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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 Could open plan offices be bad for your health?
24/05/2013 10:10 AM
Open plan offices make employees “less productive, less happy, and more likely to get sick” reports the Mail Online website. The article is actually based on a number of studies, but the one we found most interesting was a national survey from 2011, conducted in Denmark, looking at self-reported sick days of open plan workers compared to individual office workers. The study found that people working in an enclosed office space reported lower levels of sickness compared to those working in an open office. Theories offered by the researchers as to why this may be the case, include:
Still, as the researchers themselves point out, this type of study cannot prove either theory. A limitation of the study is that it relied on self-reporting. People were asked to remember and estimate the number of sick days they had over the past year. So participants could have consistently over or underestimated the time off they’d taken, depending on their circumstances. If you do think that your place of work may be impacting on your health, visit the NHS Choices Workplace health section for advice on useful steps you can take.
Where did the story come from?The study was carried out by researchers from Denmark and was funded by the Danish Ministry of Employment and the Danish Working Environment Research Fund. The study was published in the peer-reviewed Scandinavian Journal of Work, Environment and Health. The Mail Online’s reporting was generally accurate on the study in question. The website also discussed evidence from other studies looking at the impact of open plan offices on stress levels, productivity and health. We cannot comment on the accuracy of the reporting of these others studies as we have not looked at them.
What kind of research was this?This was a cross-sectional study aiming to find out whether shared and open plan offices are associated with more days off sick than cellular offices comprising one occupant. A cross-sectional study is a good way of assessing a situation at one point in time, or asking people to recall their recent experiences. The main weakness of this study type is that it cannot establish cause and effect, for example, whether open plan offices cause people to be off sick more often or whether people who are generally of sick more often tend to work in open plan offices. The method also struggles when it involves asking people to recall events of interest from the past, which can be prone to error or bias – specifically recall bias. It could be the case that people are more likely to recall being genuinely sick with the flu than when they decided to “pull a sickie” because they fancied a lie-in in bed.
What did the research involve?The research involved a subset of the results from a national survey of Danish inhabitants between 18 and 59 years of age, consisting of 2,403 employees that reported working in offices. Based on the survey results, office workers were divided into four categories according to type of office:
The different types of offices were characterised according to self-reported number of occupants in the space. Sickness absence was assessed with the question “In total, how many sick days have you taken in the last year?” The main comparison was self-reported sickness absence days depending on the type of office. The analysis was adjusted for factors that could influence the rate of days off sick (confounders), which included:
What were the basic results?The average (mean) number of self-reported sick days in the last year by number of people in the office was as follows:
Compared to cellular offices containing one person, this meant:
How did the researchers interpret the results?The researchers’ concluding remarks are included below in full: “Open plan offices have become popular because they are designed to facilitate communication and accommodate knowledge sharing. However, our study showed that occupants sharing an office had a significantly higher number of days of sickness absence than those in cellular offices. Consequently, employees, employers, and society in general pay a high price for the benefits of open plan offices in terms of sickness absence and loss of productivity.”
ConclusionThis survey-based research suggested people in open plan offices may experience more days of sickness than people who have their own office and don’t share. The results only show an association and do not prove cause and effect. Neither did the research investigate what might be causing this relationship, although it did speculate about this in its discussion of the results. The study had some strengths, including that it managed to recruit a reasonable number of people, but it also had many drawbacks that limit the conclusions that can be drawn from it. The research only looked at sick days. The Mail Online’s reporting about people in open plan offices being “less productive and less happy” was drawn from other research. This could well be accurate, but was not reviewed here. Nonetheless, in the discussion, the researchers of the Danish study pointed to five possible explanations for how open plan offices might lead to more sickness leave:
Another possible explanation, not discussed by the researchers, could be cultural. If you work in a large office where your co-workers are frequently taking days off sick, then you may be more tempted to take time off yourself. None of the above explanations were explored in the Danish study and all remain speculative. A common reason that the open-plan office environment is popular with employers is they tend to be cheaper in terms of operating costs such as heating and lighting. An arguably interesting avenue of research would be to see if the perceived economic benefits of an open-plan office were actually outweighed by the alleged disadvantages, such as increased levels of sickness and reduced productivity. Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Links To The HeadlinesOpen-plan offices make employees 'less productive, less happy, and more likely to get sick'. Mail Online, May 23 2013 Links To SciencePejtersen JH, Feveile H, Christensen KB, Burr H. Sickness absence associated with shared and open-plan offices – a national cross sectional questionnaire survey. Scandinavian Journal of Work, Environment and Health. Published online May 2011 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 |
