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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.

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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

Cancer, Pediatrics, Research, Stanford News

Existing drug shows early promise against deadly childhood brain tumor

Existing drug shows early promise against deadly childhood brain tumor

BrainModelAn existing drug may help treat the deadliest form of childhood brain cancer, according to a Stanford-led study published today in Nature Medicine. The findings are the first to show an effect of any FDA-approved drug on the cancer, which is called diffuse intrinsic pontine glioma (DIPG).

The drug, a blood-cancer medication called panobinostat, reduced tumor cell growth in a lab dish and lengthened survival time for mice with the tumor. Stanford’s Michelle Monje, MD, PhD, who led the research, cautioned that panobinostat has not yet been shown to work in children with DIPG. Her team is planning for a closely monitored clinical trial that will track the drug’s effects in DIPG patients.

From our press release about the new study:

The drug repairs a portion of the cellular machinery now known to be defective in DIPG tumor cells, the new research showed. “A key thing that is wrong with DIPG cancer cells gets corrected by panobinostat,” said Monje, who also treats DIPG patients in her role as a pediatric neuro-oncologist at Lucile Packard Children’s Hospital Stanford. However, the new data also showed that some DIPG cells develop resistance to the drug, which means it will likely need to be combined with other drugs to achieve the best results in humans. “I don’t think this is a cure, but I do think it will help,” she said.

The new panobinostat findings are one piece of a larger story about Monje’s efforts to understand DIPG. As we recently reported on Scope, her team has also found that nerve activity — in her study, the nerve firing needed to initiate walking — drives the growth of high-grade gliomas, including DIPG. In that work, the scientists uncovered a piece of the tumor’s molecular workings, called neuroligin-3, that could serve as a target for new drugs.

Neuroligin-3 is distinct from the cellular machinery affected by panobinostat. Ultimately, that’s a good thing, since doctors want to be able to attack the tumor in several ways, with more than one drug. (As an analogy, think of stopping a runaway train: It’ll be easier if you can apply the brakes and cut off the fuel supply.)

In addition to running clinical trials and continuing to study the basic molecular machinery of the tumor, the team plans to use DIPG cells in the lab to screen other drugs in combination with panobinostat. They are also collaborating with many other teams from around the world to try to make a difference in the outcome of this brain tumor, which currently has a five-year survival rate of only about one percent. The federal government’s clinical trials website lists all the trials underway on this tumor, for those who are interested.

“The goal is multimodal treatment to improve outcomes for children with DIPG,” Monje said.

Previously: Brain tumor growth driven by neuronal activity, Stanford-led study finds, Stanford brain tumor research featured on “Bay Area Proud” and New Stanford trial targets rare brain tumor
Photo by GreenFlames09

Big data, Cancer, Medicine and Society, Research, Stanford News, Videos

Collecting buried biomedical treasure – using big data

Collecting buried biomedical treasure - using big data

The answers to some of today’s most pressing biomedical questions may be hiding in medical centers – and physicians’ offices – across the country. Buried in medical files are the experiences of thousands of patients, far more than have participated in any clinical trial. These files chronicle their conditions, treatments and outcomes – valuable information that could improve care for millions of current and future patients.

But, and a big but here, accessing the data securely and transforming it into a format available for inquiry can be a logistical nightmare. And that’s where Stanford’s Daniel Rubin, MD, and his team, step in.

“We’re developing methods that will permit us to leverage national data without requiring centers to actually send the data to a central site, which overcomes a big barrier to these kinds of efforts because of privacy and other regulatory concerns,” Rubin said in the video above.

His group is concentrating on cancer and received a 2014 Big Data for Human Health Seed Grant to support the work.

“We’ve developed software that we’ve deployed at these local sites… They run it on their local data and we aggregate the results,” Rubin said. He said the primary challenge is creating a system that is open and invites broad participation, but also keeps the data secure. His project exemplifies the uses of big data. From the video:

You couldn’t do this without big data because there are so many variables that affect a patients’ disease… and you need big data to find enoguht patietns that match those charactoristics to be able to look for similar cohorts to guide decision making.

This effort is part of Stanford Medicine’s Biomedical Data Science Initiative (BDSI), which strives to make powerful transformations in human health and scientific discovery by fostering innovative collaborations among medical researchers, computer scientists, statisticians and physicians. For more on important work being done in this area, mark your calendars for Stanford’s Big Data in Biomedicine conference on May 20-22. More information is available here.

Previously: All data – big and small – informs large-scale neuroscience projectExamining the potential of big data to transform health care, Registration for Big Data in Biomedicine conference now open and Stanford researchers develop web-based tool to streamline interpretation of medical images,

AHCJ15, Cancer, Chronic Disease, Events, Medicine and Society, Palliative Care, Patient Care

Looking at cancer as a chronic illness

Looking at cancer as a chronic illness

6903202302_d9740cc15b_zMany of us think of cancer as a terminal illness, but as treatments have become more sophisticated, more and more people are living longer with cancer. So is it becoming a chronic condition like rheumatoid arthritis or insulin-dependent diabetes? A panel at this past weekend’s Association of Health Care Journalism 2015 conference addressed this question, starting with a metaphor that has really lodged itself in my brain: the Niagara Falls approach.

After she was diagnosed with stage-four breast cancer and her oncologist asked her what she wanted to accomplish, Amy Berman, RN, a grantmaker and senior program officer at the John A. Hartford Foundation, replied,”I want to do ‘Niagara Falls.'” For Berman, Niagara Falls means continuing to live with as high a quality of life as possible, and then when such quality is no longer sustainable, dramatically dropping to the inevitable end point. By contrast, a different oncologist had announced to her that they should fight the thing full-force, do everything possible to beat it, including a double mastectomy and chemotherapy until her body could no longer handle the toxicity. Berman thought this would be an inverse Niagara Falls, dramatically reducing her quality of life and then dragging on to the inevitable end.

Berman, who is something of a cancer celebrity, has lived nearly 5 years post-diagnosis at 11-20 percent odds, and she has never been hospitalized. She was beaming during her panel. “I look good,” she said, as the chuckling audience caught her joie de vivre. “And I feel the way I look.”

Berman made the point was that “as our nation ages,” providers need to have serious discussions with patients, not shield them from the truth through rosier prognoses. We need to debunk the myth that palliative care means giving up or accepting a shorter life, she said – rather, it focuses on quality of life and what’s important to patients. It also shifts care from hospital to home, and in doing so saves money: Berman passed up an estimated $1 million in treatment over the past 4 years. “This is how we need to think about care,” she said. “Managing people to live well with serious illness… My cancer cannot be cured, but I’m also not dying today.”

George Sledge, MD, professor of oncology at Stanford, a member of the Stanford Cancer Institute, and a medical writer, is on the same page about palliative care. He said he considers it a success if his patients never go to the hospital. But that doesn’t mean he brushes off the ways in which cancer is different than truly chronic diseases.

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Cancer, Research, Stanford News

Researchers prime immune system’s T cells with foreign antibodies to target cancer cell

Researchers prime immune system’s T cells with foreign antibodies to target cancer cell

Everyday our immune system defends us against bacterial and viral invaders. But there are some threats that this lifesaving system hasn’t evolved to deal with. In the case of tumors, it can’t recognize the threat – the mutated cells still appear to the immune system as “us” and the out-of-control cancer flies under its radar. Or it perceives something beneficial as a threat, attacking healthy transplant organs because the markers on the cells’ surfaces are unfamiliar.

In a paper published today in Nature, Stanford researchers came up with an ingenious hack that used the body’s organ rejection machinery to fight a wide variety of cancers. The work was done in mice, but preliminary investigations show the same mechanism working in human cancers.

Tthe most important thing is to see if we can bring this new approach into the clinic

The key lies in antibodies, the small chemicals that circulate through the body, attaching themselves to foreign proteins, including those on the surfaces of transplanted organs. These antibody protein combos are picked up by scavenging cells, called dendritic cells, and presented to T cells in a way that puts the T cells in attack mode, destroying any cells displaying these proteins.

As Edgar Engleman, MD, PhD, senior author on the paper, said, “T cells contain the bullet, but antibodies start the whole thing off.”

We don’t make antibodies to the proteins on our own cells, or rather, antibodies that recognize “self” are purged early on. So there are no antibodies to recognize the mutated proteins of tumors. But, transplant those tumor cells into someone else, and in less than a week, the T cells begin to eliminate the cancer – at least that is what’s been observed in mice.

The researchers isolated antibodies from the mice that rejected the transplanted tumors. The antibodies, along with chemicals that stimulated the dendritic cells, were injected back into the original cancer-afflicted mice. In these mice, the immune system eliminated the tumors and the mice remained cancer free for a year.

The researchers found that the technique worked against six different mouse cancers. They also took cancers from four human patients, collected antibodies from donated blood plasma, and showed that, in a lab, human dendritic and T cells seemed to behave similarly to the mice cells. The researchers’ next step will be human trials.

“I honestly think the most important thing is to see if we can bring this new approach into the clinic,” said Engleman. “That’s where we want to go.”

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: Oh, grow up! “Specialized” stem cells tolerated by immune system, say Stanford researchers, Training the immune system to attack cancer throughout the body a new clinical trial at Stanford and Video of killer T cells of immune system battling cancer

Autoimmune Disease, Cancer, Infectious Disease, Microbiology, Nutrition, Stanford News

Getting to the good gut: how to go about it

Getting to the good gut: how to go about it

In a blog post a few years ago I wrote, The Good Gutwith misplaced parenthetical self-assuredness:

Anybody who’s ever picked up an M&M off the sidewalk and popped it into his or her mouth (and, really, who among us hasn’t?) will be gratified to learn that the more germs you’re exposed to, the less likely you are to get asthma … hay fever and eczema.

I soon learned to my surprise, if not necessarily to my embarrassment, that virtually nobody – at least nobody over 6 – cops to having stooped-and-scooped as I routinely did as a kid on what I called my “lucky-sidewalk” days.

But those M&Ms may have been the best pills I ever took.

Stanford microbiologists Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, (they’re married) have written a new book, The Good Gut, about the importance of restocking our germ-depleted lower intestines.

Massive improvements in public sanitation and personal hygiene, the discovery of antibiotics and the advent of sedentary lifestyles have taken a toll on the number and diversity of microbes that wind up inhabiting our gut. According to The Good Gut, we need more, and more varieties, of them. And we need to treat them better. The dearth of friendly microorganisms in the contemporary colon is due not just to a lack of bug intake but to a lack of fiber in the modern Western diet. Indigestible to us, roughage is the food microbes feast on.

The Good Gut packages that message for non-scientists. “We wanted to convey the exciting findings in our field to the general public,” Justin Sonnenberg recently told me. “We’d noticed we were living our life differently due to our new understanding. We were eating differently and had modified both our own lifestyle and the way we were raising our children.”

In simple language, the Sonnenburgs explain how the pieces of our intestinal ecosystem fit together, what can go wrong (obesity, cancer, autoimmunity, allergy, depression and more), and how we may be able to improve our health by modifying our inner microbial profiles. Their book includes everything from theories to recipes, along with some frank discussion of digestive processes and a slew of anecdotes capturing their family’s knowledge-altered lifestyle.

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