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Breast cancer enzyme may slow tumour growth
24/05/2013 10:55 AM
"Cancer cell enzymes shown to act as 'good cops'," is the headline on the BBC News website. The BBC reports on laboratory research into an enzyme called MMP-8 and its effects on breast cancer. The research reveals that while MMP-8 appears to stimulate the growth of breast cancer cells in the short-term, it may slow tumour growth in the long-term. Scientists are likely to want to explore new treatments that use MMP-8’s ability to slow tumour growth in this way. However, this study used laboratory-grown cells, which don’t behave in the same way as tumour cells within the body. It could be the case that the effect of MMP-8 is different when studied in people. Nonetheless, this research provides new understanding about how the MMP-8 enzyme influences the growth and development of laboratory-grown breast cancer cells. And while this research has limited immediate implications for people with breast cancer it does contribute new understanding that may help to treat the disease in the future.
Where did the story come from?The study was carried out by researchers from the University of East Anglia (UK) and the University of Vermont College of Medicine (USA) and was funded by Breast Cancer Campaign, Cancer Research UK, the European Union Framework Programmes 6 and local Norfolk fundraisers. The study was published in the Journal of Biological Chemistry, a peer-reviewed science journal. It was published as an open-access article so it is free to download. The reporting of the research was mixed. While the Mail Online exaggerated the results of the study by describing a “breakthrough” that “turns previous thinking on its head”, the BBC coverage was more restrained, including comment from Cancer Research UK on how the research provides "very early clues" about how the enzyme might recruit cells to fight breast cancer.
What kind of research was this?This was a laboratory study exploring the role of an enzyme called matrix metalloproteinase-8 (MMP-8) in the growth of breast cancer tumour cells. MMP-8 performs many essential jobs in a normal cell. The researchers say it is known to activate certain immune system signals (called interleukin-6 and interleukin-8), which are types of molecules that regulate and orchestrate the actions of the immune system. The researchers comment that, traditionally, scientists thought MMP-8 helped cancer cells grow and spread, but more recent research has suggested it may also prevent cancer cell growth. This research sought to find out if, and how, MMP-8 inhibited tumour cell growth in laboratory-grown breast cancer cells. Understanding the biology and chemistry of processes involved in diseases such as cancer through laboratory studies is essential if we want to discover new ways to prevent and treat them.
What did the research involve?The researchers grew human breast cancer tumour cells in a laboratory. Some cancer cells were deliberately engineered to lack a properly functioning MMP-8 enzyme (called “mutant MMP-8”), whereas others had a fully functional version (known as the “wild-type” version). The intention was to see what effect this had on the ability of the cancer cells to grow and develop. The researchers paid particular attention to the effect of this manipulation on the immune system signalling molecules interleukin-6 (IL-6) and IL-8, which are known to be involved in the growth and development of cancer cells. Genetic changes within the cells were also measured. All the research was carried out in artificially grown laboratory cells and no tests were done in people with cancer.
What were the basic results?The research found tumour cells containing the wild-type MMP-8 had elevated levels of IL-6 and IL-8 and that, in the short-term, this was associated with higher levels of tumour cell growth. Cells lacking a working MMP-8 enzyme had lower levels of IL-6 and IL-8 and did not grow as well. However, in the longer term, activity of the MMP-8 enzyme was found to inhibit the growth of the tumour cells and it was found that the IL-6 and IL-8 levels were no longer elevated. Interestingly, the small number of cells with a working MMP-8 enzyme that did keep on growing in the long-term had somehow maintained their elevated levels of IL-6 and IL-8 but these were no longer dependent on MMP-8 activity. The relationship had changed from the short- to the long-term. This showed that in the early stages of tumour growth MMP-8 activity stimulated IL-6 and IL-8, which helped the tumour grow, but, later on, MMP-8 activity limited tumour growth and the IL-6 and IL-8 levels returned to normal. Only cancer cells where MMP-8 activity had become disconnected from IL-6 and IL-8 levels were able to keep growing in the longer term.
How did the researchers interpret the results?The researchers concluded that their research showed a “causal connection” between “MMP-8 activity and the IL-6/IL-8 network”, which showed MMP-8 influences the signalling of pro-inflammatory factors (IL-6 and IL-8) that “conventionally promote tumour cells’ growth and development”.
ConclusionThis laboratory study provides new understanding about how the MMP-8 enzyme interacts with inflammatory signals (IL-6 and IL-8). MMP-8 might be something of a double-edged sword. While it stimulates the growth of cancerous cells in the short-term, it may also suppress growth in the long-term. As with all laboratory studies, new or different discoveries need to be replicated by other research groups to ensure they are accurate and the results weren’t due to chance. Assuming the research results are valid they could provide an opportunity for cancer researchers to investigate and possibly devise new methods of using MMP-8 activity to supress breast tumour cell growth. However, the research found that some tumour cells kept growing despite the presence of MMP-8. This highlights that cancer cells differ, and that, often, what works in one place and setting may not work in others. It is important to remember that the researchers investigated breast cancer cells only, so this study alone does not tell us anything about the role of MMP-8 in other cancer types. Similarly, the research used artificially grown breast cancer cells, which may not behave in exactly the same way as tumour cells within a human body. This research into a new target for drug development provides new and interesting understanding that other researchers can build on. An improved understanding of the biology underpinning breast cancer may lead to the development of new treatments. Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Links To The HeadlinesCancer cell enzymes shown to act as 'good cops'. BBC News, May 24 2013 Breast cancer cells can suppress tumour growth 'by releasing protective proteins'. Mail Online, May 24 2013 Links To ScienceThirkettle S, Decock J, Arnold H, et al. Matrix metalloproteinase-8 (collagenase-2) induces the expression of interleukins-6 and -8 in breast cancer cells. The Journal of Biological Chemistry. Published online May 30 2013 Research could lead to 'universal' flu vaccine
23/05/2013 10:53 AM
“Scientists create new flu vaccine that works against many different strains of the virus,” The Independent reports. This headline, and several others like it, is based on early stage research into the development of alternative flu vaccine technologies. While the results of this research are promising, they do not mean that a universal flu jab has been developed. The study used a new technique where two proteins are bound together to form a nanoparticle. These nanoparticles stimulated an immune response to a greater variety of flu strains than the currently available flu jab. It is important to stress that this work was carried out in ferrets not humans. Ferrets do have biological similarities to humans, at least in the way they respond to flu and the flu vaccine, so this is a genuinely intriguing development. But it will take several years of further clinical trials to assess whether this technique can lead to a safe and effective ‘universal flu’ vaccine for humans. Currently, the best bet is to take measures to protect yourself during peak flu season. This includes regularly washing your hands, staying home from work or school if you have the flu and getting a yearly flu jab if you’re at risk of serious complications.
Where did the story come from?The study was carried out by researchers from the Vaccine Research Center, part of the US National Institutes of Health (NIH) and was supported by the NIH. The lead researcher is now based at Sanofi, a pharmaceutical company that manufactures vaccines. The study was published in the peer-reviewed journal Nature. BBC News reports the findings of the study in an appropriate manner. The headline “Universal flu jab 'edges closer'” and the warning that “a vaccine which could defeat all flu was a long way off” properly convey the stage this research is at. But most other reporting on this study failed to do this. For example, The Independent’s headline “Scientists create new flu vaccine that works against many different strains of the virus” is premature and does not reflect the early stage of technology development that this research is at. While the work is a step towards a universal vaccine, the technology has not yet been developed and tested to a point at which it could replace the annual flu jab.
What kind of research was this?This was a laboratory and animal study that investigated a new approach to generating flu vaccines. Current vaccines are designed to protect against three strains of the flu virus that health experts expect to be widely circulating in the population during any given year. This current approach is limited by the fact that the annual vaccine may not match the most common strains circulating that year. This approach also means seasonal flu vaccinations must be carried out annually to ‘catch-up’ with any changes in flu strains. The aim of this study was to develop a technique targeting a protein that is common to a wide variety of flu viruses, thus priming the body to mount an immune response to a broader range of flu strains. This research is at a fairly early stage, but it does suggest that it may be possible to develop a universal flu vaccine. The technology will need to be tested further in animals. It will then need to be proven to be safe and effective for people during clinical trials before a ‘universal jab’ could be made available.
What did the research involve?Researchers fused together two proteins – one, called ferritin, which stores iron and occurs naturally in our blood; the other, called haemagglutinin (HA), which is a viral protein responsible for the initial stages of flu infection. It works by attaching the flu virus to the cell it is going to infect. Individual ferritin proteins naturally come together and form a smooth hollow ball. Researchers thought that fusing ferritin and haemagglutinin would result in a similar sphere with HA spikes, and that the resulting nanoparticle would be recognised by antibodies. They further thought that when the spheres were injected into animals they would trigger the body to mount an immune response against a range of flu strains. To test the ability of this ferritin-haemagglutinin nanoparticle to initiate an immune response, researchers first immunised ferrets with either a traditional flu vaccine or the new complex. They measured the HA titres (titres indicate the number of antibodies the body has produced that recognise the HA spike) three weeks later, and compared the titre levels between the two groups. Researchers then tested the ability of the ferritin-haemagglutinin complex to protect against a range of flu strains. Three groups of ferrets (one immunised with the new complex, one immunised with a traditional flu vaccine and one non-immunised control group) were exposed to a variety of flu strains. The immune response across the groups was then compared.
What were the basic results?The researchers found that when the ferritin and haemagglutinin proteins were fused together, the proteins self-assembled into a nanoparticle with haemagglutinin spikes sticking out from the core. When the nanoparticle was exposed to an antibody known to target HA, the researchers found that it bound to the antibody in a similar manner as traditional flu vaccines. They say this indicates that the newly developed ferritin-haemagglutinin particles resembled the HA spike of the flu virus, which, in theory, could stimulate an immune response against a flu infection. Three weeks after immunisation, the researchers found that ferrets injected with the ferritin-haemagglutinin nanoparticle had levels of antibodies (antibody titres) that were approximately ten times higher than those seen in the ferrets injected with the traditional flu vaccine. They also found that a single injection of these nanoparticles produced an immune response similar to two immunisations with a traditional vaccine. When challenged with different flu strains, the ferritin-haemagglutinin immunised group of ferrets demonstrated an earlier immune response than the control group, and suffered less weight loss than both the traditionally immunised and non-immunised ferrets, which researchers say further demonstrates the protective effect of the new ferritin-haemagglutinin particles.
How did the researchers interpret the results?The researchers conclude that this new HA-nanoparticle technology “represents a foundation for a new generation of influenza vaccines and could be adapted to create vaccines for a wide variety of pathogens”.
ConclusionThis is promising research that takes us a step closer to developing a universal flu vaccine. Despite headlines suggesting otherwise, no universal jab has yet been developed. The researchers say that this new particle is capable of enhancing the body’s immune response compared with the currently used flu vaccine, and that the new complex offers protection against a wider variety of flu strains. It is important to remember that this research is still in its early stages. This technology development may well lead to the generation of a new type of vaccine. However, significant research is still required to move from the current stage to an available universal flu jab. Until then, the advice for protecting yourself during flu season remains the same:
Read more about preventing the spread of flu. Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Links To The HeadlinesUniversal flu jab 'edges closer'. BBC News, May 23 2013 An end to annual flu injections? Scientists develop new 'universal' jab against all strains of influenza which could last a lifetime. Mail Online, May 23 2013 Scientists create new flu vaccine that works against many different strains of the virus. The Independent, May 22 2013 Concept flu vaccine may be breakthrough. Sky News, May 23 2013 Links To ScienceKanekiyo M, Wei C, Yassine HM, et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. Published online May 22 2013 Do iPads and electric lights disturb sleep?
23/05/2013 09:47 AM
"Terrible night's sleep? Blame your mobile phone" is the advice on the Mail Online website, as "exposure to artificial light 'fools' the brain into staying awake." This – and similar headlines in the Daily Express, The Guardian and Metro newspapers – is based on a recent opinion piece in the journal Nature, which has published a dedicated supplement on the science of sleep. The opinion piece suggests that the invention of electric light has altered our sleep patterns over the last century. In particular, the widespread use of LED lights, which we rely on to view smartphones, tablets, televisions and laptops screens, is disrupting our sleep. This, the author suggests, could have potentially serious health consequences, as poorly controlled insomnia can cause both physical and mental health problems. As an opinion piece, this should not be taken as evidence that light exposure hampers our ability to sleep. However, it does suggest several ways the two may be linked. The piece offers the theory that one causes the other, but these associations have not been directly tested. But given that the author is a specialist in sleep medicine, his opinion cannot simply be dismissed out of hand.
Who wrote the opinion piece?The editorial was written by Charles Czeisler, a professor of sleep medicine at Harvard Medical School and chief of the division of sleep medicine at Brigham and Women's Hospital in Boston, US. Over the past 35 years Dr Czeisler has published widely on sleep, the impact of light on sleep, and the effect of restricted sleep on human behaviour and performance.
What arguments are made?Dr Czeisler suggests that since the invention of electric light, there has been a fundamental shift in our sleep patterns. He argues that light has enabled us to evolve into a "24/7 society", and that many of the features of this transformation – early starting times at work and school, long commutes, high doses of caffeine – lead to us getting insufficient amounts of sleep. Dr Czeisler's arguments for the link between the increasing use of electric light and disrupted sleep have highlighted several issues. The biological effect of artificial lightDr Czeisler argues that exposure to artificial light during the evening and at night could block the effects of brain cells that help promote feelings of sleepiness, as well the "sleep hormone" melatonin. At the same time, artificial light could also stimulate brain cells associated with alertness. The combination of these effects could result in many of us feeling much less sleepy in the evening than we would normally. Time-trends in light use, cost and sleepDr Czeisler reports that the cost of generating light dropped dramatically over the last 50 years, which was associated with an increase in the use of artificial light. At the same time that the use of artificial light increased, reported levels of sleep deficiency also went up. A recent study looking at data in England from 1993 to 2007 found a continual increase in people seeking treatment for sleep disorders. However, it is important to note that, as with any observational time-trend data, this argument only outlines associations between light consumption and sleep deficiency, and should not be interpreted as there being a causal relationship based on this editorial alone. Increased use of LEDsDr Czeisler suggests that the recent move from traditional incandescent light bulbs to more energy efficient solid-state light-emitting diodes (LEDs) could further disrupt our sleep. LEDs are commonly used in TVs, computer screens and handheld electronic devices such as tablets. These LEDs are typically rich in shortwave length (blue and blue-green) light, which the cells in our retina are more sensitive to. He offers the theory that time in front of these blue light-rich screens at night will be more disruptive to our sleep than incandescent lighting. Interestingly, one of the final discussion points in the editorial is about our ability to control the wavelengths emitted by LEDs. Dr Czeisler suggests that any adverse effect of exposure to these lights at night could be mitigated by replacing blue heavy light with red or orange heavy light in the evenings. This editorial offers interesting discussion points surrounding the relationship between light – especially evening or nighttime exposure to light – and difficulty sleeping.
What evidence is cited?Dr Czeisler's article makes reference to several publications, mainly centred around trends in the average number of hours adults and children sleep each night, and the prevalence of the adverse effects of sleep deprivation. As an opinion piece, the overall discussion points are narrative in nature and are not based on any individual piece of research or evidence. This specific article on its own cannot provide evidence of a direct link between light exposure and sleep deprivation. However, it is not intended to do so. It offers a broad introduction to a series of articles on the topic, and suggests we consider the ways in which technological changes may impact our ability to get a good night's sleep.
ConclusionIt is certainly possible to reduce your exposure to artificial lights. For example, you could dump your smartphone, give away your iPad, banish television from your home, and refuse to work in any job that involves using a computer. But adopting this kind of luddite lifestyle is probably not to most people's tastes. One proven method of improving your sleep is what is known as "sleep hygiene". This is where you control both physical and environmental factors in order to promote sleep. Examples of good sleep hygiene include:
Read more advice about sleep hygiene. If you have persistent insomnia (more than four weeks), contact your GP for advice. You may require more in-depth "sleep training" counselling, often done using cognitive behavioural therapy (CBT) techniques. Alternatively, there may be an underlying condition contributing towards your insomnia. Read more about the treatment of insomnia.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Links To The HeadlinesPeering at bright screens after dark could harm health, doctor claims. The Guardian, May 22 2013 Terrible night's sleep? Blame your mobile phone: How exposure to artificial light 'fools' the brain into staying awake. Mail Online, May 22 2013 How your iPad tablet could mess with a good night's sleep. Metro, May 23 2013 Links To ScienceCzeisler C. Perspective: Casting light on sleep deficiency. Nature. Published online May 23 2013 Cold weather may increase blood pressure
22/05/2013 11:22 AM
'Bad weather could raise your blood pressure and even kill you,' is the unnecessarily alarmist headline in the Daily Mail. It reports on a large, complex study that looked for any association between changes in weather and blood pressure rates. The research focused on patients at a blood pressure clinic in Glasgow and looked at two consecutive visits the patients made within a 12-month period. The researchers combined these findings with Met Office weather data from the time of these visits to assess whether changes in patients' blood pressure were related to changes in the weather. They found that decreases in temperature and sunshine, or increases in rainfall and frost, were associated with a slight increase in blood pressure. In the longer term, individuals whose blood pressure seemed sensitive to decreases in temperature and sunshine had slight increases in blood pressure. They also seemed to have overall shorter survival than people insensitive to weather changes. We know that our bodies respond to temperature changes, so it is plausible that temperature could influence blood pressure. But factors other than the weather may have had a role to play in the blood pressure results seen. It is also important to point out that the minor increases in blood pressure detected by the study could in many cases be compensated for by taking more exercise or improving your diet.
Where did the story come from?The study was carried out by researchers from the University of Glasgow. One of the study authors was supported by a Wellcome Trust Capacity Strengthening Strategic Award to the Public Health Foundation of India and a consortium of UK universities. It was published in the peer-reviewed Journal of the American Heart Association. The quality of the Daily Mail's reporting of this study is mixed. On the negative side, it presents an over-simplistic conclusion that cannot be drawn from the complex analysis used in this study. The claim made in the headline that 'bad weather...can kill you' is needlessly sensationalised. On the plus side, its story does contain useful advice from a spokesperson from Blood Pressure UK: "Until we can control the weather, we can still rely on more traditional ways of controlling our blood pressure, such as eating more fruit and vegetables, less salt and alcohol, and taking more exercise."
What kind of research was this?The researchers say that there is growing evidence that outdoor temperature has an influence on blood pressure, with blood pressure being higher in winter and lower in summer. This is believed to be because the constriction of blood vessels at colder temperatures increases blood pressure. However, it is unclear whether the temperature-related response differs among individuals. The current study aimed to examine people's individual changes in blood pressure in response to a range of weather patterns. The researchers also wanted to see whether this was predictive of longer term blood pressure control and mortality.
What did the research involve?The study included 16,010 people from the Glasgow Blood Pressure Clinic (47% male) who had been referred by their GP in order to control their high blood pressure. Information on the monthly average weather for the west of Scotland was obtained from the UK Met Office. The Met Office has used a consistent method to analyse climate patterns since 1961, and can provide weather for square kilometre grid points across the UK. Information on four aspects of weather was used in the study:
Each visit every person made to the Blood Pressure Clinic was mapped to the mean monthly weather of the west of Scotland. Mean monthly measurements for each of the four aspects of weather were ranked from the lowest to the highest measurement, and then split into four equal groups called quartiles. The lowest quartile (Q1) contained the lowest 25% of measurements and the highest quartile (Q4) contained the highest 25% of measurements. For each person, the researchers looked at pairs of consecutive clinic visits that were at least one month apart but within the same 12-month period. They were interested in pairs of visits where weather either remained constant (both visits in the same weather quartile) or where weather was very different (one visit in the lowest quartile and one visit in the highest quartile). They categorised the weather for these clinic visits as:
For each individual, the researchers examined changes in their blood pressure and heart rate between the two visits, and looked at how the size and direction of this change (up or down) related to the change in weather. The researchers used the General Register Office for Scotland to obtain information on deaths among the participants and causes of death. Mortality information was available up to 2011, allowing up to 35 years of follow-up. Analyses were adjusted for factors known to influence blood pressure (confounders), including:
What were the basic results?The average age of individuals at their first clinic visit was 51 years, and most were overweight (mean BMI was 28). The average length of follow-up for each person was 6.5 years. The researchers found that when there was consistent weather between the two clinic visits (Qn to Qn), there was:
For change from high to low weather extremes, there was:
For change from low to high weather extremes, there was:
When the researchers compared the blood pressure changes seen with consistent weather patterns, a change in the weather from the highest to lowest quartile was associated with about a 6% increase in systolic blood pressure when there was a decline in temperature and sunshine, and about a 4% increase in systolic blood pressure when there was a decline in air frost. Compared with consistent weather, a change from the lowest to highest quartile was associated with 2-6.6% increases in systolic blood pressure for all four weather characteristics assessed. Looking at longer term changes over five or more years, people whose blood pressure changed when there was a decline in temperature experienced a 2.68mmHg increase in their systolic blood pressure, and a 1.84mmHg increase in their diastolic blood pressure (the lower figure in a blood pressure measurement), compared with people whose blood pressure seemed insensitive to temperature change. A similar 1.31mmHg increase in systolic blood pressure and a 1.22mmHg increase in diastolic blood pressure was seen for people who were sensitive to a decline in sunshine. Looking at survival data, people who were insensitive to temperature or sunlight change seemed to have longer survival than people who were sensitive to a decline in temperature or sunlight. There were no significant longer term differences in blood pressure or survival between people insensitive to temperature or sunlight change, or in people sensitive to an increase in weather extremes.
How did the researchers interpret the results?The researchers have concluded that for the first time they have demonstrated the extent of alterations in blood pressure between consecutive clinic visits associated with changes in weather in people with high blood pressure. They have extrapolated that knowing a person's blood pressure response to weather could help prevent doctors making unnecessary changes to blood pressure medication.
ConclusionThis study has used a complex method of analysis in order to look at how individuals' blood pressure at consecutive visits within a one-year period varied according to changes in the weather. The study benefits from its large population sample and long follow-up. The blood pressure measurements taken at this specialist clinic are also likely to be reliable. Our bodies do respond to changes in temperature and it is biologically plausible that temperature can affect our blood pressure. The researchers have adjusted for many factors known to influence blood pressure, such as age, high BMI and kidney disease. However, it is still difficult to say with certainty that all blood pressure changes seen in people between clinic visits were solely down to changes in the weather. For example, the researchers did not have complete information about the blood pressure medications being used by the patients, or their levels of physical activity. These factors could also be influencing the findings. Another limitation is that blood pressure would have been recorded inside the clinics and may not be representative of what blood pressure would have been if it had been taken outside, with full exposure to the weather. The research was conducted in individuals from the Glasgow area and it is difficult to say whether similar responses would be seen in people in other locations, particularly people living in vastly different climates. Similarly, the study only looked at people with high blood pressure. It is not clear whether people with normal blood pressure also experience similar changes in their blood pressure in response to weather changes. The individuals in the study seem to have been variably sensitive to different changes in the weather. It is not yet clear exactly how a person's blood pressure treatment could be individualised according to their sensitivity to weather change, and whether this would successfully reduce blood pressure variability. One final important point to make is that although we have no control over the weather, we can control a wide range of factors that contribute towards high blood pressure, such as:
Read more about proven lifestyle changes you can make to reduce your blood pressure risk.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Links To The HeadlinesBad weather could raise your blood pressure and even kill you. Daily Mail, May 21 2013 Chilly days can kill by raising blood pressure. Daily Express, May 22 2013 Links To ScienceAubinière-Robb L, Jeemon P, Hastie CE, et al. Blood Pressure Response to Patterns of Weather Fluctuations and Effect on Mortality. Hypertension. Published online May 6 2013 |
