Published by
Stanford Medicine

Category

Cancer

Big data, Cancer, Genetics, Research, Science, Stanford News

Stanford researchers suss out cancer mutations in genome’s dark spots

Stanford researchers suss out cancer mutations in genome's dark spots

lighted pathOnly a small proportion of our DNA contains nucleotide sequences used to make proteins. Much of the remainder is devoted to specifying how, when and where those proteins are made. These rules are encoded in our DNA as regulatory elements, and they’re what makes one cell type different from another, and keep them from running wild like children in an unattended classroom. When things go awry, the consequences (like rampant growth and cancers) can be severe.

Geneticist Michael Snyder, PhD, and postdoctoral scholar Collin Melton, PhD, recently combined information from The Cancer Genome Atlas, a national effort to sequence and identify mutations in the genomes of many different types of cancers, with data from the national ENCODE Project, which serves as an encyclopedia of DNA functional regions, or elements. Their aim was to better understand the roles that mutations in regulatory regions may play in cancer development.

Snyder and Melton found that fewer than one of every thousand mutations in each cancer type occurs in the coding region of a gene. In contrast, more than 30 percent of the mutations occur in regulatory regions. The study was published this morning in Nature Genetics.

As Snyder explained to me:

Until recently, many mutations outside the coding regions of genes have been mostly invisible to us. Cancer researchers largely focused on identifying changes within coding regions. Using ENCODE data, we’ve been able to define some important regions of the genome and found that certain regulatory regions are often enriched for mutations. This opens up a whole new window for this type of research.

Snyder, who leads Stanford’s genetics department and directs the Stanford Center for Genomics and Personalized Medicine, likens looking for cancer-causing mutations only in coding regions as “looking under the lamppost” for keys lost at night. Until recently, the coding regions of genes were the most well-studied, and unexpected mutations stood out like a sore thumb. We’ve known there’s a lot more of the genome outside the coding regions, but until the ENCODE project was largely completed in 2012, researchers were often in the dark as to where, or even how, they should look.

Continue Reading »

Cancer, Medical Education, Stanford News, Surgery, Videos, Women's Health

Why become a doctor? A personal story from a Stanford oncologist

Why become a doctor? A personal story from a Stanford oncologist

Why become a doctor? It certainly isn’t easy, and it requires years of study and a sizable financial investment. If you ask physicians how, and why, they selected their careers, you’ll get a variety of stories that offer insight into the many benefits of pursuing medicine.

Pelin Cinar, MD, a GI oncologist here, tells her own story in this recent Stanford Health Care video.

As a child, Cinar was impressed with the respect her uncle, a gynecologist, received from family members. Then, in high school, her mother was diagnosed with cancer. Meanwhile, she began pursuing the courses that matched her interest in science. Her mother recovered but then relapsed when Cinar was in college and taking pre-med requirements.

During her medical education at the University of California-Irvine, Cinar discovered that all of her favorite rotations and subjects were based on oncology. “It took off from there,” she says in the video.

Previously: Students draw inspiration from Jimmy Kimmel Live! to up the cool factor of research, Stanford’s senior associate dean of medical education talks admissions, career paths and Thoughts on the arts and humanities in shaping a medical career

Cancer, In the News, Media, Medicine and Society

Oncology hashtag project aims to improve accuracy of online communication about cancer

Oncology hashtag project aims to improve accuracy of online communication about cancer

6399145505_49e812a63d_zThere’s lots of talk about the need for doctors to communicate better with their patients, and social media is taking off as a medium for doing so. At this year’s meeting of the American Society for Clinical Oncology, which ends in Chicago today, Matthew Katz, MD, a radiation oncologist at the University of Texas’ MD Anderson Center, exhibited a poster displaying a new series of hashtags for different types of cancer. There are at least 20: #leusm for leukemia, #melsm for melanoma, #blcsm for bladder cancer, etc. Patients and doctors alike can use them to be more accurate and specific in sharing information.

As reported in a MedCity News piece, Katz is a big believer in social media as a way for patients and doctors to communicate. He developed the hashtags to provide better access to reliable, high-quality health information for both patients and providers, and he’s quoted as saying:

Hashtags are a filter that can make it possible to make Twitter less noisy. Twitter has a lot of discussion of healthcare, but finding reliable information is not as easy… Patient-physician engagement is important, but the purpose is not to enhance therapeutic relationships. The disease-specific tags may be a way to adapt Twitter’s open platform to focus conversations and bring people together for education, advocacy and support.

Katz’s “cancer tag oncology” is based on research begun in 2013, which found that a wide variety of people did use the Twitter hashtags. Katz also founded Rad Nation, an online community of radiation oncologists.

Previously: Upset stomachs and hurting feet: A look at how people use Twitter for health information, Finding asthma outbreaks using Twitter: A look at how social media can improve disease detection, Advice for young doctors: Embrace Twitter, Twitter 101 for patients, and How using Twitter can benefit researchers
Photo by Michael Coghlan

Cancer, Dermatology, FDA, Health Policy, In the News, Public Health

Experts call on FDA for a “tanning prevention policy”

Experts call on FDA for a "tanning prevention policy"

6635416457_a62bfeb09d_zIndoor UV tanning beds are known carcinogens that are responsible for many cases of skin cancer, which is the most commonly diagnosed form of cancer in the U.S. A recently issued Call to Action to Prevent Skin Cancer from the U.S. Surgeon General states that “more than 400,000 cases of skin cancer [8% of the total], about 6,000 of which are melanomas, are estimated to be related to indoor tanning in the U.S. each year” while “nearly 1 out of every 3 young white women engages in indoor tanning each year,” making indoor tanning a serious public health issue.

In a JAMA opinion piece published yesterday, Darren Mays, PhD, MPH, from the Georgetown University Medical Center‘s Department of Oncology, and John Kraemer, JD, MPH, from Georgetown’s School of Nursing and Health Studies, argued that the FDA needs to step up its regulatory approach and restrict access to this technology – due to its limited therapeutic benefits and known damaging effects.

In 2011, California was the first state to ban access to indoor UV tanning beds to minors. The authors assert that “state-level policies restricting a minor’s access to indoor tanning devices are effectively reducing the prevalence of this cancer risk behavior among youth,” but argue that regulation at the federal level is in order:

Like tobacco products, a national regulatory framework designed to prevent and reduce indoor tanning could reduce public health burden and financial costs of skin cancer. …from a public health perspective the indoor tanning device regulations are not commensurate to those of other regulated products that are known carcinogens with very little or no therapeutic benefit.

However, the likelihood of this regulation taking place is questionable:

FDA did not leverage its authority last year to put a broader regulatory framework in place, which could have included a national minimum age requirement and stronger indoor tanning device warning labels… Critical factors seem to be aligning for such policy change to take place, but additional momentum is needed to promote change at a national scale. The US national political environment makes more expansive regulation by either FDA or Congress seem unlikely in the near future.

The authors concluded with a call for organizations other than governments to help build momentum on toward a “national indoor tanning prevention policy.” For example, they said, universities could implement “tan-free” campus policies similar to the “tobacco-free” campaign.

Previously: More evidence on the link between indoor tanning and cancers, Medical experts question the safety of spray-on tanning productsTime for teens to stop tanning?, Senator Ted Lieu weighs in on tanning bed legislation and A push to keep minors away from tanning beds
Photo by leyla.a

Biomed Bites, Cancer, Genetics, Microbiology, Research, Videos

Packed and ready to go: The link between DNA folding and disease

Packed and ready to go: The link between DNA folding and disease

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

In cells, DNA doesn’t make a lovely, languid helix as popularly depicted. It’s scrunched up, bound with proteins that smoosh one meter of DNA into just one micrometer, a millionth of its size. DNA wound around proteins form a particle called a nucleosome.

Yahli Lorch, PhD, associate professor of structural biology, has studied nucleosomes since they were first discovered more than 20 years ago, as she mentions in the video above:

When I began working on the nucleosome, it was a largely neglected area since most people considered it just a packaging and nothing beyond that.

Since I discovered that it has a role and a very important role in the regulation of gene expression, the field has grown many fold and it’s one of the largest areas in biology now.

Many diseases have been linked to the packaging of DNA, including neurodegenerative diseases, autoimmune diseases and several types of cancer such as some pancreatic cancers. Enhancing the understanding of the basic biology of DNA folding is leading to new and improved treatments for these conditions, Lorch says.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: DNA origami: How our genomes fold, DNA architecture fascinates Stanford researcher — and dictates biological outcomes and More than shiny: Stanford’s new sculpture by Alyson Shotz

Cancer, Neuroscience, Pediatrics, Research, Stanford News, Videos

How one family’s generosity helped advance research on the deadliest childhood brain tumor

How one family’s generosity helped advance research on the deadliest childhood brain tumor

Back in February 2014, Libby and Tony Kranz found themselves at the center of every parent’s worst nightmare. Their six-year-old daughter Jennifer died just four months after being diagnosed with diffused intrinsic pontine glioma (DIPG), an incurable and fatal brain tumor. At the time, the Kranzes decided to generously donate their daughter’s brain to research in hopes that scientists could hopefully develop more effective treatments for DIPG, which affects 200-400 school-aged children in the United States annually and has a five-year survival rate of less than 1 percent.

As reported in the above Bay Area Proud segment, Michelle Monje, MD, PhD, an assistant professor of neurology and neurological sciences who sees patients at Lucile Packard Children’s Hospital Stanford, and colleagues harvested Jennifer’s tumor and successfully created a line of DIPG stem cells, one of only 16 in existence in the world. More from the story:

Using Jennifer’s stem cell lines and others, Monje and her team tested dozens of existing chemotherapy drugs to see if any were effective against DIPG. One appears to be working.

The drug was able to slow the growth of a DIPG tumor in a laboratory setting. Monje’s hope is that this treatment one day could extend the life of children diagnosed with DIPG by as many as six months.

That would have more than doubled Jennifer’s life expectancy.

“It’s a step in the right direction if we can effectively prolong life and prolong quality of life,” Monje said.

Libby Kranz says that for their family, donating their daughter’s tumor to researchers “just felt right.” She and Tony hope that by aiding the research efforts, parents and families will have more, and better quality time with their sick children.

“It’s incredible and it’s humbling,” she said, “to know my daughter is part of it, and that we’re part of it too.”

Previously: Existing drug shows early promise against deadly childhood brain tumor, Stanford brain tumor research featured on “Bay Area Proud,Emmy nod for film about Stanford brain tumor research – and the little boy who made it possible and Finding hope for rare pediatric brain tumor

Cancer, Research, Science, Stanford News

Kidney cancer secrets revealed by Stanford researchers

Kidney cancer secrets revealed by Stanford researchers

I enjoyed recently writing about a collaboration among researchers from Stanford’s School of Medicine and the School of Humanities and Sciences. Oncologist Dean Felsher, MD, PhD, and chemist Richard Zare, PhD, joined forces to learn more about a kidney cancer called renal cell adenocarcinoma; their research was published in the Proceedings of the National Academy of Sciences earlier this week.

In the future, we hope to use this model to… identify those kidney cancer patients who might respond favorably to specific therapies

Together Felsher and Zare found that an aggressive form of kidney cancer has a distinct lipid profile (lipids are a class of molecules found in cell membranes; they also function in cellular signaling pathways and in energy storage). To do so, they used a new technology called desorption electrospray ionization mass-spectrometric imaging, or DESI-MSI. It sounds complicated, but it led directly to a new, previously unsuspected therapeutic approach that may soon be tested in humans. As I described in my article:

DESI-MSI creates a highly detailed, two-dimensional map of the chemical composition of a tissue sample through a process that can be loosely compared to a specialized car wash. Samples are sprayed with a thin, high-powered stream of liquid droplets that dissolve their outer surface. The resulting back spray, which contains molecules from the surface of the sample, is collected and analyzed by mass spectrometry. By moving the tissue sample around in a two-dimensional plane, it’s possible to make a chemical map of its composition.

The researchers found that the cancerous kidney tissue had a chemical composition distinct from that of healthy tissue. In particular, it had higher-than-normal levels of molecules generated as glutamine is metabolized. Blocking the activity of a protein called glutaminase, which is responsible for metabolizing glutamine, caused the animals’ tumors to grow more slowly when [Myc expression was activated].

To conduct the work, researchers in Felsher’s laboratory genetically engineered a strain of mice that could be triggered to express high levels of a cancer-associated protein called Myc in the tubules of their kidneys. These mice quickly developed an aggressive form of kidney cancer when Myc was expressed. Conversely, the kidney tumors shrank significantly when Myc expression was halted. As Felsher told me:

In the future, we hope to use this model to categorize different types of kidney cancer and identify those patients who might respond favorably to specific therapies. In the near term, we can test whether blocking glutamine metabolism is a viable approach for people with Myc-dependent liver cancer.

Previously: Unraveling the secrets of a common cancer-causing gene and Smoking gun or hit-and-run? How oncogenes make good cells go bad

Cancer, Health Policy, In the News, Public Health, Women's Health

Health hazards in nail salons: Tips for consumers

Health hazards in nail salons: Tips for consumers

3044578995_fe5151de75_zAfter exercise class the other day, my friend asked if I wanted to grab coffee and get our nails done. With nail salons on what seems like every block, having a manicure or pedicure is as easy as grabbing a latte. You don’t need an appointment and you’re done in less than an hour.

But this convenience comes at a cost. A recent investigative report in the New York Times exposed the not-so-bright side of nail salons. The articles have raised awareness of poor working conditions and health risks, and they’ve generated a vigorous public dialogue.

“It got people talking and that’s a good thing,” said Thu Quach, PhD, MPH, a research scientist at the Cancer Prevention Institute of California and research director at Asian Health Services.

An epidemiologist, Quach has spent much of her career studying harmful chemicals in nail care products and their health impacts on nail salon workers, a vulnerable workforce that is mainly comprised of low-income immigrants. In research studies she has conducted over time, Quach identified symptoms commonly experienced by salon workers, including dizziness, rashes, and respiratory difficulties, and more serious reproductive health effects and cancer.

“Unfortunately, the risks associated with chronic, long-term exposure to chemicals used in nail products have been little studied,” Quach said. “We know workers are exposed every day and their health is at risk – this is an important focus of my ongoing research.”

The California Healthy Nail Salon Collaborative (CHNSC), convened through Asian Health Services, educates salon owners, workers and consumers about health and safety issues, and advocates for stronger protections for all. Quach, who has been a CHNSC member since its inception, works closely with other members to address worker health and safety using an integrated approach of community outreach, research, and policy advocacy to address health and safety. The CHNSC has worked at the local, state, and federal level to promote changes.

Encouraging counties and cities to adopt the healthy nail salon program is a first step in their local approach. Participation is voluntary and to date three counties and one city have committed: Alameda, San Francisco, San Mateo, and Santa Monica. These counties provide training and formal recognition for salons that participate. Santa Clara has the program in the works and many salons throughout the state participate in healthy initiatives on their own.

In addition to local municipalities taking action, some manufacturers have stepped up to omit the “toxic trio” – dibutyl phthalate, toluene and formaldehyde – from their formulations. But despite rising awareness of the health hazards posed by these chemicals, many products still contain them and there is no regulatory oversight.

Continue Reading »

Cancer, In the News, Research

Cancer cells spread by “disguising themselves,” study shows

Cancer cells spread by "disguising themselves," study shows

2364853112_480ccc3519_zA team of Swedish researchers discovered what may be a key component in how cancer spreads throughout the body: by masquerading as immune cells! Sneaky little rogues.

The study was published yesterday in the journal Oncogene and was conducted primarily by researchers from the Karolinska Institutet in Stockholm. The researchers were investigating the links between inflammation and metastasis when they learned that an inflammation protein called TGF-beta, normally found only on white blood cells, attaches itself to the surface of cancer cells. The protein both attracts them to the lymphatic system and gains them entrance into it.

Scientists have known that cancer often uses the lymphatic system (a network of nodes and vessels that is part of the immune system) to travel to different regions of the body during metastasis, which is the primary way cancer becomes fatal. Swollen lymph nodes, which can be felt on the neck, can indicate metastasis in cancer patients. For breast cancer, which the researchers focused on, infiltration of the lymph system is the earliest sign of metastasis and the most powerful prognostic factor.

Do the cancer cells supplement their masquerade with other characteristics of immune cells? That’s the subject for future research, says Jonas Fuxe, PhD, a study author quoted in a press release. He also notes the significance of the results: “The possibility of preventing or slowing down the spread of cancer cells via the lymphatic system is an attractive one, as it could reduce the risk of metastasis to other organs.”

Previously: New ‘decoy’ protein blocks cancer from spreading, Studying the drivers of metastasis to combat cancer, and Using photo acoustics technology to increase accuracy of lymph node screens for cancer
Photo by Daniel Horatio Augustini

Cancer, Research, Stanford News

Ulcer-causing bacteria manipulate stomach stem cells to their own ends

Ulcer-causing bacteria manipulate stomach stem cells to their own ends

bacteria in stomach - 560Helicobacter pylori bacteria have been giving us ulcers since prehistoric times. This long-term relationship is so tight that researchers have been able to track human migration by looking at what strains of H. pylori we carry. Although it’s usually a benign relationship, in a small number of cases it can cause ulcers or even increase the risk for stomach cancer.

It’s easy to think of H. pylori as an invader that must be stopped. But sometimes it’s worthwhile to think of our bodies as ecosystems and bacteria, like H. pylori, as plucky survivors that use ingenious methods to get by.

When we change our focus this way, we can discover, as did Stanford microbiologist Manuel Amieva, MD, PhD, that the microbe isn’t just adapting to us, it’s adapting us to them. A recent paper of Amieva’s in Gastroenterology shows that the bacteria may be actively modifying stem cells in our stomachs, changing these critical cells’ behavior to suit H. pylori’s needs.

Amieva’s lab discovered tiny colonies of H. pylori, some consisting of only a few bacteria, hidden away at the bottom of the glands that line the stomach, right next to critical stem cells. These constantly dividing stem cells are what replenish the epithelial cells that line the stomach. As I explained in a press release about the study:

This unanticipated finding shed light on how H. pylori could influence cells to turn cancerous. Cancer is thought to develop slowly as the cell acquires mutations in the DNA that override cellular controls and increase cell proliferation. Even though H. pylori had been shown to manipulate cellular controls, the mature stomach’s epithelial cells don’t live long enough to acquire mutations.

Amieva showed a protein injected by the bacteria sent the stem cells into overdrive, resulting in extra-long, inflamed glands. That sort of uncontrolled cell division leads to mutations that over time can turn a stem cell cancerous.

Obviously these insights may lead new understanding of how to detect and fight stomach cancer. But Amieva is also interested in the techniques that H. pylori has developed to manipulate stem cells.

“The bacteria have been experimenting on us since we were humans,” he told me. “I think they have a lot of knowledge about us that we are tapping into.”

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: Image of the Week: Helicobacter pylori colonizing the stomach and Treating an infection to prevent a cancer: H. pylori and stomach cancer
Photo, of bacteria (in green) colonizing the base of the stomach glands, courtesy for the Amieva lab

Stanford Medicine Resources: