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Aging, Cancer, Research, Stanford News

Stanford researchers deliver double punch to blood cancer

Stanford researchers deliver double punch to blood cancer

Acute myeloid leukemia is an aggressive and deadly cancer affecting cells that turn into our blood. Now, a study published in Nature Medicine shows that a drug known to cause cell death might be effective for a particular subtype of this lethal disease.

To get an idea of just how aggressive and deadly acute myeloid leukemia is, consider the survival rates for the 13-14,000 American adults who are sickened each year. The overall survival rate is 30-40 percent, according to Stanford cancer researcher Ravindra Majeti, MD, PhD, but if patients are over 65 years old, the survival rate dips to just 5 percent. The majority of acute myeloid leukemia patients are elderly.

Apoptosis, or cell death, of tumors is the goal in cancer treatments. There are multiple pathways leading to cell death, and identifying ways to nudge cancer cells towards dying is the focus of much cancer research.

But sometimes the path to cell death is nonlinear and hard to find.

In this work, a team of Stanford cancer researchers led by Majeti and Steven Chan, MD, identified a two-pronged attack for acute myeloid leukemia cancer cells. The researchers first focused on mutated proteins called isocitrate dehydrogenase 1 and 2 (known as IDH1/2 for short). Cancer cells containing mutated IDH1/2 proteins often survive traditional chemotherapy treatments, contributing to relapse, and they exist in 15 percent of acute myeloid leukemia patients. The second focus of the Stanford researchers was the BCL-2 gene, which is known to enable cancerous growth by putting the brakes on cell death in acute myeloid leukemia and other cancer cells. Simply stopping BCL-2 activity in acute myeloid leukemia patients is not very effective, as indicated by low survival rates for the disease.

The Stanford scientists found that giving a drug that inhibits BCL-2 successfully lifted the blockade on cell death, but only in cells with mutated IDH1/2 proteins. Majeti said the drug that promotes cancer cell death by inhibiting BCL-2 is now in clinical trials.

Kimberlee D’Ardenne is a writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: The latest on stem-cell therapies for leukemia, Blood cancers shown to arise from mutations that accumulate in stem cells and Leukemia prognosis and cancer stem cells

Aging, Genetics, Immunology, Infectious Disease, Research, Stanford News

In human defenses against disease, environment beats heredity, study of twins shows

In human defenses against disease, environment beats heredity, study of twins shows

Pfc. Lane Higson and Pfc. Casey Higson, identical twins serving in Iraq with the Enhanced Combat Aviation Brigade, 1st Infantry Division. The twins, natives of Myrtle Beach, S.C., joined the Army together and have not separated since.I’m one of those people who’ve paid to have their genomes analyzed for the purpose of getting a handle on susceptibility to this or that disease as time goes by. So it was with great interest that I came across a new study of twins conducted by immunologist Mark Davis, PhD, and fellow Stanford investigators. The study, published in CELL, shows that our environment, more than our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age.

Improving gene-sequencing technologies have focused attention on the role of genes in diseases. But the finding that the environment is an even greater factor in shaping our immune response should give pause to anyone who thinks a whole-genome test is going to predict the course of their health status over a lifetime.

“The idea in some circles has been that if you sequence someone’s genome, you can tell what diseases they’re going to have 50 years later,” Davis told me when I interviewed him for a news release I wrote on the study. But, he noted, the immune system has to be tremendously adaptable in order to cope with unpredictable episodes of infection, injury and tumor formation.

Davis, who heads Stanford’s Institute for Immunity, Transplantation and Infection, is worth taking seriously. He’s made a number of major contributions to the field of immunology over the last 30 years or so.  (Not long ago, I wrote an article about one of those exploits for Stanford Medicine.)

To find out whether the tremendous differences observed between different people’s immune systems reflec tunderlying genetic differences or something else, Davis and his colleagues compared members of twin pairs to one another. Identical twins inherit the same genome, while fraternal twin pairs are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. (Little-known fun factoid: The percentage can vary from 0 to 100, in principle, depending on the roll of the chromosomal dice. But it typically hovers pretty close to 50 percent, just as rolling real dice gives you a preponderance of 6s, 7s, and 8s. Think of a Bell curve.)

Because both types of twins share the same in utero environment and, usually, pretty close to the same childhood environment as well, they make great subjects for contrasting hereditary versus environmental influence. (If members of identical-twin pairs are found to be no more alike than members of fraternal-twin pairs with respect to the presence of some trait, that trait is considered to lack any genetic influence.)

In all, the researchers recruited 78 identical-twin pairs and 27 pairs of fraternal twins and drew blood from both members of each twin pair. That blood was hustled over to Stanford’s Human Monitoring Center, which houses the latest immune-sleuthing technology under a single roof. There, the Stanford team applied sophisticated laboratory methods to the blood samples to measure more than 200 distinct immune-system cell types, substances and activities.

Said Davis: “We found that in most cases – including your reaction to a standard influenza vaccine and other types of immune responsiveness – there is little or no genetic influence at work, and most likely the environment and your exposure to innumerable microbes is the major driver.”

It makes sense. A healthy human immune system has to continually adapt to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more.

“The immune system has to think on its feet,” Davis said.

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before and Immunology escapes from the mouse trap
Photo by DVIDSHUB

Aging, Medicine and Society, Podcasts

Living loooooooonger: A conversation on longevity

Living loooooooonger: A conversation on longevity

Hourglass

As I age, I’m becoming more and more interested in how I can prolong a healthy life. I hope I have a long life but more importantly, I want a healthy one.  I’ve witnessed the other side. My father died in his late 80s; his final years ravaged by Parkinson’s. He was infantile and had bolts of anger and confusion. It wasn’t pretty. In her early 90s, my mother had a stroke. She passed away from heart complications after being aphasic for nearly a year. This 30-plus year English teacher lost all ability to converse in the final year of her life; she was reduced to incoherency. As I held their hands or fed them, I kept on telling myself, not me. This is NOT how I want to live my final days.

In recent years, aging research has been turned upside down. As Stanford bioethicist Christopher Scott, PhD, and his co-author, Laura DeFrancesco, PhD, write in Nature Biotechnology, it has a new face and it’s longevity:

How science approaches the questions of aging has changed. Lifestyle, environment, epidemiology, nutrition, genetics and the tools of big data are coming together in a host of new ways. The new approach – called longevity research – is an effort to extend the period of healthy life by slowing the biological process of aging.

I can see the scrawl on the wall: Aging research is dead. Long live longevity research.

Penn bioethicist and public-policy guru Zeke Emanuel, MD, stirred a recent debate about how long a viable  life when he thrust his body up against today’s immortality zeal of the baby boomer. In an Atlantic article entitled “Why I Hope to Die at 75,” he theorized that post-75, it’s all a pain. His article is a great read that might depress you if 75 is within focus, yet it poses one question clear for each of us: How do we want to live our final days on earth?

Will longevity research produce answers that quell the anxiety stirred by the belief that the aging process means everything is headed south? Scott and DeFrancesco signal that while aging research “failed to come up with any viable approaches, let alone therapies to forestall the ravages of aging,” longevity research in animal models “have shown that life span is indeed malleable, that it can be manipulated by genetics or the environment…” Is there a stairway to longevity emerging in science?

The Nature Biotechnology paper poses some fascinating questions as the science of longevity joins with a new generation of commercial entities that hope to seize its potential. To be sure, longevity research will need to avoid inflated hype. The authors say that Craig Venter, PhD, who has started a company, Human Longevity (HLI) is “….frustrated that the handful of fully sequences human genomes, including his own, has provided little insight into aging.” But I assume, as do the authors, that Venter’s bet is that there’s an abundance of sunshine down this path and science will emerge with ways to manipulate aging that will lead to better health and disease management. But when?

In my latest 1:2:1 podcast I take up these questions with Scott as the longevity era of science develops and matures. My colleague Krista Conger also authored a blog post earlier this week on Scott’s feature.

Previously: Golden years? Researcher explores longevity research and the companies banking on its success, Exploring the value of longevity with bioethicist Ezekiel Emanuel, Tick tock goes the clock – is aging the biggest illness of all? and Researchers aim to extend how long – and how well – we live
Photo by Michael Himbeault

Aging, Ethics, Medicine and Society, Research, Science, Stanford News

Golden years? Researcher explores longevity research and the companies banking on its success

Golden years? Researcher explores longevity research and the companies banking on its success

Elderly Japanese woman for Scott blog postAlthough I haven’t had a birthday yet this year, the transition to writing 2015 on all my checks (whoops, did I just date myself there? ahem) has made me feel older. Coincidentally, I’ve also been working on an article for an upcoming issue of Stanford Medicine magazine about aging and longevity. So, yeah. I’ve been thinking a lot about the passage of time.

That’s why I was really interested to learn that Stanford bioethicist Christopher Scott, PhD, teamed up with Nature Biotechnology senior editor Laura DeFrancesco to c0-author a feature article examining the commercialization of longevity research. The article layers research advances with the rise and fall (and rise again) of companies and organizations that have tossed their hats into the anti-aging ring since the 1990s. With it, Scott and DeFrancesco paint a picture of a dynamic field on the brink of something big. As Scott explained in an email to me:

Aging research, as we knew it in the 1990s and 2000’s, is being abandoned in favor of something much more ambitious. The central features of longevity research include an embrace of big data, a pivot away from studies hoping to find aging genes, a recognition that aging is best thought of a collection of diseases, not just one disease.

I’m fascinated by how quickly this new direction has taken off, especially since classic aging research yielded so little, and became saddled with hype. Longevity research has that same feel to it, and from an ethics and policy perspective one question is whether the promise of healthy lifespans will outrun the reality of the science.

And there’s the rub. As Scott points out, it’s not enough to just live long. No one wants a prolonged, but unhealthy, old age. We need to live long and well. The concept that gained ground is “healthspan” rather than “lifespan.” And from Google’s Calico to Craig Venter’s Human Longevity, Inc , there are a lot of bright minds (and plenty of $) focused on this problem. But there’s a lot at stake.

As Scott explained:

These are highly consequential decisions (funding research, creating new companies, establishing new scientific disciplines), technological inventions, and social changes that are being pursued on the tacit assumption that such decisions, inventions, and changes do lead to a healthier, longer life and the promise of a better future. In ethics, I think these assumptions are largely unexplored and unacknowledged.

The article is a fascinating cross-section of a rapidly growing field, but, as Scott points out, there are still many questions that scientists haven’t addressed. It’s well worth the time to read, whether you’re a writer on a deadline or just a person trying to figure out how to gracefully change that “4” into a “5” on …all your paperwork.

Previously: Exploring the value of longevity with bioethicist Ezekiel Emanuel , Tick tock goes the clock – is aging the biggest illness of all? and Researchers aim to extend how long – and how well – we live
Photo by Maya Stone

Aging, Chronic Disease, Ethics, Health Policy

Exploring the value of longevity with bioethicist Ezekiel Emanuel

baby hand in old hand - big

In a popular article in the Atlantic published this past fall, Ezekiel Emanuel, MD, bioethicist and prominent federal policy adviser, made a controversial case against longevity. Just before the recent holidays, the USC Annenberg School for Communication & Journalism sponsored a webinar during which Emanuel explained and elaborated on his message. It’s not that he “hopes to die at 75,” as the title chosen by the Atlantic suggested, but he wants a life at 75 focused on living, not on living longer.

Emanuel essentially argues for quality of life over quantity of years, and he claims that American society is becoming obsessed by the latter. I listened in on his December talk, which began with an ad from the AARP that glorifies “going on forever” – a value he says is reflected in both the medical system and our contemporary culture.

He directed his scientific criticism against the idea of the “compression of morbidity” – the belief that with enough medical advances, disabilities will go away and people will live in good health until, more or less suddenly, they die. He calls this the “rectangularization” of life: falling off a cliff instead of rolling down a gradual decline. The idea is immensely popular and money-making, but while some research claims to prove it, far more proves the opposite. There is, in fact, an expansion of morbidity as people live longer, an elongated and more gradual decline with more disabilities and less and less creativity.

Given this, Emanuel’s hope and recommendation is two-fold: that people will consider what makes their life meaningful and spend their energy cultivating that, and that medical resources will be redirected from prolonging life to improving its quality at the outset – by reducing the country’s exceptionally high rate of premature births, for example.

American life expectancy is at an all-time high at nearly 80 years, but are octogenarians living meaningfully? Last month in the New York Times, David Brooks argued against Emanuel’s earlier piece by saying that the “happiest people” are ages 82-85; in the webinar, Emanuel says this misses the point. It’s much easier to measure happiness than meaningfulness, yet the latter is the real aim of life (and, furthermore, Brooks didn’t account for the perspectives of those in nursing homes, assisted living, or suffering from dementia). Emanuel talked of patients who say cancer was “the best thing that happened to me” because it made them focus on what was meaningful in their life. The end of life is important to think about, as it helps us see what we want from life now.

“Contorting life around living as long as possible seems to me to be counter-productive,” he said. “What we should be focusing our life on is what’s meaningful, how we enrich other people and contribute to our families and society.”

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Aging, Chronic Disease, Dermatology, Stanford News

Patching up diabetic ulcers

Patching up diabetic ulcers

Like the more than 29 million people in the U.S, my mother has diabetes. Her eldest sister and my maternal grandmother both died of complications of the disease, and her one surviving sister is coping with complications that will probably claim her life in a few years. I’ve got gestational diabetes (a temporary version of the disease that occurs during pregnancy), and due to that and my family history I’m likely to develop type-2 diabetes down the line, also. So I’m always very interested in hearing about research advances related to the disease.

One such advance: As reported today in the the Proceedings of the National Academy of Sciences, Stanford researchers have developed a new skin patch that delivers a drug to aid the healing of diabetic ulcers. Diabetic ulcers (or open wounds) are one of the most common complications of the disease, with an estimated 15 percent of diabetics developing them. They often occur on the feet and are the leading cause of diabetes-related amputations. The high level of blood sugar in diabetics’ blood impairs the body’s ability to grow new blood vessels, which slows down healing of the ulcers.

Deferoxamine, or DFO, is an FDA-approved drug that can help correct this problem, but it would be toxic if taken for as long as diabetics need it to heal their ulcers. So Stanford researchers developed a local application via a skin patch. In a press release, study authors Dominik Duscher, MD, a plastic and reconstructive surgery postdoctoral fellow, and surgeon Geoffrey Gurtner, MD, talked about the findings of their work in animal models:

Not only did the wounds in the mice heal more quickly, Duscher said, but the quality of the new skin was even better than the original. The researchers also used the DFO matrix on a mouse with diabetes to see if it would prevent ulcer formation — and it did. “We were very excited by the results,” Duscher said, “and we hope to start clinical trials soon to test this in humans.”

“This same technology is also effective in preventing pressure ulcers, which are a major source of morbidity and mortality in patients with neurologic injury or the elderly,” said Gurtner, who is also the Johnson & Johnson Distinguished Professor in Surgery II. “The actor Christopher Reeve actually died from a pressure ulcer and not his spinal cord injury, which really emphasizes the extremely limited therapeutic options for these patients.”

Luckily my mother hasn’t had to deal with diabetic ulcers, though when she gets small cuts or chaps on her skin, they do take forever to heal, so she’s super-vigilant about avoiding them. The possibility of preventing more serious ulcers with this patch is a development I’ll be following closely.

Previously: A primer on preventing or delaying type 2 diabetes and New medicine? A look at advances in wound healing

Aging, Dermatology, Public Health, Videos

Don’t skip the sunscreen in wintertime

Don’t skip the sunscreen in wintertime

When you’re spending time outdoors during the wintertime, it’s easy to justify skipping the sunscreen when the sun isn’t beating down on you mercilessly and you’re bundled up instead of sporting a swimsuit. But UV rays from the sun can penetrate clouds and snow can reflect sun onto your face, hands and any other exposed skin. So it’s important to remember to take sun safety precautions even on cold or overcast days, too.

This  Stanford Health Care video featuring dermatologist Justin Ko, MD, MBA, includes important tips for preventing skin cancer year-round. As I, like many others, prepare for a family trip to Tahoe to take advantage of the recent snow, Ko’s reminder about sun safety habits during the winter comes at a good time. For example, I suspect I’ve been skimping on sunscreen: Ko says you need a shot glass-full to completely cover your body. If you’re using a spray-on sunscreen, you need to spray for a full 60 seconds.

Watch the video to learn more information about how to identify possible cancerous moles and preventing high-risk exposures, like tanning beds.

Previously: Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers, Humble anti-fungal pill appears to have a noble side-effect: treating skin cancer, Skin cancer images help people check skin more often and effectively, and The importance of sunscreen in preventing skin cancer

Aging, Cancer, Genetics, Research

Telomeres tell all about longevity and health

Telomeres tell all about longevity and health

10085714333_d8367dbe2a_oIf I were to go back to school for a PhD, I think I’d study telomeres. Telomeres, the protective caps at the end of each chromosome, shrink with aging and other stressors leaving an organism vulnerable to a various disorders and cancer.

So, telomere fan that I am, I was thrilled to sit in on a recent Psychiatry & Behavior Sciences Grand Rounds talk at Stanford featuring Elizabeth Blackburn, PhD. A professor of biology and physiology at the University of California, San Francisco,  Blackburn won the Nobel Prize in 2009 for her work on telomeres.

During the event, she gave the packed auditorium a whirlwind overview of telomere biology. Blackburn explained to attendees that telomere length is affected by both genes and the environment, and that some folks just start out with longer ones. Telomeres are maintained by an enzyme called telomerase. Slashing the amount of telomerase can cause early, immune dysfunction, cancer and diabetes. Some genetic telomere troubles manifest as disorders such as aplastic anemia or pulmonary fibrosis.

In general, telomere length correlates with what Blackburn called a “health span,” or duration of time someone stays healthy.

Recently she and colleagues measured telomere length in 100,000 people of all ages, a project they needed to develop a special robot to complete. They found that length of telomeres decreases into age 75. Then, it curves up to 95, accounting for the longevity of individuals with long telomeres. And yes, older women tend to have longer telomeres than older men.

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Aging, In the News, Neuroscience, Research, Science, Stanford News

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine’s Breakthrough of the Year

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine's Breakthrough of the Year

ballot box

Stanford research showing that an infusion of young blood recharges the brains of old mice is one of the finalists for Science magazine’s annual contest for People’s Choice for Breakthrough of the Year. Today is the last day to cast your vote. Click here if you’d like to support the work, which could lead to new therapeutic approaches for treating dementia.

Several months ago, I had the pleasure of helping break the news about this great piece of research. So, let’s face it, I take a certain amount of pride in the amount of news coverage it received and the attention it’s getting now.

But the real credit goes to Stanford neuroscientist Tony Wyss-Coray, PhD, along with his able lead author Saul Villeda, PhD, and colleagues. This important discovery by Wyss-Coray’s team revealed that infusing young mice’s blood plasma into the bloodstream of old mice makes those old mice jump up and do the Macarena – and perform a whole lot better on mousey IQ tests.

Infusing blood plasma is hardly a new technique. As Wyss-Coray told me when I interviewed him for my release:

“This could have been done 20 years ago….You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it.”

And after all, isn’t that what breakthroughs are all about? It’s still too early to say, but this simple treatment – or (more likely) drugs based on a better understanding of what factors in blood are responsible for reversing neurological decline –  could someday turn out to have applications for Alzheimer’s disease and much more.

At last count, the Wyss-Coray’s research is neck-and-neck with a competing project for first place. If you think, as I do, that a discovery with this much potential deserves a vote of confidence make sure to take a moment this afternoon to cast your virtual ballot.

Previously: The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Old blood makes young brains act older, and vice versa and Can we reset the aging clock, once cell at a time?
Photo by FutUndBeidl

Aging, Neuroscience, Stanford News, Stroke, Videos

Examining the potential of creating new synapses in old or damaged brains

Examining the potential of creating new synapses in old or damaged brains

Synapses are the structures in the brain where neurons connect and communicate with each other. Between early childhood and the beginning of puberty, many of these connections are eliminated through a process called “synaptic pruning.” Stroke, Alzheimer’s disease, and traumatic brain injury can also cause the loss of synapses. But what if new synapses could be created to repair aging or damaged brains?

Stanford neurobiologist Carla Shatz, PhD, addresses this question in the above Seattle+Connect video. In the lecture, she discusses the possibility of engaging the molecular and cellular mechanisms that regulate critical developmental periods to regrow synapses in old brains. Watch the video to learn how advances at the neural level around a novel receptor, called PirB, have implications for improving brain plasticity, learning, memory and neurological disorders.

Previously: Drug helps old brains learn new tricks, and heal, Cellular padding could help stem cells repair injuries and Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz and “Pruning synapses” and other strides in Alzheimer’s research

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