Researches Come Up with New Approach to Targeting Cancer Cells

 | Post date: 2019/05/22 | 
Researches Come Up with New Approach to Targeting Cancer Cells

A research team has come up with a new approach to targeting cancer cells that circumvents a challenge faced by currently available cancer drugs.


 
A cancer target is often a rogue protein that signals cancer cells to proliferate uncontrollably and invade organs. Modern cancer drugs have emerged that work by striking a tight bond between the drug and a particular amino acid called cysteine, one of the 20 natural amino acids that constitute our proteins. Cysteine is unique in that it can react with specific organic functional groups to form a strong molecular bond, MedicalXpress reported.
Only a few new cancer drugs that target cysteine have been recently approved by the Food and Drug Administration, or FDA. A challenge cancer researchers face is that cysteine is rarely found within binding sites of cancer targets, limiting the application of this approach to only a few drug targets.
The UC Riverside research team has now met this challenge by exploring the development of drugs that target other potentially reactive amino acids, such as lysine, tyrosine, or histidine, which occur more often within the binding site of the target.
The researchers also addressed another challenge: The target they used for proof of concept was a protein-protein interaction, or PPI, target. PPIs represent a large class of possible therapeutic targets for which designing effective drugs is particularly difficult. This is because PPIs lack a well-defined and deep-binding pocket onto which drugs can de designed to bind tightly.
"To date, there is only one drug approved by the FDA that was designed to antagonize—or block—a PPI target," said Maurizio Pellecchia, a professor of biomedical sciences in the School of Medicine, who led the research. "Only a few others have entered clinical trials. Our approach provides novel and effective avenues to derive potent and selective PPI antagonists by designing drugs that can react with lysine, tyrosine, or histidine residues that are ubiquitously present at binding interfaces of PPIs."
Pellecchia, who holds the Daniel Hays Chair in Cancer Research at UCR, explained that academic researchers, the biotechnology industry, and pharmaceutical companies are heavily pursuing the design of "covalent drugs" that bind irreversibly with their targets. Those that target cancer cells most often target cysteine because it is more reactive than all other amino acids in a protein target. Oncology drugs such as Osimertinib, Ibrutinib, Neratinib, and Afatinib have all been approved in very recent years by the FDA, he said, and all target a cysteine that is present on the binding site of their respective targets.
"Our work widens the available target space beyond cysteine," he added. "Such covalent agents could represent significant stepping stones in the development of novel drug candidates against PPIs, which represent an untapped large class of therapeutic targets not only in oncology, but also in other conditions including neurodegenerative and inflammatory diseases."
 
 

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Researchers Working on Laser Microscope to Treat Skin Diseases

 | Post date: 2019/05/22 | 
Researchers Working on Laser Microscope to Treat Skin Diseases
University of British Columbia researchers are working on a device which aims to identify skin problems and treat them immediately.

It sounds like something out of a science fiction movie – a laser microscope capable of identifying and treating skin diseases without any uncomfortable biopsies or waiting for results.
Dr. Harvey Lui, a UBC researcher, says it is possible.
“It’s actually giving us a whole new way of examining and treating tissue that may be abnormal,” he says.
“Less invasive and hopefully more efficient, and hopefully highly precise and highly accurate. That’s what we’re aiming for. This was a theory at first for us, but we’ve now proven that the theory is possible to implement this.”
He’s hopeful it will reduce the number of biopsies.
“The whole point is to minimize or decrease the need for biopsies and also to combine a diagnostic procedure looking at the tissue, with the treatment itself.”
Now these researchers hope to move ahead with clinical studies.
 
 

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Lack of Sleep Makes Brain to Literally Eat Itself

 | Post date: 2019/03/10 | 
Lack of Sleep Makes Brain to Literally Eat Itself

Researchers have found that persistently poor sleep causes the brain to clear a significant amount of neurons and synaptic connections, and recovering sleep might not be able to reverse the damage.


 
A team led by neuroscientist Michele Bellesi from the Marche Polytechnic University in Italy examined the mammalian brain's response to poor sleeping habits, and found a bizarre similarity between the well-rested and sleepless mice.
Like the cells elsewhere in your body, the neurons in your brain are being constantly refreshed by two different types of glial cell - support cells that are often called the glue of the nervous system, Science Alert reported.
The microglial cells are responsible for clearing out old and worn out cells via a process called phagocytosis - meaning "to devour" in Greek.
The astrocytes' job is to prune unnecessary synapses (connections) in the brain to refresh and reshape its wiring.
We've known that this process occurs when we sleep to clear away the neurological wear and tear of the day, but now it appears that the same thing happens when we start to lose sleep.
But rather than being a good thing, the brain goes overboard with the clearing, and starts to harm itself instead.
Think of it like the garbage being cleared out while you're asleep, versus someone coming into your house after several sleepless nights and indiscriminately tossing out your television, fridge, and family dog.
"We show for the first time that portions of synapses are literally eaten by astrocytes because of sleep loss," Bellesi told Andy Coghlan at New Scientist.
To figure this out, the researchers imaged the brains of four groups of mice:
one group was left to sleep for 6 to 8 hours (well-rested)
another was periodically woken up from sleep (spontaneously awake)
a third group was kept awake for an extra 8 hours (sleep-deprived)
And a final group was kept awake for five days straight (chronically sleep-deprived).
When the researchers compared the activity of the astrocytes across the four groups, they identified it in 5.7 percent of the synapses in the well-rested mouse brains, and 7.3 of the spontaneously awake mouse brains.
In the sleep-deprived and chronically sleep-deprived mice, they noticed something different: the astrocytes had increased their activity to actually eating parts of the synapses like microglial cells eat waste - a process known as astrocytic phagocytosis.
In the sleep-deprived mouse brains, the astrocytes were found to be active across 8.4 percent of the synapses, and in the chronically sleep-deprived mice, a whopping 13.5 percent of their synapses showed astrocyte activity.
As Bellesi told New Scientist, most of the synapses that were getting eaten in the two groups of sleep-deprived mice were the largest ones, which tend to be the oldest and most heavily used - "like old pieces of furniture" - which is probably a good thing.
But when the team checked the activity of the microglial cells across the four groups, they found that it had also ramped up in the chronically sleep-deprived group.
And that's a worry, because unbridled microglial activity has been linked to brain diseases like Alzheimer's and other forms of neurodegeneration.
"We find that astrocytic phagocytosis, mainly of presynaptic elements in large synapses, occurs after both acute and chronic sleep loss, but not after spontaneous wake, suggesting that it may promote the housekeeping and recycling of worn components of heavily used, strong synapses," the researchers report.
"By contrast, only chronic sleep loss activates microglia cells and promotes their phagocytic activity ... suggesting that extended sleep disruption may prime microglia and perhaps predispose the brain to other forms of insult."
Many questions remain, such as if this process is replicated in human brains, and if catching up on sleep can reverse the damage.
But the fact that Alzheimer's deaths have increased by an incredible 50 percent since 1999, together with the struggle that many of us have in getting a good night's sleep, means this is something we need to get to the bottom of - and fast.
 
 

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Fasting-Like Diets May Reverse Gut Inflammation: Study

 | Post date: 2019/03/10 | 

Fasting-Like Diets May Reverse Gut Inflammation: Study

A new study has found that consuming a ‘fasting-mimicking’ diet may help alleviate the symptoms and reverse the damage of inflammatory bowel disease (IBD).



Inflammatory bowel disease is an illness that covers conditions that include Crohn’s disease and ulcerative colitis. This condition can greatly reduce the patient’s quality of life, but new research out of the University of Southern California has found that a low-calorie diet may help reverse the condition.
According to the study, mice put on a fasting-mimicking diet experienced a reduction in intestinal inflammation, as well as an increase in intestinal stem cells. In a group of mice that consumed the fasting-mimicking diet for four days before resuming a normal diet (repeating this process through two cycles), researchers noted that some IBD symptoms and issues were reversed and others were mitigated, Slash Gear reported.
The diet itself appears to have played a vital role in this process, as mice that were subjected to a water-only fast didn’t experience the same degree of benefits. According to the study, this could mean that some nutrients from the mimicking diet had a part in improving inflammation. Undergoing multiple cycles of the fasting-mimicking diet resulted in increased rates of stem cell activation and colon regeneration.
What exactly is a fasting-mimicking diet? These are meal plans that involve low-calorie, low-protein, plant-based foods. Study author Valter Longo explained:
We’ve determined that the dietary components are contributing to the beneficial effects … It is really remarkable, that in the past 100 years of research into calorie restriction, no one recognized the importance of the re-feeding. Restriction is like a demolition where you take the building down. But you have to rebuild it. If you don’t do that, there’s no benefit. You are left with an empty lot, and what have you achieved?
The latest study combined with past research indicates that a fasting-mimicking diet may have similar beneficial health effects for humans suffering from IBD (or who simply eat low-quality diets and want to mitigate some of the damage). However, a randomized clinical trial will be the next step in determining whether this diet is effective and safe as a treatment option in humans.
 

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New Drug Designed to Treat Multiple Kinds of Flu

 | Post date: 2019/03/10 | 
New Drug Designed to Treat Multiple Kinds of Flu

A pill to fight the flu could be closer than expected as scientists reveal they are developing a drug which mimics the immune system.



The medication may be a promising shot at a cure because it can work against various strains of the virus and is cheap to make, experts say, New Scientist reported.
A pharmaceutical company has developed a conventional drug that mimics the effect of antibodies that are effective against a wide range of flu viruses. Conventional drugs are cheaper and easier to make and store than antibodies, and can be taken in pill form.
Mice that were give 25 times the normal lethal dose of one flu virus survived after taking the drug, which is known only as JNJ4796. It was also effective in tests on human cells grown in a dish.
The hope is that this antibody-mimicking strategy could lead to new treatments for many viral diseases, not just flu.
When we are infected by a virus, our immune system defends us by producing antibodies, which are proteins that bind to the virus and prevent them from infecting cells. But it takes days for our bodies to ramp up production, by which time people can become seriously ill.
Broadly neutralizing
Injecting antibodies can help treat viral infections, but there are several problems. First, antibodies are large proteins that are expensive to make and have to be injected directly into the blood.
Second, flu antibodies are usually specific to a single strain. So an antibody treatment for the flu that makes people ill one year will be useless the next year.
But biologists recently discovered antibodies that work against a wide variety of flu viruses because they bind to regions of the virus that seldom change. Several companies are now developing treatments that consist of these “broadly neutralizing” antibodies, some of which are already being tested in people seriously ill with flu.
They engineered JNJ4796 to bind to the same target site as one broadly neutralizing antibody. But because it is a small molecule rather than a protein, it can be taken in pill form, assuming it proves safe and effective in humans.
 
 

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