Men who develop prostate cancer after inheriting a faulty gene need immediate surgery or radiotherapy rather than being placed under surveillance, as their disease is more aggressive than other types, a new study has found.
A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust found prostate cancers spread more quickly and were more often fatal in men who had inherited a faulty BRCA2 gene than in men without the faulty gene.
The research, funded by the Ronald and Rita McAulay Foundation and Cancer Research UK, could challenge current NHS guidelines for prostate cancer, under which BRCA2 mutation carriers are offered the same treatment options as non-carriers.
It is often difficult to tell at diagnosis whether prostate cancer will be life-threatening or not, and while treatment options for early-stage disease include surgery and radiotherapy, many men instead receive active surveillance to see if the disease starts to progress.
The new study is the largest to compare prostate cancer patients with and without BRCA mutations, in order to tell whether gene testing should help to direct management options.
Senior author Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research (ICR) and Honorary Consultant in Clinical Oncology at The Royal Marsden, said: ‘It is clear from our study that prostate cancers linked to inheritance of the BRCA2 cancer gene are more deadly than other types. It must make sense to start offering affected men immediate surgery or radiotherapy, even for early-stage cases that would otherwise be classified as low-risk. We won’t be able to tell for certain that earlier treatment can benefit men with inherited cancer genes until we’ve tested it in a clinical trial, but the hope is that our study will ultimately save lives by directing treatment at those who most need it.’
The team from the ICR and The Royal Marsden, with collaborators across the UK, examined the medical records of 61 BRCA2-mutation carriers, 18 BRCA1-mutation carriers and 1,940 non-carriers.
They found BRCA1/2 mutation carriers were more likely to be diagnosed with advanced stage prostate cancers (37 per cent versus 28 per cent) or cancer that had already spread (18 per cent versus nine per cent) than non-carriers. Among those whose cancers had not spread out of the prostate at diagnosis, within five years more carriers than non-carriers had metastatic disease (23 per cent versus seven per cent).
Patients with BRCA2-mutations were also significantly less likely to survive the cancer, living an average of 6.5 years compared with 12.9 years for non-carriers. The team concluded that a BRCA2 test could be used in combination with other factors as a prognostic test. Men with a BRCA1 mutation also had a shorter average survival time of 10.5 years, but there was not a statistically significant difference with non-carriers. ICR

In the summer of 1968, a new strain of influenza appeared in Hong Kong. This strain, known as H3N2, spread around the globe and eventually killed an estimated 1 million people.
A new study from MIT reveals that there are many strains of H3N2 circulating in birds and pigs that are genetically similar to the 1968 strain and have the potential to generate a pandemic if they leap to humans. The researchers, led by Ram Sasisekharan, the Alfred H. Caspary Professor of Biological Engineering at MIT, also found that current flu vaccines might not offer protection against these strains.
‘There are indeed examples of H3N2 that we need to be concerned about,’ says Sasisekharan, who is also a member of MIT’s Koch Institute for Integrative Cancer Research. ‘From a pandemic-preparedness point of view, we should potentially start including some of these H3 strains as part of influenza vaccines.’
The study also offers the World Health Organization and public-health agencies’ insight into viral strains that should raise red flags if detected.
In the past 100 years, influenza viruses that emerged from pigs or birds have caused several notable flu pandemics. When one of these avian or swine viruses gains the ability to infect humans, it can often evade the immune system, which is primed to recognise only strains that commonly infect humans.
Strains of H3N2 have been circulating in humans since the 1968 pandemic, but they have evolved to a less dangerous form that produces a nasty seasonal flu. However, H3N2 strains are also circulating in pigs and birds.
Sasisekharan and his colleagues wanted to determine the risk of H3N2 strains re-emerging in humans, whose immune systems would no longer recognise the more dangerous forms of H3N2. This type of event has a recent precedent: In 2009, a strain of H1N1 emerged that was very similar to the virus that caused a 1918 pandemic that killed 50 million to 100 million people.
‘We asked if that could happen with H3,’ Sasisekharan says. ‘You would think it’s more readily possible with H3 because we observe that there seems to be a lot more mixing of H3 between humans and swine.’
In the new study, the researchers compared the 1968 H3N2 strain and about 1,100 H3 strains now circulating in pigs and birds, focusing on the gene that codes for the viral haemagglutinin (HA) protein.
After comparing HA genetic sequences in five key locations that control the viruses’ interactions with infected hosts, the researchers calculated an ‘antigenic index’ for each strain. This value indicates the percentage of these genetic regions identical to those of the 1968 pandemic strain and helps determine how well an influenza virus can evade a host’s immune response.
The researchers also took into account the patterns of attachment of the HA protein to sugar molecules called glycans. The virus’ ability to attach to glycan receptors found on human respiratory-tract cells is key to infecting humans.
Seeking viruses with an antigenic index of at least 49 percent and glycan-attachment patterns identical to those of the 1968 virus, the research team identified 581 H3 viruses isolated since 2000 that could potentially cause a pandemic. Of these, 549 came from birds and 32 from pigs.
The researchers then exposed some of these strains to antibodies provoked by the current H3 seasonal-flu vaccines. As they predicted, these antibodies were unable to recognise or attack these H3 strains. Of the 581 HA sequences, six swine strains already contain the standard HA mutations necessary for human adaptation, and are thus capable of entering the human population either directly or via genetic reassortment, Sasisekharan says.
‘One of the amazing things about the influenza virus is its ability to grab genes from different pools,’ he says. ‘There could be viral genes that mix among pigs, or between birds and pigs.’
Sasisekharan and colleagues are now doing a similar genetic study of H5 influenza strains. The H3 study was funded by the National Institutes of Health and the National Science Foundation. MIT

Scientists at The University of Manchester have made important advances in understanding why our immune system can attack our own tissues resulting in eye and kidney diseases. It is hoped the research will pave the way for the development of new treatments for the eye condition age-related macular degeneration (AMD) and the kidney condition atypical Haemolytic Uremic Syndrome (aHUS).
Both AMD, which affects around 50 million people worldwide, and aHUS, a rare kidney disease that affects children, are associated with incorrectly controlled immune systems. A protein called complement factor H (CFH) is responsible for regulating part of our immune system called the complement cascade. Genetic alterations in CFH have been shown to increase a person’s risk of developing either AMD or aHUS, but rarely both. Why this is the case has never been explained until now.
Researchers from the Wellcome Trust Centre for Cell Matrix Research and the Ophthalmology and Vision Research Group in The University of Manchester’s Institute of Human Development have been expanding on their previous work that demonstrated a single common genetic alteration in CFH prevents it from fully protecting the back of the human eye. The research teams of Professor Tony Day and Professor Paul Bishop found that a common genetically altered form of CFH associated with AMD couldn’t bind properly to a layer under the retina called Bruch’s membrane. Having a reduced amount of CFH in this part of the eye leads to low-level inflammation and tissue damage, eventually resulting in AMD.
However, this mutation that changes CFH function in the eye has no affect on the protein’s ability to regulate the immune system in the kidney. A cluster of genetic mutations in a completely different part of CFH are associated with the kidney disease aHUS, but these have no affect on the eyes.
In their most recent study, which was funded by the Medical Research, the Manchester researchers have identified why these mutations in CFH result in diseases in very specific tissues. Professor Day explains: ‘For the first time we’ve been able to identify why these protein mutations are so tissue specific. We’re hoping our discovery will open the door to the development of tissue specific treatments to help the millions of people diagnosed with AMD every year.’
The research team looked at the two parts of CFH affected by the mutations. Both regions are capable of recognising host tissues, through interacting with sugars called glycosaminoglycans (GAGs). Successfully recognising these GAGs lets CFH build up a protective layer on the surface of our tissues that prevents our own immune system from attacking them.
It had always been believed that the region with mutations associated with aHUS was the most important for host recognition and for years people have been researching how to readdress immune dysregulation based on this belief. However, the recent discovery of a single common genetic alteration in the other part of CFH that is associated with eye disease raised the possibility that this previous opinion was not fully accurate. The University of Manchester

Stroke, heart attacks and numerous other common disorders result in a massive destruction of cells and tissues called necrosis. It’s a violent event: As each cell dies, its membrane ruptures, releasing substances that trigger inflammation, which in turn can cause more cellular necrosis. A new Weizmann Institute study may help develop targeted therapies for controlling the tissue destruction resulting from inflammation and necrosis.
The study, conducted in the laboratory of Prof. David Wallach of the Biological Chemistry Department, focused on a group of signalling enzymes, including caspase 8, which was discovered by Wallach nearly two decades ago. Earlier studies by scientists in the United States, China and Europe had shown that this group of proteins induces ‘programmed,’ or deliberate, necrosis intended to kill off damaged or infected cells. This revelation had generated the hope that by blocking the induction of necrotic cell death by these proteins, it might be possible to prevent excessive tissue damage in various diseases.
But in the new study, Wallach’s team sounds a warning. The researchers have revealed that under conditions favouring inflammation – that is, in the presence of certain bacterial components or other irritants – the same group of signalling enzymes can trigger an entirely different process in certain cells. It can activate a previously unknown cascade of biochemical reactions that causes inflammation more directly, without inducing necrosis, by stimulating the production of hormone-like regulatory proteins called cytokines. The research, mainly based on experiments in transgenic mice lacking caspase 8 in certain immune cells, was spearheaded by postdoctoral fellow Dr. Tae-Bong Kang. Team members Seung-Hoon Yang, Dr. Beata Toth and Dr. Andrew Kovalenko made important contributions to the study.
These findings suggest that prior to developing targeted necrosis-controlling therapies, researchers need to learn more about the signals transmitted by caspase 8 and its molecular partners: Since this signalling can lead to several entirely different outcomes, the scientists need to determine when exactly it results directly in necrosis and when it does not. Clarifying this matter is of enormous importance: Tissue necrosis occurs in a variety of disorders affecting billions of people, from the above-mentioned stroke and heart attack to viral infections and alcoholism-related degeneration of the liver. Weizmann Institute

The World Health Organisation (WHO) has urged countries with possible cases of novel coronavirus to share information. The move comes after Saudi Arabia said the development of diagnostic tests had been delayed by patent rights on the NCoV virus by commercial laboratories.
Twenty-two deaths and 44 cases have been reported worldwide since 2012, the WHO says. NCoV is from the same family of viruses as the one that caused Severe Acute Respiratory Syndrome (Sars). An outbreak of Sars in 2003 killed about 770 people. However, NCoV and Sars are distinct from each other, the WHO says.
The virus first emerged in Saudi Arabia, which is where most cases have since arisen. Saudi Deputy Health Minister Ziad Memish raised his concerns at the World Health Assembly in Geneva.
‘We are still struggling with diagnostics and the reason is that the virus was patented by scientists and is not allowed to be used for investigations by other scientists,’ he said. ‘I think strongly that the delay in the development of … diagnostic procedures is related to the patenting of the virus.’
WHO chief Margaret Chan expressed dismay at the information.
‘Why would your scientists send specimens out to other laboratories on [sic] a bilateral manner and allow other people to take intellectual property rights on a new disease?’ she asked.
‘Any new disease is full of uncertainty.’
She is urging the WHO’s 194 member states to only share ‘viruses and specimens with WHO collaborating centres… not in a bilateral manner.’
She added: ‘I will follow it up. I will look at the legal implications together with the Kingdom of Saudi Arabia. No IP (intellectual property) should stand in the way of you, the countries of the world, to protect your people.’ BBC