Cancer cells' use of sugar holds the key to their destruction

Scientists have suggested a way to improve treatments that use viruses to attack cancer. It exploits the fact that cancer cells need a lot of glucose and must metabolize it rapidly to survive.

Cutting down cancer cells' sugar supply could make them more vulnerable to treatment.

Oncolytic viruses specifically target and enter cancer cells and use the cells' machinery for their own multiplication and spread.

They destroy tumors from the inside without harming nearby healthy tissue.

A recent study proposes that restricting the cancer cells' supply of glucose, and altering their ability to metabolize it, may strengthen the power of oncolytic viruses.

The research team, at the University of Oxford in the United Kingdom, used mouse models and cells from ovarian, lung, and colon tumors in order to demonstrate the effect.

Cancer Research UK sponsored the study, and a paper on the work features in the journal Cancer Research.

"Our research in the lab," says lead study author Arthur Dyer, who is currently a Ph.D. student in the university's oncology department, "showed that restricting the amount of sugar available to cancer cells makes these cancer-attacking oncolytic viruses work even better."

Cancer cells need lots of glucose

All cells need glucose as a source of energy. Normal cells use tiny internal "powerhouses" called mitochondria to convert glucose into units of chemical energy.

However, to meet their higher demand for energy, cancer cells have a faster process for metabolizing glucose that does not involve mitochondria.

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This is called the Warburg effect, after the scientist Otto Warburg, who observed it over 50 years ago.

Exploiting this uniqueness in cancer cells could open fruitful avenues for research into new treatments.

It may be possible, for instance, to develop drugs that target and disable glucose metabolism in cancer cells without stopping healthy cells from making energy. Trials of experimental drugs that aim to do this are already under way.

One of the advantages that oncolytic viruses have over drugs is that once they are inside the cell their dose increases with time, whereas with drugs it decreases.

Viruses 'more effective' around less glucose

When scientists store and grow cells in the laboratory, they give them lots of glucose. In the human body, however, the cell environment is much less rich in glucose. Also, due to poor circulation, tumors typically have even lower levels of glucose.

In their work with oncolytic viruses, Dyer and his team decided to alter the laboratory conditions to better match those of real life. They reduced the glucose levels.

They found that the oncolytic viruses were much more effective at attacking cancer cells when there was less glucose around. The viruses replicated faster under the new conditions.

They suggest that this finding could also improve laboratory testing of candidate drugs.

Further investigation revealed that adding a drug that hampers the cancer cells' glucose metabolism strengthened the viruses' ability to kill cancer cells even further.

Plans are currently under way to test the "glucose-limiting" approach in clinical trials to find out whether it could be effective in human patients.

Reducing dietary sugar not the same

The scientists are keen to point out that reducing sugar in the diet would not lead to the anticancer effects that they showed in the study.

There is no proof that starving the body of sugar lowers a person's risk of developing cancer or that it improves the chances of survival should they be diagnosed with the disease.

There is an indirect link between reduced dietary sugar and lower cancer risk that comes through tackling obesity.

High intakes of dietary sugar raise the risk of obesity, which, in turn, raises the risk of cancer.

"A lot of people," says senior study author Leonard W. Seymour, a professor of gene therapies in the university's oncology department, "think that carbohydrates are bad, but that's not the case — we need them, and cutting out sugar won't cure cancer."

"Because cancer gobbles up glucose so quickly, the cells are very vulnerable to attack from a drug that targets the sugar pathway. The same effect cannot be achieved by eliminating sugar from your diet."

Source: MedicalNewsToday

Depression: Electrical stimulation can 'significantly' improve mood

New research shows that deep brain stimulation can tackle treatment-resistant depression. Stimulating a brain area called the orbitofrontal cortex led to "significant" improvements in mood for people with moderate to severe depression.

Using DBS to target certain key areas may relieve symptoms of severe depression.

Major depressive disorder affects over 16 millionadults per year in the United States and is the "leading cause of disability worldwide."

A significant proportion of people who are living with major depression do not get any relief from existing treatments.

In fact, up to 30 percent of those affected by depression have an intractable form of the condition.

Recently, deep brain stimulation (DBS) has emerged as a potential therapy that may succeed where other treatments have failed.

In DBS, specialists surgically implant stimulating electrodes in the brain to send electrical currents to targeted areas.

In the new study, Dr. Eddie Chang and his colleagues used DBS in 25 people who had symptoms of depression. They report their findings in the journal Current Biology.

Dr. Chang is also a professor of neurosurgery at the University of California San Francisco (UCSF).

Studying depression and key brain areas

Dr. Chang explains what made the researchers focus on the orbitofrontal cortex in this study. The area "has been called one of the least understood regions in the brain," he reports, "but it is richly connected to various brain structures linked to mood, depression, and decision-making, making it very well positioned to coordinate activity between emotion and cognition."

The team had access to a clinic that specializes in epilepsy. People with epilepsy have electrodes surgically implanted in their brains as part of routine preparation for surgery.

For this study, Dr. Chang and team recruited 25 participants with epilepsy who also had mild to severe depression.

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With the electrodes already in place, the participants reported how they were feeling a few times per day using an app. This enabled the researchers to link changes in brain activity with different moods, focusing on the brain area that was most involved in depression and also accessible with DBS.

The scientists also used mild electrical stimulation on different brain regions and asked participants to say how it affected their mood using specific keywords.

Afterward, they — with the help of a specific piece of software — quantified and analyzed the words that the volunteers had used.

DBS led to a 'naturally positive mood'

The study revealed that, while stimulating most brain areas had no effect on the participants' mood, 3 minutes of stimulating the lateral orbitofrontal cortex led to significant improvements.

The successful results were only seen among those with moderate to severe depression; there was no effect in people with mild depression symptoms.

Study co-author Kristin Sellers, Ph.D. — who is a postdoctoral researcher in Dr. Chang's laboratory — reports on the results. "Patients said things like 'Wow, I feel better,' 'I feel less anxious,' 'I feel calm, cool, and collected.'"

"And just anecdotally, you could see the improvements in patients' body language. They smiled, they sat up straighter, they started to speak more quickly and naturally."

The patterns of brain activity also supported these noticeable improvements in mood. The authors note that the participants' brain activity after the stimulation resembled the brain activity that occurred when the volunteers reported feeling naturally good.

Dr. Vikram Rao, Ph.D. — an assistant professor of neurology at UCSF and the study's first author — explains what these findings mean.

"These [...] observations suggest that stimulation was helping patients with serious depression experience something like a naturally positive mood state, rather than artificially boosting mood in everyone."

Dr. Vikram Rao

"This is in line with previous observations," he adds, "that [orbitofrontal cortex] activity is elevated in patients with severe depression and suggests electrical stimulation may affect the brain in a way that removes an impediment to positive mood that occurs in people with depression."

The researchers note, however, that more studies will be needed before they can conclude that stimulating the orbitofrontal cortex improves mood in the long-term.

"The more we understand about depression at this level of brain circuitry, the more options we may have for offering patients effective treatments with a low risk of side effects," says study co-author Heather Dawes, Ph.D.

"Perhaps by understanding how these emotion circuits go wrong in the first place, we can even one day help the brain 'unlearn' depression."

Source:MedicalNewsToday

Could sonic hedgehog be the answer to hair loss?

When skin is wounded, the hair cannot regrow. In a recent study, researchers ask why this is and whether it can be reversed. They conclude that a signaling pathway called the sonic hedgehog may be critical.

Though it may seem simple, hair regrowth is complex and mysterious.

Hair loss comes in many forms. It can be a gradual, gene-driven loss known as male- or female-pattern baldness.

Alternately, it may result from an injury, such as a burn or deep wound.

However the hair has been lost, regrowing it is a technical challenge that has defied researchers since the dawn of science.

In ancient Egypt, for instance, there was a range of unusual regrowth techniques, including rubbing hippopotamus fat into the scalp.

Although science has moved on, it is still only inching toward a solution to hair loss.

The latest study to investigate regrowth was headed by cell biologist Mayumi Ito, Ph.D., an associate professor at the New York University Langone Health center in New York City.

Her team's findings were published this week in the journal Nature Communications.

Finding a new target

The scientists wanted to look for changes in the signaling pathways of damaged skin.

In particular, they were interested in the signaling of fibroblasts, cells that synthesize collagen — a structural protein that supports the shape of hair and skin. Fibroblasts also play an important role in wound healing.

The researchers honed in on the so-called sonic hedgehog signaling pathway, which cells use to communicate. The pathway is active as we develop in the womb, but its activity diminishes significantly after birth.

The sonic hedgehog signaling pathway is vital in the development of fingers and toes and also in the organization of the brain.

Here, it is worth noting that every hair follicle we have as adults developed in the womb; after birth, no new follicles generate. This helps explain why new tissue, such as scar tissue, cannot grow hair.

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In their experiments, the researchers kick-started sonic hedgehog signaling in the injured skin of mice.

As expected, within 4 weeks of sustaining the injury, hair regrowth was visible. Within 9 weeks, the hair's root and shaft structures appeared.

"Our results show that stimulating fibroblasts through the sonic hedgehog pathway can trigger hair growth not previously seen in wound healing."

Mayumi Ito, Ph.D.

Rejuvenating damaged skin

Essentially, the researchers transformed old, damaged skin back into embryonic skin.

Ito hopes that the findings will be useful for individuals who wish to regrow hair on injuries, as well as for anyone experiencing age-related hair loss.

Earlier studies showed that switching on the sonic hedgehog pathway could trigger tumor growth. To avoid this, the scientists only turned on the pathway for the fibroblasts positioned just below the skin.

The team's findings add a new dimension to our understanding. Previously, the medical community believed that hair could not regrow after an injury primarily because of the buildup of scar tissue and collagen.

As Ito explains, "Now we know that it's a signaling issue in cells that are very active as we develop in the womb, but less so in mature skin cells as we age."

Next, Ito will focus on chemicals that may activate sonic hedgehog signaling. Ultimately, she aims to find drugs that can reverse hair loss — the Holy Grail of hair research.

Although the findings mark another relatively small step toward reversing hair loss, they provide an intriguing new angle from which to view the processes involved.

Source: MedicalNews Today

Snoring can worsen heart function, especially in women

Both snoring and obstructive sleep apnea could lead to earlier impairment of cardiac function in women, according to a new study.

A recent study unlocks the health issues linked to snoring.

"Snoring" refers to a sleeping pattern in which a person breathes while emitting a snorting or grunting sound.

The National Sleep Foundation suggest that 90 million people in the United States snore.

Snoring might become more dangerous as people age, and it can also lead to heart disease.

There are different types of sleep apnea, but the most common is called obstructive sleep apnea(OSA). At least 18 million U.S. adults have sleep apnea.

This condition affects breathing patterns while sleeping, causing a person to stop breathing and start again repeatedly. About half of people who snore loudly have OSA.

When OSA occurs, the muscles in the throat that are responsible for keeping the airway open actually prevent the flow of air.

According to a new study presented recently at the annual meeting of the Radiological Society of North America — held in Chicago, IL — snoring and OSA may lead to earlier impairment of cardiac function in women than in men.

Sleep apnea and heart disease?

It is unclear whether or not sleep apnea directly causes heart disease, but some specialists believe that people with sleep apnea are at risk of developing hypertension, or high blood pressure.

Many people who have sleep apnea also have co-existing diseases. This is one of the reasons why it is harder to establish a direct link between sleep apnea and heart disease.

Is sleeping too much bad for your brain?

A recent sleep study concluded that sleeping too little or too much impacts cognitive function.

According to the American Heart Association (AHA), some people living with sleep apnea and high blood pressure who received treatment for sleep apnea also saw their blood pressure drop. Such findings show a possible link between hypertension and sleep apnea.

OSA is also associated with obesity, which is a risk factor for heart disease.

Obesity contributes to sleep apnea, and the sleep deprivation that sleep apnea causes can give rise to further obesity, in the long-term. As a person gains more weight, the throat muscles that keep the airway open relax, and sleep apnea becomes more serious.

Women who snore may be at greater risk

The researchers analyzed data associated with cardiac parameters in relation to diagnosed OSA and self-reported snoring using data from the UK Biobank.

The UK Biobank is an international health resource, open to researchers, that aims to improve the prevention, diagnosis, and treatment of diseases.

The data were of 4,877 participants who had received a cardiac MRI scan. The scientists divided them into three groups: those with OSA, those with self-reported snoring, and those with neither.

When the researchers compared the snoring group with the group without sleep disorders, they found a striking difference in the left ventricular mass in women compared with men.

Increased left ventricular mass means that the heart needs to work harder to fulfil the body's needs.

These patterns in people who self-reportedly snore may be an indication of undiagnosed OSA.

"We found that the cardiac parameters in women appear to be more easily affected by the disease and that women who snore or have OSA might be at greater risk for cardiac involvement."

Researcher Dr. Adrian Curta

OSA may be vastly underdiagnosed

The researchers also found that the number of diagnosed OSA cases in the study was extremely low, suggesting that OSA may be underdiagnosed across the board.

Dr. Curta, a radiology resident at Munich University Hospital in Germany, urges people who snore to get screened for OSA and those with OSA to seek treatment.

"I would encourage people who snore to ask their partner to observe them and look for phases during sleep when they stop breathing for a short while and then gasp for air," says Dr. Curta.

He continues, "If unsure, they can spend the night at a sleep lab where breathing is constantly monitored during sleep and even slight alterations can be recorded."

The team now hopes to conduct more research to fully understand the sex differences linked to snoring and OSA.

Source: MedicalNewsToday

This is how your brain predicts future events

Brains learn how to anticipate future occurrences from patterns. This process is called "anticipatory timing," and it allows us to successfully interact with the world around us. How does it work?

Anticipatory timing is, in part, what allows us to make the most appropriate decisions in a very dynamic world.

But what does this process rely on?

A new study conducted by researchers from the University of California, Berkeley, explains that, in anticipating an occurrence, the human brain counts on two distinct systems.

"Whether it's sports, music, speech or even allocating attention, our study suggests that timing is not a unified process, but that there are two distinct ways in which we make temporal predictions and these depend on different parts of the brain," says lead study author Assaf Breska, a postdoctoral researcher in neuroscience.

"Together," states senior study author Prof. Richard Ivry, "these brain systems allow us to not just exist in the moment, but to also actively anticipate the future."

One system, the researchers found, allows us to anticipate future occurrences based on our past experiences, while another system is based on the identification of rhythmic patterns.

How do these two systems work, however? Do they "kick in" at different times, depending on the context to which we need to respond?

Answering this question, the study authors believe, could also help us better understand how the brain works in different neurodegenerative conditions.

In turn, this would allow specialists to come up with better strategies to care for people living with such a condition.

The brain regions tasked with 'timing'

In the recent study — the findings of which now appear in the journal PNAS — the scientists worked with people with either Parkinson's disease or cerebellar degeneration.

Both of these conditions are characterized by problems with coordination and balance, though they seem to affect different regions of the brain.

While Parkinson's impacts neural pathways in the basal ganglia, which is a region embedded deep inside the cerebral cortex, in cerebellar degeneration, it is nerve cells in the cerebellum that progressively die.

The researchers compared the ways in which people with each condition used temporal cues to respond to different tests.

All of the study participants responded to two different sequences of colored squares flashing out on a computer screen. In the first exercise, the colored squares succeeded one another at a steady, rhythmic pace.

In the second exercise, the colored squares succeeded one another in a different pattern that did not follow the same steady rhythm.

During these tests, the researchers observed that participants with Parkinson's disease tended to perform better on the complex pattern exercise, while those with cerebellar degeneration responded better to the rhythmic succession test.

"We show that patients with cerebellar degeneration are impaired in using nonrhythmic temporal cues while patients with basal ganglia degeneration associated with Parkinson's disease are impaired in using rhythmic cues," says Prof. Ivry.

These findings allowed the team to identify which brain areas were linked to which anticipatory timing system. The authors concluded that rhythmic timing corresponds to the basal ganglia, whereas interval timing — based on memories of previous experience — corresponds to the cerebellum.

Source: Medical News Today

What are the symptoms of stage 4 breast cancer?

If a person has stage 4 breast cancer, this means that the cancer cells have spread to other organs in their body, such as the lungs, lymph nodes, bones, skin, liver, or brain.

Cancer stages range from 1 to 4 and indicate the extent of the disease. A doctor may also refer to stage 4 as advanced or metastatic breast cancer.

Breast cancer is the second most common cancer in women.

In this article, learn about the symptoms of stage 4 breast cancer, as well as the treatment options.

Symptoms

A person with stage 4 breast cancer may experience some symptoms specific to the breast, as well as others that affect the whole body.

Breast-related symptoms include:

a lump

pitted skin (peau d'orange, or skin that looks like orange peel)

nipple changes, such as flattening, inversion, and dimpling

redness, swelling, and warmth

Other symptoms that may appear throughout the body include:

weakness or numbness

a consistent dry cough

chest pain

loss of appetite

bloating

constant nausea

severe headaches

jaundice

vision problems

seizures and confusion

loss of balance

When breast cancer cells move to other areas of the body, they remain as breast cancer cells. For example, breast cancer that has spread to the lungs is still breast cancer, not lung cancer.

In stage 4 breast cancer, cancer spreads to different parts of the body in a process called metastasis. It may cause different symptoms depending on the affected parts of the body:

Bone metastasis

When breast cancer cells move into bone, this is called bone metastasis. It is more common for breast cancer to spread to the bones than to any other body part.

The primary symptom of bone metastasis is intermittent bone pain. At times, the pain may become persistent.

Other symptoms may include:

Sudden or sharp pain, which may indicate a fracture.

Pain in the back and neck, trouble urinating, and weakness. These symptoms can indicate a compressed spinal cord.

Fatigue, nausea, dehydration, and loss of appetite, which may indicate high levels of calcium in the blood due to bone breaking down.

Lung metastasis

Lung metastasis does not always cause symptoms, but a doctor may discover it during a CT scan, as the cells will typically form a tumor.

If symptoms do occur, they may include:

shortness of breath

wheezing

discomfort or pain in the lungs

a persistent cough

coughing up blood and mucus

Although some of the symptoms may resemble those of a common cold, lung metastasis will require treatment. Therefore, it is vital that anyone with stage 4 breast cancer makes their doctor aware of any new symptoms, even if they do not seem severe.

Brain metastasis

The risk of breast cancer spreading to the brain is generally highest in those with HER2-positive or triple-negative breast cancer, which are more aggressive subtypes of this disease.

About 10–15 percent of women with stage 4 breast cancer will develop brain metastasis.

Symptoms include:

a headache

memory problems

vision problems

seizures

slurred speech

balance problems

dizziness

stroke

If a doctor suspects that the cancer has moved into the brain, they will order an MRI to confirm the diagnosis.

Source: Medical News Today