Author: ModernMedia

Categories : CancerTags :

Lymph Nodes Found to be Key to Successful Cancer Immunotherapy

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Swollen lymph nodes. Credit: Scientific Animations CC0

New research has shown why preserving lymph nodes, often removed near tumours to prevent cancer spread, could improve patient outcomes and make immunotherapies more effective.

A team of researchers, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute), explored the cellular and molecular interactions revealing how lymph nodes play a crucial role in the fight against chronic infection and cancer.

The research, published across two papers in Nature Immunology (references and links below), showed that lymph nodes provide the right environment for stem-like T cells, an important type of immune cell, to survive, multiply and produce killer cells that can fight cancer or viruses. In other immune organs, such as the spleen, these cells don’t develop or proliferate as effectively, making lymph nodes essential for a strong immune response and successful immunotherapy.

The University of Melbourne’s Professor Axel Kallies, Laboratory Head at the Doherty Institute and senior author of both papers, said the findings have important implications for cancer therapy.

“Lymph nodes aren’t just passive waiting rooms for immune cells, they actively train and educate T cells, and send them off to do their job,” said Professor Kallies.

“Our research suggests that removing lymph nodes during cancer surgery, a common practice to prevent tumour spread, may inadvertently reduce the effectiveness of treatments, such as checkpoint blockade and CAR T cell therapies. Preserving lymph nodes could strengthen immune responses and increase the effectiveness of immunotherapy.”

This work may also help explain why some patients respond better to immunotherapy than others. The state and function of lymph nodes influence how well the immune system can produce cancer-fighting T cells, directly impacting the success of immunotherapy.

The University of Melbourne’s Dr Carlson Tsui, Postdoctoral Researcher at the Doherty Institute and first author of one of the papers, said the findings could help to develop new strategies to make immunotherapy more effective.

“Our research identifies molecular signals that are involved in the regulation of stem-like cells and in their capacity to produce effective killer cells. These findings could guide the development and refinement of immune-based treatments for cancer and chronic infection,” said Dr Tsui.

“Furthermore, our research shows that rather than only focusing on the tumour itself, therapies should also be designed to preserve and enhance lymph node function. By targeting these critical immune hubs, we could boost the body’s natural ability to fight cancer, increase the effectiveness of existing immunotherapies and help more patients respond to treatment.”

Together, the two peer-reviewed papers provide a deeper understanding of how lymph nodes shape immune responses. While they are based on work with animal models, they will guide future treatment strategies for chronic infection and cancer treatment.

Professor Shahneen Sandhu, Research Lead for the Melanoma Medical Oncology Service at the Peter MacCallum Cancer Centre, commented on the clinical implications of this work.

“While this research was done in the laboratory with pre-clinical models, we’re excited to study these findings in clinical samples from patients receiving immune checkpoint inhibitors, as part of an ongoing Melanoma Research Victoria collaboration with Professor Kallies,” Professor Sandhu said.

“Combining clinical and preclinical studies will help us translate these discoveries from bench to bedside and back, ultimately improving outcomes for cancer patients.”

  1. Tsui C, Heyden L, et al. Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade. Nature Immunology (2025). DOI: https://doi.org/10.1038/s41590-025-02276-7  
  2. Wijesinghe SKM, Rausch L, et al. Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity. Nature Immunology (2025). DOI: https://doi.org/10.1038/s41590-025-02219-2  

Source: Doherty Institute

Categories : Immune SystemTags :

Researchers Identify New Method to Protect Against Sepsis

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Photo by Furkan İnce

Sepsis is the No.1 cause of death in the intensive care unit of hospitals worldwide and a major concern for health scientists and medical professionals alike.

Dr Scott Widenmaier (PhD), an associate professor in the Department of Anatomy, Physiology and Pharmacology in USask’s College of Medicine, has zeroed in on a specific protein that might be key to helping the body fight back against the potentially life-threatening condition.

By manipulating this protein, researchers believe there is a new avenue to protect patients against sepsis. Widenmaier and his team have had their research recently published in Cellular and Molecular Gastroenterology and Hepatology.

“Sepsis is the largest cause of death in the intensive care unit globally,” Widenmaier said. “Sepsis can cause damage to organs like the heart, kidney, and lungs. It can also cause liver dysfunction, and when this occurs, the liver is not able to properly perform its functions that are useful in helping the body deal with an infection.”

Sepsis is caused by the body’s immune system response to infection causing damage to the body itself. As Widenmaier puts it, many people believe that bacteria or a virus they acquire are what causes people to get sick. However, it’s the body’s response to the infection that results in severe sickness and can escalate to sepsis – what Widenmaier identified as “a dysregulated immune response that leads to life-threatening complications.”

“The immune system releases cytokines and various factors that are trying to kill the bacteria or the virus, but the process of doing it actually dramatically changes our physiology and leads to us being really sick,” Widenmaier said.

While conventional methods for treating sepsis have been targeted at mitigating the infections that might lead to sepsis, Widenmaier said more recent studies have recognised that the body itself has built-in disease tolerance mechanism that could be harnessed to protect itself from the potential damage. In other words, when disease tolerance is working well, the process of killing the infection won’t cause the person to get nearly as sick and preserve healthy organ function.

Widenmaier and his team identified a “transcription factor” protein in the liver called NRF1, which acts as a “molecular switch” to help control the body’s own disease tolerance response. In experimental models infected with E. coli, over-expressing the NRF1 protein led to better overall responses to infection and protection against sepsis.

When over-expressed, the protein enables the liver to secrete more very low-density lipoprotein (VLDL) particles, which better protects organs against damage caused by sepsis. It’s this connection between the NRF1 “switch” and the liver’s production of VLDL that Widenmaier says may be a promising approach to improve the outcomes of patients with sepsis.

“Our lab is very interested in finding ways to either pharmacologically or genetically manipulate NRF1 to promote health,” he said.

Widenmaier credited his team – including colleagues, students and trainees – for their work in identifying this potential target for sepsis treatments and for the resulting research paper.

The next step for this research would be to see how feasible this pathway might be for treatment and whether it is still active in conditions when sepsis is very common – and while they aren’t at the stage of human trials yet, Widenmaier said he wants to delve deeply into this new area in the search for better sepsis care.

“We want to explore this quite intensively,” he said. “There’s a lot of clinical investigators across the country … I’m interested in continuing those connections and trying to strengthen them, and hopefully we can find a place where clinicians and our lab can benefit from the science.”

Source: University of Saskatchewan

Categories : Gastrointestinal Surgeries & ProceduresTags :

New Swedish Study Challenges Early Surgery for Crohn’s Disease

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A new study from Karolinska Institutet challenges previous findings that suggested early surgery is more beneficial in the long term than medical treatment for patients with Crohn’s disease. The study replicates a Danish registry study using Swedish data and finds that the results are not comparable. The study was published in Clinical Gastroenterology and Hepatology.

A few years ago, a randomised controlled trial showed that early ileocecal resection – removal of the junction between the small and large intestine – could be a reasonable alternative to advanced drug therapy for patients with Crohn’s disease. This study gained significant attention and was widely discussed around the world. Recently, a Danish research group published a registry-based study in the journal Gastroenterology, concluding that real-world data showed that early ileocecal resection was clearly superior to medical treatment in the long term.

In the new Swedish study, researchers attempted to replicate the Danish study using nationwide  Swedish registry data. They found that it is impossible to identify comparable populations in current observational data, as patients who underwent surgery or received medication during the study period differ according to existing treatment guidelines.

“It’s a comparison of apples and oranges,” says Ola Olén, professor at the Department of Medicine, Solna, Karolinska Institutet, who led the study.

The Danish researchers made several design choices that further reduced the comparability between the groups. When the Swedish researchers applied the same definitions as the Danish study, they obtained similar results. However, when they used stricter definitions that more closely resembled the original randomized study, they no longer found a significant difference between the groups.

“We argue that the Danish study cannot be interpreted as proof that early surgery is better. That may very well be the case, but the data we currently have simply cannot answer that question,” says Ola Olén.

Source: Karolinska Institutet

Categories : NeurologyTags :

Oxytocin Shines a Light into Parental Attachment and Sex Differences

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The developing brain of a two-week-old mouse pup under the microscope. The oxytocin system appears in green, the light-sensitive protein in red and cells that carry both show up in yellow. Cell nuclei are in blue. Credit: Weizmann Institute of Science

According to attachment theory, the attachment between an infant and a primary caregiver shapes the baby’s future social ties. Yet little is known about the biological mechanisms underlying childhood attachment, mainly because it is so difficult to study the young brain in natural conditions.

Now, scientists in Prof Ofer Yizhar’s laboratory at the Weizmann Institute of Science have developed a new, noninvasive research method that makes it possible to silence selected nerve cells deep within the brains of mouse pups without disrupting their natural behaviour. Using this method, the researchers investigated the role of oxytocin, a short protein released from nerve cells in the brain. While most oxytocin research has focused on adults, the new findings, published in Science, show that oxytocin also shapes the social behaviour of pups and may underlie emotional differences between males and females that emerge early in life.

Oxytocin, sometimes referred to as the “love hormone,” was once thought to simply promote sociability in adults. Over time, however, it became clear that its role is far more complex: In some circumstances, it intensifies behaviors and emotions far removed from love, such as anxiety or aggression. Recent research has also shown that young mammalian brains – including those of human children – are especially sensitive to oxytocin. In brain regions responsible for sensory processing, emotional regulation and social behavior, the number of oxytocin receptors peaks during early childhood: around ages two to three in humans, and two to three weeks in mice. Some studies have even linked oxytocin deficiency to childhood autism. Still, without sufficiently precise tools to examine neural activity deep within the developing brain, many aspects of the role of oxytocin in early life have remained a mystery.

“The findings may offer a clue as to why males and females diverge in their social behaviors and emotional worlds long before puberty”

To shed light on the subject, a team led by Dr Daniel Zelmanoff, a physician-scientist in Yizhar’s lab, developed a noninvasive technique to probe specific nerve cells in the young brain. The group, pioneers in the field of optogenetics – a technology that uses light to switch individual cells on or off – devised a method in which the targeted brain cells of mouse pups are infected with an engineered virus. This otherwise harmless virus introduces a foreign gene of mosquito origin that encodes a light-sensitive protein; when exposed to light, the protein “turns off” the nerve cell. In fact, the protein is so light-sensitive that the researchers could silence selected nerve cells deep inside the brain simply by shining red light on the pups’ heads.

“This new method allows us to peek inside the brain without disturbing the pups’ everyday lives, making it a powerful tool for studying nervous system development,” Yizhar explains. “It is especially useful for studying oxytocin because this hormone’s effects depend on social context – and our method lets us switch off the oxytocin system on demand, only during the exact situation we want to study.”

The researchers focused on oxytocin’s role during the temporary separation of a mouse pup from its mother and their reunion a few hours later – a situation familiar to every parent of a young child. The scientists observed increased oxytocin activity in the pup’s brain during separation, which returned to normal after reunion with the mother. Pups with an active oxytocin system during the separation gradually adapted to being alone in an unfamiliar environment, producing fewer ultrasonic vocalizations – the mouse equivalent of a baby’s cry. In contrast, pups whose oxytocin system was silenced did not adapt; they continued emitting distress calls at the same rate until reunited with their mothers. These findings show that the so-called “love hormone” also plays a critical role in coping with loneliness.

Attachment theory holds that children who are securely attached to their parents show distress when separated from them but are able to calm down over time, feeling free to explore their surroundings. “We discovered that mouse pups need an active oxytocin system in order to adapt to separation from their mothers,” says Yizhar. “This suggests that the oxytocin system plays a role not only in the brain of the parent, which was already known, but also in that of the infant. In addition, since oxytocin receptors are present in the sensory processing centers of the young brain, we hypothesize that this hormone also helps sharpen a pup’s senses when it is alone.”

Children do not quickly forget the experience of being separated from their parents, and this separation shapes how they behave when reunited. For example, a securely attached child separated from a parent for a few hours will seek contact upon reunion, and is quickly calmed. The researchers found that activation of the oxytocin system in mouse pups during separation not only strengthened them in the moment but also determined how they behaved when their mothers returned. These pups emitted more ultrasonic calls than usual, and the frequency of the calls grew as they got closer to their mothers. Using artificial intelligence, the team identified a distinct vocal pattern: Before attaching to the mother’s nipple, the pups made high-pitched, frequent calls; afterwards, their calls dropped in pitch and slowed in tempo.

“Activating the oxytocin system during separation increases the pup’s motivation to regain closeness to the mother when reunited,” Yizhar explains. “This is reflected in the heightened rate and unique pattern of their calls. We now understand that these ultrasonic vocalizations are much more than just crying: The high-pitched, rapid calls appear to signal a request for closeness, while the lower-pitched, slower-paced calls likely express a quick return to calm and a wish to remain attached. Of course, more research is needed to pin down the exact meaning of each vocalization type.”

In the next stage, the researchers explored whether oxytocin’s role in pups differs between the sexes, as it does in older animals. They found that female pups with an active oxytocin system emitted many more ultrasonic calls when reunited with their mothers than females with silenced oxytocin systems, whereas the calls of male pups were unaffected by the status of their oxytocin systems. “This is the first sex difference observed in oxytocin system activity at such an early stage of development,” Yizhar notes. “It may offer a clue as to why males and females diverge in their social behaviours and emotional worlds long before puberty.”

“Most known functions of oxytocin are shared by all mammals,” Yizhar concludes. “Still, future studies must check whether the hormone affects the development of social behaviour, emotional maturity and maternal attachment in the brains of children. If so, this could help us better understand what can go wrong in emotional and social development – as in autism spectrum disorder, for example – and how to intervene at an early stage.”

Source: Weizmann Institute of Science

Categories : Paediatrics Respiratory DiseasesTags :

Study Finds that Even Healthy Children Are Vulnerable to RSV

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Photo by William Fortunato

It is not only premature babies and children with underlying diseases who suffer from serious respiratory syncytial virus (RSV) infections. Even healthy, full-term babies are at significant risk of intensive care or prolonged hospitalisation – especially during the first three months of life. This is according to a comprehensive registry study from Karolinska Institutet published in The Lancet Regional Health – Europe.

RSV is a common cause of respiratory infections in young children and accounts for around 245,000 hospital admissions annually in Europe. Researchers have now analysed data from over 2.3 million children born in Sweden between 2001 and 2022 to find out who is at greatest risk of suffering serious complications or dying from an RSV infection.

Preventive treatment available

It is well-known that premature babies and children with chronic diseases are at increased risk of developing severe illness when infected with RSV. It is also known that children under three months of age are particularly vulnerable, but it has not been entirely clear how common severe disease is among previously healthy children. The study shows that the largest group among the children who needed intensive care or were hospitalised for a long period of time were under three months of age, previously healthy and born at full term.

“When shaping treatment strategies, it is important to take into account that even healthy infants can be severely affected by RSV,” says the study’s first author, Giulia Dallagiacoma, a physician and doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “The good news is that there is now preventive treatment that can be given to newborns, and a vaccine that can be given to pregnant women.”

Starting September 10, 2025, all newborns in Sweden are being offered preventive treatment with antibodies during the RSV season. The drug works much like a vaccine and protects against severe RSV infection for about six months.

Several risk factors identified

A total of 1.7 per cent of the children in the study were diagnosed with RSV infection. Among those, just under 12 per cent (4,621 children) had a severe course of illness. The median age of children who needed intensive care was just under two months, and the majority of them had no underlying disease.

The researchers identified several factors that were linked to an increased risk of needing intensive care or dying. Children who were born in the winter, or had siblings aged 0–3 years or a twin, had approximately a threefold increased risk, while children who were small at birth had an almost fourfold increased risk. Children with underlying medical conditions had more than a fourfold increased risk of severe illness or death.

“We know that several underlying diseases increase the risk of severe RSV infection, and it is these children who have so far been targeted for protection with the preventive treatment that has been available,” says the study’s last author, Samuel Rhedin, resident physician at Sachs’ Children and Youth Hospital and associate professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “However, the study highlights that a large proportion of children who require intensive care due to their RSV infection were previously healthy. Now that better preventive medicines are available, it is therefore positive that the definition of risk groups is being broadened to offer protection during the RSV season to previously healthy infants as well.”

Source: Karolinska Institutet

Publication

“Risk factors for severe outcomes of respiratory syncytial virus infection in children: a nationwide cohort study in Sweden”, Giulia Dallagiacoma, Cecilia Lundholm, Awad I Smew, Emma Caffrey Osvald, Pekka Vartiainen, Santtu Heinonen, Tobias Alfvén, Catarina Almqvist, Samuel Rhedin, The Lancet Regional Health – Europe, online 10 September 2025, doi: 10.1016/j.lanepe.2025.101447.

Categories : Mental Health PaediatricsTags :

ADHD Drugs Are Being Prescribed Too Quickly to Preschool Children

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A Stanford University-led study has found that young children with attention deficit/hyperactivity disorder (ADHD) often receive medication just after being diagnosed, which contravenes treatment guidelines endorsed by the American Academy of Pediatrics.

The findings, from published JAMA Network Open, highlight a gap in medical care for 4- and 5-year-olds with ADHD. Treatment guidelines recommend that these young children and their families try six months of behaviour therapy before starting ADHD medication.

But paediatricians often prescribe medication immediately upon diagnosis, according to an analysis of medical records from nearly 10 000 young children with ADHD who received care in eight paediatric health networks in the United States.

“We found that many young children are being prescribed medications very soon after their diagnosis of ADHD is documented,” said the study’s lead author, Yair Bannett, MD, assistant professor of paediatrics. “That’s concerning, because we know starting ADHD treatment with a behavioural approach is beneficial; it has a big positive effect on the child as well as on the family.”

Medications not appropriate to under-6s

In addition, stimulant medications prescribed for the condition cause more side effects in young patients than they do in older children, Bannett said. Before age 6, children’s bodies don’t fully metabolise the drugs.

“We don’t have concerns about the toxicity of the medications for 4- and 5-year-olds, but we do know that there is a high likelihood of treatment failure, because many families decide the side effects outweigh the benefits,” he said. Stimulant medication can make young children more irritable, emotional, and aggressive.

ADHD is a developmental disorder characterised by hyperactivity, difficulty paying attention, and impulsive behaviour.

“It’s important to catch it early because we know these kids are at higher risk for having academic problems and not completing school,” Bannett said. Early identification and effective treatment for ADHD improve children’s academic performance. Research has shown that good treatment also helps prepare individuals with ADHD for many aspects of adulthood, such as maintaining employment, having successful relationships, and avoiding trouble with the law.

Complementary treatments

Behavioral therapy and medication, the two mainstays of ADHD treatment, have different purposes.

“Behavioral treatment works on the child’s surroundings: the parents’ actions and the routine the child has,” Bannett said. The therapy helps parents and kids build skills and establish habits compatible with how the child’s brain works.

The evidence-based behavioral treatment recommended by the American Academy of Pediatrics is called parent training in behavior management. The training helps parents build strong, positive relationships with their children; offers guidance in rewarding a child’s good behaviors and ignoring negative behaviors; and recommends tools that help kids with ADHD, such as making visual schedules to help them stay organized.

In contrast, medication relieves ADHD symptoms such as hyperactivity and inattentiveness, with effects that wear off as the body breaks down each dose of the drug.

Both approaches are needed for most kids with ADHD to do well. But previous studies of preschoolers diagnosed at age 4 or 5 show that it’s best to start with six months of behavioural treatment before prescribing any medication.

Rapid prescriptions

The researchers analysed data from electronic health records for children seen at primary care practices affiliated with eight US academic medical centres. They began with 712 478 records from children aged 3, 4, or 5 years old and were seen by their primary care physician at least twice, over a period of at least six months, between 2016 and 2023.

From these records, the scientists identified 9708 children who received an ADHD diagnosis, representing 1.4% of the children in the initial sample. They found that 42.2% were prescribed medication within a month of their ADHD diagnosis. Only 14.1% of children with ADHD first received medication more than six months after diagnosis. The researchers did not have access to data on referrals to behavioural therapy, but since young children are supposed to try the therapy alone for six months before receiving medication, any who were prescribed medication sooner were likely not being treated according to academy guidelines. A smaller study of recommendations for behaviour therapy, published in 2021, found only 11% of families got the therapy in line with guidelines.

Children who were initially given a formal diagnosis of ADHD were more likely to get medication within the first 30 days than those whose medical charts initially noted some ADHD symptoms, with a diagnosis at a later time. But even among preschoolers who did not initially meet full criteria for the condition, 22.9% received medication within 30 days.

Barriers to behavioural treatment?

Because the study was based on an analysis of electronic medical records, the researchers could not ask why physicians made the treatment decisions they did. But in informal conversations with physicians, outside the scope of the study, the researchers asked why they prescribed medication.

“One important point that always comes up is access to behavioural treatment,” Bannett said. Some locales have few or no therapists who offer the treatment, or patients’ insurance may not cover it. “Doctors tell us, ‘We don’t have anywhere to send these families for behavioural management training, so, weighing the benefits and risks, we think it’s better to give medication than not to offer any treatment at all.’”

Bannett said he hopes to educate primary care paediatricians on how to bridge this gap. For example, free or low-cost online resources are available for parents who want to learn principles of the behavioural approach.

And while the study focused on the youngest ADHD patients, behavioural management therapy also helps older children with the diagnosis.

“For kids six and above, the recommendation is both treatments, because behavioural therapy teaches the child and family long-term skills that will help them in life,” Bannett said. “Medication will not do that, so we never think of medication as the only solution for ADHD.”

Source: Stanford University

Categories : CancerTags :

Aspirin Found to Halve Recurrence for Certain Colorectal Cancers

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A Swedish-led research team at Karolinska Institutet and Karolinska University Hospital has shown in a new randomised clinical trial that a low dose of the well-known medicine aspirin halves the risk of recurrence after surgery in patients with colon and rectal cancer with a certain type of genetic alteration in the tumour.

Every year, nearly two million people worldwide are diagnosed with colorectal cancer, and 20–40% develop metastases.

Previous observational studies have suggested that aspirin may reduce the risk of certain cancers and possibly also the risk of recurrence after surgery in patients with colorectal cancer harbouring mutations in genes within the PIK3 signaling pathway. These genes regulate key cellular processes such as growth and division. When mutated, these processes can become dysregulated, leading to uncontrolled cell proliferation and cancer development.

Randomised clinical trials were lacking

Prior findings have been inconsistent and no randomised clinical trials had previously confirmed the association. To address this gap, the ALASCCA trial was initiated, with the results now been published in The New England Journal of Medicine.

The current study included more than 3500 patients with colon and rectal cancer from 33 hospitals in Sweden, Norway, Denmark, and Finland. Patients whose tumours showed a specific genetic mutation in the PIK3 signalling pathway – a mutation found in approximately 40% of patients – were randomised to receive either 160mg of aspirin daily or a placebo for three years after surgery.

For patients with the genetic mutation in PIK3, the risk of recurrence was reduced by 55% in those who received aspirin compared with the placebo group.

“Aspirin is being tested here in a completely new context as a precision medicine treatment. This is a clear example of how we can use genetic information to personalise treatment and at the same time save both resources and suffering,” says first author Anna Martling, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior consultant surgeon at Karolinska University Hospital.

Less favourable environment for cancer

So how does aspirin reduce the risk of recurrence of colon and rectal cancer? The researchers believe that the effect is likely due to aspirin acting through several parallel mechanisms – it reduces inflammation, inhibits platelet function and tumour growth. This combination makes the environment less favourable for cancer.

“Although we do not yet fully understand all the molecular links, the findings strongly support the biological rationale and suggest that the treatment may be particularly effective in genetically defined subgroups of patients,” says Anna Martling.

The researchers believe that the results could have global significance and influence treatment guidelines for colon and rectal cancer worldwide. Anna Martling sees the fact that the drug is well established as a major advantage.

“Aspirin is a drug that is readily available globally and extremely inexpensive compared to many modern cancer drugs, which is very positive,” says Anna Martling.

Source: Karolinska Institutet

Categories : CancerTags :

New Cancer Drug Boosts Effectiveness of Chemotherapy – Even in Resistant Tumours

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A groundbreaking cancer drug could enhance how patients respond to chemotherapy even in treatment-resistant tumours.

The drug works by disarming a key defence mechanism that tumours use to protect themselves from treatment. In preclinical models, it has already shown promise in making chemotherapy-resistant cancers more responsive to therapy.

Chemotherapy is one of the most widely used cancer treatments, but it doesn’t always work as effectively as hoped. One major reason is that macrophages act as a barrier around tumours. These immune cells surround the blood vessels inside tumours and act like gatekeepers, blocking helpful immune cells from entering and doing their job in supporting the responses to chemotherapy.

The King’s College London scientists, who have launched a spinout company Aethox Therapeutics, found that these macrophages make a protein called heme oxygenase-1 (HO-1), which helps shield the tumour from the immune system and block the effects of chemotherapy. The new drug, KCL-HO-1i, targets this protein.

Professor James Arnold, Head of Tumour Immunology Group, King’s College London, said: “We discovered that these macrophages in cancer play a key role in blocking chemotherapy. By targeting the enzyme they produce using KCL-HO-1i, we were able to help beneficial immune cells and chemotherapy drugs become significantly more effective. In laboratory models, even chemotherapy-resistant tumours became responsive to treatment, which is a really exciting step forward.”

Unlike many cancer treatments that require hospital visits, KCL-HO1i is designed to be taken at home as a tablet between chemotherapy sessions. This makes it easier for patients to incorporate into their treatment plans without adding extra hospital burdens.

In early tests using mouse models of breast cancer, supported by funding by Cancer Research UK and Medical Research Council (MRC), the drug made tumours more responsive to a range of commonly used chemotherapies. These promising results suggest it could be used across a wide variety of cancer types and chemotherapy treatments.

The researchers hope that with funding, clinical trials on breast and other cancers could begin within two years.

Professor James Spicer, Professor of Experimental Cancer Medicine, King’s College London, said: “Chemotherapy remains a key part of treatment for many patients with cancer, but too often it is not as effective or long-lasting as we might like. This research has identified a key reason for these limitations, and discovered a drug that we are keen to test in the clinic alongside established chemotherapy drugs”.

This breakthrough is the result of a multidisciplinary collaboration between researchers including Professors James Arnold, James Spicer, and Miraz Rahman and their research teams at King’s College London.

If human trials are successful, KCL-HO-1i could become a valuable companion drug to existing cancer therapies – helping more patients to benefit from the treatments that are already available and reduce the need for more aggressive cancer therapies in the future.

Professor Miraz Rahman, Professor of Medicinal Chemistry, King’s College London
Categories : EndocrinologyTags :

Sleep and Growth Hormones Tightly Regulate One Another

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Photo by Zhenzhong Liu on Unsplash

As every bodybuilder knows, a deep, restful sleep boosts levels of growth hormone to build strong muscle and bone and burn fat. And as every teenager should know, they won’t reach their full height potential without adequate growth hormone from a full night’s sleep.

But why lack of sleep – in particular the early, deep phase called non-REM sleep — lowers levels of growth hormone has been a mystery.

In a study published in the current issue of the journal Cell, researchers from University of California, Berkeley, dissect the brain circuits in mice that control growth hormone release during sleep and report a novel feedback mechanism in the brain that keeps growth hormone levels finely balanced.

The findings provide a map for understanding how sleep and hormone regulation interact. The new feedback mechanism could open avenues for treating people with sleep disorders tied to metabolic conditions like diabetes, as well as degenerative diseases like 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.”

Because growth hormone regulates glucose and fat metabolism, insufficient sleep can also worsen risks for obesity, diabetes and cardiovascular disease.

The sleep-wake cycle

The neurons that orchestrate growth hormone release during the sleep-wake cycle – growth hormone releasing hormone (GHRH) neurons and two types of somatostatin neurons – are buried deep in the hypothalamus, an ancient brain hub conserved in all mammals. Once released, growth hormone increases the activity of neurons in the locus coeruleus, an area in the brainstem involved in arousal, attention, cognition and novelty seeking. Dysregulation of locus coeruleus neurons is implicated in numerous psychiatric and neurological 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.”

The researchers, working in the lab of Yang Dan, a professor of neuroscience and of molecular and cell biology, explored the neuroendocrine circuit by inserting electrodes in the brains of mice and measuring changes in activity after stimulating neurons in the hypothalamus with light. Mice sleep for short periods – several minutes at a time – throughout the day and night, providing many opportunities to study growth hormone changes during sleep-wake cycles.

Using state-of-the-art circuit tracing, the team found that the two small-peptide hormones that control the release of growth hormone in the brain – GHRH, which promotes release, and somatostatin, which inhibits release – operate differently during REM and non-REM sleep. Somatostatin and GHRH surge during REM sleep to boost growth hormone, but somatostatin decreases and GHRH increases only moderately during non-REM sleep to boost growth hormone.

Released growth hormone regulates locus coeruleus activity, as a feedback mechanism to help create a homeostatic yin-yang effect. During sleep, growth hormone slowly accumulates to stimulate the locus coeruleus and promote wakefulness, the new study found. But when the locus coeruleus becomes overexcited, it paradoxically promotes sleepiness, as Silverman showed in a study published earlier this year.

“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.”

Because growth hormone acts in part through the locus coeruleus, which governs overall brain arousal during wakefulness, a proper balance could have a broader impact on attention and thinking.

“Growth hormone not only helps you build your muscle and bones and reduce your fat tissue, but may also have cognitive benefits, promoting your overall arousal level when you wake up,” Ding said.

Source: University of California – Berkeley

Categories : Expert Opinion Medical IndustryTags :

The Future of Pharmacies in South Africa Lies in Sustainable Expansion

On By ModernMedia
Photo by National Cancer Institute on Unsplash

By Christina Mooki, Head of Acquisition Operations at Merchant Capital

Pharmacies, especially ones in rural areas, are often the cornerstone of their communities. Beyond filling prescriptions, they provide medication, medical equipment, and counselling, sometimes serving as multi-service clinics in small towns and outlying areas. When people cannot wait weeks for a doctor’s appointment or need trusted advice, the local pharmacy is their first stop.

In many outlying areas, it is not just the most practical option, but often the only one. With the country’s high and rising burden of chronic disease, this role will only grow in importance.

The sector is indeed expanding. In just two years, 2020 and 2021, about 648 new community pharmacies opened across South Africa. By 2021, the total number stood at roughly 3580 outlets, and nearly 70% of these were independent rather than corporate-owned. That is over 2000 small businesses carrying community healthcare.

Christina Mooki, Head of Acquisition Operations at Merchant Capital

But every pharmacy is also a business. Behind the scenes, owners are juggling supplier deliveries, unpredictable supply chain issues, negotiating credit terms, paying staff, and trying to keep overheads under control. Balancing that with the responsibility of keeping communities healthy makes pharmacy ownership uniquely challenging and uniquely important.

Why more pharmacies are needed

A growing number of South Africans are living with chronic illness such as diabetes, hypertension, and HIV. These patients cannot miss their repeat medications and local pharmacy access becomes essential. Independent outlets do more than only dispense medicine, they also cut travel time, keep treatment within reach, and help build local economies.

Around the world, the role of a pharmacy is expanding. They are no longer limited to handing out prescriptions. According to Deloitte, many pharmacies are transforming into community health hubs by adding point-of-care testing, preventative health screening, and digital services to meet the changing expectations of modern consumers. Locally, they are also incorporating retail services to diversify their offerings further.

Running a pharmacy like a retailer

Passion for helping people will take you far as a pharmacist, but on its own, it will not keep the doors open. Independent pharmacies need to be run with the same discipline as any other retailer. Cash flow must be watched so staff are paid and suppliers are not left waiting. Shelves must carry the medicines that matter most without tying up money in products that sit for months. Costs like rent and electricity creep up quickly, and if unchecked, margins vanish.

Strong supplier relationships also make a difference. Paying on time, negotiating fairly, and keeping that trust intact can protect a business when times are tough. And like any other retailer, pharmacy owners have to be careful about how much debt they take on. Too much, too soon, can put even a busy store under pressure.

When these basics are in place, a pharmacy is not just a trusted point of care. It is also a resilient business that can think about growing, instead of simply surviving.

Where funding helps

Growth always asks for money before it offers returns. Anyone who has opened a second branch, hired staff, or added delivery knows this reality. The bills arrive first, and only later does the revenue follow. For a small independent owner working on thin margins, that can feel like a brick wall.

This is also the point where funding can be an enabler rather than a burden. At Merchant Capital, we treat pharmacies like retail businesses because that is what they are. They need capital that moves quickly, without red tape, and repayment models that flex with real turnover rather than with a rigid schedule. That flexibility gives owners breathing space, the confidence to back their instinct, invest in a new outlet, upgrade systems, or respond to their community.

Looking ahead

Independent pharmacies have already shown how vital they are to South Africa’s healthcare system. The next step is ensuring more of them open in the areas where they are most needed. With sound business management and access to the right kind of funding, these enterprises can grow their footprint, create jobs, and continue to provide reliable access to healthcare.