Important pieces of the puzzle to understand what drives diseases such as Alzheimer's and Parkinson's are still missing today. One crucial obstacle for researchers is that it is impossible to examine a living brain cell in someone who is affected by the disease. With the help of a new method for cell conversion, researchers at Lund University in Sweden have found a way to produce diseased, aging brain cells on a large scale in a cell culture dish.

After performing a biopsy on the patient, the skin cells are transformed into brain cells that effectively imitate the disease and the age of the patient. The fact that the cells can now be produced in large quantities enables researchers to carry out a series of experiments that were previously not possible.

A few years ago, Malin Parmar's research team was one of the first in the world to convert human skin cells directly into brain cells without passing the stem cell state. The discovery shocked the researchers and was perceived as almost impossible. The team is now approaching a point where the discovery is about to bear fruit on a wide scale. By following a new method that involves slightly changing the genetic code that triggers cell conversion, the researchers were able to multiply the production of disease-specific brain cells.

"Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein's impact in the cells during the conversion process, we've seen completely different results. Since then, we've been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy", says Malin Parmar, professor of developmental and regenerative neurobiology at Lund University.

The increase in production will have far-reaching effects. The new volumes enable research projects that were simply not viable before. Among other things, it opens up research areas linked to new drug testing, the establishment of more accurate disease models and the development of diagnostics to detect the diseases at an earlier stage.

The new cells are not only able to imitate the disease but also the patient's age. By studying the cell in the culture dish, the researchers can now monitor the mechanisms of the disease in an "old" brain cell over time. Neurodegenerative diseases are commonly referred to as "aging brain diseases" and in order to understand them, we must better appreciate how the age specifically affects the course of the disease. The Lund researchers' discovery can hopefully contribute a crucial piece to the puzzle with regard to the connection between the onset of disease and cell aging, something which previous research based on animal experiments and stem cells has failed to provide.

"This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on these cells to get closer to the diseases", says Johan Jakobsson, leader of the molecular neurogenetics research group at Lund University.

See more here:
Large-scale Production of Living Brain Cells Enables Entirely New Research - Laboratory Equipment

The times, they are a-changing.

Since Gregor Mendel unwittingly became the father of genetics by writing down his botanical observations, we have been progressing along swimmingly in our understanding and application of biology.

In the past few years, we ourselves have made some measured leaps forward in the field of biotechnology, some small someless so. Yet with the monumental achievements we have made thus-far from the advent of vaccines to our understanding of how our bodies age and degenerate, we have yet to make that quantum leap forward. That quantum leap may itself not be that far off and if anything is a good indicator of that its observable in the nature of the biotech we are currently developing.

With any huge leap forward, however, come new challenges and a slew of new questions that desperately need to be answered.

This next step in our journey isnt quite like when we eradicated major diseases or began transplanting organs because it isnt about extending human life a mere few additional years. We are taking about a doubling in the years a human may live. Thats right, double.

Now, before you write this off as sci-fi or wishful thinking, let me walk you through exactly what breakthroughs are currently occurring. It all has to do with CRISPR gene-line editing and 3-dimensional printing.

We are at the point where we can take normal somatic cells like the ones from your skin, coax them back into stem cells then re-engineer them into just about any type of cells we want. This means shortly we will be able to take skin cells and make them into heart tissue, or liver, or pancreatic or any number of different ones.

Next, the advances in 3-dimensional printing may shortly be able to take your newly minted cells and print them onto a blank scaffolding in the shape of just about any organ you may need.

Think of that: if you need a new heart it could be as simple as scratching some skin from your arm, reprogramming the cells and then printing you a whole new organ. Not a transplant from a donor, your own cells. This means no rejection and no waitlists. When an organ fails we replace it, again and again and again.

What is to become of a human race that is capable of living seemingly without end? This brings up some serious questions that would have to be answered quickly.

For starters, we see that the current population growth of our species is unsupportable as we resist green energies and advanced farming methods. If humans were to begin to live twice as long or longer we must figure out what we are going to do.

Now the radicals would suggest we simply control the populations but I dont believe that is necessary or even morally right. All we must do is increase our carrying capacity. I must admit that was not my own musing but one my father suggested to me.

If we are able to increase how much food and energy we produce without damaging the planet there is virtually no limit to how many humans can live at once. But the question is, will we resist it as we are now? Will the prospect of living healthily well over a century spur us to begin to accept scientific consensus? Or will we continue down our current path of selfishness and greed? Only time will tell.

Excerpt from:
Is doubling our life span desirable? - Price Sun Advocate

One of the coolest things about working in the beauty industry is being in the know and having the ability to tell readers, friends and family about a new product or brand that really works the way it claims. When Beauty Pie, the self-professed Buyers Club for Beauty Addicts came onto the scene and the cosmetic line was just as good as it promised, it was an exciting discovery. Most luxury beauty products retail for about 10x what they actually cost to make, is one of Beauty Pies mantras, and now the "Netflix of Beauty" is out to revolutionize the skin carebuying process the same way it did with makeup when it launched six months ago.

You May Also Like: I Tried the Netflix of Beauty and the $2$4 Products Are Totally Legit

The digital-only, UK-based brand was started by Marcia Kilgore, founder of other notable brands like Bliss Spa and Soap & Glory, so its no wonder that the membership club has now ventured into skin care, too. Now, a monthly membership of just $10 allows you to not only buy high-quality $7 foundations, $3 mascaras and $5 lipsticks, but you can also get all of your skin care needs meet for less than $13.

For the launch of its new skin care line, Beauty Pie has tapped the best Swiss suppliers and leading cosmetic chemists to create a line with ingredients and formulations that rival high-end luxury brands. The 11 newly released products range from the hydrating Swiss-Korean Jeju Daily Antioxidant Superinfusion Essence Serum ($8 for members/ $80 for nonmembers) and the creamy Double-Phase Daily Deep Rinse-Off Cleanser ($5 for members/ $32 for nonmembers) to a Fruitzyme Five Minute Facial ($6 for members/ $60 for nonmembers).

With ingredients like kiwiberry stem cells, meadowfoam seed oils, pomegranate enzymes and oil-absorbing kaolin clay, were excited to try the serums, masks, moisturizer, cleanser and eye cream and judge for ourselves whether the products stand up to their makeup counterparts. Beauty Pie's concept of luxury products at factory prices is a concept that will never get old and one worthy of throuougly exploring.

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$5 High-Quality Skin Care ExistsHere's the Proof - NewBeauty Magazine (blog)

If youve ever been concerned about hair loss in the past, this could be your lucky day. A new experiment carried out by Michael Rosenblum, assistant professor of dermatology at the University of California has proved just how useful regulatory T cells (tregs) are when it comes to hair loss. Previously scientists were led to believe that these cells single task was to inform other cells when to attack. However, what Rosenblum discovered when he shaved the mouse he was experimenting on, he noticed that the hair never grew back.

From the study, Rosenblum and team discovered that tregs in the skin had high levels of Jagged 1 (Jag1) which has the duty of calling in the stem cells through a process called Notch signaling. Removing the tregs reduced the notch signaling and when Jag1 was added the stem cells were called which then activated the process of follicle regeneration.

This study will be of particular interest to one type of hair loss sufferer: those with alopecia areata. This is an autoimmune disease that impedes hair follicle regeneration and affects as many as 1.7 percents of the U.S. population. Until now, very little has been known about what causes hair loss, but this research will give doctors and scientists everywhere new direction and a potential cure.

As well as hair regeneration, this process could be used to correct other skin related problems such as wound repair. What we found here is that stem cells, and immune cells have to work together to make regeneration possible, says Rosenblum. So dont despair if youre losing your hair, help is on the way!

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Say Goodbye to Hair Loss and Hello to Body Regeneration - TrendinTech

Minneapolis, MN, June 26, 2017 (GLOBE NEWSWIRE) -- BioSig Technologies, Inc.(OTCQB:BSGM), a medical device company developing a proprietary platform designed to address an unmet technology need for the $4+ billion electrophysiology (EP) marketplace, today announced that the American Heart Associations 13thAnnualBasic Cardiovascular Sciences (BCVS) 2017 Scientific Sessions: Pathways to Cardiovascular Therapeuticshas accepted two abstracts for presentation that feature novel preclinical findings with BioSigs PURE EP System. The conference will be held July 10-13 in Portland, Oregon and includes the next best thing in cardiovascular research.

The abstracts, entitled, Use of a Novel Electrogram Filter to Visualize the Conduction Tissue Signals in the Ventricle in Sinus Rhythm and Arrhythmia: Canine Studies and "Assessment of Catheter Position Above or Below the Aortic Valve by Evaluation of Characteristics of the Electrogram: An Acute Canine Study", werewritten in collaboration with electrophysiologists from Mayo Clinic and will be presented during scientific poster sessions from 4:30pm 7pm on July 10 and 12, respectively.

BioSig is extremely pleased to have two abstracts, featuring our PURE EP System, accepted into the Basic Cardiovascular Sciences Conference sponsored by the American Heart Association, stated Mr. Ken Londoner, Chief Executive Officer and Chairman of BioSig Technologies. Our collaboration with Mayo Clinic physicians has resulted in seven publications to date featuring BioSigs platform technology. And, we intend to strive towards improving visualization of cardiac signal information during EP procedures to help bring benefits to those patients who suffer with, and doctors who treat, arrhythmia.

About the Basic Cardiovascular Sciences Conference

The 13th Annual BCVS 2017 Scientific Sessions: Pathways to Cardiovascular Therapeutics has become the premier conference for molecular cardiovascular biology and disease. Sponsored by the American Heart Association Basic Cardiovascular Sciences Council, the worlds leading organization of cardiovascular scientists, this conference strives to improve basic cardiovascular regulation through new therapies and insights in cardiovascular disease, as well as research in fields like microRNAs, cardiac gene and cell therapy, cardiac development, as well as tissue engineering and iPS cells.

BCVS 2017 convenes basic and translational cardiovascular scientists from around the world with the common goal to discover pathways to cardiovascular therapeutics and promoting cardiovascular health. This meeting has become the go to meeting for intra- and interdisciplinary cross-fertilization of ideas and incorporation of new approaches from the general scientific community and plays a pivotal role in the training of junior scientists and trainees. The program includes a diversity of speakers representing the best cardiovascular scientists from around the world.

About BioSig Technologies

BioSig Technologies is a medical device company developing a proprietary technology platform designed to improve the $4+ billion electrophysiology (EP) marketplace ( http://www.biosigtech.com). Led by a proven management team and a veteran, independent Board of Directors, Minneapolis-based BioSig Technologies is preparing to commercialize its PURE EP(TM) System. The technology has been developed to address an unmet need in a large and growing market.

The PURE EP System is a novel cardiac signal acquisition and display system which is engineered to assist electrophysiologists in clinical decision making during procedures to diagnose and treat patients with abnormal heart rates and rhythms. BioSigs main goal is to deliver technology to improve upon catheter ablation treatments for prevalent and deadly arrhythmias. BioSig has partnered with Minnetronix on technology development and is working toward FDA 510(k) clearance and CE Mark for the PURE EP System.

Forward-looking Statements

This press release contains forward-looking statements. Such statements may be preceded by the words intends, may, will, plans, expects, anticipates, projects, predicts, estimates, aims, believes, hopes, potential or similar words. Forward-looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Companys control, and cannot be predicted or quantified

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Novel Findings Obtained with the PURE EP System to be Presented at American Heart Association's BCVS Scientific ... - Cardiovascular Business

Ottawa Sun

Jonathan Pitre still ailing as doctors search for answers Ottawa Sun Pitre checked back into hospital earlier this month just three days after being released following a stem cell transplant that had successfully taken root in his bone marrow. Bone marrow stem cells produce most of the body's blood cells, and are ... and more »

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Jonathan Pitre still ailing as doctors search for answers - Ottawa Sun

Hot air: Triona McCarthy on how to smeel good

Independent.ie

Want to smell good, look good, and feel fantastic? The scentsational Triona McCarthy shows us her weekly round-up of lotions and potions to keep you looking hawt!

http://www.independent.ie/life/hot-air-triona-mccarthy-on-how-to-smeel-good-35845624.html

http://www.independent.ie/incoming/article35592585.ece/c3491/AUTOCROP/h342/mg%20Trionna.jpg

Want to smell good, look good, and feel fantastic? The scentsational Triona McCarthy shows us her weekly round-up of lotions and potions to keep you looking hawt!

Created by an Irish female natural beauty entrepreneur, YourBeautyTonic has everything your skin needs to boost beauty. Its key ingredients, collagen and hyaluronic acid, are the building blocks of youthful skin, and it also contains vitamins and minerals.

YourBeautyTonic, above, costs 59.95 for 30 days' supply, and is available from independent health stores, selected pharmacies and online at yourtonic.com

WAX ON, WAX OFF...

I'm off to Inchydoney, in west Cork this weekend, so I'm waxed.

The gals at Brazilia are so profesh, and they make the waxing experience so easy, painless, and, actually, almost pleasurable.

I don't know if I'm quite ready to rock a teeny-weny little bikini like Emily Ratajkowski, above, but you never know!

Brazilia, 50 South William St, D2, tel: (01) 675-0000; 4 Sandyford Office Park, D18, tel: (01) 293-4858, or see brazilia.ie

LET US SPRAY

Image PREVENTION + Pure Mineral Sunscreen Spray 30+ SPF, below, 47.50, is so quick and effective. Before walking Maxi and Mini to Montessori in the morning, I cleanse and moisturise my face, and spray on this ultra-lightweight, anti-pollution, anti-aging, pure mineral sunscreen spray with superior UVA/UVB and infrared protection.

Infused with antioxidants and plant stem cells, it nourishes and hydrates my skin with organic ingredients, including jojoba and sweet almond oil - and, best of all, it's free of parabens and chemicals.

TRIONA'S TRICK

We have my kiddies, Maxi and Mini, to thank for this week's beauty trick. If, like me, you don't like your Beauty Blender sponge getting all grubby in the bottom of your make-up bag, simply pop it into an empty Kinder Egg container to protect it!

CULT PRODUCT

Inspired by Poppy Delevingne's wedding make-up, this Charlotte Tilbury Instant Look In A Palette, above, 69, in Beauty Glow, is perfect for popping in your purse for on the go - goof-proof glam, as it has everything a gal needs to get gorgeous.

This is the fourth versh released, and definitely my fave, as the rose-gold and bronze tones are darker and more dramatic. I found the previous versions a bit too wishy-washy colour-wise, whereas this slays.

TRIONA'S TOP TIP

'Summer lovin' had me a blast,

Summer lovin' happened so fast'

I love a bit of Grease, but not on my head!

However, if like me, you have long hair and it's leaving you hot and bothered this summer, why not try a chic model-off-duty topknot.

Kate Moss pulls this look off so well, making it look stylish and hot, yet so nice and cool, as the hair's up and off your neck.

Best of all, a high bun has a cheekbone-lifting effect, so it's a win-win.

Slick your hair back with Shockwaves Ultra Strong Power Hold Gel, above, 2.50, which also helps fight frizzy fine hairs around your forehead, making you look hot in a good way!

If you're hitting the beach, make sure to layer this Philip Kingsley Sun Shield, below, 30, marksandspencer.ie, as hair can burn just like the skin when it's left unprotected.

This super-lightweight nourishing mist provides an invisible shield of protection over the hair. I always make sure I have it in my beach bag for myself and Will and the kids.

Best of all, it guards against colour fade from sun exposure, and diminishes damage and dryness caused by UV rays, chlorine and salt water.

'Summer days driftin' away, to uh-oh those summer nights'

Sunday Independent

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Hot air: Triona McCarthy on how to smeel good - Independent.ie

When Shannon DeAndrea saw a knot on her 18-month-old sons head last July, she thought he had just fallen.

But more popped up and wouldnt go away. He also began feeling sick.

I finally decided he needed to see a pediatrician, said DeAndrea, who lives in Blairs.

She was told he had ear infections and her son, Nathan, was put on rounds of antibiotics. The knots were normal, she was told.

Another medical provider said he looked anemic. Blood work revealed his hemoglobin was dangerously low.

We ended up in the ER, DeAndrea said. They couldnt figure out why he was anemic.

Shannon and Nathan were sent to Roanoke, where he was diagnosed with a stage 4 neuroblastoma on Aug. 23. He had a tumor in his abdomen that spread to his bone marrow. He had spots on his skull, ribs and spine.

Neuroblastomas are cancers that begin in early nerve cells of the sympathetic nervous system, according to the American Cancer Society.

Since his diagnosis, her son now 2 has had several rounds of chemotherapy and two stem cell transplants and is doing well.

Now hes just like a normal 2-year-old, DeAndrea said. Hes running around with his sister. Hes eating well.

Dr. William Clark is associate professor of medicine and attending physician at Virginia Commonwealth University Massey Cancer Center Stem Cell Transplantation Program. Clark said the procedure is used for conditions including multiple myeloma, lymphoma, sickle cell anemia and leukemia.

Stem cell transplants are used to replace bone marrow that has been destroyed by cancer or destroyed by the chemo and/or radiation used to treat the cancer, according to the American Cancer Society.

High doses of chemo (sometimes along with radiation), work better than standard doses to kill cancer cells. However, high doses can also kill the stem cells and cause the bone marrow to stop making blood cells, which are needed for life. The transplanted stem cells replace the bodys stem cells after the bone marrow and its stem cells have been destroyed by treatment, according to the American Cancer Society.

Two types of stem cell transplants include autologous, which uses stem cells from the patients own body, and allogeneic using stem cells from another person, Clark said.

For leukemia patients, most of the time, we give them stem cells from someone else, Clark said. Chemotherapy helps lower the leukemia disease burden, but the new immune system provided by the new stem cells can fight against the cancer cells and get rid of them, he said.

Virginia Commonwealth Universitys cancer center performs an average of about 160-195 stem cell transplants per year, Clark said. Slightly more than half are autologous procedures, and the rest are allogeneic, he said.

Whitt Clement, former delegate who represented the Danville area in the General Assembly, underwent a stem cell transplant for acute myeloid leukemia in September 2015.

The most important aspect for patients is being self-aware and their own best advocates, Clement said.

My experience was that the patient has to ask a lot of questions throughout the process, he said.

He suspected something was wrong when he noticed his platelet count declining over seven years. He went to a hematologist and had a bone marrow biopsy that revealed his condition.

If I had not taken the initiative myself and gone to see a hematologist, matters would have progressed to the point where I would have been symptomatic, Clement said.

Finding the perfect match in a donor is also important, Clement said. Fortunately, he had a sibling who met all the criteria and donated stem cells.

A person can get great matches from unrelated donors, but its preferable for a donor to be a sibling, said Clement, partner at Hunton & Williams law firm in Richmond.

Your body has an easier time tolerating the new stem cells, he said.

Clement served in the Virginia House of Delegates from 1988-2002, and as Virginias secretary of transportation from 2002-2005 under Gov. Mark Warner.

For someone with multiple myeloma, the transplant does not cure the disease but delays the time it returns by up to seven and a half years, Clark said.

Lymphoma, leukemia and sickle cell anemia can be cured with the procedure, Clark said. Lymphoma can be cured in about 50 to 80 percent of cases, depending on the lymphoma, Clark said.

The first 30 days after the transplant are the most critical, Clement said. During that time, different organs can have varying reactions to the new cells. It can affect the kidneys, liver, gastrointestinal tract, skin, and cause other side effects.

The idea is that the closer the match, the less likely youll have those adverse reactions, he said.

The process includes being put on an immunosuppressant to prevent the immune system from attacking the new cells, Clement said.

He credits the quality of his recovery to asking lots of questions and being his own advocate tape recording conversations with medical providers, coming in with written questions.

Ive been able to recover better because of that, he said.

Its a long journey and so a person confronted with the transplant situation has got to prepare himself for a long journey that requires a lot of questions along the way, Clement said.

There are about 20 million potential stem cell/bone marrow donors in the BeTheMatch Registry in the United States, Clark said.

Stem cell transplants began in the late 50s/early 60s with the first successful procedure done in an identical twin, Clark said. However, stem cell transplants were limited until medicines that prevent rejections became available.

The number of procedures increased in the 1980s, Clark said.

Danville resident Susan Mathena, cancer patient navigator at Danville Regional Medical Center, became a donor about 20 years ago because she wanted to help people. Mathena has also been an organ donor since she got her drivers license.

I see patients all the time that need stem cell transplants, Mathena said. We always need a source of bone marrow donation.

Though she will age out of the stem cell donor list soon, she could still be contacted if she is the only match for someone in need, she said.

Clark will speak next month on stem cell/bone marrow transplants at Ballou Recreation Center at an event held by the Cancer Research and Resource Center of Southern Virginia in Danville.

Thousands of patients with blood cancers like leukemia or other diseases like sickle cell anemia need a bone marrow/stem cell transplant to survive, including some of our own community members, said Kate Stokely Powell, coordinator at the center.

Clarks presentation offers an opportunity in Southside for people battling illness, medical students and professionals and the public to learn from an expert in the field of stem cell transplants, Powell said.

Doctors, hospitals and families affected by a blood cancer disease have done a great job of building a massive database of blood types for potential donor matches, Clement said.

For DeAndrea and her son, Nathan, the first transplant included four or five days of chemo. The new stem cells following the chemo that killed off his old stem cells from the transplant were like a rescue, she said.

Its wiping you out and then giving you your cells back to restart your immune system, DeAndrea said.

A second round of heavy chemo was to try to kill what was left of the cancer and replenish cells, she said.

It was rough, it was a nightmare, DeAndrea said. It was by far the worst phase of his treatment, but I believe, in the long run, its worth it.

She said the procedures should increase Nathans chances for survival and prevent a relapse.

Nathan just finished radiation Tuesday and will go in for a biopsy of his bone marrow this week, DeAndrea said.

Well find out next week where we stand as far as the cancer goes, she said.

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After two stem cell transplants and several rounds of chemo, 'now he's just like a normal 2-year-old' - GoDanRiver.com

Featured post

Stem Cell Research is an amazing field right now, and promises to be a powerful and potent tool to help us live longer and healthier lives. Just last month, for example, Stem Cell Therapy was used to restore sight in patients with severe retinal deterioration, allowing them to see clearer than they had in years, or even decades.

Now, there is another form of Stem Cell Treatment on the horizonthis one of a very different form. Stem Cells have now been used as a mechanism to deliver medical treatment designed to eliminate cancer cells, even in hard to reach places. One issue with current cancer treatments is that, treatments that are effective at treating tumors on the surface of the brain cannot be performed safely when the tumor is deeper within the brains tissues.

Stem Cells have the fantastic ability to transform into any other kind of cell within the human body, given the appropriate stimulation. As of today, most of these cells come from Embryonic Lines, but researchers are learning how to backwards engineer cells in the human body, reverting them back to their embryonic state. These cells are known as Induced Pluripotent Stem Cells.

How Does This Stem Cell Cancer Treatment Work?

Using genetic engineering, it is possible to create stem cells that are designed to release a chemical known as Pseudomonas Exotoxin, which has the ability to destroy certain tumor cells in the human brain.

What is Pseudomonas Exotoxin?

Pseudomonas Exotoxin is a compound that is naturally released by a form of bacteria known as Pseudomonas Aeruginosa. This chemical is toxic to brain tumor cells because it prevents polypeptides from growing longer, essentially preventing the polypeptides from growing and reproducing. When used in a specific manner, this toxin has the ability to destroy cancerous and malignant tissue without negatively impacting healthy tissue. In addition to its potential as a cancer treatment, there is also evidence that the therapy could be used for the treatment of Hepatitis B.

PE and Similar Toxins Have been Used Therapeutically in the Past

As of now, this chemical, which we will refer to for the rest of the article as PE, has been used as a cancer treatment before, but there are major limitations regarding the use of PE for particular cancers, not because of the risks of the treatment, but because of the lack of an effective method to deliver the medication to where it is needed.

For example, similar chemicals have been highly effective in the treatment of a large number of blood cancers, but havent been nearly as effective in larger, more inaccessible tumors. The chemicals break down or become metabolized before they can fully do their job.

How do Stem Cells Increase the Effectiveness of PE Cancer Treatment

Right now, PE has to be created in a laboratory before it is administered, which is not very effective for these embedded cancers. By using Stem Cells as an intermediary, it is possible to deliver the medication to deeper areas of the brain more effectively, theoretically highly increasing the efficacy of the treatment.

The leader of this Stem Cell Research is Harvard researcher Dr. Khalis Shah. His goal was to find an effective means to treat these deep brain tumors which are not easily treated by methods available today. In utilizing Stem Cells, Dr. Shah has potentially found a means by which the stem cells can constantly deliver this Cancer Toxin to the tumor area. The cells remain active and are fed by the body, which allows them to provide a steady stream of treatment that is impossible to provide via any other known method.

This research is still in its early stages, and has not yet reached human trials, but in mice, the PE Toxin worked exactly as hypothesized and was able to starve out tumors by preventing them from replicating effectively.

Perhaps this might seem a bit less complicated than it actually is. One of the major hurdles that had to be overcome was that this Toxin would normally be strong enough to kill the cell that hosted it. In order for the Stem Cells to release the cancer, they had to be able to withstand the effects of PE, themselves. Using genetic engineering, Dr. Shah and his associates were able to create a cell that is capable of both producing and withstanding the effects of the toxin.

Stem Cell delivered medical therapy is a 21st century form of medical treatment that researchers are just beginning to learn how to effectively utilize. Essentially, this treatment takes a stem cell and converts it into a unique symbiotic tool capable of feeding off of the host for energy in order to perform a potentially life-saving function. Its really quite fascinating.

How Does PE Not Damage or Kill Brain Cells Indiscriminately?

You might be concerned about the idea of a patient having a toxin injected into the brain to cure a disease. It sounds almost like a dangerous, tribal, homeopathic remedy. In reality, the researchers have been able to harness the destructive power of the toxin and re-engineer it so that it directly targets cancer cells while having limited negative effects on healthy, non-cancerous tissue.

The toxin does its damage after it has been absorbed by a cell. By retooling the toxin so that it does not readily absorb into healthy cells, the dangers associated with having such a potentially dangerous toxin in the brain are seriously and significantly mitigated.

Beyond that, Dr. Shah and his associates have been able to take steps to effectively turn off PE while it is inside the host stem cell, and only activates when it has entered the cancerous tissue. Dr. Shah explains that, although this research has only been conducted in animal subjects, there is no known reason why the effectiveness and safety of the treatment would not be applicable to human patients.

In this treatment, surgeons remove as much of the tumor as possible from the brain, and insert the engineered Stem Cells submerged in a sterile gel in the area where the tumor was removed or partially still exists. Researchers found that, when they used this treatment on laboratory rats, they could tell through imaging and analysis that the modified PE toxin effectively killed the cancer cells, and that this cancer treatment effectively lengthened the life of the rat, as compared to control subjects.

Whats the Next Step?

Of course, cancer treatment is far more complex than a single treatment, no matter how effective that treatment may be. Because human cancer treatment is a comprehensive therapy approach, the end goal of this research is to create a form of therapy in which the method used in animal subjects is combined with other existing approaches, increasing and maximizing the effectiveness of the comprehensive treatment.

Featured post

A recent change in how well we understand stem cells may make it easier for scientists and researchers to gather stem cells for use in scientific research as well as medical application. A new study was released in the research publication, Cell, which was performed by representatives from the University of California San Francisco.

One of the issues which hinder the use of stem cells as a more widespread treatment or field of research is that researchers and patients have a bottleneck of available healthy stem cell lines which can be used for research. Researchers hope that this new discovery will allow future scientific discoveries and applications in the areas of creating new and healthy tissue for patients with kidney failure or any other form of organ tissue failure. The future of medical therapy lies with Stem Cell Research, but many other forms of treatment, including Hormone Replacement Therapy, are already in practice today.

Researchers have discovered that it is possible to essentially flip a switch in an adult cell, reverting it back to the preliminary state at which cells existed in one of the earliest stages of developmentthe embryonic stem cell. Medical researchers hypothesize that Stem Cell treatments could be used for a variety of medical health issues which plague the world today, including kidney failure, liver disease, and Type-1 and Type-2 Diabetes.

Use of Embryonic Stem Cells Contentious

There is an ethical issue in Stem Cell Research today. Many Pro-Life Advocates are vociferously against the use of Embryonic Stem Cells harvested from procedures such as fertility treatments designed for conception. They believe that the use of embryonic stem cells harvested from donors and couples looking to conceive is unethical.

Using current research, it may be possible to bypass this ethical quandary completely by using adult cells and converting them into embryonic stem cells. Furthermore, because these stem cells are genetic derivatives of the patient from which the adult cells were harvested, this potentially paves the way for patient-specific medical treatments using stem cells.

After adult cells have been converted back into Embryonic Stem Cells, it will be possible to convert them into any possible cell that the patient needs or would benefit from.

Hijacking the Blueprint of the Cell Allows Scientists to Revert Adult Cells to their Earliest State

Researchers have increased the capacity to produce Embryonic Stem Cells by identifying previously unrecognized biochemical processes which tell human cells how to develop. In essence, researchers have discovered how the body blueprints cells, and can change the blueprints so that a new cell is made.

By utilizing these newly recognized pathways, it is possible to create new stem cells more quickly than ever before. One of the researchers explains the implications of this research. Dr. Miguel Ramalho-Santos is an associate professor of obstetrics, medicine, and cancer research at the University of California San Francisco. Dr. Ramalho-Santos is also a member of the Broad Center of Regenerative Medicine and Stem Cell Research.

He explains that these stem cell discoveries have the ability to alter the way that the medical sciences can take advantage of stem cells with regard to both cancer research and regenerative medicine. Dr. Ramalho-Santos was the lead researcher for this study, and the research was largely funded by the Director of the National Institutes of Health New Innovator Award, granted to promising young researchers which are leading highly innovative and promising medical research studies.

Dr. Ramalho-Santos research builds off of earlier research which discovered that it was possible to take adult cells and turn them back into embryonic stem cells. These stem cells dont have any inherent aging processes, and they can be turned into any other kind of tissue. In the process of this conversion, the adult cells lose all of their unique characteristics, leaving them in an ultimately immature and malleable state.

This earlier research was conducted by researchers from UC San Francisco in partnership with Dr. Shinya Yamanaka from Kyoto University and Gladstone Institutes. These entities all gained a piece of the Nobel Prize in Physiology or Medicine from their part in the study.

Pluripotent Stem Cells vs. Embryonic Stem Cells

Thus far, weve described these cells as Embryonic Stem Cells, but in fact, the more accurate term for these cells are Induced Pluripotent Stem Cells (IPS). These cells are biologically and functionally similar to Embryonic Stem Cells, but have a different name because they are sourced from adult cells. The difference between Induced Pluripotent Stem Cells and Embryonic Stem Cells is that Induced Pluripotent Stem Cells do seem to retain some of the characteristics of their previous state, which appears to limit their ability to convert into any other type of cell. This new research identifies new pathways by which it may be possible to increase the number of cells that an individual IPS Cell can turn into, perhaps allowing them to convert into any other kind of human cell.

Induced Pluripotent Stem Cells are not explicitly considered an alternative to Embryonic Stem Cells, but are considered a different approach to produce similar cells. If researchers fully uncover the mechanisms of how to reprogram these cells, it will lower many barriers to stem cell research and the availability of stem cell treatments.

As of today, researchers have figured out how to make these Induced Pluripotent Stem Cells, but the percentage of adult cells which are reverted successfully is quite low, and frequently, these cells still show some aspects of specialization, which limits their use.

How Do Scientists Make Stem Cells From Adult Cells?

There are genes within every cell which have the ability to induce pluripotency, reverting the cell to an earlier stage of specialization. The initial stage of this process is the result of activating Yamanaka Factors, specific genes that initiate this reversion process.

As of today, this process of de-maturation is not completely understood, and researchers realized from the start that the cells they created were not truly identical to Embryonic Stem Cells, because they still showed signs of their former lives, which often prevented them from being successfully reprogrammed.

The new research conducted by Dr. Ramalho-Santos appears to increase our knowledge regarding how these cells work, and how to program them more effectively. Dr. Ramalho-Santos and his team discovered more genes associated with these programming/reprogramming processes, and by manipulating them, they have increased the viability and range of particular stem cells.

It appears that these genetic impulses are constantly at play to maintain the structure and function of a cell, and that by systematically removing these safeguards, it is possible to increase the ability to alter these cells.

This research increases researchers ability to produce these stem cells, by increasing the ability of medical scientists to produce adequate numbers of stem cells, while also increasing the range of potential treatment options by more effectively inducing the total pluripotency which is available in Embryonic Stem Cells. This research may also help scientists treat certain forms of cancer which are the result of malfunctions of these genes.

Introduction

[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

[Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

The genetics of skin cancer is an extremely broad topic. There are more than 100 types of tumors that are clinically apparent on the skin; many of these are known to have familial components, either in isolation or as part of a syndrome with other features. This is, in part, because the skin itself is a complex organ made up of multiple cell types. Furthermore, many of these cell types can undergo malignant transformation at various points in their differentiation, leading to tumors with distinct histology and dramatically different biological behaviors, such as squamous cell carcinoma (SCC) and basal cell cancer (BCC). These have been called nonmelanoma skin cancers or keratinocytic cancers.

Figure 1 is a simple diagram of normal skin structure. It also indicates the major cell types that are normally found in each compartment. Broadly speaking, there are two large compartmentsthe avascular cellular epidermis and the vascular dermiswith many cell types distributed in a largely acellular matrix.[1]

Figure 1. Schematic representation of normal skin. The relatively avascular epidermis houses basal cell keratinocytes and squamous epithelial keratinocytes, the source cells for BCC and SCC, respectively. Melanocytes are also present in normal skin and serve as the source cell for melanoma. The separation between epidermis and dermis occurs at the basement membrane zone, located just inferior to the basal cell keratinocytes.

The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations. The bottom layer is formed of basal keratinocytes abutting the basement membrane. The basement membrane is formed from products of keratinocytes and dermal fibroblasts, such as collagen and laminin, and is an important anatomical and functional structure. As the basal keratinocytes divide and differentiate, they lose contact with the basement membrane and form the spinous cell layer, the granular cell layer, and the keratinized outer layer or stratum corneum.

The true cytologic origin of BCC remains in question. BCC and basal cell keratinocytes share many histologic similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name rodent ulcer.[3]

Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source. Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can transform into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Langerhans cells, or dendritic cells, are a third cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[5]

The dermis is largely composed of an extracellular matrix. Prominent cell types in this compartment are fibroblasts, endothelial cells, and transient immune system cells. When transformed, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, and other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[6]

Epidermal appendages are also found in the dermal compartment. These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles. These structures are generally formed in the first and second trimesters of fetal development. These can form a large variety of benign or malignant tumors with diverse biological behaviors. Several of these tumors are associated with familial syndromes. Overall, there are dozens of different histological subtypes of these tumors associated with individual components of the adnexal structures.[7]

Finally, the subcutis is a layer that extends below the dermis with varying depth, depending on the anatomic location. This deeper boundary can include muscle, fascia, bone, or cartilage. The subcutis can be affected by inflammatory conditions such as panniculitis and malignancies such as liposarcoma.[8]

These compartments give rise to their own malignancies but are also the region of immediate adjacent spread of localized skin cancers from other compartments. The boundaries of each skin compartment are used to define the staging of skin cancers. For example, an in situ melanoma is confined to the epidermis. Once the cancer crosses the basement membrane into the dermis, it is invasive. Internal malignancies also commonly metastasize to the skin. The dermis and subcutis are the most common locations, but the epidermis can also be involved in conditions such as Pagetoid breast cancer.

The skin has a wide variety of functions. First, the skin is an important barrier preventing extensive water and temperature loss and providing protection against minor abrasions. These functions can be aberrantly regulated in cancer. For example, in the erythroderma associated with advanced cutaneous T-cell lymphoma, alterations in the regulations of body temperature can result in profound heat loss. Second, the skin has important adaptive and innate immunity functions. In adaptive immunity, antigen-presenting cells engender a TH1, TH2, and TH17 response.[9] In innate immunity, the immune system produces numerous peptides with antibacterial and antifungal capacity. Consequently, even small breaks in the skin can lead to infection. The skin-associated lymphoid tissue is one of the largest arms of the immune system. It may also be important in immune surveillance against cancer. Immunosuppression, which occurs during organ transplant, is a significant risk factor for skin cancer. The skin is significant for communication through facial expression and hand movements. Unfortunately, areas of specialized function, such as the area around the eyes and ears, are common places for cancer to occur. Even small cancers in these areas can lead to reconstructive challenges and have significant cosmetic and social ramifications.[1]

While the appearance of any one skin cancer can vary, there are general physical presentations that can be used in screening. BCCs most commonly have a pearly rim (see Figure 3) or can appear somewhat eczematous. They often ulcerate (see Figure 3). SCCs frequently have a thick keratin top layer (see Figure 4). Both BCCs and SCCs are associated with a history of sun-damaged skin. Melanomas are characterized by asymmetry, border irregularity, color variation, a diameter of more than 6 mm, and evolution (ABCDE criteria). (Refer to What Does Melanoma Look Like? on NCIs website for more information about the ABCDE criteria.) Photographs representing typical clinical presentations of these cancers are shown below.

Enlarge

Figure 2. Superficial basal cell carcinoma (left panel) and nodular basal cell carcinoma (right panel).

Enlarge

Figure 3. Ulcerated basal cell carcinoma (left panel) and ulcerated basal cell carcinoma with characteristic pearly rim (right panel).

Enlarge

Figure 4. Squamous cell carcinoma on the face with thick keratin top layer (left panel) and squamous cell carcinoma on the leg (right panel).

Enlarge

Figure 5. Melanomas with characteristic asymmetry, border irregularity, color variation, and large diameter.

Basal cell carcinoma (BCC) is the most common malignancy in people of European descent, with an associated lifetime risk of 30%.[1] While exposure to ultraviolet (UV) radiation is the risk factor most closely linked to the development of BCC, other environmental factors (such as ionizing radiation, chronic arsenic ingestion, and immunosuppression) and genetic factors (such as family history, skin type, and genetic syndromes) also potentially contribute to carcinogenesis. In contrast to melanoma, metastatic spread of BCC is very rare and typically arises from large tumors that have evaded medical treatment for extended periods of time. BCCs can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name rodent ulcer. With early detection, the prognosis for BCC is excellent.

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types. There are different patterns of sun exposure associated with each major type of skin cancer (BCC, squamous cell carcinoma [SCC], and melanoma).

While there is no standard measure, sun exposure can be generally classified as intermittent or chronic, and the effects may be considered acute or cumulative. Intermittent sun exposure is obtained sporadically, usually during recreational activities, and particularly by indoor workers who have only weekends or vacations to be outdoors and whose skin has not adapted to the sun. Chronic sun exposure is incurred by consistent, repetitive sun exposure, during outdoor work or recreation. Acute sun exposure is obtained over a short time period on skin that has not adapted to the sun. Depending on the time of day and a persons skin type, acute sun exposure may result in sunburn. In epidemiology studies, sunburn is usually defined as burn with pain and/or blistering that lasts for 2 or more days. Cumulative sun exposure is the additive amount of sun exposure that one receives over a lifetime. Cumulative sun exposure may reflect the additive effects of intermittent sun exposure, chronic sun exposure, or both.

Specific patterns of sun exposure appear to lead to different types of skin cancer among susceptible individuals. Intense intermittent recreational sun exposure has been associated with melanoma and BCC,[2,3] while chronic occupational sun exposure has been associated with SCC. Given these data, dermatologists routinely counsel patients to protect their skin from the sun by avoiding mid-day sun exposure, seeking shade, and wearing sun-protective clothing, although evidence-based data for these practices are lacking. The data regarding skin cancer risk reduction by regular sunscreen use are variable. One randomized trial of sunscreen efficacy demonstrated statistically significant protection for the development of SCC but no protection for BCC,[4] while another randomized study demonstrated a trend for reduction in multiple occurrences of BCC among sunscreen users [5] but no significant reduction in BCC or SCC incidence.[6]

Level of evidence (sun-protective clothing, avoidance of sun exposure): 4aii

Level of evidence (sunscreen): 1aii

Tanning bed use has also been associated with an increased risk of BCC. A study of 376 individuals with BCC and 390 control subjects found a 69% increased risk of BCC in individuals who had ever used indoor tanning.[7] The risk of BCC was more pronounced in females and individuals with higher use of indoor tanning.[8]

Environmental factors other than sun exposure may also contribute to the formation of BCC and SCC. Petroleum byproducts (e.g., asphalt, tar, soot, paraffin, and pitch), organophosphate compounds, and arsenic are all occupational exposures associated with cutaneous nonmelanoma cancers.[9-11]

Arsenic exposure may occur through contact with contaminated food, water, or air. While arsenic is ubiquitous in the environment, its ambient concentration in both food and water may be increased near smelting, mining, or coal-burning establishments. Arsenic levels in the U.S. municipal water supply are tightly regulated; however, control is lacking for potable water obtained through private wells. As it percolates through rock formations with naturally occurring arsenic, well water may acquire hazardous concentrations of this material. In many parts of the world, wells providing drinking water are contaminated by high levels of arsenic in the ground water. The populations in Bangladesh, Taiwan, and many other locations have high levels of skin cancer associated with elevated levels of arsenic in the drinking water.[12-16] Medicinal arsenical solutions (e.g., Fowlers solution and Bells asthma medication) were once used to treat common chronic conditions such as psoriasis, syphilis, and asthma, resulting in associated late-onset cutaneous malignancies.[17,18] Current potential iatrogenic sources of arsenic exposure include poorly regulated Chinese traditional/herbal medications and intravenous arsenic trioxide utilized to induce remission in acute promyelocytic leukemia.[19,20]

Aerosolized particulate matter produced by combustion of arsenic-containing materials is another source of environmental exposure. Arsenic-rich coal, animal dung from arsenic-rich regions, and chromated copper arsenatetreated wood produce airborne arsenical particles when burned.[21-23] Burning of these products in enclosed unventilated settings (such as for heat generation) is particularly hazardous.[24]

Clinically, arsenic-induced skin cancers are characterized by multiple recurring SCCs and BCCs occurring in areas of the skin that are usually protected from the sun. A range of cutaneous findings are associated with chronic or severe arsenic exposure, including pigmentary variation (poikiloderma of the skin) and Bowen disease (SCC in situ).[25]

However, the effect of arsenic on skin cancer risk may be more complex than previously thought. Evidence from in vivo models indicate that arsenic, alone or in combination with itraconazole, can inhibit the hedgehog pathway in cells with wild-type or mutated Smoothened by binding to GLI2 proteins; in this way, these drugs demonstrated inhibition of BCC growth in these animal models.[26,27] Additionally, the effect of arsenic on skin cancer risk may be modified by certain variants in nucleotide excision repair genes (xeroderma pigmentosum [XP] types A and D).[28]

The high-risk phenotype consists of individuals with the following physical characteristics:

Specifically, people with more highly pigmented skin demonstrate lower incidence of BCC than do people with lighter pigmented skin. Individuals with Fitzpatrick skin types I or II were shown to have a twofold increased risk of BCC in a small case-control study.[29] (Refer to the Pigmentary characteristics section in the Melanoma section of this summary for a more detailed discussion of skin phenotypes based upon pigmentation.) Blond or red hair color was associated with increased risk of BCC in two large cohorts: the Nurses Health Study and the Health Professionals Follow-Up Study.[30]

Immunosuppression also contributes to the formation of nonmelanoma (keratinocyte) skin cancers. Among solid-organ transplant recipients, the risk of SCC is 65 to 250 times higher, and the risk of BCC is 10 times higher than in the general population.[31-33] Nonmelanoma skin cancers in high-risk patients (i.e., solid-organ transplant recipients and chronic lymphocytic leukemia patients) occur at a younger age and are more common, more aggressive, and have a higher risk of recurrence and metastatic spread than nonmelanoma skin cancers in the general population.[34,35] Among patients with an intact immune system, BCCs outnumber SCCs by a 4:1 ratio; in transplant patients, SCCs outnumber BCCs by a 2:1 ratio.

This increased risk has been linked to the level of immunosuppression and UV exposure. As the duration and dosage of immunosuppressive agents increases, so does the risk of cutaneous malignancy; this effect is reversed with decreasing the dosage of, or taking a break from, immunosuppressive agents. Heart transplant recipients, requiring the highest rates of immunosuppression, are at much higher risk of cutaneous malignancy than liver transplant recipients, in whom much lower levels of immunosuppression are needed to avoid rejection.[31,36] The risk appears to be highest in geographic areas of high UV radiation exposure: when comparing Australian and Dutch organ transplant populations, the Australian patients carried a fourfold increased risk of developing SCC and a fivefold increased risk of developing BCC.[37] This speaks to the importance of rigorous sun avoidance among high-risk immunosuppressed individuals.

Individuals with BCCs and/or SCCs report a higher frequency of these cancers in their family members than do controls. The importance of this finding is unclear. Apart from defined genetic disorders with an increased risk of BCC, a positive family history of any skin cancer is a strong predictor of the development of BCC.

A personal history of BCC or SCC is strongly associated with subsequent BCC or SCC. There is an approximate 20% increased risk of a subsequent lesion within the first year after a skin cancer has been diagnosed. The mean age of occurrence for these nonmelanoma skin cancers is the mid-60s.[38-43] In addition, several studies have found that individuals with a history of skin cancer have an increased risk of a subsequent diagnosis of a noncutaneous cancer;[44-47] however, other studies have contradicted this finding.[48-51] In the absence of other risk factors or evidence of a defined cancer susceptibility syndrome, as discussed below, skin cancer patients are encouraged to follow screening recommendations for the general population for sites other than the skin.

Mutations in the gene coding for the transmembrane receptor protein PTCH1, or PTCH, are associated with basal cell nevus syndrome (BCNS) and sporadic cutaneous BCCs. PTCH1, the human homolog of the Drosophila segment polarity gene patched (ptc), is an integral component of the hedgehog signaling pathway, which serves many developmental (appendage development, embryonic segmentation, neural tube differentiation) and regulatory (maintenance of stem cells) roles.

In the resting state, the transmembrane receptor protein PTCH1 acts catalytically to suppress the seven-transmembrane protein Smoothened (Smo), preventing further downstream signal transduction.[52] Stoichiometric binding of the hedgehog ligand to PTCH1 releases inhibition of Smo, with resultant activation of transcription factors (GLI1, GLI2), cell proliferation genes (cyclin D, cyclin E, myc), and regulators of angiogenesis.[53,54] Thus, the balance of PTCH1 (inhibition) and Smo (activation) manages the essential regulatory downstream hedgehog signal transduction pathway. Loss-of-function mutations of PTCH1 or gain-of-function mutations of Smo tip this balance toward constitutive activation, a key event in potential neoplastic transformation.

Demonstration of allelic loss on chromosome 9q22 in both sporadic and familial BCCs suggested the potential presence of an associated tumor suppressor gene.[55,56] Further investigation identified a mutation in PTCH1 that localized to the area of allelic loss.[57] Up to 30% of sporadic BCCs demonstrate PTCH1 mutations.[58] In addition to BCC, medulloblastoma and rhabdomyosarcoma, along with other tumors, have been associated with PTCH1 mutations. All three malignancies are associated with BCNS, and most people with clinical features of BCNS demonstrate PTCH1 mutations, predominantly truncation in type.[59]

Truncating mutations in PTCH2, a homolog of PTCH1 mapping to chromosome 1p32.1-32.3, have been demonstrated in both BCC and medulloblastoma.[60,61] PTCH2 displays 57% homology to PTCH1, differing in the conformation of the hydrophilic region between transmembrane portions 6 and 7, and the absence of C-terminal extension.[62] While the exact role of PTCH2 remains unclear, there is evidence to support its involvement in the hedgehog signaling pathway.[60,63]

BCNS, also known as Gorlin Syndrome, Gorlin-Goltz syndrome, and nevoid basal cell carcinoma syndrome, is an autosomal dominant disorder with an estimated prevalence of 1 in 57,000 individuals.[64] The syndrome is notable for complete penetrance and extremely variable expressivity, as evidenced by evaluation of individuals with identical genotypes but widely varying phenotypes.[59,65] The clinical features of BCNS differ more among families than within families.[66] BCNS is primarily associated with germline mutations in PTCH1, but families with this phenotype have also been associated with alterations in PTCH2 and SUFU.[67-69]

As detailed above, PTCH1 provides both developmental and regulatory guidance; spontaneous or inherited germline mutations of PTCH1 in BCNS may result in a wide spectrum of potentially diagnostic physical findings. The BCNS mutation has been localized to chromosome 9q22.3-q31, with a maximum logarithm of the odd (LOD) score of 3.597 and 6.457 at markers D9S12 and D9S53.[64] The resulting haploinsufficiency of PTCH1 in BCNS has been associated with structural anomalies such as odontogenic keratocysts, with evaluation of the cyst lining revealing heterozygosity for PTCH1.[70] The development of BCC and other BCNS-associated malignancies is thought to arise from the classic two-hit suppressor gene model: baseline heterozygosity secondary to germline PTCH1 mutation as the first hit, with the second hit due to mutagen exposure such as UV or ionizing radiation.[71-75] However, haploinsufficiency or dominant negative isoforms have also been implicated for the inactivation of PTCH1.[76]

The diagnosis of BCNS is typically based upon characteristic clinical and radiologic examination findings. Several sets of clinical diagnostic criteria for BCNS are in use (refer to Table 1 for a comparison of these criteria).[77-80] Although each set of criteria has advantages and disadvantages, none of the sets have a clearly superior balance of sensitivity and specificity for identifying mutation carriers. The BCNS Colloquium Group proposed criteria in 2011 that required 1 major criterion with molecular diagnosis, two major criteria without molecular diagnosis, or one major and two minor criteria without molecular diagnosis.[80] PTCH1 mutations are found in 60% to 85% of patients who meet clinical criteria.[81,82] Most notably, BCNS is associated with the formation of both benign and malignant neoplasms. The strongest benign neoplasm association is with ovarian fibromas, diagnosed in 14% to 24% of females affected by BCNS.[74,78,83] BCNS-associated ovarian fibromas are more likely to be bilateral and calcified than sporadic ovarian fibromas.[84] Ameloblastomas, aggressive tumors of the odontogenic epithelium, have also been proposed as a diagnostic criterion for BCNS, but most groups do not include it at this time.[85]

Originally posted here: IPS Cell Therapy IPS Cell Therapy

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IPS Cell Therapy IPS Cell Therapy - genetherapy.me

Photo of Jonathan Pitre and his mother, Tina Boileau, taken in Minnesota. Tina Boileau / -

Doctors in a Minnesota hospital continue to search for answers to a mysterious infection that has left Jonathan Pitre feverish, nauseated and short of breath.

Pitre, 17, of Russell, has been in the University of Minnesota Masonic Childrens Hospital for the past two weeks, suffering from an array of complications more two months after his stem cell transplant. Doctors are also trying to adjust his medications to better deal with his increased pain levels.

Hes having a tough run, said his mother, Tina Boileau, and I really dont know when it will get better.

The teenager suffers from a severe form of epidermolysis bullosa (EB), a painful and progressive skin disease that has left deep, open wounds on his body.

Last week, Pitres face and neck became swollen in response to what doctors believed was some kind of viral infection. That swelling has been brought under control, but a battery of tests has yet to reveal the source of the infection, which continues to cause problems.

Pitres breathing is laboured and hes running a high-grade fever of about 104 F (40 C); he has also developed bleeding and painful sores in his mouth.

We still have no idea what were dealing with, said Boileau. Its frustrating because Im at the point where it would be nice to see that all that Jonathan has gone through has been worth it.

Doctors are monitoring Pitre for graft-versus-host-disease (GVHD), but all of his tests have so far been inconclusive.Anyone who receives stem cells from another person is at risk of developing GVHD, a condition in which the donors white blood cells turn on the patients own tissues and attack them as foreign. It can range from mild to life-threatening.

About one-third of the almost 50 EB patients who have had a stem cell transplant at the Masonic Childrens Hospital have experienced the condition.

Pitre checked back into hospital earlier this month just three days after being released following a stem cell transplant that had successfully taken root in his bone marrow. Bone marrow stem cells produce most of the bodys blood cells, and are responsible for arming its immune system.

Pitre has been in Minnesota since mid-February to undergo the transplant, his second. The first ended in disappointment on Thanksgiving Day last year.

Tests show Pitres latest transplant remains fully engrafted, and there are signs that it has started to improve the condition of his skin.

Originally posted here:
Jonathan Pitre still ailing as doctors search for answers - Ottawa Citizen

Richard Sennott, Star Tribune file During a family portrait in 2000, Molly Nash gives her 4-week-old brother, Adam, a kiss. Molly Nash received some umbilical blood from her brother, saving her from a fatal genetic disease.

Adam Nash was dubbed Little Frankenstein by the New York Post in 2000 because he was conceived via in vitro fertilization specifically so doctors at the University of Minnesota could collect stem cells from his umbilical cord blood to save his sister, Molly.

Today, back home in Colorado, Adam has a drivers license and helps disabled children ski. His sister once weeks from death due to a condition called Fanconi anemia is debating whether to focus on oceanography or graphic design in college. And IVF to produce an ideal child for a siblings stem cell transplant is common, albeit with lingering ethics concerns.

A squirrelly trio of teens is vindication for Adams mother, Lisa Nash, who felt the weight of the ethical questions when the Us Dr. John Wagner suggested IVF in 1995.

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'Little Frankenstein,' conceived so Minnesota doctors could save sister, is now a happy teen - Minneapolis Star Tribune

Bellicum Pharmaceuticals Inc (NASDAQ: BLCM) was at its volatile best all this week. After a 14-percent gain Monday, the stock pulled back slightly Tuesday and retreated by less than 2 percent Wednesday.

It rallied over 10 percent Thursday, only to slip by about 7 percent Friday amid the Bellicum's presentation at the European Hematology Association conference, in Spain.

Bellicum Pharma is into the business of developing cellular immunotherapies for various forms of cancer, including both hematological and solid tumors, as well as orphan inherited blood disorder.

Following Bellicum's update at the EHA meeting, Cantor Fitzgerald said the company announced additional data from its ongoing phase 1/2 study with BPX-501 in patients receiving blood stem cell transplant due to malignant and non-malignant blood diseases. The data provided in the update was from 98 patients at 180-days of follow up or greater, as opposed to the 81 number reported previously in the abstract.

Giving the key takeaways, analysts Elemer Piros and Justin Kim said:

GvHD occurs after the transplant of a bone marrow or stem cell belonging to another individual, as the transplanted cells treat the recipient's body as foreign and attack it.

Detailing the data, Cantor Fitzgerald said BPX-501 treatment led to a 5-percent rate of transplant-related mortality, with a 3-percent non-relapse mortality and 15-percent disease relapse rate among malignant disease patients. The performance of the patients, according to the firm, was well above historical matched unrelated donor, or MUD, publications. The results of the study showed 6878 percent 1-year overall survival.

Source: Bellicum Pharma

The firm reminded that the E.U. primary endpoint of the study would assess event-free survival composite of death, GvHD and infection at six months compared with approximately 40 matched MUD patients.

"We expect the observation MUD study, which is in the process of being initiated, to provide relevant context for BPX-501," the firm said.

The firm estimates that an additional $100 million in capital is required to reach commercialization, which it thinks could be sourced from potential licensing fees or from issuing new equity.

A such, Cantor Fitzgerald reiterated its Overweight rating on the shares of Bellicum and the $35 price target it has for its shares.

At time of writing, Bellicum shares were down a steep 7.33 percent at $12.95.

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Despite A Volatile Trading Week, Bellicum's EHA Presentation Merits A Second Look - Benzinga

SOUTH SAN FRANCISCO, CA--(Marketwired - June 22, 2017) - VistaGen Therapeutics Inc.(NASDAQ: VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, announced today a peer-reviewed publication in the Scandinavian Journal of Pain of two Phase 1 clinical studies of the effects of AV-101 (4-Cl-KYN), the Company's CNS prodrug candidate, as a potential non-opioid treatment for neuropathic pain. Safety data from both the single and multi-dose Phase 1 studies indicated that oral AV-101 was extremely safe and well tolerated, with no meaningful difference in adverse events (AEs) at any dose between AV-101 and placebo. Recently published statistically-significant positive results in four well-established preclinical models of pain associated with tissue inflammation and nerve injury, together with the excellent clinical safety profile, pharmacokinetic (PK) characteristics and consistent reductions in three pain measures (allodynia, mechanical and heat hyperalgesia) demonstrated by these studies, support future Phase 2 clinical studies of AV-101 as a potential new non-opioid treatment alternative for neuropathic pain.

The publication, titled "Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study: Investigation of the Safety, Pharmacokinetics, and Antihyperalgesic Activity of L-4 chlorokynurenine in Healthy Volunteers," by lead author, Mark Wallace, MD, and co-authors, Alexander White, MD, Kathy A Grako, PhD, Randal Lane, Allen (Jo) Cato, PhD and H. Ralph Snodgrass, PhD, was recently published in the Scandinavian Journal of Pain (DOI: 10.1016/j.sjpain.2017.05.004) and is available online at http://www.scandinavianjournalpain.com/article/S1877-8860(17)30128-3/fulltext.

"The excellent safety data and consistent reductions in allodynia pain and mechanical and heat hyperalgesia during the two Phase 1 clinical studies of AV-101 support our belief in its potential to treat neuropathic pain without the negative side-effects experienced with most of the drugs used today to treat pain. Additional clinical trials of AV-101 in neuropathic pain are warranted," reported Mark Wallace, MD, Distinguished Professor of Clinical Anesthesiology at the University of California, San Diego.

"The positive results published in these studies further support our belief that AV-101 has the potential to reduce pain effectively and safely, without causing burdensome side effects like gabapentin and many other neuropathic pain treatments, such as opiates, on the market today. The opioid epidemic, which stems in part from prescribing opiate analgesics for outpatient procedures, makes it imperative that we find new analgesics devoid of abuse potential. Importantly, AV-101 does not bind to opioid receptors, and yet may still have efficacy in neuropathic pain," stated Mark A. Smith, MD, PhD, Chief Medical Officer, VistaGen Therapeutics. "Additionally, a key observation from these Phase 1 studies in normal volunteers was spontaneous reports of 'feelings of well-being' in subjects exposed to AV-101, especially those in the highest dose group of 1440 mg, while none of the subjects on placebo reported any such feelings. Importantly, these feelings were NOT characterized as feeling intoxicated or psychotic as has been often reported by subjects taking ketamine for major depressive disorder. We are optimistic about AV-101's potential as a new treatment alternative for major depressive disorder, without ketamine-like side effects, and for neuropathic pain, without gabapentin-like side effects or opioid abuse potential."

Study Summary and Key Findings:

Two Phase 1 Clinical Studies -

About AV-101AV-101 (4-CI-KYN) is an oral CNS prodrug candidate in Phase 2 development in the U.S., initially as a new generation treatment for major depressive disorder (MDD). AV-101 also has broad potential utility in several other CNS indications where modulation of NMDA receptors, activation of AMPA pathways and/or key active metabolites of AV-101 may achieve therapeutic benefit, including neuropathic pain and epilepsy, as well as addressing symptoms associated with neurodegenerative diseases, such as Parkinson's disease and Huntington's disease.

AV-101 is currently being evaluated in a Phase 2 monotherapy study in MDD, a study being fully funded by the U.S. National Institute of Mental Health (NIMH) and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, as Principal Investigator.

VistaGen is preparing to advance AV-101 into a 180-patient, U.S. multi-center, Phase 2 adjunctive treatment study in MDD patients with an inadequate response to standard FDA-approved antidepressants, with Dr. Maurizio Fava of Harvard University as Principal Investigator.

About VistaGenVistaGen Therapeutics, Inc. (NASDAQ: VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is in Phase 2 development, initially as a new generation oral antidepressant drug candidate for major depressive disorder (MDD). AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Huntington's disease, and L-Dopa-induced dyskinesias associated with Parkinson's disease and, other disorders where modulation of NMDA receptors, activation of AMPA pathways and/or key active metabolites of AV-101 may achieve therapeutic benefit.

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell technology, internally and with collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking StatementsThe statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, including neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the Phase 2 clinical development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

Excerpt from:
VistaGen Announces Peer-Reviewed Publication in the Scandinavian Journal of Pain Highlighting Orally-Available AV ... - Markets Insider

A BRAVE Barrow girl is delighted to be back at school after eight months away fighting leukemia and recovering from complications following a stem cell transplant.

Bubbly Aimee Robinson returned to St James' CE Junior School this week to a warm welcome from her friends and teachers, who have all missed having her at the Barrow primary.

The eleven-year-old last attended the Blake Street school for three weeks in September as she is a patient at the Royal Manchester Children's Hospital, where she has battled leukemia.

Following aggressive chemotherapy, Aimee had a stem cell transplant using umbilical cord blood. She did well following the transplant and spent time in isolation. But she later developed graft versus host disease. This is when particular types of white blood cell in the donated bone marrow or stem cells attack a bodies own cells.

Aimee had to spend further time in isolation as she recovered from GVHD.

Aimee, who was first diagnosed with leukemia in January 2016, is now in remission and the treatment for GVHD is also working. She was eventually allowed home to Barrow last month, but she has treatment at the Manchester hospital every fortnight.

Medics then gave her the okay to return to school this week to complete her final year of primary school, Year Six, before she prepares to attend Furness Academy in September.

Aimee, who is a house captain and school council member at St James' school, said: "It feels great to be at school with my friends. St James' is the best school ever."

Her great friend Abbie Gelling, 11, said it is really great to have Aimee back, as they had to keep in touch through FaceTime, texts and letters.

Angela Rawlinson, the headteacher at St James' CE Junior School, said: "We are so thrilled to have Aimee back at school. It's such great news. Aimee loves school and learning.

"It was very important for Aimee to get back to school before they all move on to secondary school."

The St James' school community raised 3,000 to help Aimee and her family who have spent so much time away from home. The community also fundraised to support the pupil.

Aimee has been doing her schooling at hospital with input from St James' school.

Aimee's mum Joanne Robinson, said: "Aimee has been raring to get back to school, she missed all her friends and teachers. She wanted to go back as soon as possible.

"Nothing bothers Aimee, she just gets on with it. She is a superstar.

"There is no sign of the leukemia now, her bone marrow is working brilliantly."

Mrs Robinson thanked all the medics, the St James' community and the wider community.

She said: "Thank you to everyone for the love and support they have given our family over the past 18 months and for the support we continue to receive."

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Brave Aimee delighted to be back at Barrow school after months in hospital - NW Evening Mail

Fiona Geekie, a nurse practitioner for TheCentral London Community Healthcare NHS Trust, donated bone marrow to a person she had never met earlier this year.

According to Fiona, about 2,000 people in the UK require a bone marrow or stem cell transplant every year.

For most of them its their last chance of surviving blood cancer, she added.

The nurse, who is a member of the Merton enhanced rapid intervention team,described why she went on the register to donate through the Anthony Nolan Trust 15 years ago.

Three quarters cant find a matching donor in their family so rely upon the generosity of a complete stranger already on the bone marrow register. So I joined up, it was simple.

Last Christmas Fiona was called for blood tests as she was a possible match for someone.

I was surprised to be called in the first place and I must confess I was a little apprehensive, Fiona admitted.

However, she continued: But then I thought what if someone in my family needed a bone marrow transplant. Its the most fantastic gift you can give to total stranger.

After donating, Fiona said she felt quite emotional and wanted the recipient to get well again.

She concluded: Overall, it was a wonderful experience and I have no hesitation in recommending all young people aged 16-30 to consider joining the bone marrow donor register.

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Nurse goes the extra mile and donates bone marrow to a complete stranger through the Anthony Nolan Trust - Your Local Guardian

June 23, 2017

Imagine being able to take cells from your skin, transform them into other types of cells, such as lung, brain, heart or muscle cells, and use those to cure your ailments, from diabetes to heart disease or macular degeneration. To realise this, however, challenges still remain, Professor Janet Rossant, a pioneer in the field, says.

All across the world, scientists have begun clinical trials to try and do just that, by making use of the incredible power and versatility of stem cells, which are special cells that can make endless copies of themselves and transform into every other type of cell.

While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. The scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.

"There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants," said Professor Janet Rossant, a pioneer in the field.

The mouse that changed everything

A speaker at the recent Commonwealth Science Conference 2017 held in Singapore and organised by Britain's Royal Society and Singapore's National Research Foundation, Prof Rossant gave an overview of stem cells' origins, history, uses and potential.

Now a senior scientist at The Hospital for Sick Children (also known as Sick Kids) in Toronto, Canada, after a decade as its chief of research, she was the first scientist to demonstrate the full power of stem cells in mice.

In the early 1990s, scientists believed that stem cells could only become certain types of cells and carry out limited functions. Based on her own research and that of others, however, Prof Rossant believed that they were capable of far more.

Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. "We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish," she said.

"That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body," she added.

When scientists learned how to remove stem cells from human embryos in 1998, however, controversy ensued. Many lobbied against the cells' use in medical research and treatment due to the moral implications of destroying even unwanted embryos to gain the cells.

In Canada, Prof Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field. These guidelines helped to keep the field alive in Canada, and were influential well beyond the country's borders.

In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These revolutionary, induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.

The challenges in the way

While stem cells have been used for medical treatment in some cases bone marrow transplants, for example, are a form of stem cell therapy there are several challenges that need to be overcome before they can be used more widely to treat diseases and injuries.

"We need to get better at turning stem cells into the fully mature cells that you need for therapy. That's going to take more work. Another issue is that of scale-up. If you're going to treat a patient, you need to be able to grow millions of cells," said Prof Rossant.

She added: "Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that's also one of the most scary things about them, because that's also how cancer works.

"Furthermore, because we need to genetically manipulate cells to get IPS cells, it's very hard to know whether we've got completely normal cells at the end of the day. These are all issues that need to be resolved."

She noted that some scientists are working on making "failsafe" IPS cells, which have a built-in self-destruct option if they become dangerous. "Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration," she said.

In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and test drugs. "That's the biggest use of IPS cells right now," Prof Rossant said.

Sick kids and how to help them

At SickKids, which is Canada's largest paediatric research hospital, she has been using stem cells to study cystic fibrosis, a frequently fatal genetic disorder that causes mucus to build up and clog some organs such as the lungs. It affects primarily children and young adults.

SickKids discovered the CFTR gene that, when mutated, causes the disease. It was also the first to produce mature lung cells, from stem cells, that can be used to study the disease and test drugs against it.

Even better, Prof Rossant and her team were able to turn skin cells from cystic fibrosis patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalising treatment for each patient.

"Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug," Prof Rossant explained. "With our work, we can make sure that each patient gets the right drug at the right time."

In 1998, Prof Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placenta defects and pregnancy problems.

By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs' effectiveness and uncover potential side effects, as well as develop personalised medicines.

"There are still huge amounts of opportunities in pluripotent stem cells," said Prof Rossant, who has won numerous awards for her research, including the Companion of the Order of Canada and the 2016 Friesen International Prize in Health Research.

She is also president and scientific director of the Toronto-based Gairdner Foundation, which recognises outstanding biomedical research worldwide, and a professor at the University of Toronto's molecular genetics, obstetrics and gynaecology departments.

"Meetings like the Commonwealth Science Conference are a fantastic opportunity for scientists to come together, learn about each other's work and establish new relationships, which will help to push science forward, including in stem cell research," she said.

She noted: "The world of science is becoming increasingly interdisciplinary, so this kind of meeting of minds across nations, cultures and scientific fields is really the way of the future."

Explore further: Cardiac stem cells from heart disease patients may be harmful

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Stem cells: the future of medicine - Medical Xpress

A quick glance at your calendar will reveal that we're now in 2017. 2017, you may recall, is the year when contraversial surgeon Sergio Canavero has promised to perform the world's first human head transplant.

But just how feasible is a human head transplant? Is it the stuff of science fiction, or does it have a basis in current scientific thinking? Read on for everything you need to know about 2017 most alarming scientific development.

The most recent news comes from the journal CNS Neuroscience and Therapeutics, where Xiaping Ren from the Harbin Medical University claims to have successfully repaired severed spinal cords in rats using the same principals that Dr Canavero wants to use on humans before the year is out.

Nine rats were treated with polyethylene glycol (PEG). Eight were still alive a month after the operation, and by day 28 they had regained the ability to walk two were described as being "basically normal".

Canavero told Newsweek that this showed his critics were wrong: "Critics said the transected spinal cord is unrecoverable and thus a human head transplant is impossible...The scans show the reconstructed cord. No pain syndrome emerged over the duration of the study, again rebutting a critics worse than death remark."

Time will tell the team plans to move onto dogs next. It shoud be noted, however, that even if this is right and even if it is applicable to humans, this relates to repairing severed spinal cords not attaching a new head. If the research is accurate, it is indeed a point for Canavero and his proposed methods but we're a long way from it being anything close to the finished article.

A human head transplant is exactly what it sounds like taking one living head and putting it onto a new body.

But actually, thats a little misleading. In real terms, its a body transplant, as the head will be gaining a new body to control. However, as the term whole body transplant is already used to mean transferring the brain between bodies, calling it a head transplant makes it clear that the whole head is to be switched, brain included.

Until recently, a head transplant seemed totally implausible, but the Italian scientist Dr Sergio Canavero believes its possible, and intends to conduct the first surgery in 2017.

Canavero outlines the procedure in detail here, but these are the basics of the process. Remember: dont try this at home, kids.

The donor body and the head to be attached are first cooled down to 12-15C to ensure that the cells last longer than a few minutes without oxygen. The tissue around the neck is then cut, with the major blood vessels linked with tiny tubes. The spinal cord on each party is then severed cleanly with an extremely sharp blade.

"Post coma, Canavero believes the patient would immediately be able to move, feel their face and even speak with the same voice."

At this point, the head is ready to be moved, and the two ends of the spinal cord are fused using a chemical called polyethylene glycol, encouraging the cells to mesh. This chemical has been shown to prompt the growth of spinal cord nerves in animals, although Canavero suggests that introducing stem cells or olfactory ensheathing cells into the spinal cord could also be tried.

After the muscles and blood supply are successfully connected, the patient is kept in a coma for a month to limit movement of the newly fused neck, while electrodes stimulate the spinal cord to strengthen its new connections.

Following the coma, Canavero anticipates that the patient would immediately be able to move, feel their face and even speak with the same voice. He believes physiotherapy would allow the patient to walk within a year.

He explains his suggested methods in the TED talk below.

Sceptical would be a nice way of putting it. Horrified would, in most cases, be more accurate.

Dr Hunt Batjer has attracted headlines for being particularly blunt: I would not wish this on anyone. I would not allow anyone to do it to me as there are a lot of things worse than death.

Dr Jerry Silver witnessed the 1970s monkey head transplant experiment more on which later and describes the procedure as bad science, adding that just to do the experiments is unethical. This is a particular blow to Canavero, as he states that Silvers own work in reconnecting rats spinal cords should give hope to the human head transplant. Silver dismisses this: To sever a head and even contemplate the possibility of gluing axons back properly across the lesion to their neighbours is pure and utter fantasy in my opinion.

Dr Chad Gordon, professor of plastic and reconstructive surgery and neurological surgery at Johns Hopkins University, agrees that Canaveros claims are scientifically implausible. He told BuzzFeed: Theres no way hes going to hook up somebodys brain to someones spinal cord and have them be functional.

On the conservative side, were about 100 years away from being able to figure this out, he continued. If hes saying two, and hes promising a living, breathing, talking, moving human being? Hes lying.

Dr Paul Myers, associate professor of biology at the University of Minnesota at Morris, puts it even more explicitly: This procedure will not work... Try it with monkeys first. But he cant: the result would be, at best, a shambling horror, an animal driven mad with pain and terror, crippled and whimpering, and a poor advertisement for his experiment. And most likely what hed have is a collection of corpses that suffered briefly before expiring.

Others wonder whether Canavero might simply be enjoying the limelight with a PR stunt, including Dr Arthur Caplan, director of ethics at the NYU Langone Medical Centre. Describing the doctor as nuts, he explained to CNN: Their bodies would end up being overwhelmed with different pathways and chemistry than theyre used to, and theyd go crazy.

"We'll probably see a head on a robot before we see it on [another] body," he told Live Science.

Dr John Adler of Stanford University's school of medicine is slightly more optimistic... but not much more. "Conceptually, much of this could work, but the most favourable outcome will be little more than a Christopher Reeve level of function," he told Newsweek.

Canavero is aware of this criticism, claiming that silently hes received a lot of support from the medical community. Of Dr Batjers comments that the surgery would be a fate worse than death, Canavero is scathing. Hes a vascular surgeon. A vascular surgeon of the brain, yes, but he knows nothing, he argued. How can you say such a thing? Its incredible.

"The world is moving, the critics are dwindling. Of course, there will always be critics. Science teaches us that when you propose something groundbreaking, you must be confronted by criticism. If no critics really step forward, you are saying nothing special," he told Medical News Today.

Dr Canavero also believes that the operation could essentially be used to revive the dead, if brains were suitably frozen and stored. In an interview with German magazine Ooom, Canavero said: "We will try to bring the first of the company's patients back to life, not in 100 years. As soon as the first human head transplant has taken place, i.e. no later than 2018, we will be able to attempt to reawaken the first frozen head.We are currently planning the world's first brain transplant, and I consider it realistic that we will be ready in three years at the latest."

No-one has ever attempted a human head transplant before, and attempts on animals have to put it charitably had limited success.

Image: from Motherboard, uploaded under fair use from a 1959 issue of Life

The photo above really does show a dog with two heads and its not a fake. This was the work of Soviet scientist Vladimir Demikhov, and for four days the hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died.

Demikhov tried the experiment more than 24 times, but was unable to find a way of avoiding the dogs dying shortly after surgery. Although the results are horrifying to see, Demikhovs research did pave the way for human organ transplants.

"For four days this hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died."

But back to the topic of head transplants. The first time a straight swap was successful, was by Dr Robert White, in an experiment on a rhesus monkey in 1970. I feel the need to qualify the word successful with quotation marks, because although the monkey did live, he didnt live very long. Eight days, to be exact, and as the spinal cord wasnt attached to its new body, the monkey was paralysed for its remaining days. However, it could indeed see, hear, smell and taste before the body rejected the foreign head.

According to Canavero in his paper on human head transplants, the monkey lived eight days and was, by all measures, normal, having suffered no complications. However, Dr Jerry Silver who worked in the same lab as Dr White has more haunting memories. He toldCBS: I remember that the head would wake up, the facial expressions looked like terrible pain and confusion and anxiety in the animal. The head will stay alive, but not very long. It was just awful. I dont think it should ever be done again.

More recently, Chinese doctor Xiaoping Ren claims to have conducted head transplants on more than 1,000 mice. The Wall Street Journal reports to have witnessed a mouse with a new head moving, breathing, looking around and drinking. But, crucially, none of these mice have lived longer than a few minutes.

Still, Dr Rens studies continue, and the latest reports are said to be promising, offering a possible answer to the risk of severe blood loss (or brain ischemia) during transplantation. The experimental method that we have described can allow for long-term survival, and thus assessment of transplant rejection and central nervous system recovery, bringing us one step closer to AHBR in man, the researchers wrote.

Ren himself has not ruled out taking part in the first human head transplant operation, according to the Daily Mail. "A human head transplant will be a new frontier in science. Some people say it is the last frontier in medicine. It is a very sensitive and very controversial subject but if we can translate it to clinical practice, we can save a lot of lives," he said.

"Many people say a head transplant is not ethical. But what is the essence of a person? A person is the brain not the body. The body is just an organ," he added.

In January 2016, Canavero told New Scientist that a head transplant had been successfully completed on a monkey in China, although details were sparse. "The monkey fully survived the procedure without any neurological injury of whatever kind," he said, although the article notes that the monkey only kept alive for 20 hours after the surgery for "ethical reasons," limiting its use as a comparison somewhat.

In September 2016, Canavero revealeda further trial of the head transplant on dogs.New Scientisthas seen video footage of a dog appearing to walk three weeks after its spinal cord was severed, with Canavero claiming that the outcome is the result of the same techniques he plans to use on Spiridonov next year.

However, speaking to a number of scientists for their view on the new evidence, New Scientistcould find few sceptics converted. "These papers do not support moving forward in humans," said Jerry Silver a neuroscientist at Cape Western Reserve University in Ohio.

"The dog is a case report, and you cant learn very much from a single animal without controls. They claim they cut the cervical cord 90 per cent but theres no evidence of that in the paper, just some crude pictures," added Silver.

In May 2017, Canavero claimed success with another animal model: rats. Canavero and his team of Chinese surgeons claimed they were able to transplant the head of a donor rat onto the back of a larger one, creating a two-headed animal. The creature's donor head was allegedly able to blink and respond after the operation, although it only lived for 36 hours, which may not inspire confidence even with rodents' reduced lifespans.

You could say so, though Canavero doesn't see it quite like that. In fact, controversially he sees it more as a failure of other types of medicine, telling Medical News Today, "It will be about curing incurable neurological disorders for which other treatments have failed big time, so gene therapy,stem cells- they all just came to nothing. We have failed despite billions of dollars being poured into this sort of research."

"So actually, head transplant or body transplant, whatever your angle is, is actually a failure of medicine. It is not a brilliant success, a brilliant advancement to medical science. When you just haven't tackled biology, you don't know how to treat genes, you don't really understand, and you really need to resort to a body transplant, it means that you've failed. So this must not be construed as a success of medical research," he added.

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Human head transplant: Chinese researchers claim success with rats - Alphr

Researchers from Singapore have developed a 3D tissue model than can be used to test drugs for their effects on the heart in a more realistic manner.

Asian Scientist Newsroom | June 22, 2017 | In the Lab

AsianScientist (Jun. 22, 2017) - Researchers at the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research (A*STAR) have engineered a three-dimensional heart tissue from human stem cells to test the safety and efficacy of new drugs on the heart. Their research has been published in Biofabrication.

Cardiotoxicity, which can lead to heart failure and even death, is a major cause of drug withdrawal from the market. So it is important to test as early as possible whether a newly developed drug is safe for human use. However, cardiotoxicity is difficult to predict in the early stages of drug development, said Professor Jackie Y. Ying, Executive Director at IBN.

A big part of the problem is the use of animals or animal-derived cells in preclinical cardiotoxicity studies due to the limited availability of human heart muscle cells. Substantial genetic and cardiac differences exist between animals and humans. There have been a large number of cases whereby the tests failed to detect cardiovascular toxicity when moving from animal studies to human clinical trials.

Existing screening methods based on 2D cardiac structure cannot accurately predict drug toxicity, while the currently available 3D structures for screening are difficult to fabricate in the quantities needed for commercial application.

To solve this problem, the IBN research team fabricated their 3D heart tissue from cellular self-assembly of heart muscle cells grown from human induced pluripotent stem cells. They also developed a fluorescence labelling technology to monitor changes in beating rate using a real-time video recording system.

The new heart tissue exhibited more cardiac-specific genes, stronger contraction and higher beating rate compared to cells in a 2D structure.

Using the 3D heart tissue, we were able to correctly predict cardiotoxic effects based on changes in the beating rate, even when these were not detected by conventional tests. The method is simple and suitable for large-scale assessment of drug side effects. It could also be used to design personalized therapy using a patients own cells, said lead researcher Dr. Andrew Wan, who is Team Leader and Principal Research Scientist at IBN.

The researchers have filed a patent on their human heart tissue model, and hope to work with clinicians and pharmaceutical companies to bring this technology to market.

The article can be found at: Lu et al. (2017) Engineering a Functional Three-Dimensional Human Cardiac Tissue Model for Drug Toxicity Screening.

Source: A*STAR; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Testing For Cardiotoxicity In 3D - Asian Scientist Magazine

"Being named a Red Herring Top 100 winner is an incredible honor," said StemoniX CEO Ping Yeh. "We truly believe in the importance of what we're doing and in making medicine more effective and safer for everyone. This award is affirming not only for us, but also for our investors, who continue to make it possible for us to pursue our mission of making sure medicine works the first time. Our commitment to improving our technology, and our work with some of the country's top producers of therapeutic cures, will ensure we achieve our vision."

StemoniX was born out of Yeh's own medical battle. 5 years ago, he survived a frightening bout with cancer. During treatment, his only option to beat the disease was a drug that may have destroyed his heart. There was no way for doctors to test the effectiveness of that treatment or Ping's survival rate ahead of time. Convinced there had to be a better way to test medication, he poured his life savings into starting StemoniX. In only three years, the company has made scientific breakthroughs that may forever alter how people are treated.

"Every year, Red Herring North America Top 100 selects an amazing group of disruptive companies. But a few carry an exceptional weight because they will change the world. StemoniX is one of them," said Red Herring chairman Alex Vieux. "Ping Yeh and his team are receiving continued and increased market validation for their technology. StemoniX will revolutionize drug discovery research and has pioneered a novel approach. Hence the jury was enthused at the opportunity to recognize StemoniX among the Top 100 Red Herring North America 2017."

StemoniX is on a mission to accelerate the discovery of new medicines. The company develops and scalably manufactures human induced pluripotent stem cell (iPSC)-derived cardiac and neuronal platforms for drug discovery and development. Their human models enable scientists to quickly and economically conduct research with improved outcomes in a simplified workflow. StemoniX microHeart products, which come in high-density plate formats, provide researchers with structurally aligned human iPSC-derived cardiac cells that exhibit accelerated features of maturity resembling heart tissue.

StemoniX microBrain products will launch later this year, containing physiologically relevant human iPSC-derived neural microtissue in high-density plates with biology, activity and functional maturity that mimic brain tissue.

StemoniX also offers Discovery as a Service. The company has the ability to develop custom-iPSC-based disease models, test compounds with its in-house screening capabilities and operationalize their customers' human iPS cells at large scale for high throughput screening.

Following StemoniX's Top 100 win, they are invited to present at the Top 100 Global event in November that will encompass the best-in-show from the Top 100 Europe, North America and Asia.

About StemoniX: StemoniX is transforming how medicine is discovered. By using skin or blood to create functioning microHearts and microBrains, StemoniX is making it possible to test medication on humans without that medication ever entering their bodies. This method of drug testing will speed up the search for new cures and enable the ability to test drug effectiveness on an individual person, so medicine works correctly the first time. Learn more at stemonix.com.

Media Contact: Ryan Gordon Phone Number: 612-440-7836 Email: ryan.gordon@stemonix.com Website: stemonix.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/stemonix-wins-red-herring-top-100-award-300477971.html

SOURCE StemoniX, Inc.

http://stemonix.com

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StemoniX Wins Red Herring Top 100 Award - PR Newswire (press release)

Matthew Medinas doctors diagnosed him with a rare blood disease a few months ago and told him he would probably die without a bone marrow transplant.

With that prognosis came another: The 40-year-old Los Angeles police officer had a less than 50% chance of finding a donor because he is not white.

Most successful matches for bone marrow transplants involve a donor and patient of the same ethnicity. But the majority of the 25 million registered donors nationwide are white, and Medina is Filipino. So far, no match has been found.

Youre basically looking for a genetic twin, said Athena Mari Asklipiadis, who runs Mixed Marrow, an L.A.-based organization that is trying to increase diversity in the bone marrow donor registry. Its not like we have more of a chance we would get a disease, or that were harder to match, its just that theres not representation in the national registry.

Its a familiar problem for any nonwhite person who has needed a bone marrow transplant.

A white American of European descent has a 75% chance of finding a perfect match in the national donor registry, compared with a 40% chance for Filipinos. Few Filipinos in the U.S. have signed up as potential donors, and there is no registry in the Philippines.

Researchers are experimenting with ways to perform bone marrow transplants on people who cant find matches. But while those treatments are being perfected, thousands of people are diagnosed every year with leukemia, lymphomas and other blood diseases whose only hope for a cure is a marrow transplant. And for them, it can come down to ethnicity.

Medinas wife, Angelee, has watched dozens of people at sign-up events across Southern California, particularly in the Filipino community, volunteer to donate bone marrow with the hope of curing her husband. Were very thankful for that, she said. Were hoping something comes up.

For now, Medina is being kept alive with transfusions.

All you want is for that loved one to have a chance, said Officer Dante Pagulayan, Medinas partner at the LAPD and a childhood friend. Thats what were praying for.

Medina went to the doctor in March because he had a rash. His blood work revealed something far more dangerous.

Medina was diagnosed with aplastic anemia, a disease in which the bone marrow stops working. Bone marrow is spongy material inside bones that produces the essential components of blood white blood cells, red blood cells and platelets.

Between 600 and 900 Americans are diagnosed with aplastic anemia each year, according to the Aplastic Anemia and MDS International Foundation. The disease can be caused by exposure to toxic chemicals or a virus, but most cases, including Medinas, are unexplained.

One day he wakes up and the doctor tells him he has this. It could happen to anyone, said Pagulayan, who went to high school and Cal State Long Beach with Medina and now works alongside him in the gang unit in the LAPDs Harbor Division.

Blood transfusions can sustain Medina for now, but the only possible cure for aplastic anemia is a transplant, said Dr. Len Farol, a bone marrow transplant specialist at City of Hope National Medical Center and one of Medinas physicians.

Medina is quarantined at his home in Bellflower, where he lives with his wife and two young daughters. But he needs a transplant soon because his immune system is so weakened from his disease that exposure to a common virus could kill him, Farol said.

Doctors checked to see if Medinas sister could be a match, but she wasnt siblings provide a match only about 25% of the time. They started combing through the registry, but trying to find a donor there can be like finding a needle in a haystack, Farol said.

Doctors look to see if the patient and potential donor share eight cell markers called human leukocyte antigens, or HLA. All eight have to match, but thats rare because there are thousands of possibilities for each marker, experts say.

There could be billions of combinations, said Stephen Spellman, director of immunobiology and observational research for the Center for International Blood and Marrow Transplant Research. Within any group, finding a match for HLA is difficult.

Spellman said that people whose ancestors are from the same place tend to have the same markers because they evolved over time in response to different pathogens and diseases that were present in their environment.

According to a 2014 report in the New England Journal of Medicine, a person of white European descent has the highest chance of finding a perfect match eight out of eight HLA markers in the national registry of any ethnic group.

What's your chance of finding a perfect match? If you're...

Source: HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry, New England Journal of Medicine, 2014

Pagulayan, who is also Filipino, said neither he nor Medina knew ethnicity would affect his chances of being cured. Finding out that less than 1% of people in the registry were Filipino was very disheartening, he said.

There are international registries, but the vast majority of people worldwide whove signed up to donate bone marrow are from the U.S and Europe.

Plus, nonwhite populations in general tend to have more genetic diversity. African Americans, for example, have highly diverse genetics because of mixing with other groups since arriving in the United States, experts say. Filipinos are also very diverse because of the countrys long history of colonization.

Still, experts say that everyone who wants to help Medina should sign up for the registry, regardless of ethnicity.

Matches often break down along ethnic lines, but not always. Sometimes markers in one population also appear in another, or people dont know their lineage.

Maya Chamberlin, who is half Indian and half white, had two bone marrow transplants after she was diagnosed with a rare blood disease called HLH in 2009 when she was 4.

Mayas first donor was half Japanese and half Latino, and her second was half Japanese and half Filipino.

So you never know how this works until you get on the registry, said her mother, Mina Chamberlin, who lived in Torrance when Maya was diagnosed but has since relocated to Cincinnati to be closer to physicians who specialize in her daughters disease. You just never know.

Angelee Medina canceled her familys vacation to Mexico scheduled for this summer. Shed been commuting to a job as a graphic designer 20 miles from home when Matt was diagnosed, but found a closer place to work so she could take care of the kids and be near her husband.

It was very, very overwhelming in the beginning, she said. With all the support were getting from everyone around us, it feels hopeful.

More than 1,000 people have signed up to donate bone marrow over the past few months through dozens of drives for Medina, said Chris Chen, a recruitment coordinator for Little Tokyo-based nonprofit A3M, which focuses on getting more Asians to sign up for the Be the Match registry to donate bone marrow.

Potential donors submit cell samples by having the inside of their cheek swabbed. The cells are then analyzed to determine their HLA markers.

About 70% of transplants employ a process called peripheral blood stem cell donation, which is similar to a blood donation but can take several hours. In the other 30% of cases, donors are admitted to the hospital and anesthetized so doctors can remove marrow from their pelvic bone with a needle.

Ayumi Nagata, recruitment manager for A3M, knows that asking people to volunteer for a medical procedure they dont need themselves can be a hard sell. But she tries to impress upon them how they could be the cure for someones cancer or other disease and save their life.

How often do we have that kind of opportunity? Nagata said.

The Medinas 8-year-old daughter, Cassiah, made a sticker thats distributed at donor drives that says, Keep calm and help our daddy fight! When Angelee picked up Cassiah from day care recently, she found out that her daughter had been asking the other kids parents: Did you get swabbed? Have you gotten swabbed yet?

Doctors are testing ways to perform transplants on patients who cant find a bone marrow match. Some are using umbilical cord blood, donated by mothers whove just given birth, which scientists say has a lower chance of rejection even if its not a complete match.

Haploidentical transplants, in which the donor and patient share only half of the eight markers, have also been successful in clinical trials, Spellman said.

Medinas doctors think his best shot is still a perfect match for a bone marrow transplant, his wife said.

Thats just what were waiting for, she said. I remind him one day soon, hopefully everything will be better.

What to know about joining the bone marrow registry

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An LAPD officer needs a bone marrow transplant. His ethnicity limits his chances of getting one - Los Angeles Times