Scientists have discovered new potential targets for treating squamous cell lung cancer, which causes approximately 400,000 deaths per year worldwide.

Squamous cell lung cancer kills more people each year than breast, colorectal, or prostate cancer, ranking second only to lung adenocarcinoma in the number of deaths it causes.

But unlike the most common form of lung cancer, squamous cell carcinoma has no treatments aimed at the specific genetic alterations that drive it.

Now The Cancer Genome Atlas (TCGA) Research Network, led in part by scientists at the Broad Institute, Dana-Farber Cancer Institute, and Harvard Medical School, has identified many potential therapeutic targets based on the large number and variety of DNA alterations they discovered in most of the tumours they studied.

"This study clearly shows that squamous cell carcinoma, like lung adenocarcinoma, is a cancer with diverse genomic causes, many of which are potentially susceptible to drug inhibition," said Matthew Meyerson, co-leader of the project within TCGA, Broad senior associate member, and professor of pathology at Dana-Farber Cancer Institute and Harvard Medical School.

"This provides many new therapeutic opportunities for squamous cell carcinoma that would be suitable for clinical trials," he noted.

The first targeted treatments for lung adenocarcinoma, erlotinib (Tarceva) and gefitinib (Iressa), were aimed at mutations in the EGFR gene. Unfortunately, and like other drugs being tested in clinical trials that target several other genes altered in lung adenocarcinoma, they do not help patients with squamous cell carcinoma.

The TCGA effort, a multicenter consortium funded by the National Institutes of Health, is the first comprehensive genomic characterization of this lung cancer subtype.

As in the three previous TCGA reports on the brain cancer glioblastoma, on ovarian cancer, and on colorectal cancer, the scientists used multiple large-scale approaches to highlight key molecular defects. They sequenced the protein-coding segments of the genomes of 178 squamous cell carcinoma tumors, along with normal tissue from the same patients.

The researchers also sequenced the whole genomes of 19 tumor and normal tissue pairs. They mapped a diverse catalog of genomic alterations, including the rearrangements of chromosomes and other structural changes in regions of the genome that might not encode proteins but could control nearby genes involved in cancer development.

The comprehensive study confirmed some previously identified genomic alterations. For example, the TP53 gene was altered in 90 percent of the tumours and the CDKN2A gene was inactivated in 72 percent of tumours. These genes normally prevent cancer, but when they are switched off, tumours can grow unimpeded. CDKN2A may be susceptible to a kinase inhibitor, presenting an opportunity for clinical trials.

Overall the researchers identified mutations or amplifications in three families of tyrosine kinases, which are enzymes that act like power switches for many cellular functions. Frequently altered in cancer, they are already being investigated as therapeutic targets in other cancers. The researchers also found genomic alterations in signalling pathways that could present important opportunities for treatment.

In another striking finding, the researchers discovered mutations in the HLA-A gene that hampered its function in tumours. HLA genes direct the arm of the immune system that discriminates between its own tissues and foreign invaders. This is the first cancer in which these mutations have been found, but they are likely to occur in other cancers, Meyerson said.

"To our knowledge, this is the first example of a tumour that has a genomic mechanism for evading an immune response. This may be important in understanding the immune response to squamous cell carcinoma and also in envisioning how immune-regulatory therapy might be used for this disease," he said.

While much works needs to be done, the scientists see many opportunities.

Their work was published online in Nature.

Half of all women given overnight sleep tests for a new study were found to have mild-to-severe sleep apnoea.

Scientists in Sweden monitored the sleep patterns of 400 adult women overnight and found that half experienced at least five episodes an hour when they stopped breathing for longer than 10 seconds - the minimum definition of sleep apnoea.

Among women with hypertension or who were obese - two risk factors for sleep apnoea - the numbers were even higher, reaching 80 to 84 per cent of women.

Many of the women in the study represent mild cases of sleep apnoea.

'How important is the mild sleep apnoea, we don't know,' said Dr. Karl Franklin, the lead author of the study and a professor at Umea University in Sweden.

Terry Young, a professor in the School of Medicine and Public Health at the University of Wisconsin, said mild sleep apnoea is important to pay attention to.

'We see that it doesn't go away and it gets worse,' she said.

Sleep apnoea is tied to a higher risk of stroke, heart attack and early death.

One recent study also found that women who have sleep apnoea are more likely to develop memory problems and dementia.

Franklin said his group wanted to get updated evidence of how common the condition is.

The researchers selected 400 women between the ages of 20 and 70 from a larger population sample of 10,000, and asked them to sleep overnight at home with sensors attached to their bodies.

The sensors measured heart rate, eye and leg movements, blood oxygen levels, air flow and brain waves.

Each apnoea event was defined by at a least a 10-second pause in breathing accompanied by a drop in blood oxygen levels.

Women who had an average of five or more of these events during each hour of sleep were considered to have sleep apnoea.

The study, which was funded by the Swedish Heart Lung Foundation, found that apnoea became more common in the older age groups.

Among women aged 20-44, one quarter had sleep apnoea, compared to 56 percent of women aged 45-54 and 75 per cent of women aged 55-70.

Young said these numbers are higher than her own estimate, but that's likely because she used a more strict definition of sleep apnea than Franklin's group.

Franklin also said his equipment, being newer, is more sensitive in detecting interruptions in breathing.

Severe sleep apnoea, which involves more than 30 breathing disruptions per hour, was far less common.

Just 4.6 per cent of women 45-54 and 14 per cent of women 55-70 had severe cases.

Among women of all ages with hypertension, 14 per cent had severe sleep apnoea, and among women who were obese, 19 per cent had severe apnoea.

Franklin said that if physicians are looking for sleep apnoea among women, examining those who are obese, over 55 or have hypertension is a good place to start.

Young said sleep apnoea is often thought of as a condition of men, but identifying women with it is especially beneficial, because her research has shown that women are good at sticking with treatment.

'The prejudice of excluding women (as potentially having sleep apnoea) has been rampant for a long time. It's gotten better, however, and the (public health) gain in identifying women with sleep apnoea is great,' she said.

Sleep disruption may be the earliest sign of Alzheimer's, scientists say.

Clumps of sticky protein forming in the brain, called plaques, are thought to be a key feature of the disease.

Researchers found when the first signs of these plaques appeared in the brains of mice their sleep/wake cycle was significantly disrupted.

This could provide an easily detectable early warning sign, according to the study in Science Translational Medicine.

Author Dr David Holtzman, from Washington University said: 'If sleep abnormalities begin this early in the course of human Alzheimer's disease, those changes could provide us with an easily detectable sign of pathology.

'As we start to treat Alzheimer's patients before the onset of dementia, the presence or absence of sleep problems may be a rapid indicator of whether the new treatments are succeeding.'

Dr Holtzman's lab has previously shown that levels of a main 'ingredient' of the plaques - amyloid beta - rise when healthy mice are awake and drop when they are asleep. The same was later found to be true in humans.

The new research showed that when the first indicators of brain plaques appear, the natural fluctuations in amyloid beta levels stop in both mice and humans.

Dr Holtzman said: 'We suspect that the plaques are pulling in amyloid beta, removing it from the processes that would normally clear it from the brain.'

With mice, this meant that their sleep dropped from an average 40 minutes per hour of daylight to 30 minutes once plaques began to form.

To confirm that amyloid beta was directly linked to the changes in sleep, researchers gave a vaccine against amyloid beta to a new group of mice.

As these mice grew older, they did not develop brain plaques and their sleeping patterns remained normal while amyloid beta levels in the brain continued to rise and fall regularly.

Scientists now are evaluating whether sleep problems occur in patients who have markers of Alzheimer's disease, such as plaques in the brain, but have not yet developed memory or other cognitive problems.

Dr Holtzman said: 'If these sleep problems exist, we don't yet know exactly what form they take-reduced sleep overall or trouble staying asleep or something else entirely.

'But we're working to find out.'

Dr Marie Janson of Alzheimer's Research UK said: 'There has already been research linking changes in sleep patterns to a decline in thinking skills, but these results suggest that disrupted sleep may also be a warning sign of Alzheimer's.

'Changes to sleeping patterns can occur for many reasons and are very common in the elderly. If research confirms specific sleep changes as a possible early marker of Alzheimer's, it could prove a useful strategy for doctors to identify patients at risk of the disease.

'It's thought that any new treatments for Alzheimer's will need to be given as early as possible, so detecting the disease early is crucial allowing potential new drugs to be trialled in the right people at the right time.'

Half a million people are affected by Alzheimer's in the UK, which is the most common form of dementia. It is a progressive condition and 98 per cent of cases are detected in patients aged over 65.

Problems sleeping may be an early sign of Alzheimer's if a study in mice also applies to people, say researchers.

Clumps of protein, called plaques, in the brain are thought to be a key component of the illness.

A study, published in the journal Science Translational Medicine, showed that when plaques first developed, the mice started having disrupted sleep.

Alzheimer's Research UK argued that if the link was proven it could become a useful tool for doctors.

The hunt for early hints that someone is developing Alzheimer's is thought to be crucial for treating the disease.

People do not show problems with their memory or clarity of thought until very late on in the disease. At this point, parts of the brain will have been destroyed, meaning treatment will be very difficult or maybe even impossible.
'Detectable sign'

It is why researchers want to start early, years before the first symptoms.

One large area of research is in plaques of beta amyloid which form on the brain.

Levels of the beta amyloid protein naturally rise and fall over 24 hours in both mice and people. However, the protein forms permanent plaques in Alzheimer's disease.

Experiments at Washington University showed that nocturnal mice slept for 40 minutes during every hour of daylight. However, as soon brain plaques started to form the mice were sleeping for only 30 minutes.

One of the researchers, Prof David Holtzman, said: "If sleep abnormalities begin this early in the course of human Alzheimer's disease, those changes could provide us with an easily detectable sign of [the disease]."

"If these sleep problems exist, we don't yet know exactly what form they take, reduced sleep overall or trouble staying asleep or something else entirely."

However, findings in mice do not always apply to people as there are many reasons for disrupted sleep.

Dr Marie Janson, from the charity Alzheimer's Research UK, called for more studies in people to see if there was a link between sleeping patterns and Alzheimer's.

She added: "There has already been research linking changes in sleep patterns to a decline in thinking skills, but these results suggest that disrupted sleep may also be a warning sign of Alzheimer's.

"If research confirms specific sleep changes as a possible early marker of Alzheimer's, it could prove a useful strategy for doctors to identify patients at risk of the disease."

It may sound like a couch potato's dream, but two-and-a-half minutes of exercise could be just as good as a 90-minute run, a study has revealed.

Research suggests that short, sharp bursts of exercise are better at warding off heart disease than much longer but less strenuous sessions, the Daily Mail reported.

Academic Stuart Gray asked a group of men aged between 18 and 35 to either do high-intensity sprints on an exercise bike, or walk for half an hour on a treadmill.

Those on the exercise bike pedalled as hard as they could for 30 seconds, rested for up to four minutes and then repeated the pattern four times.

This meant that, in all, they did two and a half minutes of exercise strenuous enough to make them sweat and leave them out of breath

The others walked at the sort of brisk pace recommended in government health guidelines.

A day later, they came back into the lab and ate a fatty breakfast and lunch consisting of bread, mayonnaise and cheese

Their blood was then tested to see how quickly the levels of fat in their blood fell as fat lingering in the blood after eating is known to trigger the first in a series of steps that can lead to clogging of the arteries and heart disease.

The results revealed that walking cut fat by 11%, compared with not doing any exercise.

But the short sharp bursts of exercise cut it by 33% the sort of effect expected from a 90-minute run.

Dr Gray, of Aberdeen University, told the British Science Festival in the city that short bursts of intensive exercise may somehow spur the liver into taking in more fat from the blood, before storing it or burning it off.

He said that, while the high intensity training "won't necessarily" improve strength, it does boost endurance.

He added that the short duration of the exercise was "highly important as time is often cited as the main barrier to taking part in exercise."