Scientists identify unique pathway for treating deadly brain cancer in kids

Researchers have discovered a new pathway that can attack and improve survival rate in an incurable type of brain cancer among children.

The study suggested that the pathway disrupts the cellular process that contributes to Diffuse Intrinsic Pontine Gliomas (DIPG).

DIPG is a highly aggressive and inoperable type of tumour that grows in the brain stem and usually strikes children less than 10 years old. Most patients do not survive more than a year after diagnosis.

Earlier studies identified a genetic mutation called PPM1D- which is critical for cell growth and cell stress response-- as a contributor to DIPG. Previous efforts to directly attack the PPM1D mutation, however, proved futile in controlling DIPG.

This study has discovered a vulnerability in the metabolic process for creating NAD,, a metabolite that is necessary for all cell life.

This is really an amazing new way to attack this cancer. We found that the mutated gene PPM1D essentially sets the stage for its own demise, said one the study authors.

Researchers found that mutated PPM1D silences a gene called NAPRT, which is key to the production of the NAD metabolite. With NAPRT unavailable, the cell switches to another protein needed to create NAD called NAMPT. By using a drug that inhibits the production of NAMPT, researchers found they could essentially starve to death those cancer cells with the PPM1D mutation.

Researchers had long thought DIPG was a childhood version of adult brain tumours, and so similar treatments for adult gliomas were tested extensively in children and failed. 

The researchers chose to look at the tumour in terms of its potential vulnerabilities, and  thus began a year-ling molecular journey to understand what role the PPM1D mutation played in altering cancer metabolism.

When epigenetic silencing results were analysed, we were gratified to discover that DIPG cells with the PPM1D mutation had created a vulnerability to a key enzyme for which small molecule inhibitors were already available, said one the study's contributing authors.

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Targeting protein may stop ovarian cancer cells from spreading

Preventing a protein from performing its job may keep a certain type of ovarian cancer cell from growing and dividing uncontrollably in the lab, says researcher.

In a study, the researchers identified the protein as a potential therapeutic target for high-grade serous ovarian cancer cells.

Approximately 70 % of patients with this type of ovarian cancer relapse with the chemo-resistant disease, increasing the need for new approaches to treatment.

Another researcher has identifies a potential method to put high-grade serous ovarian cancer cells in a " sleep state" called senescence.

One of the biggest problems of cancer cells is they can grow forever without stimulus. By inducing senescence, the cells can no longer divide and grow, she said.

Cells break down and build up the chemicals needed for supporting life through various cycles and pathways in a process known as metabolism.

A hall mark of cancer cells is that their metabolic processes are often different from normal, healthy cells, said lead author of the paper.

The metabolites in each line of cells were quantified using spectometry. After comparing differences in their metabolic processes, the lab found that the cancerous cells prefer to use sugars in the citric acid cycle, instead of making lactate, the more common route.

Many therapies target glycolysis, but that may not be the best approach, she said. She noted that often when targeting glycolysis, there could be toxic damage to normal and healthy tissues.

The government has already approved a drug that targets the mutant form of the protein. One of the drugs that target the mutant form can also target the wild-type form. One of our long-term goals is to try and re-purpose this already -approved drug as a treatment for this form of ovarian cancer, she said.

The research team has found that inhibiting the wild-type form of the protein may be an effective strategy for future therapies for all stages of high-grade serous ovarian cancer. When these cells spread to other parts of the body, they adopt a form that is different from the original cancer cells.

It is important that therapies are effective at later stages, as this is when ovarian cancer patients are typically diagnosed, she said.

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The Benefits, Uses and Side Effects of CBD Oil

As more states legalize the use of marijuana, a product known as CBD oil has increased in popularity. There is a chemical compound found in the cannabis plant, CBD, or cannabidiol. This is non-intoxicating and does not cause the noticeable euphoric effects associated with tetrahydrocannabinol, also known as THC, another marijuana compound. Bear in mind that products marketed as CBD oil may contain THC.  

 

It is believed that CBD might affect your health by attaching to receptors in the body's endocannabinoid system - a complex biological system that is involved in maintaining certain aspects of your health. Emerging research illustrates that endocannabinoids may play a role in regulating such functions as memory, sleep and mood, and also metabolic processes like energy balance. 

When you purchase CBD oil, what you are getting is a carrier oil which contains CBD and other active compounds. CBD oil comes in many forms, including soft gel capsules, tinctures, and under-the-tongue sprays. There are some forms of CBD oil which can be directly applied to the skin. They come in the form of products like creams and salves. The concentration of CBD varies from product to product. 

 

Uses

It has been claimed that CBD oil can treat a wide variety of health issues that range from everyday ailments to chronic medical conditions. These issues include: 

• Acne
• Anxiety
• Chronic pain
• Depression
• Epilepsy
• Glaucoma
• Insomnia
• Loss of appetite and body weight
• Muscle spasms
• Parkinson's disease

CBD oil has also been said to promote sounder sleep. It can reduce inflammation and pain, fight oxidative stress, improve heart health, support weight loss and protect against some forms of cancer. 
The benefits
CBD oil is used for various health-related purposes, but there isn't a great deal of research on the oil's potential health benefits. But, there is significant support for its effectiveness in the treatment of some forms of epilepsy. In fact, the FDA approved a drug used for epilepsy, Epidiolex, a drug made with a purified form of CBD oil, in June 2018. This drug is used for the treatment of seizures associated with two rare and severe forms of epilepsy in patients two years of age and older. It is the first-FDA-approved drug that contains a purified drug substance derived from marijuana. 

In addition, CBD has also shown promise in the treatment of anxiety disorders, according to a report published in the journal Neurotherapeutics in 2015. When looking at results from experimental research, clinical trials and epidemiological studies, the authors discovered evidence that CBD may help treat generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. However, the authors caution that human-based research on CBD and anxiety is rather limited at this point. 


Furthermore, a small study published in the journal JCI Insight in 2017, discovered that CBD may help prevent stress-related changes in blood pressure, affecting heart health. The study examined nine healthy male volunteers who took a single dose of either CBD or a placebo. In comparison to those given the placebo, those treated with CBD had lower blood pressure before and after experiencing a stressful event. 

CBD oil has also been found to offer some form of benefit to those who suffer from an addiction. This was stated in a review published in the Journal of Substance Abuse in 2015. In their analysis of 14 previously published studies, scientists determined that CBD may offer therapeutic effects in people with opioid, cocaine, and/or psychostimulant addiction. They also discovered that CBD may be beneficial in the treatment of cannabis and tobacco addiction. There is some evidence that CBD may block or reduce the effects of THC on the mind. 

Some side effects
There is some research which indicates that the use of CBD oil, may trigger a number of side effects, some of which include: 

• Anxiety
• Changes in appetite
• Changes in mood
• Diarrhea
• Dizziness
• Drowsiness
• Dry mouth
• Nausea
• Vomiting

Some concern has also indicated that the use of CBD oil may lead to increased levels of liver enzymes - a marker of liver damage or inflammation. 

Safety concerns
It is important that you are aware that CBD oil may interact with several medications, including some types of anti-epileptic drugs. A report from the AAP, American Academy of Pediatrics published in the journal Pediatrics cautions pregnant women and nursing mothers, recommending they avoid marijuana use due to possible adverse developmental effects to their baby. In one study, it was found that children with refractory epilepsy treated with CBD experienced an aggravation of seizures, sleepiness, digestive disturbances, and irritability. 

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Breath test to detect multiple cancers early begins large trial

Several illnesses are known to create signature smells from the body, including typhoid fever reported to smell like baked bread and the aroma of acetone, said to be similar to rotten apples, on the breath of diabetics. Recent research has also shown that a person's breath could also indicate the presence of cancer. 

 

To test this theory, researchers have launched a two-year trial into a clinical device, called the Breath Biopsy, to find out if exhaled airborne molecules can be useful for cancer detection. 

 

In the body's normal metabolic processes, molecules called volatile organic compounds (VOCs) are produced. It's thought that cancer can create a different pattern of VOCs, which researchers hope to identify using the device. "Our goal is, can we spot these subtle differences?,"a researcher said.

 

The trial, which is being run by the Cancer specialists, is recruiting up to 1,500 participants, including healthy people to act as a control group. 

 

Patients with stomach and esophageal cancers will initially be asked to try the test, before expanding to patients with prostate, kidney, bladder, liver and pancreatic cancers.

 

Participants will be asked to breathe into the device for 10 minutes to provide a sample, which will be analyzed by researchers.

The idea is to identify if cancer signals are similar or different and how early any signals could be picked up. If some people go on to develop cancer, their samples will be compared to those who don't develop the disease.

Late diagnosis

"We urgently need to develop new tools, like this breath test, which could help to detect and diagnose cancer earlier, giving patients the best chance of surviving their disease,"  the trial investigator said in a statement. 

 

Almost half of cancers are diagnosed at a late stage in England, according to researchers. Some of the reasons are due to patients' fears of invasive tests, a lack of knowledge of cancer signs and symptoms, and the lack of early detection tests for certain cancers. 

 

Early detection can be a matter of life and death added the Prof., who added that around 85% of people with lung cancer are diagnosed at a late stage, "and they will die in one or two years [because] by the time doctors diagnose it, it is too late." 

 

There are more than 360,000 new cancer cases in the UK every year, according to Cancer experts. Globally, an estimated 18.1 million new cases of cancer were reported in 2018, according to the World Health Organization.

The need for trials

In 2017, researchers told that they had developed a device which -- using nanorays to analyze breath -- can identify Parkinson's disease, various cancers, kidney failure, multiple sclerosis and Crohn's disease with 86% accuracy.

 

But the experimental technology analyzing breath had a number of issues it had to address: including the problem of storing breath that is not immediately analyzed. 

 

The Prof. agreed that it is hard to "capture, store, and transport" breath, but added that the Breath Biopsy device has been developed to solve those issues. He said the device captures chemicals using a cartridge, which "acts like a sponge," and it is then transported to a lab where it is analyzed. 

 

If the trial turns into a success, the researchers hope the breath biopsies will be used in doctors' practices to figure out whether patients should be referred for further diagnostic tests. 

 

"Through this clinical trial we hope to find signatures in breath needed to detect cancers earlier -- it's the crucial next step in developing this technology," the researcher said.

 

Today's widespread interest in breath analysis stems from the relatively recent discovery -- within the past 20 years or so -- that nitric oxide, a common pollutant, works as a signaling molecule in the cardiovascular system, a professor told. The three scientists who made the discovery won a Nobel Prize for their efforts in 1998.

 

The theory behind the technology is that each of us has a unique chemical "fingerprint." Each disease also has a particular chemical signature, which can be detected on our breath.

 

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Secrets of longevity protein revealed

Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent study, researchers revealed the three-dimensional structure of one of these proteins, beta-Klotho, illuminating its intricate mechanism and therapeutic potential.

The study findings, could have implications for therapies developed to treat a wide range of medical conditions, including diabetes, obesity, and certain cancers, the researchers said.

The Klotho family of two receptor proteins are located on the surface of cells of specific tissues. The proteins bind to a family of hormones, designated endocrine FGFs, that regulate critical metabolic processes in the liver, kidneys, and brain, among other organs. To understand how beta-Klotho works, the research team used X-ray crystallography, a technique that provides high-resolution, three-dimensional views of these proteins.

The researchers’ analysis yielded several insights. First, beta-Klotho is the primary receptor that binds to FGF21, a key hormone produced upon starvation. When bound to beta-Klotho, FGF21 stimulates insulin sensitivity and glucose metabolism, causing weight loss. This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as type 2 diabetes in obese patients, the researchers said.

“Like insulin, FGF21 stimulates metabolism including glucose uptake,” said a senior author. “In animals and in some clinical trials of FGF21, it shows that you can increase burning of calories without changing food intake, and we now understand how to improve the biological activity of FGF21.” The authors also describe a new variant of FGF21 that has 10 times higher potency and cellular activity.

Additionally, the research team presented evidence of how a structurally-related enzyme, glycosidase, which breaks down sugars, evolved into a receptor for a hormone that lowers blood sugar—which may not be a coincidence, the researcher added.

Having untangled the structure of beta-Klotho, the researchers have a platform for exploring potential therapies for multiple diseases. By developing drugs that enhance the pathway, he said, researchers can target diabetes and obesity. Conversely, using agents that block the pathway, they hope to explore therapies for conditions such as liver cancer and bone diseases, among others.

“The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward,” the researcher said.

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New anti-ageing protein may combat obesity, cancers

Scientists have revealed the three-dimensional (3D) structure of an anti-ageing protein, that may not only increase human lifespan but also help develop therapies for age-related diseases such as diabetes, obesity and cancers.

 The Klotho proteins -- alpha and beta -- named after the Greek goddess Clotho, who spun the thread of life, play an important role in the regulation of longevity and metabolism. 

 Both work in tandem with molecules called endocrine FGFs, which regulate metabolic processes in tissues and organs including the brain, liver and kidneys, among other organs. 

In the study,  the team found that beta-Klotho is the primary receptor that binds to FGF21 -- a key hormone produced upon starvation. 

FGF21 has the potential for boosting insulin sensitivity and glucose metabolism, causing weight loss.
This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as Type 2 diabetes in obese patients, the researchers said, in a paper published . 

"Like insulin, FGF21 stimulates metabolism including glucose uptake. In animals and in some clinical trials of FGF21, it shows that you can increase burning of calories without changing food intake, and we now understand how to improve the biological activity of FGF21," said a researcher.
A new variant of FGF21 with 10 times higher potency and cellular activity was also unveiled.

By developing drugs that enhance the pathway, the researcher said, researchers can target diabetes and obesity.

Conversely, using agents that block the pathway, they also hope to explore therapies for conditions such as liver cancer and bone diseases, among others.

"The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward," the researcher said.

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