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  • Oestrogen causes DNA mutations – is this how it fuels cancer? - Cancer Research UK - Science blog
    system a force for good From comic books to cancer the word mutant has negative connotations Mutations are mistakes or variations in the genes in our cells that can be passed on as cells divide And cancer is thought to develop when a single cell picks up mutations that cause it to grow out of control But mutation can be a force for good too its how our immune system generates the extraordinary diversity needed to fight the thousands of different invaders it will encounter over our lifetime And an important step in this is a process called somatic hypermutation B cells are antibody factories Our blood contains specialised white blood cells called B cells Their job is to take samples of foreign nasties like bacteria and viruses floating around the body The B cells then become activated and make antibodies that bind to the specific bit of the bug they ve encountered They then release millions of these antibodies into the bloodstream to mop up and neutralise any remaining invaders Although exactly how this activation occurs is still the subject of much research it s clear that a key player is an enzyme called Activation Induced Deaminase or AID which is manufactured inside B cells just after they ve encountered a new invader AID causes somatic hypermutation a process which chemically changes B cells antibody genes to contain hundreds of new mutations This allows the body s B cells to produce a whole slew of new antibodies A subsequent process of elimination then selects the right antibody for a given invader from the population of activated B cells What s this got to do with oestrogen The first clue that oestrogen might help regulate our immune system came from two observations Firstly women often have faster immune responses than men Secondly it has been known for some time that certain autoimmune diseases were more common amongst women than men This hinted that something about being female might cause a person s immune system to be more active Enter Dr Svend Petersen Mahrt at Cancer Research UK s Clare Hall laboratories who s been studying AID s role in cancer for some time His team set out to investigate whether this enzyme might explain the differences between men s and women s immune systems First working with B cells isolated from the pancreases of mice they showed that oestrogen switched AID on and that another hormone called progesterone could switch it back off Oestrogen activates AID and causes DNA mutations click to enlarge They then showed that the AID gene contains a tiny switch known as an Oestrogen Response Element Oestrogen flips this switch so cells produce more AID enzyme which in turn increases the number of mutations in antibody genes see diagram But what about cancer So oestrogen helps to regulate the immune system But recently other scientists have found that AID can cause a specific cancer causing mutation to occur called a c myc IgH translocation known to

    Original URL path: http://scienceblog.cancerresearchuk.org/2009/01/12/oestrogen-causes-dna-mutations-%E2%80%93-is-this-how-it-fuels-cancer/ (2016-02-11)
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  • Six Citizen Science milestones from 2014 – number four is out of this world - Cancer Research UK - Science blog
    the best treatments to offer them based on different tumour characteristics Tens of thousands of you have helped Paul this year and contributed accurate analysis that could help people with breast cancer in the future Over 4 kilometres of DNA analysed in Genes In Space The sheer volume of genetic material that s been mapped is something to be truly proud of In fact if you unravelled the DNA that s collectively been analysed it would stretch more than three times the height of Ben Nevis And most importantly this analysis will help Dr Oscar Rueda from our Cambridge Research Institute locate genetic faults that lead to breast cancer But that DNA could actually stretch even further To maximise accuracy each sample was analysed by at least 50 different players If we factor that in it s fair to say that the amount of genetic data analysed would reach over 200km That s the same altitude that the world s first artificial satellite Sputnik reached in 1957 3 bladder cancer characteristics investigated thanks to Reverse The Odds Watch Anne discussing the project on YouTube Dr Anne Kiltie from the Oxford Institute for Radiation Oncology is using the data you ve analysed through Reverse The Odds to better understand bladder cancer The analysis could help patients make decisions about their treatment in the future Thanks to our Citizen Scientists Anne has already begun investigating three different tumour characteristics What s more she ll be able to study 19 characteristics over all nine more than she would have been able to without Reverse The Odds 33 876 lung cancer cell images analysed in Reverse The Odds Professor Gareth Thomas from the University of Southampton is exploring how the immune system responds to lung cancer He s interested in finding out if we can predict whether patients will benefit from treatments that encourage the body s natural defences to fight the disease And the incredible number of lung cancer images classified by playing Reverse The Odds this year will help him do exactly that All in all that s an amazing contribution towards research tackling the world s biggest cancer killer That s just a snapshot of 2014 and there s so much to be proud of But our mission is far from over There s still a vast amount of data to be analysed through Citizen Science We hope 2015 is going to be just as big as 2014 But to make that happen we need you to keep playing And if you haven t joined us yet you can find out about our free easy to use games and support our scientists here And if you want to be among the first to hear about new games and our progress sign up to hear more Josh Lee is a marketing executive in the Cancer Research UK Citizen Science team Image Phone image by Adam Fagen via Flickr under CC BY NC SA 2 0 Share this article More on this topic

    Original URL path: http://scienceblog.cancerresearchuk.org/2014/12/18/six-citizen-science-milestones-from-2014-number-four-is-out-of-this-world/ (2016-02-11)
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  • Report from GameJam: accelerating science outside the laboratory - Cancer Research UK - Science blog
    genetic fingerprint of cancer patients But to develop drugs for specific patient groups scientists must know which genetic faults cause the disease This means analysing mindboggling amounts of genetic data The data resembles a squashed up radio wave with sharp peaks and troughs correlating to gene behaviour in tumour cells There are two million squiggley lines of gene data per patient comparable with a telephone directory containing 20 000 pages Trained scientists scrutinize this data using computer algorithms to search for new genetic clues But the algorithms aren t perfect which means they can miss key genes or mutations important in cancer We re counting on the GameJam participants to solve this problem in 48 hours They must design a game to detect changes in the data indicating when there are either too many copies of certain genes or too few The game must be social so people can share it It should have a reward system so people play it again And it has to be fun Dr Chris Lintott chair of the Citizen Science Alliance sums up the mood This is fabulous but scary We re tackling not one but two difficult problems doing important science AND trying to create a usable game Luckily we ve got the right people There is a talk from Amazon Web Services and Facebooks experts and the ice breaker is done away with there s no need Everyone s in groups cracking on straight away The pizzas arrive And the 48 hour GameJam begins The first stage is idea generation what is the basic idea the teams will follow up in the morning What about some kind of steady hand game What if we make the data represent 3D space players could tilt their phone to roll balls around Everyone chips in and thoughts are scribbled down We could translate the line into colours How about using an accelerometer James Lau a games producer explains We re all here for the same reason It s the combination of tackling a fascinating challenge while knowing that what we come up with is helping a very worthy cause It s very exciting Day 2 number crunching Some of the participants have had three hours sleep One girl has brought a sleeping bag And it s going to be a seriously long day People quaff their first coffee of the morning there are cans of energy drinks at hand for later and the pace of work is red hot The groups have already chosen the ideas they want to develop But considering each game must incorporate 40 data files some 846 090 pieces of information equivalent to the data on one person s chromosomes the solution will be anything but simple Six Cancer Research UK scientists mingle helping the programmers incorporate the data into their games Above all says researcher Dr Oscar Rueda the game must distinguish between real differences in the genetic data and background artifacts or false results In other words accuracy is

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/03/05/report-from-gamejam-accelerating-science-outside-the-laboratory/ (2016-02-11)
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  • Stargazing to spot cancer - Cancer Research UK - Science blog
    kind of analysis still largely relies on expert pathologists looking down the microscope at tumour samples and scoring the presence of particular protein molecules Regular readers of the blog will know that Cancer Research UK recently launched the world s first citizen science cancer project Cell Slider to help break this data bottleneck But for some time scientists have also been looking at ways to automate the process and train machines to do the hard work Today our scientists published their latest progress towards this goal Writing in the British Journal of Cancer Dr Ali and his team show how the automated techniques the astronomers use to analyse deep sky images can also detect subtle differences in protein levels between healthy and cancerous breast cells They used the automated technique to measure the levels of three different proteins in tumour samples from more than 2 000 patients high levels of these proteins are linked to more aggressive cancers Then they compared the results to the same task done by a pathologist looking down a microscope to score the samples Reassuringly the automated technique seems to be just as accurate as the human version but crucially is many times quicker analysing up to 4 000 individual images a day The team now plans to carry out a much larger study to confirm the accuracy of the test using samples from more than 20 000 breast cancer patients This new development is exciting and could change the way that samples are analysed in the future if the technique passes muster in the larger study This in turn could speed up the discovery of more effective treatments for breast cancer by allowing researchers to analyse huge amounts of data in record time But there are still hurdles to be overcome One of the issues with using machines to analyse this data is that they re simply not as good as pathologists at identifying the presence of cancer cells in the first place We also don t yet know if they are able to pick up trickier to spot molecules in certain parts of the cell And computer analysis techniques may not be sensitive or specific enough to reliably score certain markers Until these barriers can be reliably overcome this process urgently needs the human touch And this is where you come in Robots vs humans CellSlider needs your help We recently teamed up with Citizen Science Alliance to launch CellSlider the first ever public cancer research project that you can do from the comfort of your own home CellSlider uses similar data to that analysed by the Cambridge team but employs the eyes and brains of thousands of people rather than a super computer So far our army of helpers have made hundreds of thousands of classifications of cancerous cells cutting the time needed for this kind of analysis from 18 months to just three So the jury s still out on whether machines can truly beat humans in the world of pathology

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/02/20/stargazing-to-spot-cancer/ (2016-02-11)
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  • Dances with Pharma: part 1 – why are drugs so expensive? - Cancer Research UK - Science blog
    drugs are so expensive is because they cost a lot to develop and manufacture As the graphic on the right shows on average a new drug will take more than 12 years to develop from start to finish at a cost of more than 1 billion and the bill is increasing as time goes by This financial burden falls mainly on the shoulders of pharmaceutical pharma companies The biggest costs for any one drug are usually the clinical trials and regulatory processes necessary to make sure a new treatment is safe and effective Because peoples safety is paramount taking shortcuts to cut costs is not an option The manufacturing process itself can also influence cost A significant number of modern day drugs have to be made or purified from living cells called biologics they are technically more difficult and costly to manufacture than man made chemicals This family of treatments include antibodies such as trastuzumab aka Herceptin And moving away from one size fits all treatments like conventional chemotherapy towards more tailored treatments that reflect the genetic makeup of individual cancers means that while a drug may be better suited to some patients the days of the single blockbuster drug are over Instead the future of cancer treatment lies in a multitude of different targeted therapies with correspondingly smaller potential markets pushing the price of drugs up But there are other factors that come into play too which could and should be questioned to try and reduce development costs and make drugs cheaper 2 The price of failure When a pharma company launches a new drug its price tag usually reflects the cost not only of making that one particular successful drug but also the large sums of money and time spent on other treatments that failed along the way Drugs can fail for two main reasons the side effects are unacceptable and or it doesn t work well enough Again the reasons leading up to this are complex Sometimes scientists working for industry don t get the same results as the scientists who first carried out experiments on a new drug so development is halted In other cases it s a result of researchers not fully understanding how a drug affects cells so not anticipating its adverse effects And lastly if there is no clinical test to prove the drug s hitting its target doctors might not know if patients are receiving the correct dose in clinical trials On top of this people are complex Despite extensive testing in the lab a promising drug doesn t always translate into an effective medicine because it s difficult to model the intricacies of human disease in the lab Furthermore every cancer patient is a unique individual meaning there is a wide range in how people respond to treatments and what side effects they experience something scientists don t yet fully understand Lastly cancer itself is a hugely complex family of diseases The progression of one size fits all into more personalised treatment has led to improvements in survival but at the same time means testing new treatments is more complicated For example modern targeted treatments will often only work for a certain group of patients based on a particular fault driving their cancer so doctors need to have strict criteria to select the right group of patients to enrol in a clinical trial If a new treatment is tested in patients who don t stand to benefit from it the trial results will make it look like the drug doesn t work well wasting huge amounts of money and even worse potentially losing a promising treatment It s important that the research community as a whole continues looking into the reasons behind drugs failing during development and works hard to improve it to help get better treatments to patients faster 3 The long game What are clinical trials Watch the animation on YouTube Another factor driving up drug prices is the length of time a company will have to wait before they start to make money from a new medicine The discovery development and testing of a new drug is a slow process in itself but then the red tape and layers of bureaucracy to get a new drug approved and in the clinic for patients further compounds the problem Patents effectively a form of copyright that companies take out in the early stages of research to own their discoveries are usually only valid for 20 years so the clock is already ticking long before a drug makes it to market Given that it can take 10 15 years to go through the development and trials process that doesn t leave long for a company to make money before the patent expires and other companies can make and sell the drug too This gives the original company a solid incentive to set the initial price as high as they can Cutting the red tape administrative costs and time taken for drug licensing and approval could help reduce drug prices by getting treatments to patients faster and widening the window of time during which companies can profit 4 Profit margins Of course as well as the above scientific reasons pharma companies are obviously companies and are therefore duty bound to generate profit for the shareholders who invested in them in the first place And their profit margins are continuing to grow at a rate that some consider excessive They are also multinational organisations and so have to generate profits in many different countries Sometimes that means prices and profits in one country affect prices in another From a company s point of view it can make sense to set prices according to this international market even if that means one or more countries can t afford it They also spend large sums on advertising and marketing too especially in countries other than the UK where healthcare is funded in different ways This money must also be recouped from drug sales 5 Me

    Original URL path: http://scienceblog.cancerresearchuk.org/2014/12/16/dances-with-pharma-part-1-why-are-drugs-so-expensive/ (2016-02-11)
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  • The wisdom of the crowd – using crowdfunding to pay for research - Cancer Research UK - Science blog
    most likely to have the biggest impact Clearly not all peer review is good peer review But funding bodies usually try hard to get constructive comments back to researchers on their applications They may want to come back for another go or re focus their project for another funding agency With crowdfunding you don t get the benefit of expert feedback and advice You don t get to work with big agencies Without wanting to sound like turkeys voting against Christmas research can be a lot easier with the backing of a big agency We and other charity funders provide effective packages over a stable period of time and give researchers a route in to a bigger collaborative network We back up the grant with support from the press office our technology transfer team our science writers and our public engagement experts We do get help in return our researchers help us with peer review take part in fundraising events and advise us on our strategy But we try if possible to make it a partnership and to recognise that our job is to raise money and give it to them and their job is to do good science And we still manage to spend 80p in every donated 1 directly on research The small proportion of money that is spent on the grants administration and peer review is well spent if we invest the rest in research that brings the most benefit to patients It s also worth noting that crowdfunding websites can still come with admin overheads too On some sites you can expect up to 10 of the donations to be taken in admin and platform fees Public interaction Public interaction is great fun and is crucial for raising money But it is hard work We have a team of people around the country that are engaging with thousands of people every day explaining why an investment in us is an investment in some of the best cancer research in the world Other funders are doing this too taking advantage of blogging and social media to engage with their supporters and create a community Look at the American Cancer Society Wellcome Trust and British Heart Foundation for some examples If you look at the sites on the top things that cause a crowdfunding request to fail high up the list are failing to devote enough time to networking or looking after donors The crowd expects If you are an artist people can look and see what you have already done If they like it they will fund more in the expectation that they will get more of the same If they don t like it when you produce it well so be it you can t blame the artist if you don t like their art Science doesn t work like that An idea could be brilliant It could change the world The donors could benefit personally if it works But it might not Or it might just be wrong Lots of ideas in science are wrong but on so many occasions getting a negative result can actually increase what we know by ruling out alternative theories But what do you tell your donors if that is the case Will they appreciate the high failure rate in research Here s just one example the pathway to get a new drug into the clinic Now this is classic territory for crowdfunding the money needed to take lab results through to the clinic and something that frustrates scientists who can t get the funding to try out their ideas But there is a high attrition rate at each stage of the process For every 10 000 compounds identified in the lab 250 will be screened in animals and only 10 of these will show the desired safety and efficacy to be tested in humans Of these 10 on average only one or two will end up being approved for clinical use And this process can take over 10 years and cost millions of pounds overall And there are lots of arguments about whether or not this is the fault of the drugs companies or regulatory bodies and it should get better as drug design becomes more rational but there will always be a failure rate Albert Einstein is famously quoted as saying If we knew what it was we were doing it would not be called research We do crowdfund Ninety per cent of our donations are for less than 10 and this makes up a substantial proportion of our funding And you only get that level of support from lots of individuals if you can create a sense of mission if you do engage people We spend a lot of our time telling our supporters what the researchers are doing what their money is spent on what progress we are making All that feedback needed for a crowdfunded project is actually a central part of our work And we see the opportunity of crowdfunding and we are learning how it can be used to maximum effect We run something called MyProjects and the web page looks remarkably similar to many of the crowdfunding sites There are the details of the projects updates from the researchers the tally of money raised Supporter can choose to give money to the research that means the most to them whether it s childhood cancers clinical trials or cancer nurses Yes the money comes through us but it means the science has already been through the important quality control step before thousands of pounds are spent So public empowerment through crowdfunding opens up some great opportunities that we and others are exploring But exciting as it is we need to be very careful about making sure crowdfunded research achieves its objectives given the pitfalls that lie in its path Matt Kaiser Research Funding Manager and Simon Vincent Head of Personal Awards and Training Share this article More on this topic Tags Cancer in

    Original URL path: http://scienceblog.cancerresearchuk.org/2012/10/22/the-wisdom-of-the-crowd-using-crowdfunding-to-pay-for-research/ (2016-02-11)
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  • Absolute versus relative risk – making sense of media stories - Cancer Research UK - Science blog
    any Heart is 25 per cent so 25 in 100 or one in four But the absolute risk of picking the Queen of Diamonds as poker players may know is much lower it s just one card among 52 which works out as just under 2 per cent So we can say that the risk of picking any Heart is over ten times greater than picking the Queen of Diamonds We ve just compared two risks and come up with a relative risk a way of comparing risks to find out how much more likely one is compared to the other Let s step away from the world of cards and into a fictitious but perhaps more relevant example Time for another example Loch Ness monster not shown Shocking news from Scotland Loch Ness Monsters that eat fishermen are ten times more likely to develop cancer than those that don t But assuming they read this headline how worried should the monsters be by this news Ten times more likely is a relative risk But 10 times what To get a clear picture of the dangers of eating fishermen we need to know the size of the two underlying absolute risks the headline compares the likelihood of Loch Ness monsters getting cancer if they don t eat fishermen and the likelihood of cancer if they do It turns out that two out of every 100 000 monsters who refrain from eating fisherman develop cancer That s their absolute risk 2 in 100 000 or if you prefer 0 002 per cent And on average 20 out of every 100 000 fisherman eating monsters develop cancer or 0 02 per cent Comparing the two risks we can see that the risk for fisherman eaters is indeed 10 times bigger and this means that for every 100 000 monsters that eat fishermen 18 more monsters will develop cancer Relative risk tells you nothing about actual risk The size of the initial absolute risk is what s really important here If the initial risk is very small even a huge increase may not make much absolute difference But for a risk that is quite large already smaller increases can still have a big impact Let s go back to the real world headlines we began with to see how much difference this can make The headline finding of a study published in June 2012 was that having several CT scans as a child could make you three times as likely to develop leukaemia or brain cancer as an adult This sounds quite worrying and we could make it sound even scarier still another way of saying three times as likely is a 200 per cent increased chance of cancer But digging a little deeper into the research as much of the coverage sensibly did showed that because the chances of developing these cancers are so small 0 4 per 10 000 children aged 0 9 develop brain tumours and 0 6 per 10

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/03/15/absolute-versus-relative-risk-making-sense-of-media-stories/ (2016-02-11)
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  • Lower awareness isn’t behind the UK’s poorer survival - Cancer Research UK - Science blog
    revealed this week in a new ICBP paper published in the British Journal of Cancer This looked at international differences in what people know about cancer symptoms and in what they believe about cancer and whether this could explain international cancer survival differences The good news is that people in this country were just as aware of the key symptoms of cancer as people in other countries On average people in each country in the study recognised eight out of 11 of the most common cancer symptoms People were also asked what they might expect to happen after a cancer diagnosis Researchers asked them to say whether they agreed with statements like cancer can often be cured or is cancer a death sentence This is important because there is evidence to suggest negative attitudes can be linked to being diagnosed later Encouragingly more than nine out of 10 people in the UK thought that cancer can often be cured while more than seven out of 10 disagreed with the statement that cancer is a death sentence Again this is similar to what people believe in other countries These findings broadly reflect reality as over the last 40 years cancer survival rates have doubled in the UK Although it may not seem like it at first glance these findings are valuable because they show us that the differences in cancer survival internationally aren t likely to be explained solely by differences in people s knowledge or attitudes There were also several other thought provoking findings from the same study which give the ICBP team more leads to investigate Worried about wasting the doctor s time People in the UK are more worried about wasting GPs time Substantially more people in the UK than in other countries said that there were specific reasons why they would not go to their doctor even if they had a symptom they thought was serious I worry about wasting the doctor s time was the most common issue that prevented people going to see their GP More than three out of 10 people in the UK compared with fewer than one in 10 in Sweden said this would stop them making an appointment It s hardly surprising that people responded this way as it s been a widely held view of the public and the media that doctors are overworked Whether or not this is true many of us believe it and a knock on effect is likely to be that some of us are reluctant to add to GPs workload People also said that they would be embarrassed worried over what the doctor may find or too busy and that this may stop them going to their doctor At Cancer Research UK we re working hard to let people know that if there is something different about their body that s concerning them their doctor will want to know And the Be Clear on Cancer campaigns run by the Department of Health aim to encourage

    Original URL path: http://scienceblog.cancerresearchuk.org/2013/01/30/lower-cancer-awareness-doesnt-explain-the-uks-poorer-survival/ (2016-02-11)
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