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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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Police and drugs advice service issue warning over ‘deadly batch’ of heroin

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POLICE have asked the media to issue a warning over a batch of heroin.

The drug circulating in west Wales, first detected in Llanelli, is particularly dangerous, it has been confirmed.

“We are warning drug users to take extra care following reports of a particularly harmful batch of heroin circulating in the Llanelli area” said a Dyfed-Powys Police spokesperson.

“We have reasons to believe some drugs being distributed and used in the Carmarthenshire area at present have been contaminated with other substances and could be extremely dangerous for anyone taking them.

“We would also appeal to drug users to seek medical attention immediately if they become unwell.

“Please share this information with anyone you believe could come into contact with these drugs.

”In an emergency or if you think someone’s life is at risk always dial 999.”

Earlier this week Barod, the drug and alcohol abuse service reported a dangerous and toxic heroin circulating in Pembroke Dock which a spokesperson described as being ‘potentially deadly’.

To comes as Public Health England issued a formal alert about the risks of heroin containing fentanyl or carfentanyl.

The warning reads: “There is significant evidence from a small number of post-mortem results of recent drug user deaths and from police seizures that some heroin may contain fentanyl or carfentanyl added by dealers.

“These are highly potent synthetic opioids and very small amounts can cause severe or even fatal toxicity.

“Those of you in contact with heroin users should be alert to the increased possibility of overdose arising from heroin cut with these synthetic opioids, be able to recognise possible symptoms of overdose and respond appropriately.”

The fentanyls are a group of synthetic opioids; some have legitimate uses while others are illicit drugs.

Fentanyl is about 100 times more potent than morphine and is a licensed medicine used to treat severe and terminal pain. Carfentanyl is 4,000 – 10,000 times more potent than morphine and principally used as an animal tranquilliser.

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Health

Covid-19 restriction relaxations in Wales brought forward

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THE WELSH GOVERNMENT will be accelerating elements of its programme to relax Covid-19 restrictions as cases of new infections continue to fall across Wales, the First Minister today announced.

People will be able to form an extended household, visit the gym or take part in organised outdoor activities a week earlier than planned, as the public health situation – and vaccination rates – continue to improve.

The First Minister last week set out a detailed timetable for moving Wales firmly into alert level three. But some of these measures will now be introduced sooner than planned as cases have fallen markedly from 37 cases per 100,000 people to fewer than 21 per 100,000 this week.

The pressure on hospitals also continues to ease. Confirmed cases in hospital beds continue to reduce, and now stands at 89. This is 26% lower than last Thursday and is the lowest position since 22 September 2020.

The planned opening date for organised outdoor activities and outdoor wedding receptions will be moved forward to Monday 26 April from 3 May.

And, from Monday 3 May, a week earlier than previously signalled, gyms, leisure centres and fitness facilities will be able to reopen for individual or one-to-one training. Extended households will also be allowed again, enabling two households to meet and have contact indoors.

First Minister, Mark Drakeford said:

“The public health situation in Wales continues to improve thanks to everything you are doing to help us control this awful virus. Cases of the virus are falling and our incredible vaccination programme continues to go from strength to strength.

“Last week, we set out our programme to further re-open the economy and relax the restrictions we have lived with for so long, as part of our careful, step-by-step approach to keeping everyone safe. This week, because of the improvements we continue to see, we can bring forward some of our plans.

“This is only possible because of the efforts everyone is making to protect themselves and their loved ones.”

From Monday 12 April, the following relaxations will go ahead:

  • The full return of children to schools for face-to-face education, all post-16 learners will return to further education and training centres, and university campus’ will be able to open for blended face-to-face/online learning for all students;
  • All remaining shops will reopen, completing the phased reopening of non-essential retail;
  • All remaining close contact services will open, including mobile services;
  • Travel restrictions on traveling into and out of Wales will be lifted. However, restrictions on travel to countries outside the Common Travel Area without a reasonable excuse, remain in place. The Common Travel Area means the United Kingdom, the Channel Islands, the Isle of Man and the Republic of Ireland;
  • Wedding ‘show-arounds’ by appointment are allowed;
  • Restrictions on political canvassing are removed, subject to canvassers doing so safely.
  • Further easements to restrictions in the coming weeks will be subject to the public health situation remaining favourable. These will be confirmed at the next three-weekly review of the coronavirus regulations on 22 April.

On Monday 26 April:

  • Outdoor attractions, including funfairs and theme parks, would be allowed to reopen;
  • Outdoor hospitality can resume, including at cafes, pubs and restaurants. Indoor hospitality will remain closed except for takeaways;
  • Organised outdoor activities for up to 30 people can again take place (previously Monday 3 May);
  • Weddings receptions can take place outdoors for up to 30 people (previously Monday 3 May).

On Monday 3 May (previously Monday 10 May):

  • Gyms, leisure centres and fitness facilities can reopen. This will include individual or one-to-one training but not exercise classes;
    Extended household will again allow two households to meet and have contact indoors.
  • As set out in the revised Coronavirus Control Plan, a small number of outdoor pilot events of between 200 and 1,000 people are also being planned.
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Health

Third COVID-19 vaccine arrives in Wales following Moderna approval

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THIS WEEK marked another key milestone in our fight against the COVID-19 pandemic with the arrival of supplies of the Moderna vaccine.

A third vaccine for use in Wales significantly adds to our defences in the face of coronavirus and will help to protect our most vulnerable.

Elle Taylor, an unpaid carer from Ammanford, became the first person in the UK to receive the vaccine Glangwili Hospital in Carmarthen.

Speaking after receiving the vaccine, the 24-year-old, who works at a further education college, said: “I’m extremely excited and happy.

“I’m an unpaid carer for my grandmother so it is especially important to me that I get it, so I can care for her properly and safely.

“My grandmother has had her first dose and she is going for her second dose on Saturday.”

Ros Jervis, Director of Public Health for Hywel Dda University Health Board, added: “We’re delighted to be able to use the Moderna vaccine for deployment across west Wales.

“We will be using this new vaccine, alongside Oxford Astra-Zeneca, to continue the vaccine roll out to our communities in Carmarthenshire, Ceredigion and Pembrokeshire.

“We are incredibly lucky to have a third vaccine in Wales, with a long shelf life and the ability to be easily transported, to help deliver the vaccination programme to small clinics across our rural communities.”

194,057 people in our three counties have now received their first dose of the vaccine, and 47,087 people are fully vaccinated having received both doses.

The Health Board has offered a first dose of the vaccine to all those in priority groups 5-9 by Sunday 18 April.

Hywel Dda said that to ensure no one is left behind, this week the health board has launched an appeal asking people in groups 1 to 9 who have not been contacted to get in touch to arrange their first vaccine dose.

Second doses are essential for longer term protection, so it’s important that everyone comes forward for their full course when called.

When you will be contacted for your second vaccine dose depends on which vaccine you have received.

A Health Board spokesperson said: “We are asking anyone who received the Pfizer vaccine and has not received a second vaccine appointment yet, to get in touch as soon as possible on 0300 303 8322. Please note our phone lines get terribly busy at times and you may have to wait for the call to be answered.

“We aim to complete all second Pfizer vaccine doses by week commencing Monday 12 April.

“To check which vaccine you received, look at the card given to you when you received your first vaccine. It will say if you received either the Pfizer BioNtech
vaccine, or the Oxford AstraZeneca vaccine.

“If you received a first vaccine dose of the Oxford AstraZeneca vaccine, we politely ask that you do not contact your GP practice or health board at this time to ask about a second vaccine appointment. You will be contacted when it is your turn for a second dose – we are calling those who received a Pfizer first dose at this time.

“Care home residents, people aged over 80 and all other priority groups who have received the Oxford AstraZeneca vaccine at the GP surgery will be contacted between 11 to 12 weeks following their first vaccine with an appointment time.”

The Health Board says that confidence is building around the effectiveness of the vaccines. Emerging evidence is clear on the impact of the vaccine in preventing severe disease and hospitalisation. That is now playing out in admissions to our hospitals, and thankfully, numbers of deaths from coronavirus being reported.

UK and EU regulators have also been clear about the safety of the vaccines. The benefits of vaccination outweigh any possible risks. All three vaccines are both safe and effective.

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