Tag: 4/9/23

Categories : Cancer GeneticsTags : Leave a comment

New Genes, Natural Toxins Offer Hope for Patients with Head and Neck Cancer – and Maybe Others

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Photo by National Cancer Institute on Unsplash

Research led by Queen Mary University of London and published in Molecular Cancer has revealed two new genes that cause head and neck cancer patients to be resistant to chemotherapy. The study also shows that silencing either gene can make cancer cells that were previously unresponsive chemotherapy subsequently respond to it.

The two genes discovered actively ‘work’ in most human cancer types, meaning the findings could potentially extend to other cancers with elevated levels of the genes.

The researchers also looked through a chemical library, commonly used for drug discovery, and found two substances that could target the two genes specifically and make resistant cancer cells almost 30 times more sensitive to a common chemotherapy drug called cisplatin. They do this by reducing the levels of the two genes and could be given alongside existing chemotherapy treatment such as cisplatin. One of these substances is a fungal toxin – Sirodesmin A – and the other – Carfilzomib – comes from a bacterium. This shows that there may be existing drugs that can be repurposed to target new causes of disease, which can be cheaper than having to develop and produce new ones.

The research is the first evidence for the genes NEK2 and INHBA causing chemoresistance in head and neck squamous cell carcinoma (HNSCC) and gene silencing of either gene overturning chemoresistance to multiple drugs.

The scientists first used a method known as data mining to identify genes that may be affecting tumour responsiveness to drug therapy. They tested 28 genes on 12 strains of chemoresistant cancer cell lines, finding 4 ‘significant’ genes that were particularly responsive that they then investigated further and tested multidrug-resistance.

Senior study author Dr Muy-Teck Teh, from Queen Mary University of London, said: “These results are a promising step towards cancer patients in the future receiving personalised treatment based on their genes and tumour type that give them a better survival rate and treatment outcome.

“Unfortunately, there are lots of people out there who do not respond to chemotherapy or radiation. But our study has shown that in head and neck cancers at least it is these two particular genes that could be behind this, which can then be targeted to fight against chemoresistance.

“Treatment that doesn’t work is damaging both for the NHS and patients themselves. There can be costs associated with prolonged treatment and hospital stays, and it’s naturally extremely difficult for people with cancer when their treatment doesn’t have the results they are hoping for.”

90% of all head and neck cancers are caused by HNSCCs, with tobacco and alcohol use being key associations. In the UK, there are 12 422 new cases of head and neck cancer each year, and the overall 5-year survival rate of patients with advanced HNSCC is less than 25%. A major cause of poor survival rates of HNSCC is because of treatment failure that stems from resistance to chemotherapy and/or radiotherapy.

Unlike lung and breast cancer patients, all HNSCC patients are treated with almost the same combinations of treatment irrespective of the genetic makeup of their cancer.

Source: Queen Mary University of London

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Statins Might Reduce the Risk of Colorectal Cancer in Those with Ulcerative Colitis

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Photo by Towfiqu Barbhuiya on Unsplash

New research published in eClinicalMedicine suggests that statins might protect patients with ulcerative colitis from developing and dying from colorectal cancer. The study, by Karolinska Insitut researchers, also found that statin treatment was associated with a lower risk of death regardless of cause in patients with ulcerative colitis or Crohn’s disease.

First author Jiangwei Sun notes that previous studies have shown that the risk of colorectal cancer in patients with IBD, such as ulcerative colitis and Crohn’s disease, is 50% higher than in the general population. This is likely to be because of the chronic gut inflammation that these patients have. Researchers have long sought drugs that can reduce the inflammation-related cancer risk.

“Even though more studies are needed to confirm our results, our study suggests that statins can prevent colorectal cancer in patients with inflammatory bowel disease (IBD), which is a high-risk group for this kind of cancer,” says Dr Sun.

The observational study conducted by Dr Sun and his colleagues compared over 10 500 IBD patients from around the country, of whom half were statin users; the other half of the group, who were matched with the first, were not. After a follow-up period of, on average, 5.6 years, 70 of the statin group and 90 of the non-statin group had been diagnosed with colorectal cancer.

The effect increased over time

The protective effect was directly proportional to the length of time the patient had been on statins and could be demonstrated after two years’ treatment.

There were also fewer deaths from colorectal cancer in the statin group (20) than in the non-statin group (37) during the study period, and deaths regardless of cause (529 versus 719).

The study shows that some 200 IBD patients need to be treated with statins to avoid one case of colorectal cancer or death from the cancer within ten years of treatment onset. The protective effect was only statistically valid for patients with ulcerative colitis.

“We think this is because the study contained fewer patients with Crohn’s disease,” explains Dr Sun. “More and larger studies compiling data from patient populations in many countries will probably be needed to achieve statistical significance for Crohn’s disease.”

Significantly fewer deaths

To avoid death regardless of cause during the same ten-year period, the number of treated patients dropped to 20, on account of how statins also protect against more common conditions, such as cardiovascular disease. Statins were linked to fewer deaths in both ulcerative colitis and Crohn’s disease patients.

The study was based on the ESPRESSO-cohort, which is run by its initiative-taker Jonas F Ludvigsson, paediatrician at Örebro University Hospital and professor at Karolinska Institutet, and the study’s last author.

“In that we can combine tissue data from patients with colorectal cancer with data from Swedish health registries, we’re uniquely placed to study the long-term effects of drugs for IBD,” he says. “Our hope is that these studies will improve the care of IBD patients.”

The most solid evidence so far

According to the researchers, the new results provide the most solid evidence so far that statins could be an effective prophylactic for colorectal cancer among people with IBD. However, more knowledge must be gathered before the treatment can be recommended in general guidelines.

“More studies are needed to ascertain if there is a causal relationship, at what point of the pathological process statins should be administered, what a reasonable dose would be and how long treatment needs to last if it’s to be of benefit,” says Dr Sun.

Source: Karolinska Institut


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Clinical Researchers Discover Four New Factors that Predict Atrial Fibrillation

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UK researchers have developed a new way of identifying patients at risk of atrial fibrillation (AF). While not life threatening, the condition increases people’s risk of having a transient ischaemic attack (TIA) or stroke by up to five times. A new study, published in the European Journal of Preventive Cardiology, reveals four specific factors that can predict which patients will have atrial fibrillation.

The researchers investigated clinical and echocardiographic parameters for AF and found that the combination of advanced age, increased DBP, increasing lateral PA (time interval from the beginning of the P wave on the surface electrocardiogram to the beginning of the A′ wave on pulsed wave tissue Doppler of the lateral mitral annulus), and impaired LA reservoir strain is associated with AF. Other studies have linked most of these factors have been linked with an increased risk of AF in stroke survivors.

The team went on to create an easy tool for doctors to use in practice to identify those at high risk, which they hope will help diagnose and treat more patients, reducing their risk of future strokes.

Lead researcher Prof Vassilios Vassiliou, from UEA’s Norwich Medical School and Honorary Consultant Cardiologist at the Norfolk and Norwich University Hospital, said: “Identifying who is at high risk and more likely to develop atrial fibrillation is very important.

“This is because it requires specific treatment with anticoagulants, commonly known as blood thinners, to reduce the risk of future strokes.

“Patients who have had a stroke usually undergo multiple investigations to determine the cause of the stroke, as this can influence the treatment they receive long-term.

“These investigations include prolonged monitoring of the heart rhythm with a small implantable device called a loop recorder, and an ultrasound of the heart, called an echocardiogram.”

The research team collected data from 323 patients across the East of England, treated at Cambridge University Hospitals NHS Foundation Trust, who had had a stroke with no cause identified- known as Embolic Stroke of Undetermined Source.

They analysed medical records as well as data from prolonged heart rhythm monitoring. They also studied their echocardiograms.

Prof Vassiliou said: “We determined how many of these patients were found to have atrial fibrillation up to three years following their stroke, and went on to perform a thorough assessment to identify if there are specific parameters that are connected with atrial fibrillation identification.

“We identified four parameters that were linked with the development of atrial fibrillation, which were consistently present in patients that had this arrhythmia. We then developed a model that can be used to predict who will show atrial fibrillation in the next three years, and is therefore at increased risk of another stroke in the future.”

“This is a very easy tool that any doctor can use in clinical practice,” he added.

“And it can potentially help doctors provide more targeted and effective treatment to these patients, ultimately aiming to highlight the people at higher risk of this arrhythmia that can benefit from prolonged heart rhythm monitoring and earlier anticoagulation to prevent a future stroke.”

Source: University of East Anglia

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Study Reveals Global Differences in Sleep Patterns

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Photo by Cottonbro on Pexels

Using data from a consumer sleep tracker, a new study has shown that not only do people in Asia go to sleep later and have shorter sleep, they also have lower sleep quality than those in other parts of the world. The study, published in Sleep Medicine, also showed that South Africans, Australians and New Zealanders went to bed and rose earlier than the other parts of the world included in the research, but also got the most sleep.

This finding surfaced after a team of researchers from the Centre for Sleep and Cognition at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) in partnership with Oura Health Oy (Finland), analysed 50 million nights of anonymised sleep data, contributed by over 220 000 users of the “Oura Ring”, a consumer sleep tracker, from across 35 countries. Most of the users were working adults, aged between 30 and 55 years. To provide a comprehensive analysis of sleep measures for each user, the team gathered sleep data from multiple nights across a whole year – on average, each user contributed 242 nights of data. Weekday and weekend sleep were analysed separately to assess the impact of the working week on sleep patterns.

The results showed that people in Asia have shorter sleep, and display higher variability in both sleep timing and duration on weekdays. They also fall asleep later than those living in Europe, Oceania and North America. Previous studies have shown that shorter sleep duration is usually associated with higher sleep efficiency as people try to make the most of their sleep opportunity; however, in this study, despite sleeping less, people in Asia also had lower sleep efficiency. This may be because factors that result in short sleep (eg, work-related anxiety) also lead to lower quality sleep.

People often sleep for longer at the weekends than during the week, a phenomenon known as weekend sleep extension. While there was a clear association between shorter weekday sleep and longer weekend sleep extension, suggesting that people caught up on sleep at the weekend, even after accounting for this, people in Asia had the shortest weekend sleep extension.

While there are many socio-cultural factors that affect sleep patterns, the team hypothesises that because it plays such a fundamental role in our lives, work (and the broader work culture) is one of the most influential factors affecting how we sleep. Previous evidence from time use studies have demonstrated a strong association between long work hours and short sleep. Additionally, there is evidence that preoccupation with work demands and the inability to stop thinking about work contribute to sleep disturbances.

Dr Adrian Willoughby, Senior Research Fellow at NUS Medicine’s Centre for Sleep and Cognition, said, “In Europe, weekends are generally considered time for relaxation, and engaging in social activities with friends and family. In Asia, however, people may use the weekends to catch up on work, do the things they didn’t have time for during the week or attend to more family responsibilities. We think that longer working hours and the difference in work culture in Asia means that people don’t catch up on sleep as much at the weekends, but try to catch up whenever they have the opportunity over the course of the week.”

Prof Michael Chee, Director of the Centre for Sleep and Cognition at NUS Medicine said, “Sleep is a significant issue to address, especially for people living in Asia, who seem to sleep less than other global regions. Access to such a large dataset has allowed us to have unique insights into global sleep patterns. This research enables us to work towards our goal of giving customised sleep advice that considers individual sleep needs, environment factors and larger socio-cultural pressures that affect sleep. We want people to practise sleep routines that fit different contexts, but also promote health, well-being and performance.”

Source: National University of Singapore, Yong Loo Lin School of Medicine