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Pike River widow ‘on the up’ after stem cell treatment for cancer – Stuff.co.nz

December 25th, 2019 8:44 am

Pike River widow Anna Osborne is "on the up" and out of hospital in time for Christmas.

Osborne, whose husband Milton died in the 2010 Pike River mine disaster, had stem-cell treatment for Hodgkinlymphoma in October.

She had been told she only had a month to a year to live without it.

Phil Walter/Getty

Anna Osborne, from the Pike River Family Reference Group, embraces Prime Minister Jacinda Ardern at the mine entrance earlier this year.

Friend and Pike River mother SonyaRockhouse said Osborne's treatment went well, but there was still a long road ahead.

READ MORE:*Pike River mine tunnel entry an important moment for widow*Pike River re-entry team breaks through into mine drift*Pike River widow 'full of nerves' for mine drift re-entry*The road to getting back into Pike River

"I think the treatment is working for now. She just got her bloods done and they were good and they are the most important thing," she said.

Kevin Stent/Stuff

Osborne and Sonya Rockhouse at the announcement the Government would re-enter the Pike River mine.

Osbornewasdiagnosed with Hodgkinlymphoma in 2002 when she was 36.

She had radiation for six weeks and went into remission, but the cancercame back just before the Pike River tragedy in November 2010, when 29 men where killed in a series of explosions at the coal mine. Osborne helped campaign for thelegalisation of medicinal cannabiswhile undergoing chemotherapy in 2015.

Her stem-cells wereharvested and frozenin August. The stem cell transplanttook place in Christchurch in October aftersix days of intensive chemotherapy.

JOANNE CARROLL/Stuff

Anna Osborne, pictured during treatment for Hodgkins lymphoma in 2016.

The treatment had its own risks.

Osborne was in isolation for five weeks but after shereturned home, she hadsome set backs and small complications,Rockhousesaid.

"She was so crook. She lost a lot of weight. She's had two or three trips to hospital since then," she said.

Supplied/Pike River Recovery Agency

Mine worker Bryan Heslip offers a hand to Osborne and Rockhouse after entering the Pike River mine drift during the re-entry operation.

"She's on the up now,but [there is] still a long way to go. She's at home and is getting some colour back in her cheeks, [and is] starting to look like her old self."

Rockhouse said Osborne was focusing on her recovery and hoped to be able to go to the Pike River mine for the next milestone, which was removing the 170m seal expected to take place in January.

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This Is How Human Head Transplants Could Be Achieved, According To A Neurosurgeon – Sky Statement

December 25th, 2019 8:44 am

The idea of transplanting a human head onto another persons body may sound like the stuff of science fiction and thats because it is. But while penning a fictional story about the worlds first cranial exchange, neuroscientist Bruce Mathew came up with an idea that he says could soon become a real-life procedure.

Speaking to The Telegraph, Mathew who was previously the clinical lead for neurosurgery at Hull University Teaching Hospitals NHS Trust explained that a head could be grafted onto another body if the entire spinal cord is transplanted along with it.

Initially our intention was to just brainstorm an idea and it seemed rather silly, but then I realized, it actually isnt. If you transplant the brain and keep the brain and spinal cord together its actually not impossible, he said.

The spinal cord is the most profound thing imaginable. You need to keep the brain connected to the spinal cord. The idea that you cut the spinal cord is utterly ridiculous.

Obviously this is not an easy thing to do, and while recent advances have opened up the possibility of reattaching individual severed nerves, the prospect of connecting an entire spinal column is still some way out of reach.

Yet with surgical technologies improving at a rapid rate, Mathew says it is not entirely unrealistic to think that it will probably happen in the next 10 years.

At the moment, you can connect one or two nerves, but with robotics and artificial intelligence well soon be able to do 200 nerves, he explained.

Of course, there are likely to be many complications with such a procedure, as the recipients body will probably reject such a large amount of donor material. While Mathew hasnt figured out all the solutions in detail, he says that transferring gut bacteria along with the head and spinal cord, and stem cell transplants, may help to ensure that the transplant is accepted.

At present, Mathew has no plans to take his idea any further than the pages of his science fiction novel, although Italian neurosurgeon Sergio Canavero has spent the last few years actively attempting to achieve a human head transplant.

In 2017 he announced that he had successfully transplanted the head of one human corpse onto another, and previously claimed to have grafted a donor head onto a monkey although the animal never regained consciousness and would probably have been paralyzed if it had, as the spinal cord remained unattached.

Despite this, Canavero apparently has a willing human donor, and of course, there are thousands of people (and sometimes just heads) across the world cryonically frozenin the hope medicine and technology of the future will be able to revive them. Perhaps it will happen one day, but were not quite there yet.

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Fatty Meal Interrupts Gut’s Communication With The Body, But Why? – Duke Today

December 24th, 2019 7:50 am

DURHAM, N.C. -- A high-fat meal can silence communication between the intestine and the rest of the body, according to a new Duke University study in zebrafish.

While using the fish to examine cells that normally tell the brain and the rest of the body whats going on inside the gut after a meal, a team of Duke researchers discovered that a high-fat meal completely shuts down that communication for a few hours.

The cells they were looking at are the enteroendocrine cells, which occur sparsely throughout the lining of the gut, but play a key role in signaling the body about the all-important alimentary canal. In addition to releasing hormones, the cells also have a recently-discovered direct connection to the nervous system and the brain.

These cells produce at least 15 different hormones to send signals to the rest of the body about gut movement, feelings of fullness, digestion, nutrient absorption, insulin sensitivity and energy storage.

But they fall asleep on the job for a few hours after a high-fat meal, and we dont yet know if thats good or bad, said John Rawls, an associate professor of molecular genetics and microbiology in the Duke School of Medicine.

Since enteroendocrine cells are key players in digestion, the feeling of being full and subsequent feeding behavior, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more.

This is a previously unappreciated part of the postprandial (after-meal) cycle, Rawls said. If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signaling, which could in turn contribute to the development of insulin resistance and Type 2 diabetes.

To understand the silencing better, the researchers tried to break the process down step by step in zebrafish.

After they first sense a meal, the enteroendocrine cells trigger a calcium burst within seconds, initiating the signaling process. But after that initial signal theres a delayed effect later in the after-meal period. Its during this later response that the silencing occurs, said Rawls, who also directs Dukes Microbiome Center.

The silenced cells change shape and experience stress in their endoplasmic reticulum, a structure that assembles new proteins. It seems that these enteroendocrine cells, which are specialized to synthesize and secrete proteins like hormones and neurotransmitters, become overstimulated and exhausted for a while.

The team tried the high-fat diet on a line of germ-free zebrafish raised in the absence of any microbes, and found they didnt experience the same silencing effect. So they began looking for gut microbes that might be involved in the process.

After screening through all the kinds of bacteria found in the gut, they saw that the silencing appeared to be the work of a single type of gut bacteria, called Acinetobacter. These bugs are normally less than 0.1 percent of the total gut microbiome, but they increased 100-fold after a high-fat meal and were the only bacteria able to induce the silencing effect.

Next we want to understand how Acinetobacter evokes this interesting response, said Lihua Ye, a postdoctoral fellow and lead author on this paper. We also suspect other bacteria might also have this capability.

Rawls said they arent sure why silencing occurs, nor whether it has any positive effect on the fish. It might be a way to prevent excessive signaling about the fat, but by being silenced completely like this, the cells wont be communicating anything else either.

We dont understand yet what the long-term impact of enteroendocrine silencing would be on metabolic health, Rawls said. This may be a maladaptive response to high-fat feeding that impairs the normal regulatory functions of these cells, leading to metabolic disorders like insulin resistance. But its also possible that the silencing is a beneficial adaptation to protect the animal from over-stimulation of the gut cells.

The study appeared as an accepted manuscript at the open-access journal eLife on Dec. 3. This research was funded by the National Institute of Diabetes and Digestive and Kidney Disease (R01-DK093399, R01 DK109368, R01-DK081426) and the Pew Charitable Trusts.

CITATION: High-Fat Diet Induces Microbiota-Dependent Silencing of Enteroendocrine Cells, Lihua Ye, Olaf Mueller, Jennifer Bagwell, Michel Bagnat, Rodger Liddle, John Rawls. eLife, Dec. 3, 2019. DOI: 10.7554/eLife.48479

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Scientists’ articles have been published in top journals – Mirage News

December 24th, 2019 7:50 am

The Department of Sports and Health Tourism, Sports Physiology, and Medicine of the Faculty of Physical Education has had its anniversary celebration 10 years from its founding. The staff of the department made a good gift for the anniversary: they published three articles in Q1 journals in the areas of medicine, biochemistry, genetics, and molecular biology.

2019 was a very busy year for the department: the team carried out two projects with the support of the Russian Science Foundation. The first is devoted to the study of myokines special proteins that are produced by muscles during physical exercise (the project manager is Professor Leonid Kapilevich, head of the department). In the second project, the effect of physical exertion on the compensation of type 2 diabetes mellitus was studied (the project manager is Professor Alexander Chibalin, a staff member of TSU and Karolinska Institute, Sweden). This resulted in 15 scientific articles in journals included in the international databases Web of Science and Scopus, including three articles in journals from the first quartile.

The article Transcriptomic Changes Triggered by Ouabain in Rat Cerebellum Granule Cells: Role of 3- And 1-Na +, K + -ATPase-mediated Signaling was published in PLoS ONE (the USA journal, impact factor 6.26, 27th of 2,836 journals in the category Medicine Myology). In this work, the role of monovalent ions (sodium and potassium) as regulators of intracellular processes was studied.

This is a fundamentally new approach, explains Leonid Kapilevich. Traditionally, calcium is considered the main ion that is the regulator of cellular metabolism, especially in muscles. However, the team showed that it is the ratio of sodium and potassium in the cell that is able to regulate the process of gene transcription, moreover, regardless of calcium.

The article Elevation of Intracellular Na + Contributes to Expression of Early Response Genes Triggered by Endothelial Cell Shrinkage was published in the journal Cellular Physiology and Biochemistry (published in Sweden, impact factor 5.11, 51stof 2,124 journals in Biochemistry, Genetics and Molecular Biology ). This article continues the research whose results are described in the previous article. Here, an attempt is made to understand how sodium ions affect the metabolic processes in the cell. It was found that one of the most likely ways is by changing the osmotic pressure of the cytoplasm and, as a consequence, the volume of the cell and its components.

The article Low AS160 and High SGK Basal Phosphorylation Associates with Impaired Incretin Profile and Type 2 Diabetes in Adipose Tissue of Obese Patients was published in the journal Diabetes Research and Clinical Practice (published in the Netherlands, impact factor 3.26, 26th of 133 journals in Internal Medicine). The study examined molecular changes in adipose tissue in patients with diabetes, which contribute to impaired glucose metabolism and can serve as a target for the therapeutic effect of exercise.

The tenth anniversary against the background of the centennials of other departments and faculties looks, of course, modest, but even for this short period the department has something to be proud of, says Leonid Kapilevich. During this time, two doctoral and nine masters theses were defended at the department, 15 student manuals were published, 115 articles were published in journals included in international databases, five monographs, and two grants from the Russian Science Foundation were won.

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How to live longer: Adding this drink to your diet could increase your life expectancy – Express

December 24th, 2019 7:49 am

Life longevity may seem beyond ones control, but many healthy habits may lead a person to reaching a ripe, old age. These include drinking coffee or tea, exercising, getting enough sleep and limiting alcohol intake. Taken together, these habits can boost a persons health and put them on the path to a long life. There is another healthy habit one should try and incorporate into their diet which is backed by science and promoted by health advocates. What is it?

Apple cider vinegar is the most popular type of vinegar in the natural health community.

It is claimed to lead to all sorts of benefits, many of which are supported by science.

Some of the benefits of apple cider vinegar include aiding in weight loss, reducing cholesterol, lowering blood sugar levels and improving symptoms of diabetes.

Adding apple cider vinegar into your diet could also help boost life longevity.

READ MORE: How to live longer: Best diet to increase life expectancy - foods to eat and avoid

Apple cider vinegar is made in a two-stop process, related to how alcohol is made. First the apples are crushed to yeast, which ferment the sugars and turns them into alcohol.

Secondly, bacteria is added to the alcohol solution, which further ferment the alcohol and turn it into acetic acid, the main active compound in vinegar.

Organic, unfiltered apple cider vinegar also contains mother which are strands of proteins, enzymes and friendly bacteria that give the produce its murky appearance.

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Some people believe that the mother is responsible for most of the health benefits, although there are currently no studies to support this.

Apple cider vinegar only contains about three calories per tablespoon, which is very low.

There are not many vitamins or minerals in it, but it does contain a small amount of potassium.

How can apple cider vinegar help to increase life expectancy?

Several risk factors of heart disease can be improved by apple vinegar consumption.

In a study with the US National Library of Medicine National Institutes of Health, the dietary acetic acid in apple cider vinegar was analysed on animals.

The study found that consuming apple cider vinegar could help to lower cholesterol and triglyceride levels, along with several other heart disease risk factors.

Some health experts believe that apple cider vinegar contains anti-cancer effects. In another study, the effects of apple cider vinegar on cancer cells was analysed.

The study concluded that the vinegar can kill cancer cells and shrunk tumours. However, all of the studies were done in isolated class in test tubes, or rats, which proves nothing about what happens in a living, breathing human.

Apple cider vinegar is not a miracle or a cure-all product, however, the vinegar does clearly have some important health benefits and could aid in living a longer and healthier life.

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Human Genome Recovered From 5700-Year-Old Chewing Gum – Smithsonian.com

December 24th, 2019 7:49 am

Modern chewing gums, which often contain polyethylene plastic, could stick around for tens or even hundreds of years, and perhaps much longer in the right conditions. Some of the first chewing gums, made of birch tar and other natural substances, have been preserved for thousands of years, including a 5,700-year-old piece of Stone Age gum unearthed in Denmark.

For archaeologists, the sticky stuffs longevity can help piece together the lives of ancient peoples who masticated on the chewy tar. The ancient birch gum in Scandinavia preserved enough DNA to reconstruct the full human genome of its ancient chewer, identify the microbes that lived in her mouth, and even reveal the menu of a prehistoric meal.

These birch pitch chewing gums are kind of special in terms of how well the DNA is preserved. It surprised us, says co-author Hannes Schroeder, a molecular anthropologist at the University of Copenhagen, Denmark. Its as well-preserved as some of the best petrous [skull] bones that weve analyzed, and they are kind of the holy grail when it comes to ancient DNA preservation.

Birch pitch, made by heating the trees bark, was commonly used across Scandinavia as a prehistoric glue for attaching stone tools to handles. When found, it commonly contains toothmarks. Scientists suspect several reasons why people would have chewed it: to make it malleable once again after it cooled, to ease toothaches because its mildly antiseptic, to clean teeth, to ease hunger pains, or simply because they enjoyed it.

The gums water-resistant properties helped to preserve the DNA within, as did its mild antiseptic properties which helped to prevent microbial decay. But the find was also made possible by the conditions at the site, named Syltholm, on an island in southern Denmark, where thick mud has perfectly preserved a wide range of unique Stone Age artifacts. Excavations began at the site in 2012 in preparation for the construction of a tunnel, affording the Museum Lolland-Falster a unique chance for archaeological field work.

No human remains have yet been found at Syltholmunless you count the tiny strands of DNA preserved in the ancient gum Schroeder and colleagues described today in Nature Communications.

The discarded gum yielded a surprising amount of information about its 5,700-year-old chewer. She was a female, and while her age is unknown, she may have been a child considering similar birch pitch gums of the era often feature the imprints of childrens teeth.

From the DNA, researchers can start to piece together some of the ancient womans physical traits and make some inferences about the world she lived in. We determined that she had this striking combination of dark skin, dark hair, and blue eyes, Schroeder says. Its interesting because its the same combination of physical traits that apparently was very common in Mesolithic Europe. So all these other ancient [European] genomes that we know about, like La Braa in Spain, they all have this combination of physical traits that of course today in Europe is not so common. Indigenous Europeans have lighter skin color now but that was apparently not the case 5,000 to 10,000 years ago.

The gum-chewers family ties may also help to map the movement of peoples as they settled Scandinavia.

The fact that she was more closely related genetically to people from Belgium and Spain than to people from Sweden, which is just a few hundred kilometers farther north, tells us something about how southern Scandinavia was first populated, Schroeder says. And it looks like it was from the continent. This interpretation would support studies suggesting that two different waves of people colonized Scandinavia after the ice sheets retreated 12,000 to 11,000 years ago, via a southern route and a northeastern route along todays Norwegian coast.

The individual was part of a world that was constantly changing as groups migrated across the northern regions of Europe. We may expect this process, especially at this late stage of the Mesolithic, to have been complex with different groups, from south, west or even east, moving at different times and sometimes intermingling while perhaps other times staying isolated, Jan Stor, an osteoarchaeologist at Stockholm University, says via email.

Additional archaeological work has shown that the era was one of transition. Flaked stone tools and T-shaped antler axes gave way to polished flint artifacts, pottery and domesticated plants and animals. Whether the regions turn to farming was a lifestyle change among local hunter-gatherers, or spurred by the arrival of farming migrants, remains a matter of debate.

This is supposed to be a time when farming has already arrived, with changing lifestyles, but we find no trace of farmer ancestry in her genome, which is fairly easy to establish because it originated in the Near East. So even as late as 5,700 years ago, when other parts of Europe like Germany already had farming populations with this other type of ancestry present, she still looked like essentially western hunter-gatherers, like people looked in the thousands of years before then, Schroeder says.

The lack of Neolithic farmer gene flow, at this date, is very interesting, adds Stor, who wasnt involved in the research. The farming groups would probably have been present in the area, and they would have interacted with the hunter-gatherer groups.

The eras poor oral hygiene has helped add even more evidence to this line of investigation, as genetic bits of foodstuffs were also identifiable in the gum.

Presumably not long before discarding the gum, the woman feasted on hazel nuts and duck, which left their own DNA sequences behind. The dietary evidence, the duck and the hazel nuts, would also support this idea that she was a hunter-gatherer and subsisted on wild resources, Schroeder says, noting that the site is littered with physical remains which show reliance on wild resources like fish, rather than domesticated plants or animals.

It looks like in these parts maybe you have pockets of hunter-gatherers still surviving, or living side-by-side with farmers for hundreds of years, he says.

Scientists also found traces of the countless microbes that lived in the womans mouth. Ancient DNA samples always include microbial genes, but they are typically from the environment. The team compared the taxonomic composition of the well-preserved microbes to those found in modern human mouths and found them very similar.

Satisfied that genetic signatures of ancient oral microbes were preserved in the womans gum, the researchers investigated the specific species of bacteria and other microbes. Most were run-of-the-mill microflora like those still found in most human mouths. Others stood out, including bacterial evidence for gum disease and Streptococcus pneumoniae, which can cause pneumonia today and is responsible for a million or more infant deaths each year.

Epstein-Barr virus, which more than 90 percent of living humans carry, was also present in the womans mouth. Usually benign, the virus can be associated with serious diseases like infectious mononucleosis, Hodgkins lymphoma and multiple sclerosis. Ancient examples of such pathogens could help scientists reconstruct the origins of certain diseases and track their evolution over time, including what factors might conspire to make them more dangerous.

What I really find interesting with this study is the microbial DNA, Anders Gtherstrm, a molecular archaeologist at Stockholm University, says in an email. DNA from ancient pathogens holds great promise, and this type of mastics may be a much better source for such data than ancient bones or teeth.

Natalija Kashuba, an archaeologist at Uppsala University in Sweden, and colleagues have also extracted human DNA from ancient birch gum, from several individuals at a 10,000-year-old site on Swedens west coast. Its really interesting that we can start working on this material, because theres a lot of it scattered around Scandinavia from the Stone Age to the Iron Age, she says, adding that gums may survive wherever birches were prevalentincluding eastward toward Russia, where one wave of Scandinavian migration is thought to have originated.

The fact that the discarded artifact survived to reveal so much information about the past isnt entirely due to luck, Kashuba says. I think we have to thank the archaeologists who not only preserved these gums but suggested maybe we should try to process them, she says. If it hadnt been for them, Im not sure most geneticists would have bothered with this kind of material.

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The most mind-blowing human health discoveries of 2019 – Business Insider

December 24th, 2019 7:49 am

sourceDepartment of Foreign Affairs and Trade/flickr

In 2019, scientists continued searching for vital clues about how people might live healthier, longer, richer lives.

Nutrition researchers learned more about the best diets for every person, cancer researchers found new ways to program immune cells to attack, vaping turned deadly as investigators zeroed in on a sticky substance of concern, and possibly, a third gene-edited baby was born.

Here are 26 of the biggest, most enlightening, and exciting health discoveries of the year.

This was the second time that scientists suspected they mightve cured someone with HIV.

The first person thought to be cured of HIV, the virus that causes AIDS, was an American man named Timothy Brown, previously known as the Berlin patient. He received a bone-marrow transplant in 2007 to help treat his aggressive leukemia.

The second person who may have been cured has Hodgkins lymphoma and lives in the UK.

The reason these specific bone-marrow transplants seem to be capable of curing HIV is that both donors had a genetic mutation in a protein called CCR5 that made them more resistant to a common kind of HIV, which both men had.

Chinese scientist He Jiankui shocked the science world when he announced in 2018 the birth of twin girls born to be more resistant to HIV infection.

Jiankui edited a gene called CCR5 in the girls before birth, using the cut-and-paste CRISPR-cas9 DNA-modification method on their embryos. (CCR5 is the same gene that was mutated in both HIV-resistant bone-marrow donors, mentioned above.)

In 2019, Jiankui announced that another Chinese woman was pregnant with a third CRISPR gene-edited baby. Its not clear when, or if, her baby was ever born, but the infant should have come into the world some time around mid-year if all went according to plan.

Genetically-modified people are controversial because their gene changes can be passed on to future generations, and we know little about the long-term effects of being gene-edited.

In November, The New York Times reported that doctors tested out a procedure for the first time in the US that could one day pave the way for editing genes of cancer patients, using CRISPR to help their immune systems attack cancers. (Doctors in China say theyre already doing this.)

In the US trial, doctors removed some immune cells from three cancer patients bodies, and essentially genetically turbocharged them to fight cancer, before infusing the cells back into the patients.

But if you think you have the special sleep-starving gene that allows people to operate optimally on less than six hours of sleep a night, you probably dont.

It shows up in about one in every 25,000 people, according to The New York Times.

Scientists are hopeful that by studying the genes of more short sleepers, theyll be able to develop better therapies for people who dont get such great sleep.

Chelsea was hit by a drunk driver in 2013, and the accident burned over 60% of his body and face. His is the 15th full face transplant performed in the US.

Mercks Ervebo drug has been tried out during Ebola outbreak situations before, and is currently being trialed in the Democratic Republic of the Congo.

The vaccine is approved for use in people 18 and up, and the first doses are expected to be ready to go to market in late 2020.

One person died after contracting E. coli from a poop transplant, which is becoming a more popular way to treat debilitating C. difficile gut infections.

The measles is said to be so contagious that 90% of people exposed to the virus (who are not vaccinated or immune from a previous illness) will get it.

Residents in high-income countries around the world, where more parents are hesitating to vaccinate their kids, (including England, France, and Japan) have started to witness just how virulent the measles can be.

The US, a country that had declared the measles eliminated from its soil in 2000, has seen more than 1,200 documented measles cases so far in 2019. The World Health Organization called the vaccine hesitancy fueling measles outbreaks around the world one of the top 10 threats to global health of the year.

In earlier eras, it was kind of the norm to be vaccinated. It wasnt something that people questioned, Dr. Amesh Adalja told Business Insider earlier this year. But in the wake of the false links to autism that occurred in the mid 1990s, that whole celebrity culture picking up these false stories, we ended up in this type of a mess.

This doesnt mean that there is anything like a gay gene, or that people who have the variants will necessarily be gay.

Genetics is less than half of this story for sexual behavior but its still a very important contributing factor, study co-author Benjamin Neale, a psychiatric geneticist at the Broad Institute in Cambridge, Massachusetts told the Associated Press in August. Its effectively impossible to predict an individuals sexual behavior from their genome.

Normally, a climb like that takes at least a month (or more) for a sea-level adapted body to achieve.

Primarily, I think I really wanted to see if it could be done, Vogel told Insider, when reached by phone inside the oxygen-starved training chamber she sits in for a few hours at work every day. I am a researcher and a scientist at heart, and I really wanted to be able to collect data and see what happens to the body when you actually do something like this.

Kipchoge is the first person to ever complete a sub-2 hour marathon (at 1 hour, 59 minutes, and 40 seconds), but his run wont count as a world record, because he did it with help from a world-class pacing crew, and laser beams guiding his way along the pavement, among other perks other marathoners dont usually get.

I expect more people all over the world to run under 2 hours after today, he said.

Theres just a limit to how many calories our guts can effectively absorb per day, study co-author Herman Pontzer, an associate professor of evolutionary anthropology at Duke University, said in a press release. This defines the realm of whats possible for humans.

The limit, they found, is that a person can only ever burn calories up to 2.5 times their resting metabolic rate. After that, a body begins to break down its own stores for sustenance.

In one US study that tracked health outcomes over almost three decades, people who reported eating more vegetables and other plants (about 4 to 5 servings a day), and consuming little to no processed or red meat (less than a serving per day) had an average of 18 to 25% lower risk of death than people who routinely fuel up on meat and other animal products.

The new study also found that plant-eaters tended to have healthier hearts, developing fewer heart attacks and strokes, and dying from heart issues less often.

When you compare the amount of sugar in a serving of fruit juice to soda, the drinks are remarkably alike, so it shouldnt be a shock that juices might hurt long-term health just like soda.

They contain some vitamins, a little bit of dietary fibers, and no food additives, French epidemiologist Mathilde Touvier told Business Insider when her study was released. But they also contain lots of sugar.

Intermittent fasting has many different forms, but one of the most popular is a type practiced by celebrities like Terry Crews that involves fasting for 16 hours a day, and eating during a remaining 8-hour window (for Crews, thats from 2 p.m. to 10 p.m.)

Im not saying food is our enemy, absolutely not, we need to eat otherwise we die, study author and cancer researcher Dr. Miriam Merad said when her study on intermittent fasting was released in August. But it is true that we probably eat too much we eat too often.

Previous lab research, though scant, also suggests that people who fast or restrict calories may have fewer heart issues, better cholesterol levels, lower stroke risk, and fewer instances of diabetes.

Other nutrition pros still maintain the fasting that we do overnight when were asleep is enough.

Scientists had 1,100 adults in the US and UK eat the same common foods (like muffins for breakfast and sandwiches for lunch), and tracked participants glucose levels before and after meals. The results showed that no two individuals reactions were the same more evidence that theres no such thing as a perfect, one-size-fits-all diet.

Even we were surprised by the results, Tim Spector, an epidemiologist and professor at Kings College in London who led the study, told Business Insider. Just because some diet or recommendation is out there doesnt mean that you fit it.

Spector still suggests most people could benefits from eating more fruit, vegetables, nuts, seeds, whole grains, and fermented foods, while skipping junk food.

Nutrition experts at the National Institutes of Health provided some of the first evidence, in the journal Cell Metabolism, that there is something inherently bad about the way our bodies take in processed, ready-to-eat and ready-to-heat foods and that it makes us eat substantially more every day and get fatter over time than we would if we were regularly eating fresh, home-cooked meals.

Participants in the study, conducted in a highly-controlled laboratory setting, consumed on average 500 more calories a day on an ultra-processed diet, when meals included foods like hot dogs, freezer pancakes, and canned chili, versus when they ate fresh meals with home cooked chicken or beef, steamed vegetables, fresh fruit, nuts and greens on offer. While eating processed foods, people in the study gained about two pounds in two weeks.

Its a very big difference, and its an important difference, lead researcher Kevin Hall told Business Insider in May. There really is a causal relationship between ultra-processed foods and how many calories people choose to eat.

Research from a small study of 68 families at the University of Oklahoma suggested kids who dont have siblings tend to be more likely to fuel up on junk food, like refined grain products and sugary drinks.

Its not just about the child, study co-author Chelsea Kracht, a post-doc researcher at Pennington Biomedical Research Center, told Insider. The childs family situation is also what people need to think about with childrens nutrition.

Researchers suspect that more ritualized meal times in larger families might play a role.

What we dont want is people to think that having more children will somehow make you healthier, Kracht said. There were children with siblings who were overweight and only children who were perfectly healthy, so thats not the case.

In a win for coffee lovers of the Golden State, the California Office of Environmental Health Hazard Assessment (OEHHA) ruled after consulting over 1,000 scientific studies that drinking coffee does not pose a significant risk of cancer.

We found coffee is a complex mixture of numerous chemicals that includes both known carcinogens but also some anti-carcinogens that protect against cancer, including antioxidants, Sam Delson, a spokesman for the OEHHA, told Business Insider. You know, nothing is 100% risk-free, but Im a cancer survivor myself, and happy to drink coffee.

A study published in June suggests that microplastics tiny, often invisible pieces of plastic are in our water, food, air, and stomachs at alarming rates. Scientists have evidence that the average American woman may ingest around 98,000 tiny plastic particles every year, while the average man consumes 121,000.

Theres no good evidence yet that any of this plastic detritus is having a major effect on our bodies, but its definitely trashing the planet.

If you are a concerned citizen that is worried about plastic pollution, and you have access to a well-managed pipe supply, a water supply, why not drink from that? You know, why not reduce pollution, said Bruce Gorden, De Frances colleague.

The Apple Heart Study, a collaboration between the tech giant and Stanford University, was designed to measure whether the Apple Watch can detect irregular heartbeat issues.

The results of the study, which tracked more than 400,000 watch-wearers over an average of about four months per person, suggests that the devices perform pretty well at alerting people when they have irregular heartbeats.

The watches, which used flashing LED lights to detect heart rates, werent perfect though. They missed diagnosing some heart issues, and also alerted some other people who dont have heart conditions at all with false positives, which could lead to more healthy people flocking to healthcare providers for care they dont need, as Business Insiders Erin Brodwin noted when the study was released.

More than 40 people are dead, and over 2,200 others have reported vaping-related lung injuries to the US Centers for Disease Control.

One 18 year old (lungs pictured above) had to have surgery to remove blisters on his lungs, while another 17-year-old needed a double lung transplant after vaping.

We are definitely seeing in the ED [emergency room] and in the lung clinic, more patients coming in who are starting to have respiratory issues, heart and lung surgeon Junaid Khan told Insider.

Theres also some emerging evidence (from studies in mice) about a link between vaping and lung cancer risk. More research in people is needed to know for sure, but lung experts are concerned that vaping may contribute to more cancer cases because it promotes inflammation in the lungs and mouth.

The oily Vitamin E compound is generally considered safe to swallow or apply topically to the skin, but investigators monitoring the outbreak of deadly vaping lung injuries across the US are starting to suspect its not a good idea to inhale the substance.

Vitamin E acetate is enormously sticky, Jim Pirkle, from the CDCs environmental health lab, said in November. You can think of it to be just like honey. And so when it goes into the lung, it does hang around.

Trace amounts of asbestos a known cancer causer were found in concealer and sparkly makeup marketed to kids at Claires.

The find underscores a larger contamination issue across the beauty industry, one that isnt limited to asbestos contamination.

It wasnt surprising to me, because theres no regulation, gynecologist Shruthi Mahalingaiah told Business Insider in June.

The FDA also recently warned consumers about dangerous bacteria in a no-rinse cleansing foam used by hospital patients, alerted tattoo artists about ink contaminated with microorganisms, and found yeast in Young Living essential oils moisturizer.

While these findings are concerning, our results in no way imply that we shouldnt be legalizing marijuana, lead study author Magdalena Cerd, an associate professor and director of the Center for Opioid Epidemiology and Policy at NYU Langone Health, told Business Insider. If use is increasing, states need to be able to understand whats going on so they can respond appropriately.

The results, from a study of more than 70,000 people (mostly women) published in September from researchers at Harvard and Boston University, found that optimistic people tend to live, on average, 11 to 15% longer than others who are more grumpy.

This held true regardless of a persons socioeconomic status, smoking status, diet, or health condition, suggesting there may be something about the optimism thats keeping people alive.

Other research suggests that more optimistic people may be able to regulate emotions and behavior as well as bounce back from stressors and difficulties more effectively, senior study author Laura Kubzansky said in a press release.

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Scientists hope MND cure is a step closer after stem cell breakthrough discovery – The National

December 24th, 2019 7:48 am

SCIENTISTS hope a cure for motor neurone disease (MND) is a step closer after a research breakthrough identified cells key to the degenerative condition.

There is currently no known cure for MND, which causes signals from motor neurone nerve cells in the brain and spinal cord needed to control movement to gradually stop reaching the muscles.

Notable people who have lived with MND include Scottish rugby star Doddie Weir and Stephen Hawking.

Researchers used stem cell technology to identify a type of cell that can cause motor neurones to fail.

Using stem cells from patient skin samples, they found glial cells, which normally support neurones in the brain and spinal cord, become damaging to motor neurones in the patients with the condition.

By testing different combinations of glial cells and motor neurones grown together in the lab, researchers found glial cells from MND patients can cause motor neurones in healthy people to stop producing the electrical signals needed to control muscles.

READ MORE:BBCSports Personality of the Year award to honour Doddie Weir

Gareth Miles, a professor of neuroscience at the University of St Andrews, helped lead the joint project with the University of Edinburgh.

Miles said: We are very excited by these new findings, which clearly point the finger at glial cells as key players in this devastating disease.

Interestingly, the negative influence of glial cells seems to prevent motor neurones from fulfilling their normal roles, even before the motor neurones show signs of dying.

We hope that this new information highlights targets for the development of much-needed treatments and ultimately a cure for MND.

The joint research was published in the scientific journal Glia.

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Stem Cell Therapy Market Consumer Outlook 2025 | MEDIPOST Co., Ltd., Osiris Therapeutics, Inc. – Market Research Sheets

December 24th, 2019 7:47 am

Stem Cell Therapy Market: Snapshot

Of late, there has been an increasing awareness regarding the therapeutic potential of stem cells for management of diseases which is boosting the growth of the stem cell therapy market. The development of advanced genome based cell analysis techniques, identification of new stem cell lines, increasing investments in research and development as well as infrastructure development for the processing and banking of stem cell are encouraging the growth of the global stem cell therapy market.

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One of the key factors boosting the growth of this market is the limitations of traditional organ transplantation such as the risk of infection, rejection, and immunosuppression risk. Another drawback of conventional organ transplantation is that doctors have to depend on organ donors completely. All these issues can be eliminated, by the application of stem cell therapy. Another factor which is helping the growth in this market is the growing pipeline and development of drugs for emerging applications. Increased research studies aiming to widen the scope of stem cell will also fuel the growth of the market. Scientists are constantly engaged in trying to find out novel methods for creating human stem cells in response to the growing demand for stem cell production to be used for disease management.

It is estimated that the dermatology application will contribute significantly the growth of the global stem cell therapy market. This is because stem cell therapy can help decrease the after effects of general treatments for burns such as infections, scars, and adhesion. The increasing number of patients suffering from diabetes and growing cases of trauma surgery will fuel the adoption of stem cell therapy in the dermatology segment.

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

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Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

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Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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DNA Tests Make a Fun Gift But Here’s What You Need to Know Before You Unwrap – ScienceAlert

December 24th, 2019 7:46 am

You've likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you don't find a DNA testing kit under your own Christmas tree, there's a good chance someone you know will.

Whether you're motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work - before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users - and important personal implications that consumers should consider.

My main area of research is around clinical genome sequencing, where we look through all of a person's DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared.

Another option is Living DNA, which has a smaller dataset but provides more precise information on the UK and Ireland.

The most popular health kit is from 23andMe. Depending on the user's preference, results include information on predispositions for diseases such as diabetes and Alzheimer's, as well as on the likelihood of having certain traits such as hair colour and taste.

This company also offers ancestry analysis, as well as ancestry and trait-only kits that don't provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

A direct-to-consumer DNA testing kit. (Shutterstock)

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to "survey" the user's genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group.

For example, if your results say that you are 42 per cent Southeast Asian, it's because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled "Southeast Asian." The same goes for traits and health conditions.

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. They're also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service you're using, and determine whether you're comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Some users may feel they learn more about themselves. For others, results may bring people closer together - not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Veritas, a US Genetic Sequencing Company, Suspends US Operations Due to Decreased Funding; CFIUS Thought to be Leading Cause – Lexology

December 24th, 2019 7:46 am

According to news articles published in early December, Veritas Genetics, a Massachusetts-based company that hoped to lower the cost of whole-genome sequencing, is suspending its U.S. operations because of a lack of investment. Articles theorize that the decreased funding was driven mainly by new CFIUS regulations and heightened CFIUS scrutiny.

Early in December 2019, Veritas announced that its adverse financing situation had forced the suspension of its U.S. business. Veritas has stated that it is assessing potential paths forward, and there are rumors that one such path is the sale of the company. Veritas will no longer sell its tests, which include genetic testing for diseases and cancers (such as the BRCA test), in the United States. Veritas will continue to operate and sell its tests outside the United States.

Veritas first launched in 2014, and since 2015 it had raised $50 million in financing. Major investors included Chinese companies, such as Lilly Asia Ventures, which invested $10 million into the company, and Simcere Pharmaceutical. However, there has been increased scrutiny in the past two years for transactions that involve Chinese investors, especially when sensitive personal information, such as genetic information, is at stake. This year, for example, CFIUS forced iCarbonX, the Chinese, majority owner of U.S. company PatientsLikeMe, to divest its stake in the U.S. company.

According to news reports, recent CFIUS activity may have scared away not only Chinese investors but also non-Chinese investors reluctant to invest in a company with Chinese ownership. Non-Chinese investors may fear that Veritass Chinese ownership will lead to increased CFIUS scrutiny of any investment into Veritas, regardless of the investors nationality. Investors may also worry that CFIUS scrutiny could delay their return on investment if their firms are forced to stall business to address CFIUSs concerns.

No doubt the proposed CFIUS regulations from September also concern foreign investors: the proposed regulations explicitly target U.S. companies that maintain or collect sensitive personal data of U.S. citizens. While most sensitive personal data only triggers the proposed regulations if the U.S. business maintains or collects such data on greater than one million individuals, companies with genetic data are considered to be covered businesses no matter how many individuals are involved. Thus, companies like Veritas will always fall under CFIUS jurisdiction if a foreign person would acquire certain rights in the company. These rights include:

Several genetic and biopharmaceutical companies expressed concern in public comments to the regulations that the proposed regulations, specifically including all genetic data in the definition of sensitive personal data, would stymie foreign investment in these companies. Several companies argued that the Department of the Treasury should revise the proposed CFIUS regulations to require that genetic data be identifiable. Companies often are in possession of anonymized genetic information, which these companies argued does not pose a risk to national security. We await publication of the final regulations and whether CFIUS will make any changes to the definition of sensitive personal data, particularly as it pertains to genetic information. It is to be seen whether U.S. companies in other industries will face similar funding obstacles as foreign investors grow more wary of CFIUS.

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CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative…

December 23rd, 2019 5:51 pm

VANCOUVER, Washington, Dec. 23, 2019 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today continued promising clinical responses from its metastatic triple-negative breast (mTNBC) Phase1b/2 trial and its trial investigating leronlimab for the treatment of metastatic breast cancer (MBC).

Further data from the first mTNBC cancer patient continues to show no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood and additional reductions in CCR5 expression on cancer-associated cells at 11 weeks of treatment with leronlimab. Additional data in an emergency IND protocol involving one MBC patient demonstrated shrinkage of tumor (via MRI) after three weeks of treatment with leronlimab.

In the first patient, were encouraged to see that after 11 weeks these additional data provide further preliminary evidence of efficacy, as demonstrated by sustained undetectable levels of CTCs and a reduction of cancer-associated macrophage like cells (CAMLs), said Bruce Patterson, M.D., Chief Executive Officer of IncellDx. Thus far, the data have been consistent with previous studies evaluating leronlimab as a long-term therapy for HIV+ patients, with no serious adverse effects reported in the mTNBC trial.

CytoDyns second patient enrolled is a stage 4 MBC patient. The metastasis progressed to the liver, lung and brain. This patient was enrolled through an emergency IND. The patient was on Herceptin and Perjita for over 1.5 years. Herceptin is known to stop working after about 12 months, while Perjita is effective for approximately 1.5 years. This patient received her first injection of leronlimab on November 25, with one 700 mg dose each week.

Regarding the second patient, Nader Pourhassan, Ph.D., president and chief executive officer of CytoDyn, stated: It is very exciting to see ongoing results that demonstrate leronlimabs potential as a therapeutic option to treat patients with mTNBC and MBC with HER2+ condition. This second patient was enrolled in an emergency IND.

Added Dr. Patterson, The results from two subsequent scans of the metastatic lesions for this second patient demonstrated shrinkage of the tumors at both timepoints following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors.

Dr. Pourhassan continued, Due to these very promising clinical data, we feel that the 98% inhibition of metastasis shown by our animal studies may soon become a reality for many cancer patients throughout the world. We are cautiously optimistic and believe we have enough results in an unmet medical need population to justify filing for Breakthrough Therapy Designation in January 2020.

About Triple-Negative Breast CancerTriple-negative breast cancer (TNBC) is a type of breast cancer characterized by the absence of the three most common types of receptors in the cancer tumor known to fuel most breast cancer growthestrogen receptors (ER), progesterone receptors (PR) and the hormone epidermal growth factor receptor 2 (HER-2) gene.1TNBC cancer occurs in about 10 to 20 percent of diagnosed breast cancers and can be more aggressive and more likely to spread and recur.2,3Since the triple-negative tumor cells lack these receptors, common treatments for breast cancer such as hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective.4Currently, there are no targeted therapies approved to treat triple-negative breast cancer.5About Leronlimab (PRO 140)The U.S. Food and Drug Administration (FDA) has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH. Leronlimab has successfully completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab can significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98 percent in a murine xenograft model. CytoDyn is therefore conducting aPhase 2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019. Additional research is being conducted with leronlimab in the setting of cancer and NASH with plans to conduct additionalclinical studies when appropriate.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation and may be important in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of graft-versus-host disease (GvHD).

About CytoDynCytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a key role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and in immune-mediated illnesses, such as graft-vs.-host disease (GvHD) and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in 2019 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab (PRO 140) as a once-weekly monotherapy for HIV-infected patients and, plans to initiate a registration-directed study of leronlimab monotherapy indication, which if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab (PRO 140) can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients, with some patients on leronlimab monotherapy remaining virally suppressed for more than four years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and has received clearance to initiate a clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at http://www.cytodyn.com.

Forward-Looking StatementsThis press releasecontains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i)the sufficiency of the Companys cash position, (ii)the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv)the Companys ability to enter into partnership or licensing arrangements with third parties, (v)the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi)the Companys ability to achieve approval of a marketable product, (vii)the design, implementation and conduct of the Companys clinical trials, (viii)the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix)the market for, and marketability of, any product that is approved, (x)the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi)regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii)general economic and business conditions, (xiii)changes in foreign, political, and social conditions, and (xiv)various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form10-K, and any risk factors or cautionary statements included in any subsequent Form10-Q or Form8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CONTACTS

Media:Grace FotiadesLifeSci Public Relationsgfotiades@lifescipublicrelations.com(646) 876-502

Investors: ir@cytodyn.com

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BeiGene Announces Acceptance of a Supplemental New Drug Application in China for REVLIMID in Relapsed or Refractory Indolent Lymphoma – BioSpace

December 23rd, 2019 5:51 pm

BEIJING, China and CAMBRIDGE, Mass., Dec. 22, 2019 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced that the China National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) for REVLIMID (lenalidomide), in combination with rituximab, for the treatment of patients with relapsed or refractory indolent lymphoma (follicular lymphoma or marginal zone lymphoma). REVLIMID was first approved in China in 2013 for the treatment of multiple myeloma in combination with dexamethasone, in adult patients who have received at least one prior therapy, and the label for the combination was expanded in 2018 to include adult patients with newly-diagnosed multiple myeloma (NDMM) who are not eligible for transplant. It is currently marketed in China by BeiGene under an exclusive license from Celgene Logistics Sarl, a Bristol-Myers Squibb company.

This milestone for REVLIMID marks another step in the expansion of our hematology franchise into non-Hodgkins lymphoma (NHL) in China, where significant unmet medical needs remain. Together with the pending approvals of tislelizumab for Hodgkins lymphoma and zanubrutinib for mantle cell lymphoma and chronic lymphocytic leukemia as well as Revlimid for multiple myeloma, Vidaza for myelodysplastic syndromes and acute myeloid leukemia and additional products from the collaboration we have announced with Amgen, we are working to build a market-leading presence in the treatment of hematological cancers in China, said Dr. Xiaobin Wu, General Manager of China and President of BeiGene. We are excited about this opportunity and look forward to working closely with Bristol-Myers Squibb and the NMPA to bring this chemotherapy-free treatment option to patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma in China as soon as possible.

The sNDA is supported by a clinical, non-clinical, and chemistry, manufacturing and control (CMC) data package, including the results from the pivotal Phase 3 AUGMENT study (NCT01938001) sponsored and conducted by Bristol-Myers Squibb. AUGMENT is a randomized, double-blind, multicenter trial in which a total of 358 patients with relapsed or refractory follicular or marginal zone lymphoma were randomized 1:1 to receive REVLIMID and rituximab (R2) or rituximab and placebo. With a median follow-up of 28.3 months (range: 0.1 to 51.3 months), R2 demonstrated clinically meaningful and statistically significant improvement in progression-free survival (PFS), evaluated by an independent review committee (IRC), relative to the control arm with a 54% reduction in the risk of progression or death (hazard ratio [HR] = 0.46; 95% confidence interval [CI]: 0.34, 0.62; p < 0.0001). The median PFS was 39.4 months for the R2 arm and 14.1 months for the control arm with an improvement by more than 2 years. Overall response rate (ORR), a secondary endpoint, was 78% in the R2 arm vs. 53% in the control arm, as assessed by the IRC. Duration of response (DoR) was significantly improved for R2 vs. control with median DoR of 37 vs. 22 months, respectively (P =0.0015; HR: 0.53; 95% CI, 0.36-0.79). The most frequent adverse event (AE) in the R2 arm was neutropenia (58%), vs. 22% in the control arm. Additional commonly observed AEs in more than 20% of patients included diarrhea (31% in the R2 arm vs. 23% in the control arm), constipation (26% vs. 14%), cough (23% vs. 17%), and fatigue (22% vs. 18%). Adverse events that were reported at a higher rate (>10%) in the R2 arm were neutropenia, constipation, leukopenia, anemia, thrombocytopenia and tumor flare.

About follicular lymphoma (FL) and marginal zone lymphoma (MZL)

FL and MZL are two major types of indolent lymphomas;1 FL is the most common subtype, constituting approximately 20% to 25% of all NHL,2 followed by MZL (approximately 5% to 17% of all NHLs).3 NHL incidence in China is 88,090 according to the World Health Organizations Globocan 2018 database.4 Given the incurable nature of relapsed or refractory FL/MZL, the efficacy and safety limitations of current treatment options, and the fact that patients are typically older and with comorbidities, a high unmet medical need exists for the development of novel treatment options with new differentiated mechanisms of action and a more tolerable safety profile that can improve the quality of response and PFS in the setting of previously treated FL/MZL.

About REVLIMID

In China, REVLIMID was approved in combination with dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma (MM) who are not eligible for transplant in 2018. It received approval in China in 2013 for the treatment of multiple myeloma in combination with dexamethasone in adult patients who have received at least one prior therapy.

REVLIMID is approved in Europe and the United States as monotherapy, indicated for the maintenance treatment of adult patients with newly diagnosed MM who have undergone autologous stem cell transplantation. REVLIMID as combination therapy is approved in Europe, in the United States, in Japan and in around 25 other countries for the treatment of adult patients with previously untreated MM who are not eligible for transplant. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in Europe for the treatment of patients with mantle cell lymphoma (MCL) and in the United States for the treatment of patients with MCL whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In Switzerland, REVLIMID is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

U.S. Indications for REVLIMID

REVLIMID (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of adult patients with multiple myeloma (MM).

REVLIMID is indicated as maintenance therapy in adult patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT).

REVLIMID is indicated for the treatment of adult patients with transfusion-dependent anemia due to low-or intermediate-1risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

REVLIMID is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

REVLIMID in combination with a rituximab product is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL).

REVLIMID in combination with a rituximab product is indicated for the treatment of adult patients with previously treated marginal zone lymphoma (MZL).

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

REVLIMID is only available through a restricted distribution program, REVLIMID REMS.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS program.

Information about the REVLIMID REMS program is available at http://www.celgeneriskmanagement.com or by calling the manufacturers toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patients underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus.

Severe Hypersensitivity Reactions: REVLIMID is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS.

REVLIMID REMS Program: See Boxed WARNINGS. Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. Patients may require a dose interruption and/or dose reduction. MM: Monitor complete blood counts (CBC) in patients taking REVLIMID + dexamethasone or REVLIMID as maintenance therapy, every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. MDS: Monitor CBC in patients on therapy for del 5q MDS, weekly for the first 8 weeks of therapy and at least monthly thereafter. See Boxed WARNINGS for further information. MCL: Monitor CBC in patients taking REVLIMID for MCL weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. FL/MZL: Monitor CBC in patients taking REVLIMID for FL or MZL weekly for the first 3 weeks of Cycle 1 (28 days), every 2 weeks during Cycles 2-4, and then monthly thereafter.

Venous and Arterial Thromboembolism: See Boxed WARNINGS. Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and the regimen should be based on the patients underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision.

Increased Mortality in Patients With CLL: In a clinical trial in the first-line treatment of patients with CLL, single-agent REVLIMID therapy increased the risk of death as compared to single-agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials.

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID and in patients with FL or MZL receiving REVLIMID + rituximab therapy, an increase of hematologic plus solid tumor SPM, notably AML, have been observed. In patients with MM, MDS was also observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment.

Increased Mortality With Pembrolizumab: In clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with MM with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID + dexamethasone. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.

Severe Cutaneous Reactions: Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. Consider REVLIMID interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue REVLIMID for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS.

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with REVLIMID. The patients at risk of TLS are those with high tumor burden prior to treatment. Closely monitor patients at risk and take appropriate preventive approaches.

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of REVLIMID for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL, FL, or MZL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physicians discretion.

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection.

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before starting REVLIMID treatment and during therapy.

Early Mortality in Patients With MCL: In another MCL study, there was an increase in early deaths (within 20 weeks); 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (10 x 109/L).

Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to REVLIMID has been reported. Permanently discontinue REVLIMID for angioedema and anaphylaxis.

ADVERSE REACTIONS

Multiple Myeloma

Myelodysplastic Syndromes

Mantle Cell Lymphoma

Follicular Lymphoma/Marginal Zone Lymphoma

DRUG INTERACTIONS

Periodically monitor digoxin plasma levels due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin-stimulating agents or estrogen-containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dexamethasone and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin.

USE IN SPECIFIC POPULATIONS

Please see full Prescribing Information, including Boxed WARNINGS, for REVLIMID.

Please see the rituximab full Prescribing Information for Important Safety Information at http://www.rituxan.com.

About BeiGene

BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and immuno-oncology cancer therapeutics. With a team of over 3,000 employees in the United States, China, Australia, and Europe; BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. In the United States, BeiGene markets and distributes BRUKINSA (zanubrutinib) and in China, the Company markets ABRAXANE (paclitaxel for injection [albumin bound]), REVLIMID (lenalidomide), and VIDAZA (azacitidine) under a license from Celgene Logistics Sarl, a Bristol-Myers Squibb company.5

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGenes plans and expectations for further development and commercialization of REVLIMID in China and the potential implications for patients. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGenes limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the section entitled Risk Factors in BeiGenes most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

______________________1 Bello C, Zhang L, Naghashpour M. Follicular lymphoma: current management and future directions. Cancer Control. 2012;19:187-95.

2 Sousou T, Friedberg J. Rituximab in indolent lymphomas. Semin Hematol. 2010; 47(2):133-42.

3 Zinzani, P. L. (2012). The many faces of marginal zone lymphoma. Hematology, 2012(1), 426432.

4 https://gco.iarc.fr/

5 ABRAXANE is registered trademark of Abraxis Bioscience LLC, a Bristol-Myers Squibb company; REVLIMID and VIDAZA are registered trademarks of Celgene Corporation, a Bristol-Myers Squibb company.

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BeiGene Announces Acceptance of a Supplemental New Drug Application in China for REVLIMID in Relapsed or Refractory Indolent Lymphoma - BioSpace

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20 Things That Have Changed for the Better Since 2010 – 24/7 Wall St.

December 23rd, 2019 5:51 pm

By Hristina ByrnesDecember 23, 2019 3:32 pm

If you are someone who at least tries to stay informed about what is going on in the world, your faith in humanity may be long gone. Daily headlines are predominantly about negative subjects such as ugly politics, crime, and how we are killing the planet. While these important topics need attention, there is plenty of good news to share as well.

24/7 Tempo reviewed dozens of articles from multiple online sources on various topics to compile a list of 20 things that have improved in the United States and around the world since 2010.

Many people may react with incredulity at the possibility that things could be getting better. For example, according to Pew Research Center, Americans believe crime is up, but thats not true. In 18 of 22 Gallup polls conducted between 1993 and 2018, at least 60% of Americans said there was more crime than the previous year even though the national violent and property crime rates during most of that period were trending down.

The 2010s will go down in history as a decade of many newsworthy stories and, fortunately, many of them were good news albeit less talked about than the grimmer headlines. And for even more positive news, take a look at the 15 best health news over the last decade.

Click here to see 20 things that have changed for the better since 2010.

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‘I think murderers ought to be scared to death of it…’ Genetic genealogy leads to arrest of Florida man in 40-year-old cold case murder -…

December 23rd, 2019 5:50 pm

It always comes back to haunt you.

Thats what Union County Sheriff Brad Whitehead says of crime in general, after his office helped detectives in Colorado arrest a suspect, at last, in a 40-year-old rape-murder case.

On January 16, 1980, Helene Pruszynski a 21-year-old radio intern was raped and murdered in a vacant field in Douglas County, Colo. Her body was found the next morning.

Finding a suspect would take much longer.

It was a combination of DNA, existing technology that was available, but then the dogged police work, 18th Judicial District Attorney (CO) George Brauchler said at a press conference almost 40 years later, upon the arrest and formal charging of James Curtis Clanton, now 62.

It was an investigation that turned up occasional suspects but just as many dead ends. Clanton, who at the time of Pruszynskis death went by the name Curtis Allen White, had been convicted of rape in Arkansas in 1975 but was paroled less than four years later. He also was arrested in Palm Beach County, Fla. on a domestic battery charge in 1998.

But despite DNA found at the crime scene, investigators couldnt connect Clanton to the crime in Colorado, at least not until some of those dead ends spawned different approaches.

RELATED: Florida man charged with murder, kidnapping in 1980 death of Colorado radio intern

In one key instance, investigators had begun to suspect a man named William White Jr., who had a criminal history. Whites DNA would prove to be an imperfect match with evidence at the Pruszyinski murder scene and he was cleared. But then detectives used a relatively new technique called genetic genealogy, which allows investigators to essentially climb "up" a family tree from an eliminated suspect to ancestors often with the help of online DNA databases to find viablesuspects among common descendants. It would turn out, White and Clanton are brothers.

Eventually, it was determined that Clanton was living in Lake Butler, Fla. and had resided there at least a decade. According to Whitehead, Clanton had no encounters with local law enforcement during those years.

In a town where Whitehead says many people grow up together and know each other, it wasnt difficult to learn that Clanton was a regular at the Full House Lounge on Fourth Avenue.

He was always a laid-back, cool guy," Tom Christakes told First Coast News at a bar. "I dont know him other than just coming here and playing pool.

Christakes added that hed been acquainted with Clanton for about five years.

I actually taught him how to bank playing pool, just a couple weeks ago,: he said. But Im, like, completely shocked.

Investigators in Douglas County, Col. asked the Union County Sheriffs Office to try getting a sample of Clantons DNA. Thats when a deputy who knew the owner of the Full House Lounge arranged a plan to retrieve a beer mug after Clanton used it. The mug was retrieved Nov. 30.

Within days, Whitehead says a DNA match was confirmed. Police arrested Clanton without incident at his home Dec. 11.

He parked his truck where he normally always does, Douglas County Sheriff Tony Spurlock said in a press conference Dec.16. Got out of his truck and was walking away from it, when he was taken in to custody.

Whitehead added, I believe once he saw us, that he felt like he knew his past had caught up with him.

Clanton was extradited to Colorado, where he was formally charged with four murder-related counts and one of kidnapping on Monday, Dec. 16. The District Attorneys office in Colorados 18th judicial district tells First Coast News its still considering whether to pursue the death penalty against Clanton.

Whatever that decision will be, District Attorney Brauchler offered a stern-yet-satisfied summation of Clantons arrest particularly the modern methods that he says solved the cold case.

There are crimes yet unsolved today that I have great optimism because of cases like this, that were going to end up solving, Brauchler told the media. And I think the public ought to feel good about that, and I think murderers ought to be scared to death of it.

In a statement on Facebook, a woman named Janet Johnson, who says Helene Pruszynski was her sister, asked that her familys privacy be respected, offering the following statement:

"I want people to know what a special person Helene was. My sister was my best friend. She was a loving daughter, sister, aunt, & friend. Helene was on track to do great things, she had a bright future ahead of her. There has not been a day that goes by that we haven't missed her. The detectives and everyone else who helped to make this day happen are my heroes. I look forward to justice being served.

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BEYOND LOCAL: DNA tests might be a fun holiday gift, but beware of the hype – TimminsToday

December 23rd, 2019 5:50 pm

This article, written byMichael Mackley, Dalhousie University, originally appeared on The Conversation and is republished here with permission:

Youve likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you dont find a DNA testing kit under your own Christmas tree, theres a good chance someone you know will.

Whether youre motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users and important personal implications that consumers should consider.

Health, traits and ancestry kits

My main area of research is around clinical genome sequencing, where we look through all of a persons DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared. Another option is Living DNA, which has a smaller dataset but provides more precise information on the U.K. and Ireland.

The most popular health kit is from 23andMe. Depending on the users preference, results include information on predispositions for diseases such as diabetes and Alzheimers, as well as on the likelihood of having certain traits such as hair colour and taste. This company also offers ancestry analysis, as well as ancestry and trait-only kits that dont provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

How these tests work

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to survey the users genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group. For example, if your results say that you are 42 per cent Southeast Asian, its because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled Southeast Asian. The same goes for traits and health conditions.

How they differ from clinical tests

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

Before you spit in a tube, stop and think

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. Theyre also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service youre using, and determine whether youre comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Bottom line: Its all for fun

Some users may feel they learn more about themselves. For others, results may bring people closer together not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Seattle Genetics Announces Submission of Tucatinib New Drug Application to the U.S. FDA for Patients with Locally Advanced or Metastatic HER2-Positive…

December 23rd, 2019 5:50 pm

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tucatinib. This NDA requests FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. The submission is based on the results of HER2CLIMB, a randomized pivotal trial comparing tucatinib added to trastuzumab and capecitabine versus trastuzumab and capecitabine alone. HER2CLIMB trial results were presented on December 11, 2019 at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.

Todays submission marks another important milestone for Seattle Genetics and tucatinib, and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. We look forward to working with the FDA on the review of this application.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab, and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline, and confirmed objective response rate. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1, 2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, and gastric cancers. HER2 mediates cell growth, differentiation, and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate, and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic, or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival, and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

About Seattle Genetics

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops, and commercializes transformative medicines targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the companys industry-leading antibody-drug conjugate (ADC) technology designed to bring a powerful medicine directly to cancer cells. ADCETRIS is approved for the treatment of several types of CD30-expressing lymphomas, and PADCEV is approved to treat adults with metastatic urothelial cancer. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer, and in clinical development for metastatic colorectal cancer. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland, and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting; the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses and anticipated development activities including ongoing and future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that the New Drug Application submission based on the HER2CLIMB trial may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all or with the requested label; the difficulty and uncertainty of pharmaceutical product development; the risk of adverse events or safety signals; and the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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Mosaic Angelman Should Be in Differential Diagnosis of AS, Study Says – Angelman Syndrome News

December 23rd, 2019 5:49 pm

Clinicians should consider mosaic Angelman syndrome in the differential diagnosis of people who show milder symptoms of the disorder, a study suggests.

The study, Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome, was published in Molecular Genetics & Genomic Medicine.

Angelman syndrome (AS) is a genetic neurodevelopmental disorder usually associated with severe intellectual disability, difficulty speaking, loss of movement control (ataxia), and epileptic seizures. It is normally caused by the loss or malfunction of the maternal copy of the ubiquitin protein ligase E3A (UBE3A) gene in neurons from specific regions of the brain.

However, in some people, these genetic defects that affect the normal function of the UBE3A gene are only present in a handful of their cells. This phenomenon, known as mosaicism, can happen if one of the first cells of an embryo acquires a mutation in the UBE3A gene which is then passed on to their daughter cells as the embryo grows.

People with mosaic Angelman syndrome (mAS) typically have milder symptoms than those with Angelman syndrome. For instance, they experience milder expressive language delay with greater ability to attain meaningful words than typical Angelman patients.

In this study, researchers from the Vanderbilt University Medical Center and their collaborators set out to describe the clinical symptoms of mAS in a larger group of individuals to help clinicians with the differential diagnosis of Angelman syndrome.

The study included data from 22 people with mAS, whose caregivers filled out surveys at the medical center. Data from four additional patients was obtained from the Angelman Natural History Study, an observational study that followed the course of the disease in 302 Angelman patients over more than eight years. Clinical data from people with mAS was then compared to historical data from individuals with Angelman.

Findings revealed that nearly all mAS patients (90%) had some form of developmental delay. However, unlike those with Angelman, less than 15% of survey respondents said that mAS children showed signs of severe developmental delays before reaching the age of 1.

Compared with the significant language impairments seen in children with Angelman, 59% of the children with mAS retained the ability to articulate more than 20 words, with a fifth (20%) of them able to speak more than 1,000 words.

Other core features of Angelman, including ataxia, gait abnormalities, and limb tremulousness, were found in less than 33% of mAS children.

Additional clinical features of Angelman syndrome were also evident in patients with mAS: The three most prominent findings included abnormal sleep/wake cycles and decreased sleep in 73% of patients, followed by obesity in 64% of patients and heat sensitivity in 45% of patients, the researchers wrote. Constipation, a common problem in [Angelman syndrome] patients was also noted in the mAS cohort, with 72% of patients endorsing constipation.

Although children with mAS had milder speech impairments and were better able to engage in daily activities, they still faced many behavioral challenges that were typical in Angelman syndrome.

Anxiety was the most frequently endorsed behavior reported in our cohort, present to some degree in 95% of mAS patients and rated as severe in 43% of patients. Hyperactivity was commonly endorsed, reported in 59% of patients, the researchers wrote.

Overall these data encourage specialists to broaden the clinical features of [Angelman syndrome], said the researchers, who added that clinicians should consider tests to rule out mAS in individuals with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 11

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Cancer therapy may be aided by induced macropinocytosis, a rarely reported form of cell death – The Mix

December 23rd, 2019 5:49 pm

In preclinical experiments, a metabolic inhibitor killed a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues.

In preclinical experiments, a metabolic inhibitor killed a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues.In laboratory experiments, a metabolic inhibitor was able to kill a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues through a non-apoptotic route catastrophic macropinocytosis.

In mouse xenograft studies, the inhibitor acted synergistically with a common chemotherapy drug, cyclophosphamide, to reduce tumor growth. Thus macropinocytosis, a rarely described form of cell death, may aid in the treatment of cancer.

Understanding the signaling pathways underlying macropinocytosis-associated cell death is an important step in developing additional effective strategies to treat neoplasms that are resistant to apoptosis induced by chemotherapy, said Mohammad Athar, Ph.D., professor in the University of Alabama at Birmingham Department of Dermatology.

The inhibitor, OSI-027, affects the mTOR pathway, which plays a critical role in regulation cellular growth and metabolism. Significantly, this potent inhibitor simultaneously targets two distinct protein complexes of the mTOR pathway, mTORC1 and mTORC2. Aberrant activation of these components has been associated with many cancer types.

Macropinocytosis starts with formation of ruffles on the surface of a cell that reach out from the cell membrane. These ruffles then fuse back with the cell membrane, creating a bubble that holds extracellular fluid, and the bubble moves inside the cell to become a vacuole filled with fluid. In catastrophic micropinocytosis, large numbers of these vacuoles form inside the cell and then fuse together, causing cell death.

The UAB researchers showed that dual inhibition of the two mTORC1 and -C2 complexes was necessary for highly effective cell death through macropinocytosis.

In early experiments, the researchers found that OSI-027, and a related dual inhibitor, PP242, induced extensive vacuolization in a wide range of human cancer cell lines, including two subtypes of rhabdomyosarcoma. These vacuoles were then shown to be macropinosomes.

Xenograft mouse experiments with human rhabdomyosarcoma tumors showed that OSI-027 blocked tumor growth by inducing macropinocytosis; furthermore, the addition of the chemotherapy agent cyclophosphamide acted synergistically to enhance efficacy of tumor size reduction.

Mohammad Athar, Ph.D.In mechanistic studies, Athar and colleagues found that macropinocytosis depended on activation of the MAP kinase MKK4, which was induced by the presence of reactive oxygen species. However, the full role of MKK4 is not well understood, they say.

Previous work by others had shown that several specific inducers of macropinocytosis induced macropinocytosis mainly in glioblastomas and colorectal cells. In contrast, Athar said, our study demonstrates that the dual inhibitors we tested induce catastrophic vacuolization in tumor cell lines from a wide range of organs, including skin, breast, cervix, lung and soft tissues.

The effects were much less pronounced in immortalized human keratinocytes.

Our data reveal that therapeutic targeting of mTORC1 and mTORC2, together with standard care treatment, Athar said, may be an effective approach to block the pathogenesis of recurrent rhabdomyosarcoma and perhaps other drug-resistant invasive neoplasms of diverse tissue types as well. The underlying mechanism by which tumors become responsive to treatment involves macropinocytosis, a unique form of cell death.

Co-authors with Athar of the study, Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells, published Proceedings of the National Academy of Sciences, are Ritesh K. Srivastava, Changzhao Li and Jasim Khan, UAB Department of Dermatology; and Louise T. Chow and Nilam Sanjib Banerjee, UAB Department of Biochemistry and Molecular Genetics.

Support came from National Institutes of Health grant ES026219 and funds from the Anderson Family Endowed Chair through UAB.

At UAB, Athar holds the Eric W. Baum, M.D., Endowed Professorship in Dermatology, and Chow holds the Anderson Family Chair in Medical Education, Research and Patient Care in the School of Medicine. Both are senior scientists in the ONeal Comprehensive Cancer Center at UAB.

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An Alzheimer’s research pioneer, right here at Penn – Penn: Office of University Communications

December 23rd, 2019 5:49 pm

A primary project for Garrett Gibbons, a postdoctoral researcher at the Center for Neurodegenerative Disease Research (CNDR), is to develop novel tau antibodies as possibletherapies to treat Alzheimers disease. When in the thick of it, the scientific process becomes a huge, timelyand sometimes redundanttask.

One particular experiment comes to mind: Gibbons and his colleagues were injecting tau into mice models, which the mice developed antibodies against, and when they were harvested, the cells were paired with another cell to make a hybridoma. The problem? After two times running the full experiment, the antibodies still didnt meet certain criteria to be applicable.

Gibbons, quite disheartened, told his adviserVirginia Man-Yee Lee, a Perelman School of Medicine professor and director of CNDR, that the benchmark was too high.

Virginia was like, Well, try again, Gibbons recalled. She pushed back and said how she thought we could do better.

Although admittedly frustrated at the time, Gibbons rethought the project, and, ultimately, underwent a revamped test a third time.

And we got better antibodies, performing better than the previous ones, he said. They are now the candidates that we are evaluating as immunotherapy in mice, as potential treatments for Alzheimers disease.

It is safe to say, noted Gibbons, that without this kind of persistence from Lee, Alzheimers research wouldnt be nearly as developed as it is today. A pioneer in the field of neurodegenerative diseases, Lee was recently recognized for her four decades of work with a $3 million Breakthrough Prize in Life Sciences, an award backed by major technology leaders from companies including Google and Facebook.

Growing up in Hong Kong in a very traditional Chinese family, my mother never wanted me to become a professional, let alone a scientist, Lee said to the crowd, while accepting her Breakthrough Prize at the Oscars of Science in Silicon Valley in early November. Thankfully John Trojanowski, my life partner and collaborator, convinced me to embark on this wonderful journey with him, identifying proteins that are involved in devastating neurological diseases, which affect more and more of us, but have no effective treatment.

Lee, with a background in biochemistry and neuroscience, and Trojanowski, who studied pathology and neuropathology, have toiled alongside each other at Penn since the mid-1980s. They began work in Alzheimers research when it was very uncommon to do soin fact, their mentors urged them to stay far, far away from it.

What [our mentors] saw as a swamp, said Trojanowski, we saw as a huge challenge and opportunity that has led to an engaging career.

Before Lee and Trojanowski, prior studies had determined that an Alzheimers patients brain progressively accumulates plaques, abnormal clusters of protein fragments called beta-amyloid, that build up between nerve cells, and tangles, which form inside dying cells. Using this as a starting point, the duo detected their first major finding in 1991: that tau is the building block protein of the neurofibrillary tangles.

In 1997, Lee and Trojanowski found that Lewy bodies, the hallmark brain pathology of Parkinsons disease, are formed by alpha-synuclein. Knowing what causes Lewy bodies is important to Alzheimers researchers because about 50 percent of Alzheimers patients have Lewy bodies that contribute to cognitive deficits.

Then, in 2006, they discovered the pathological protein deposits in amyotrophic lateral sclerosis, or ALS, and frontotemporal degeneration, or FTD, are formed by TDP-43, a multifunctional DNA- and RNA-binding protein, and these deposits are also present in a large number of Alzheimers patients brains.

Lee was specifically recognized for the Breakthrough Prize for discovering TDP-43 protein aggregates in FTD and ALS, and revealing that different forms of alpha-synuclein, in different cell types, underlie Parkinsons disease and Multiple System Atrophy.

This is exceptionally important work, and we are very proud that it is taking place at Penn. Penn President Amy Gutmann

The discoveries led by Dr. Lee and her team are extraordinary, and absolutely worthy of the prestigious Breakthrough Prize, said Penn President Amy Gutmann, who went to Silicon Valley to support Lee in receiving her honor. Dr. Lee and her team have worked to fully understand the different segments of Alzheimers disease and other related disorders, using that knowledge to develop models that are becoming the foundation for therapies that will, hopefully, stop or reverse these diseases. This is exceptionally important work, and we are very proud that it is taking place at Penn.

Its rewarding, Lee said, to reflect on how researchers are becoming increasingly interested in TDP-43s involvement in neurodegenerative diseases, and the biology that is able to follow, now.

It is gratifying that people can, and people are very interested in, using the system that weve built to identify potential therapies, Lee explained. I am really optimistic that maybe some treatment for Alzheimers and Parkinsons will become available in the next, lets say, one or two decades.

Gibbons, who can distinctly remember being a teenager and watching his grandfather cope with all the stages of Alzheimers, as well as the impact it had on his family, knew rather early it would be a field he would want to pursue. But, it wasnt until he was immersed in the research that he realized how complicated it really was.

When I first got to Penn, I was kind of blown away with the challenge and sort of became cynical and pessimistic, Gibbons said. But I like the way that Dr. Lee continues to forge ahead and isnt overwhelmed as a young investigator, that gives me a lot of inspiration and hope. Of course there will be failures, and of course science is hard. This is worthwhile, and we will get there.

In terms of Lee as a leader, Mike Henderson, a research associate in her lab, said he appreciates the way she guides him in his learning, but also provides him with the independence needed to encourage innovative, out-of-the box thinking.

She really shows you what it takes to be a good scientist in the field, he said, adding how inquisitive Lee always is. Shes very curious and I think thats really what has driven her lab and what has made her so successful.

The main reason Henderson came to Penn, he noted, was to work not only with Lee and Trojanowski, but also with the team theyve assembled through the creation of the CNDR, which celebrated its 25th year in 2018. About 50 people are part of the center today.

From the Maloney Building on Penns campus, where CNDR is housed, Lee and Trojanowski have been able to foster multidisciplinary collaborations between basic and clinical scientists, and provide resources to enable the very best research projects, including a brain and biosample bank, a drug discovery program, data management and biostastic support, and expertise in biochemistry, histology, molecular biology, microscopy, tissue culture, and genetics.

John and I spent a lot of time developing an infrastructure to do this type of work, and Penn has been such a fantastic environment, said Lee, who acknowledged all of her collaboratorsstudents, postdocs, and staff scientistsat the Breakthrough event. I truly want to thank them for their dedication and commitment, she said.

Talking later, Trojanowski added, They have made possible all that we have accomplished.

There is no doubt about it: Talking about his beloved wife of 40-plus years is probably one of Trojanowskis favorite things to do. Shes always pushing herself to be better, and shes always pushing me to be better. She is driven, hardworking, very bright, determinedall of the things that you expect to see and need to see in people that are going to be as successful as she is.

Not only is she passionate about science, he adds, shes determined to solve any problem she ever sets her eyes on. Plus, shes an amazing preceptor, trainer, encourager of science in young people. She is just exceptional, he added.

Trojanowski attended the Breakthrough event with his wife, thrilled to stand by her side on such an exciting day. Its an outstanding recognition, he said.

One might think a $3 million check in the bank could be a ticket out of work, but for Lee, she was back in Philadelphia after just a couple days. As always, she rode her bike to the officeready and willing to take on her next challenge.

What Id like to do in the next 10 to 20 years, Lee said, is really work with companiespharmaceutical companies and biotechnology companiesto come up with treatments.

Virginia Man-Yee Lee is the John H. Ware 3rd Endowed Professor in Alzheimers Research in the Department of Pathology and Laboratory Medicinein the Perelman School of Medicine.

John Q. Trojanowski is the William Maul Measey - Truman G. Schnabel, Jr., M.D. Professor of Geriatric Medicine and Gerontology in the Department of Pathology and Laboratory Medicinein the Perelman School of Medicine.

The Breakthrough Prize in Life Sciences, founded in 2013, honors transformative advances toward understanding living systems and extending human life. It is sponsored by Sergey Brin, Priscilla Chan and Mark Zuckerberg, Pony Ma, Yuri and Julia Milner, and Anne Wojcicki.

Homepage photo: Today, about 50 people make up the Center for Neurodegenerative Disease Research, led by Lee and Trojanowski, who both expressed how thankful they are for such a great team.

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