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Diseases and Conditions

Starving Tumors: A New Approach to Making Cancer Treatment Work Better

Pancreatic cancer cells are known for being hard to treat, partly because they change the environment around them to block drugs and immune cells. Scientists discovered that these tumors use a scavenging process—called macropinocytosis—to pull nutrients from nearby tissue and keep growing. By blocking this process in mice, researchers were able to change the tumor’s environment, making it softer, less dense, and easier for immune cells and therapies to reach.

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The battle against cancer has long been an uphill struggle. Despite advances in treatment, the disease still claims too many lives. However, scientists have made a groundbreaking discovery that could change the game – starving tumors to make cancer treatment more effective.

Cancer cells and tumors do not exist in isolation. They interact with their surrounding environment, which is composed of immune cells, connective tissue, blood vessels, and proteins and carbohydrates that provide structure and other supportive functions. Pancreatic ductal adenocarcinoma (PDAC) cells, for instance, use a cellular scavenging process called macropinocytosis to grab extra nutrients from the extracellular matrix.

Macropinocytosis affects the area surrounding the tumor, making connective tissue stiffer and preventing immune cells from reaching the tumor. Researchers at the NCI-Designated Cancer Center at Sanford Burnham Prebys published findings in Cancer Cell demonstrating that blocking macropinocytosis reshapes the tumor microenvironment to be less fibrous and allows more access to immune cells.

The researchers observed that nearby fibroblasts, which typically form connective tissue and produce many components of the extracellular matrix captured during macropinocytosis, are coerced to become cancer-associated fibroblasts (CAF) that help tumors grow. These CAFs provide metabolites and growth signals, as well as helping in other ways.

When macropinocytosis was blocked, CAFs experienced metabolic stress due to deprivation of glutamine, one of the 20 amino acids used to build proteins throughout the body. PDAC relies heavily on glutamine, so CAFs in the pancreatic cancer tumor microenvironment are regularly starved of it.

Preventing macropinocytosis led to a change to a different subtype of CAF marked by the expression of genes that promote inflammation. This altered CAF population had fewer myofibroblasts, which make the tumor microenvironment stiff and fibrotic, and more inflammatory CAFs, which allow for greater access to immune cells.

The research team found significant changes in the tumor neighborhood resulting from preventing macropinocytosis in CAFs. There were fewer deposits of collagen that make the tumor microenvironment stiff or fibrotic, more access for CD4+ and CD8+ T cells to infiltrate the tumor, and vascular expansion, which promotes drug delivery.

The investigators then tested the effects of combining a treatment to block macropinocytosis with immunotherapy and chemotherapy. They found that this combination significantly suppressed tumor metastasis and prolonged mouse survival.

These findings have significant implications for cancer patients, particularly those with PDAC, which is the third leading cause of cancer deaths despite accounting for only three percent of cases. The scientists will continue to explore how to prevent tumors from scavenging energy to reshape the tumor microenvironment into one that makes cancer treatments more effective.

As lead author Yijuan Zhang, PhD, said, “We believe this is a very promising strategy to pursue for developing combination therapies for cancer patients.”

Birth Control

A Safer, Cheaper Vision Correction Method May Be on the Horizon

Scientists are developing a surgery-free alternative to LASIK that reshapes the cornea using electricity instead of lasers. In rabbit tests, the method corrected vision in minutes without incisions.

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This revolutionary approach to vision correction is called electromechanical reshaping (EMR). This method utilizes electrical impulses to reshape the cornea, potentially providing a safer and more affordable alternative to traditional LASIK surgery. Researchers at Occidental College have made significant progress in this area, with initial studies demonstrating promising results on rabbit eyeballs.

The researchers’ innovative technique involves using platinum “contact lenses” that provide a template for the corrected shape of the cornea. By applying an electric potential to these contact lenses, they create a precise pH change within the tissue, loosening its rigidity and making it malleable. This enables them to reshape the cornea without any incisions or ablative procedures.

In their experiments on rabbit eyeballs, the team successfully reshaped the corneas of 12 separate specimens, 10 of which were treated as if they had myopia (nearsightedness). The treatment effectively corrected the focusing power of the eye in all “myopic” eyeballs. Moreover, the cells within the eyeball survived this procedure because the researchers carefully controlled the pH gradient.

The researchers emphasize that while these initial results are promising, their work is still in its early stages. They plan to conduct further animal studies and investigate the potential of EMR for treating a range of vision problems, including astigmatism, near- and far-sightedness. However, the team’s scientific funding uncertainties have put them on hold.

Despite these challenges, the researchers remain optimistic about the potential of this new technique. They believe that if successful, EMR could provide a widely applicable, vastly cheaper, and potentially even reversible method for vision correction, surpassing current treatments like LASIK.

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Children's Health

Uncovering the Inaccuracy: Why Common Blood Pressure Readings May Miss 30% of Hypertension Cases

Cambridge scientists have cracked the mystery of why cuff-based blood pressure monitors often give inaccurate readings, missing up to 30% of high blood pressure cases. By building a physical model that replicates real artery behavior, they discovered that low pressure below the cuff delays artery reopening, leading to underestimated systolic readings. Their work suggests that simple tweaks, like raising the arm before testing, could dramatically improve accuracy without the need for expensive new devices.

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The measurement of blood pressure has been a cornerstone of medical practice for decades. However, despite its widespread use, research suggests that common cuff-based blood pressure readings may be inaccurate and potentially miss up to 30% of hypertension cases.

A team of researchers from the University of Cambridge has shed new light on this issue by building an experimental model that explains the physics behind these inaccuracies. Their findings, reported in the journal PNAS Nexus, have significant implications for patient health outcomes and highlight the need for more accurate measurement methods.

The auscultatory method, which relies on inflating a cuff around the upper arm to measure blood pressure, has long been considered the gold standard. However, this study reveals that it overestimates diastolic pressure while underestimating systolic pressure. The researchers attribute this discrepancy to a previously unidentified factor: the delayed reopening of arteries due to low downstream pressure.

To replicate this condition in their experimental rig, the Cambridge team used tubes that lay flat when deflated and fully closed when inflated with cuff pressure. This setup allowed them to study the effects of downstream blood pressure on artery closure and reopening, leading to a better understanding of the mechanics behind inaccurate readings.

The researchers propose several potential solutions to address this underestimation, including raising the arm before measurement to produce a predictable downstream pressure. This simple change does not require new devices but can make blood pressure measurements more accurate.

If new devices for monitoring blood pressure are developed, they may incorporate additional inputs that correlate with downstream pressure, such as age, BMI, or tissue characteristics, to adjust ‘ideal’ readings for each individual.

The study’s authors emphasize the need for clinical trials to test their findings in patients and collaborate with clinicians to implement changes to clinical practice. Funding from organizations like the Engineering and Physical Sciences Research Council (EPSRC) will be essential to support further research and development.

By uncovering the inaccuracies in common blood pressure readings, this study has significant implications for patient health outcomes and highlights the need for more accurate measurement methods. The proposed solutions have the potential to improve diagnosis and treatment of hypertension, ultimately saving lives and reducing healthcare costs.

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Allergy

“The Silent Invader: How a Parasitic Worm Evades Detection and What it Can Teach Us About Pain Relief”

Scientists have discovered a parasite that can sneak into your skin without you feeling a thing. The worm, Schistosoma mansoni, has evolved a way to switch off the body’s pain and itch signals, letting it invade undetected. By blocking certain nerve pathways, it avoids triggering the immune system’s alarms. This stealth tactic not only helps the worm survive, but could inspire new kinds of pain treatments and even preventative creams to protect people from infection.

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A new study published in The Journal of Immunology has made an intriguing discovery about how a parasitic worm evades detection and what it can teach us about pain relief. Researchers from Tulane School of Medicine found that the Schistosoma mansoni worm, which causes schistosomiasis, suppresses neurons in the skin to avoid triggering an immune response.

When this worm penetrates human skin, typically through contact with infested water, it produces molecules that block a protein called TRPV1+, which is responsible for sending pain signals to the brain. This clever mechanism allows the worm to infect the skin largely undetected.

The researchers believe that the S. mansoni worm evolved this strategy to enhance its own survival and found that blocking TRPV1+ also reduced disease severity in mice infected with the parasite. The study suggests that identifying the molecules responsible for suppressing TRPV1+ could lead to new painkillers that do not rely on opioids.

Moreover, the researchers discovered that TRPV1+ is essential for initiating host protection against S. mansoni infection. When this protein is activated, it triggers a rapid mobilization of immune cells, which induces inflammation and helps fight off the parasite. This finding highlights the critical role of neurons in pain-sensing and immune responses.

The study’s lead author, Dr. De’Broski R. Herbert, emphasizes that identifying these molecules could inform preventive treatments for schistosomiasis. He envisions a topical agent that activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni.

This groundbreaking research has the potential to revolutionize our understanding of pain relief and immune responses, offering new avenues for developing innovative therapies that could benefit millions worldwide.

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