditions like pancreatitis or bile duct obstruction, and some people do not produce the marker at all due to genetic differences. As a result, neither marker alone is reliable enough for screening.

Newly Identified Proteins Improve Detection

By examining stored blood samples, the researchers identified two additional proteins that appear to be elevated in people with early-stage pancreatic cancer: aminopeptidase N (ANPEP) and polymeric immunoglobin receptor (PIGR). These newly identified biomarkers showed clear differences between cancer patients and healthy individuals.

When combined with CA19-9 and THBS2, the four-marker panel demonstrated strong performance. It correctly distinguished pancreatic cancer cases from non-cases 91.9% of the time across all stages, with a false positive rate of 5% in non-cases. For early-stage (stage I/II) cancer, the test detected 87.5% of cases.

“By adding ANPEP and PIGR to the existing markers, we’ve significantly improved our ability to detect this cancer when it’s most treatable,” said the study’s lead investigator, Kenneth Zaret, Ph.D., University of Pennsylvania’s Perelman School of Medicine.

Distinguishing Cancer From Other Conditions

An important advantage of the test is its ability to differentiate pancreatic cancer from other non-cancerous pancreatic conditions, including pancreatitis. This helps reduce the risk of misdiagnosis and unnecessary concern for patients.

Next Steps Toward Screening

“Our retrospective study findings warrant further testing in larger populations, particularly in people before they show symptoms,” Zaret said. “Such ‘prediagnostic’ studies would help determine if the test could be used as a screening tool for people at high risk of developing the disease based on family history, genetic screening results or personal history of pancreatic cysts or pancreatitis.”

The study was supported by NIH grants U01CA210138, P50CA102701, S10 OD023586-01, P30 DK020579, UL1 TR002345, P30CA091842, and U01CA210138.

In a study published in Science Advances, researchers from the University of Adelaide found that losing the enzyme Caspase-2 causes liver cells to grow abnormally. This uncontrolled growth leads to inflammation, scarring, and a much higher likelihood of developing liver cancer.

These results challenge the growing interest in Caspase-2 inhibitors as a treatment to manage or prevent fatty liver disease. The findings suggest that targeting this pathway could have unintended consequences over time.

Caspase-2’s Role in Liver Cell Stability

According to lead researcher Dr. Loretta Dorstyn from the Centre for Cancer Biology, Caspase-2 is essential for keeping liver cells genetically stable. It also plays a separate role in regulating fat levels within the liver.

“Liver cells normally have extra copies of genetic material- known as polyploidy — and while this feature can help the liver cope with stress, our study shows that without the enzyme Caspase-2, abnormally high levels of polyploidy in the liver can be damaging,” Dr. Dorstyn said.

To investigate this further, scientists used genetically modified mice. In animals missing the enzyme, or carrying a nonfunctional version, liver cells became unusually large and showed significant genetic and cellular damage.

Long-Term Damage and Tumor Formation

“Over time, these mice developed chronic liver inflammation and characteristics of hepatitis-like liver disease including, scarring, oxidative damage and a type of cell death linked to inflammation. As the animals aged, they were much more likely to develop liver cancer.”

Older mice without functional Caspase-2 developed liver tumors far more often than normal mice. In some cases, cancer rates were up to four times higher, consistent with hepatocellular carcinoma.

Dr. Dorstyn noted that the findings overturn the assumption that inhibiting Caspase-2 is always beneficial.

“While inhibiting this enzyme can be protective in young animals or may help prevent fatty liver disease in the short term, our study shows that its long-term loss is clearly detrimental.

“Our study demonstrates that Caspase-2 is essential for removing damaged and abnormal liver cells as we age. Without it, these cells accumulate, and can become cancerous, while also creating an environment that predisposes the liver to cancer.”

Implications for Fatty Liver Treatments and Drug Development

Senior author Professor Sharad Kumar said the results carry important warnings for future therapies.

“There has been significant interest in targeting Caspase-2 to treat metabolic liver disease and reduce liver cancer risk,” Prof Kumar said.

“Our data shows that this approach could have serious unintended consequences later in life, increasing susceptibility to chronic liver inflammation, fibrosis and cancer.”

Liver disease continues to rise globally, driven by ageing populations, obesity, and metabolic conditions. In 2022 alone, liver cancer caused nearly 760,000 deaths worldwide, according to the World Cancer Research Fund, making it the sixth most common cancer.

The study, titled ‘Caspase- 2 deficiency drives pathogenic liver polyploidy and increases age- associated hepatocellular carcinoma in mice’, was published in Science Advances.

This area, called the lateral parafacial region, is located in the brainstem, the oldest part of the brain responsible for automatic functions like breathing, digestion, and heart rate.

“The lateral parafacial region is recruited into action causing us to exhale during a laugh, exercise or coughing,” says lead researcher Professor Julian Paton, director of Manaaki Manawa, Centre for Heart Research at Waipapa Taumata Rau, University of Auckland.

“These exhalations are what we call ‘forced’ and driven by our powerful abdominal muscles.

“In contrast, a normal exhalation does not need these muscles to contract, it happens because the lungs are elastic.”

How Breathing and Blood Pressure Are Connected

The team found that this brain region is also linked to nerves that constrict blood vessels, which increases blood pressure.

“We’ve unearthed a new region of the brain that is causing high blood pressure. Yes, the brain is to blame for hypertension!” says Paton.

“We discovered that, in conditions of high blood pressure, the lateral parafacial region is activated and, when our team inactivated this region, blood pressure fell to normal levels.”

These findings suggest that certain breathing patterns, particularly those involving strong abdominal muscle use, can contribute to elevated blood pressure. Identifying abdominal breathing in people with hypertension may help pinpoint the cause and guide more targeted treatment.

The study was recently published in the journal Circulation Research.

A Potential New Treatment Target

‘Can we target this brainstem region?’

The researchers then explored whether this part of the brain could be treated with medication.

“Targeting the brain with drugs is tricky because they act on the entire brain and not a selected region such as the parafacial nucleus,” says Paton.

A key breakthrough came when the team discovered that this region is activated by signals originating outside the brain. These signals come from the carotid bodies, small clusters of cells in the neck near the carotid artery that monitor oxygen levels in the blood.

Because the carotid bodies can be safely targeted with medication, they offer a promising alternative approach.

“Our goal is to target the carotid bodies, and we are importing a new drug that is being repurposed by us to quench carotid body activity and inactivate ‘remotely’ the lateral parafacial region safely, i.e., without needing to use a drug that penetrates the brain.”

This discovery could lead to new ways to treat high blood pressure, especially in people with sleep apnoea, where carotid body activity increases when breathing stops during sleep.

Over time, researchers have identified several kinds of time crystals, each with unique properties that could be useful in different applications.

A New Sound-Levitated Time Crystal

Physicists at New York University have now created a new version of a time crystal. In this system, tiny particles float on a cushion of sound and interact by exchanging sound waves. During these interactions, the particles behave in a way that appears to break Newton’s Third Law of Motion, which states that for every action, there is an equal and opposite reaction (i.e., forces always occur in balanced pairs). In this experiment, however, the particles do not follow that balance. Instead, they move in a nonreciprocal way, meaning their interactions are uneven and not mirrored.

The results, published in Physical Review Letters, point to new possibilities for using time crystals in technology and industry. Unlike many previous experiments, this system is visible to the naked eye and operates on a compact device about one foot tall that can be held in your hand.

“Time crystals are fascinating not only because of the possibilities, but also because they seem so exotic and complicated,” says Physics Professor David Grier, director of NYU’s Center for Soft Matter Research and the paper’s senior author. “Our system is remarkable because it’s incredibly simple.”

Insights Into Biology and Circadian Rhythms

The study, carried out with Mia Morrell, an NYU graduate student, and Leela Elliott, an NYU undergraduate, may also help scientists better understand biological timing systems such as circadian rhythms. Similar to these time crystals, some biochemical processes in the body involve nonreciprocal interactions, including how the body breaks down food.

How Sound Waves Keep Particles Floating

The time crystal itself is made from small styrofoam beads, similar to packing material, that are held in place by sound waves. This setup acts as an “acoustic levitator,” allowing the beads to remain suspended and still in mid-air.

“Sound waves exert forces on particles — just like waves on the surface of a pond can exert forces on a floating leaf,” explains Morrell. “We can levitate objects against gravity by immersing them in a sound field called a standing wave.”

When the levitated beads interact, they do so by scattering sound waves between one another.

Uneven Forces and Broken Symmetry

Larger beads scatter more sound than smaller ones. As a result, a larger particle has a stronger effect on a smaller particle than the smaller particle has on the larger one. This creates an imbalance in how they influence each other.

“Think of two ferries of different sizes approaching a dock,” says Morrell. “Each one makes water waves that pushes the other one around — but to different degrees, depending on their size.”

Because these interactions are carried by sound waves, they are not limited by Newton’s Third Law. This allows the beads to begin oscillating on their own while floating in mid-air, producing a steady rhythm that reflects the unusual forces at play.

The research was supported by grants from the National Science Foundation (DMR-21043837, DMR-2428983).