Tag: 28/11/24

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Why Does Tamoxifen Work Only for Some Patients but not Others?

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Photo by Danilo Alvesd on Unsplash

A new study has shown that variation in the microbiota of the human gut impacts the pharmacokinetics of tamoxifen and thus the effectiveness of the drug. The finding, published in the journal mBio, suggests that in the future, doctors may use a simple stool test to check for certain bacteria in the gut and help predict tamoxifen’s effectiveness for them.

Tamoxifen is a selective oestrogen receptor modulator used to prevent breast cancer. It prevents breast cancer cells from being able to use oestrogen to grow.

“The key takeaway from this study is that while tamoxifen is a common and important treatment for preventing breast cancer recurrence, nearly 50% of patients don’t respond well to it,” said lead study author Yasmine Alam, a PhD candidate in the Department of Biological Chemistry, University of California Irvine. “Since tamoxifen is taken orally and passes through the gut, this difference in how patients respond may be linked to the gut microbiome – the trillions of bacteria in our intestines, which vary greatly from person to person. Our study aims to better understand how these gut bacteria influence the way tamoxifen is absorbed, broken down and recycled in the body, with the goal of improving treatment outcomes for breast cancer patients.”

In the new study, the researchers set out to define the role that gut microbes play in how tamoxifen is processed (ie, absorption, distribution, metabolism and excretion), given its significant variable efficacy across patients. The researchers provided tamoxifen to mice that had no gut microbiome and to mice with a human microbiome (introduced to the mice by a human faecal sample). They found that mice with gut bacteria had higher amounts of tamoxifen in their bloodstream. The scientists then went on to explore what part of the gut microbiome was responsible for controlling the level of drug in the bloodstream. By examining the faecal samples from people, they linked a specific enzyme in bacteria, beta-glucuronidase, as a key factor that allows the drug to enter the bloodstream.

Tamoxifen is absorbed into the bloodstream from the intestine. Tamoxifen is carried by the bloodstream to the liver, where it is converted to its cancer-fighting form. Sometimes a sugar molecule can get attached to it, which signals the body to dump the cancer-fighting form of the drug back into the intestine. This drug can only get out of the intestine by taking the sugar off the molecule – and the researchers found that beta-glucuronidase in gut bacteria can eat the sugar off the drug so it can go on to fight breast cancer.

“Specifically, we found that certain enzymes produced by gut bacteria, called β-glucuronidase, play a role in how tamoxifen is broken down. These enzymes help recycle tamoxifen back into the bloodstream, which can make the drug more effective,” Alam said. “We discovered that a particular type of bacteria, Bacteroides fragilis, was strongly linked to the ability of these enzymes to affect tamoxifen levels in the blood in a positive way. This suggests that the gut microbiome plays an important role in how tamoxifen works in the body.”

The long-term goal of the study is to pave the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.

Source: American Society for Microbiology

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Many Could Easily Add Five Years to Their Lifespan

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Photo by Teona Swift on Unsplash

If everyone was as active as the top 25% of the population, individuals over the age of 40 could add five years to their life, according to a new study led by Griffith University researchers. 

Physical activity has long been known to be good for health, however estimates have varied regarding how much benefit could be gained from a defined amount of activity, both for individuals and for populations. 

This latest study, published in the British Journal of Sports Medicine, used US-based accelerometer data to gain an accurate view of a population’s physical activity levels instead of relying on survey responses as per other studies, and found the benefits were around twice as strong as previous estimates.  

It found the most active quarter of people in the community had a 73% lower risk of death than their least active counterparts. For that least active quartile, a single one-hour walk could potentially return a benefit of around six additional hours of life.  

Lead researcher Professor Lennert Veerman said this cohort had the greatest potential for health gains.  

“If you’re already very active or in that top quartile, an extra hour’s walk may not make much difference as you’ve, in a sense, already ‘maxed out’ your benefit,” he said.   

“If the least active quartile of the population over age 40 were to increase their activity level to that of the most active quartile however, they might live, on average, about 11 years longer.

“This is not an unreasonable prospect, as 25 per cent of the population is already doing it.  It can be any type of exercise but would roughly be the equivalent of just under three hours of walking per day.” 

The research team suggested low levels of physical activity could even rival the negative effects of smoking, with other research finding each cigarette could take 11 minutes from a smoker’s life.  

By extension, a more active lifestyle could also offer protective effects against heart disease, stroke, certain cancers and other chronic illnesses, with the study’s findings highlighting a need for national physical activity guidelines to be revisited using these methods.  

Dr Veerman said physical activity had been vastly underestimated in its capacity to improve health outcomes, suggesting even modest increases in movement could lead to significant life-extension benefits.  

“If there’s something you could do to more than halve your risk of death, physical activity is enormously powerful,” he said.  

“If we could increase investment in promoting physical activity and creating living environments that promote it such as walkable or cyclable neighbourhoods and convenient, affordable public transport systems, we could not only increase longevity but also reduce pressure on our health systems and the environment.”  

Source: Griffith University

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Scientists Find a Molecule that Promotes Gut Healing and Stifles Tumour Growth

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Researchers at Karolinska Institutet have found a molecule that can both help the intestines to heal after damage and suppress tumour growth in colorectal cancer. The discovery could lead to new treatments for inflammatory bowel disease (IBD) and cancer. The results are published in the journal Nature.

Many patients with inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis do not respond to available treatments, highlighting the need to identify novel therapeutic strategies. In this study, researchers propose that promoting mucosal healing through tissue regeneration could be a valid alternative to immunosuppressive drugs.  

“However, it’s virtually impossible to promote tissue regeneration without the risk of inducing tumour growth, as cancer cells can hijack the body’s natural healing processes and start to grow uncontrollably,” says lead author Srustidhar Das, research specialist in Eduardo Villablanca’s research group at Karolinska Institutet. “We’ve now identified a molecule that can help the intestines to heal after damage while suppressing tumour growth in colorectal cancer.” 

New drug candidates 

In their search for new ways to treat IBD, the researchers have identified a handful of molecules with drug-candidate potential. They found that activation of a protein called the Liver X receptor (LXR) can promote regeneration and suppress tumour growth in colorectal cancer. 

“The discovery of both these functions was astonishing,” says last author Eduardo J. Villablanca, docent at Karolinska Institutet. “We now need to study how LXR controls tumour formation more closely.” 

The researchers used a collection of advanced technologies to conduct their study, which included mapping the transcriptome of intestinal cells. The researchers also cultivated what are known as 3D organoids: small, three-dimensional cell structures that mimic the function and structure of the body’s own organs, albeit in miniature format. 

They then used spatial transcriptomics to map the gene expression in the different tissues, a technique that has been developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet in Sweden. 

Third most common cancer 

Patients, the third most common type in Sweden, are often treated with chemotherapy and radiotherapy, but this can cause irritation and swelling of the bowel mucosa with subsequent chronic intestinal inflammation. 

“Thus, this new therapeutic molecule has the potential to treat not only IBD patients but also cancer patients to prevent chronic bowel disorders after radiotherapy and/or chemotherapy,” says Eduardo J. Villablanca. 

Source: Karolinska Institutet

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Pregnancy Complications make Women Less Inclined to Have More Children

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Women who suffer severe complications during their first pregnancy or delivery are less inclined to have more babies, according to a study published in JAMA by researchers at Karolinska Institutet. For Sweden, given its recent steady decline in birth rate, the researchers propose monitoring in antenatal care to address the problem.

“The clinical monitoring of these women is essential, and they need individualised advice on possible future pregnancies,” says the study’s first author Eleni Tsamantioti, doctoral student at the Department of Medicine in Solna, Karolinska Institutet.

Reduced fertility

Birth rates and fertility have both been in steady decline in Sweden over the past years. In this new population-based study, the researchers have studied the association between severe maternal morbidity in first-time mothers and the likelihood of their having a second baby. The study comprised over a million women in Sweden who had their first baby between 1999 and 2021.

“We found that the likelihood of having more children was much lower in women who had experienced severe complications during their first pregnancy, delivery or postnatal period,” says the study’s last author Neda Razaz, associate professor at the same department. “Such events can often have a physical and mental impact on women for a long time to come.”

All in all, 3.5% of the first-time mothers in the study suffered serious complications and were 12% less likely to have a second baby. Most impacted were women who had experienced cardiac complications, a ruptured uterus or severe mental health problems, who were 50% less likely to have another birth than women who had not experienced such complications.

Monitoring in antenatal care

Women who needed respiratory care or who suffered a cerebrovascular accident like stroke or intracranial haemorrhage were 40% less likely to have a second baby. Acute kidney failure, severe preeclampsia and blood clotting were also associated with a lower probability of a second pregnancy. The researchers also compared the women with any sisters they had to control for familial factors. 

“The reasons are hard to speculate on and may result from multiple factors, such as decreased desire for more children, trauma, infertility related to psychiatric medications, or lack of health counselling,” says Tsamantioti. “Proper support and monitoring by antenatal care staff is therefore essential for women who have suffered serious health problems during pregnancy or delivery.”

Source: Karolinska Institutet

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Cervical Cancer Deaths in Young Women Plummet after Introduction of HPV Vaccine

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Cervical cancer. Credit: Scientific Animations CC4.0

Cervical cancer deaths have plunged dramatically among women under age 25, and researchers at MUSC Hollings Cancer Center believe this is likely due to HPV vaccination. Their study, published in JAMA, is the first to suggest the impact of HPV vaccination on cervical cancer deaths.

“We observed a substantial reduction in mortality – a 62% drop in cervical cancer deaths over the last decade, likely due to HPV vaccination,” said senior author Ashish Deshmukh, PhD, co-leader of the Cancer Prevention and Control Research Program. “We cannot think of any other reason that would have contributed to such a marked decline.”

The human papillomavirus, or HPV, causes nearly all cases of cervical cancer. The HPV vaccine was introduced in 2006. At first, it was available only to adolescents, but eligibility has since been expanded to include adults up to age 45 in some cases. In South Africa, an HPV vaccination programme started in 2014 for girls in public schools.

Previous studies have looked at the rates of HPV infection, precancer and cervical cancer incidence since the introduction of the vaccine, and all of those indicators have declined. The next logical step was to look at death rates, Deshmukh said.

Although cervical cancer is rare in women under age 25, it does occur. By examining deaths in this age group, researchers were able to see the early impact of the vaccine. Women who were 25 in 2021, the final year included in this study, would have been 10 years old when the vaccine was introduced.

The researchers looked at cervical cancer deaths in three-year blocks of time. Through the 1990s, there were between 50 and 60 cervical cancer deaths nationally in women under the age of 25 in each three-year block of time. During the 2019–2021 time period, there were only 13 deaths.

However, the team sounded an alarm. Healthy People 2030 has a goal of reaching an 80% HPV vaccination rate, but the Centers for Disease Control and Prevention reported earlier this year that only about 60% of 13 to 15 year olds have received the recommended doses.

“There has been a decline in HPV vaccination post COVID-19 in the most recent generation of U.S. adolescents. This is troubling as a decline in vaccination uptake would potentially lead to smaller gains,” Deshmukh said.

Source: Medical University of South Carolina

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The Sound of Traffic Increases Stress and Anxiety

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People experienced less stress and anxiety while listening to nature soundscapes, but the addition of road traffic noise increased their stress and anxiety

Photo by Lucas Davies on Unsplash

Manmade sounds such vehicle traffic can mask the positive impact of nature soundscapes on people’s stress and anxiety, according to a new study published November 27, 2024, in the open-access journal PLOS ONE by Paul Lintott of the University of the West of England, U.K., and Lia Gilmour of the Bat Conservation Trust, U.K.

Existing research shows that natural sounds, like birdsong, can lower blood pressure, heart, and respiratory rates, as well as self-reported stress and anxiety. Conversely, anthropogenic soundscapes, like traffic or aircraft noise, are hypothesized to have negative effects on human health and wellbeing in a variety of ways.

In the new study, 68 student volunteers listened to three 3-minute soundscapes: a nature soundscape recorded at sunrise in West Sussex, U.K., the same soundscape combined with 20 mile per hour road traffic sounds, and the same soundscape with 40 mile per hour traffic sounds. General mood and anxiety were assessed before and after the soundscapes using self-reported scales.

The study found that listening to a natural soundscape reduced self-reported stress and anxiety levels, and also enhanced mood recovery after a stressor. However, the benefits of improved mood associated with the natural soundscape was limited when traffic sounds were included. The natural soundscape alone was associated with the lowest levels of stress and anxiety, with the highest levels reported after the soundscape that included 40 mile per hour traffic.

The authors conclude that reducing traffic speed in urban areas might influence human health and wellbeing not only through its safety impacts, but also through its effect on natural soundscapes.

The authors add: “Our study shows that listening to natural soundscapes can reduce stress and anxiety, and that anthropogenic sounds such as traffic noise can mask potential positive impacts. Reducing traffic speeds in cities is therefore an important step towards more people experiencing the positive effects of nature on their health and wellbeing.”

Provided by PLOS