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Research solves pancreatic cancer mystery

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A NEW technique to study tissue samples in 3D has revealed that pancreatic cancers can start and grow in two distinct ways, solving a decades-old mystery of how tumours form.

The new method could help researchers to get more information from tissue biopsies and may lead to improved treatments for pancreatic cancers. The technique was developed by scientists at the Francis Crick Institute, and their results are published in Nature. The work was supported by the European Research Council and core funding from the MRC (one of the Crick’s founding partners).

The pancreas is a crucial organ that sits behind our stomach and plays a key role in digestion. It relies on a network of ducts linking it to other digestive organs, and the most common pancreatic cancers are found in the ducts. However, until now it has only been possible to see 2D slices of these ductal cancers, which contained an unexplained variety of abnormal shapes.

“To investigate the origins of pancreatic cancer, we spent six years developing a new method to analyse cancer biopsies in three dimensions,” explains Dr Hendrik Messal from the Francis Crick Institute, co-lead author of the research paper. “This technique revealed that cancers develop in the duct walls and either grow inwards or outwards depending on the size of the duct. This explains the mysterious shape differences that we’ve been seeing in 2D slices for decades.”

By analysing developing cancers in 3D, the team defined two distinct types of cancer formation: ‘endophytic’ tumours which grow inwards and ‘exophytic’ tumours which grow outwards. To find out what makes cancer cells grow in a particular way, they analysed detailed 3D images and worked with biophysicists at the Crick who created sophisticated computer models.

“We made a simulation of the ducts, describing individual cell geometry to understand tissue shape,” explains biophysicist Dr Silvanus Alt, co-lead author of the paper. “The model and experimental results both confirmed that cancer grew outwards when the diameter of the duct was less than approximately 20 micrometres, around a fiftieth of a millimetre.”

The work was made possible by an interdisciplinary collaboration between two research groups at the Crick, led by Dr Axel Behrens and Dr Guillaume Salbreux. Axel’s group works on stem cells and pancreatic cancer, while Guillaume focuses on using physics to understand biological processes.

“I think we first started discussing this when we bumped into each other in the bike shed,” says Axel. “It’s amazing what can come out of a chance encounter, we now have a patented technique to see the three-dimensional shapes of cancers and a biophysical understanding of the emergence of tumours. Now that we know pancreatic cancer can develop in these two different ways, we can start looking at whether one is likely to be more aggressive or spread in a different way. Many years from now, this could lead to improved diagnostic or treatment options.”

The team also applied the technique to other organs and found that cancers in the airways of the lungs and ducts in the liver behave in the same way. This shows that the mechanism the teams discovered is not specific to the pancreas and also applies to other cancers.

“Both the data and our models indicate that the two different mechanisms of tumour growth are purely down to the innate physics of the system,” explains Dr Guillaume Salbreux. “Like most cancers, ductal pancreatic cancer starts with a single defective cell that starts dividing. We found that very quickly, when there are only a few cells, the tumour has already started to grow either inwards or outwards depending on duct diameter. Defining this fundamental process will help us to better understand how cancer grows in many places across the body.”

Dr Mariana Delfino-Machin, Programme Manager for Cancer at the MRC, said: “Pancreatic cancer remains a very difficult disease to treat but understanding that it can grow in different ways will inform the development of more accurate treatments in the future.

“These findings came about thanks to researchers working in very different fields coming together to successfully tackle the same problem.”

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Important step for Welsh cancer treatment

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THE FIRST NHS Wales cancer patient to receive proton beam therapy in Wales has started treatment at the Rutherford Cancer Centre South Wales in Newport.

The Newport centre is approved by the Welsh Health Specialised Services Committee (WHSSC) to provide high energy proton beam therapy to adult patients, referred from the NHS in south Wales.

Professor Roger Taylor, Senior Clinical Advisor and Consultant Clinical Oncologist at the Rutherford Cancer Centre South Wales, said: “The availability of proton beam therapy at a local clinic is an important step forward in cancer care in the UK and we are pleased to be able to provide treatment for this young man.

“Whilst proton therapy is not a panacea for all types of cancer, we have seen where it can be beneficial in treating a range of tumours. Working with the NHS in Wales means that adult patients have an option to be treated closer to home.”

Jamie Powell, Centre Manager at the Rutherford Cancer Centre South Wales, said: “Providing access to the Rutherford Cancer Centres for NHS patients is something we have been working towards and we are pleased to announce this on World Cancer Day. Our centre and services in Newport are supported by NHS Wales clinical, hospital and research facilities and we look forward to continuing to provide excellent care in a high-quality and technologically advanced environment.”

The Rutherford Cancer Centre South Wales was the first clinic in the UK to provide high energy proton beam therapy and treated the first non-NHS patient with high energy proton beam therapy in the UK in April of last year.

Rupert Lowe, chairman of Proton Partners International, said: “As someone who had to travel abroad to receive proton beam therapy, I am delighted to be reporting on World Cancer Day today that the situation is changing at last in the UK.

“We were extremely proud to treat the first proton beam therapy patient in the UK last April and scores more have benefited from this treatment without having to travel abroad. We are also pleased to see the development of proton beam therapy facilities within the NHS.

“We are delighted to have been commissioned by health commissioners in Wales to treat adult NHS patients with proton beam therapy and are very proud that our first NHS patient began treatment today.

“The UK Government recently set out an ambitious 10-year plan for the NHS which includes major commitments to tackling cancer. We firmly believe that given the magnitude of the challenge, a collaborative approach among healthcare providers will achieve the best results for patients.”

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Gene study on depression’s origins

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HUNDREDS of genes have been newly linked to depression, shedding light on the origins of the condition and highlighting personality types that could be at risk.

The international study, involving more than two million people, is the largest of its kind. It could inform treatments for the condition, which affects one in five people in the UK and is the leading cause of disability worldwide.

Scientists led by the University of Edinburgh studied information pooled from three large datasets of anonymised health and DNA records and pinpointed 269 genes that were linked to depression.

They also used an innovative statistical method to identify sections of DNA that were common in people with depression and in those who adopted lifestyle behaviours such as smoking.

The findings suggest that depression could be a driving factor leading some people to smoke, but more research is needed to explain why, the team says.

Results also show that neuroticism – a tendency to be worried or fearful – could lead people to become depressed, which could shed light on personality factors that put people at risk. The statistical approach – known as Mendelian randomisation – allows scientists to look at how a condition impacts on behaviour, while ruling out other influences such as age or income.

Anonymised data, used with donor consent, is held by UK Biobank, the personal genetics and research company 23andMe and the Psychiatry Genomics Consortium.

Experts say that the study reflects the importance of data science in understanding mental health.

The study, published in Nature Neuroscience, was funded by the MRC and Wellcome.

Professor Andrew McIntosh, of the University of Edinburgh’s Centre for Clinical Brain Sciences, who led the research, said: “These findings are further evidence that depression is partly down to our genetics.

“We hope the findings will help us understand why some people are more at risk of depression than others, and how we might help people living with depression and anxiety more effectively in future.”

Sophie Dix, Director of Research at mental health charity MQ, who was not involved in the research, said: “This study adds to the weight of evidence that genes are one of the key risk factors in depression, which is also impacted by life events such as social environment and trauma. The value of this could really be seen when looking into the development of personalised treatments – a welcome step, given the dearth of innovation in identifying new approaches. We have seen very little advancement in nearly 50 years for people living with depression and right now the avenues available are not working for everyone.

“The power of this big genetic study is that it can point to systems in the brain which adds to our currently limited understanding in this area. By increasing our understanding of these systems, and how the social environment affects biological risk factors, we can begin to identify new targets for treatments that could help the millions of people worldwide affected by depression.”

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Dechox yourself

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HUNDREDS and thousands of chocoholic residents in Wales say they would find it easier to give up sex, coffee and social media than chocolate, according to a new British Heart Foundation (BHF) survey.

The figures, which reveal the country’s unhealthy obsession with chocolate, show that a staggering one in six respondents would find it easier to give up sex (15%) and a fifth would rather kick their coffee habit (18%) than chocolate. If these results were repeated countrywide, around 380,000 adults would find it easier to give up sex and 460,000 would rather ditch caffeine than chocolate.

Around a quarter polled (around 590,000 adults) would rather give up social media or nights in, watching their favourite shows on Netflix (23%).

The figures have been released on the eve of the BHF’s Dechox campaign – the charity’s annual challenge to get people to give up chocolate for the month of February to raise funds for the BHF’s life-saving research.

Wales’ infatuation with chocolate is clear to see and it seems that many can’t get the sweet stuff off their mind. On average, people think about chocolate three times a day – the equivalent of 1,095 times a year.

This leads to the average person eating chocolate five times a week, consuming around 180g – the equivalent of four small chocolate bars. In total, the adult population in Wales consumes an estimated 463 tonnes of chocolate a week – the same weight as 37 double-decker buses.

For many people, the extent of their love for chocolate leads to them keeping it hush-hush by indulging away from prying eyes. Around a third of people (31%) have admitted to waking up in the middle of the night and eating chocolate, and over two-fifths of the population in Wales have waited until a partner, friend or family member has left the room before tucking into their chocolate treats (42%).

People just can’t seem to live without chocolate, with only one in six people (15%) previously attempting to erase chocolate from their diet. This February, the BHF is encouraging everyone to put their will power to the test by giving up chocolate for the entire month to help raise money for life-saving research into heart and circulatory diseases.

Adam Fletcher, Head of BHF Cymru, said: “Our love of chocolate is plain to see and we are undoubtedly infatuated with the sweet stuff. From the moment we wake up to go to sleep, this survey reveals the lengths people will go to so they don’t have to part with their chocolate.

“By challenging yourself to a Dechox this February, you will be able to put your will power to the test whilst raising funds for our vital research. Ditching the chocolate for 28 days will leave you feeling like you’ve conquered something huge and the money you raise will help fund breakthroughs to help beat heart and circulatory diseases for good.”

Send chocolate packing and challenge yourself to a Dechox this February. Give up chocolate for a month, and raise funds for BHF’s life-saving research.

Find out more at: www.bhf.org.uk/dechox

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