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Cancer, Imaging, Research

Researchers develop molecular target for brain cancer

Researchers develop molecular target for brain cancer

cai CD146 cancer detection_labels_560x270

About 23,000 new cases of brain and central nervous system tumors are diagnosed annually, and more than 15,000 patients are expected to die of brain cancer this year in the United States, according to the American Cancer Society. Glioblastoma multiforme is the most common brain malignancy, but it remains incurable with only 5 percent of patients surviving at least 5 years after diagnosis. This bleak scenario has motivated the search for a better molecular target for glioblastoma multiforme diagnosis and therapy.

Weibo Cai, PhD, an associate professor of radiology and medical physics, and his research team at the University of Wisconsin-Madison searched the Cancer Genome Atlas database and identified an effective biomarker for the deadly glioblastoma multiforme: the CD146 gene, which is highly active in glioblastoma.

CD146 genes place unique CD146 proteins on the surface of cells. Cai’s team developed an antibody that selectively latches onto the CD146 proteins concentrated on the glioblastoma tumors. They also tagged the antibody with a radioactive copper isotope, so the tumors could be easily identified and localized with a positron emission tomograph (PET), an imaging scanner commonly used to detect cancer.

Cai tested their antibody by implanting animal models with human glioblastoma tumors, injecting them with the antibody and imaging them with a small animal PET scanner. The copper-labeled antibody preferentially accumulated in the tumors, allowing PET imaging to accurately identify tumors as small as 2 mm. Their study results were recently reported in the Proceedings of the National Academy of Sciences.

As Cai explained in a university news release:

We’ve created a tag that – at least in our mouse model – is highly specific for this aggressive brain cancer. If the technique proves out in further tests, it could be used to diagnose some strains of aggressive glioblastoma, and also to evaluate treatment progress or even to test potential drugs.

The researchers also found high activity of CD146 in ovarian, liver, and lung tumors so their antibody could have a wide range of applications. However, there is a lot of research to be done before the technique could be used in the clinic. Cai said in the news release, “This targets tumors with the worst survival, but I want to emphasize that human trials are some years in the future.”

Jennifer Huber, PhD, is a science writer with extensive technical communications experience as an academic research scientist, freelance science journalist, and writing instructor.

Previously: You know it when you see it: a precision health approach to diagnosing brain cancerA Stanford neurosurgeon discusses advances in treating brain tumors, and A century of brain imaging
Images by Weibo Cai/Department of Radiology, University of Wisconsin-Madison. On the left, the antibody is linked to a label that shows up in a PET scanner, and the aggressive cancer shines brightly. On the right, a similar cancer without the molecular marker is less obvious.

Bioengineering, Cancer, Imaging, Public Safety, Research, Stanford News, Technology

A new way to scan for plastic explosives could someday detect cancerous tumors

A new way to scan for plastic explosives could someday detect cancerous tumors

14591799636_128fbe50ee_zSci-fi shows and superhero films are full of gadgets and beings that have the power to remotely scan their environment for hidden things. For us mere mortals this superability may sound unachievable, but now Stanford engineers are working to develop a safe and portable way to detect concealed objects by scanning with microwaves and ultrasound.

As this Stanford Report story explains, the idea began with a challenge posed by the Defense Advanced Research Projects Agency: Design a way to detect buried plastic explosives from a safe distance without touching the surface of the ground.

A team of electrical engineers led by assistant professor Amin Arbabian, PhD, and research professor Pierre Khuri-Yakub, PhD, took up the challenge, paying homage to the scanning device made popular by sci-fi show Star Trek in the process. They created a tricorder-like device that senses the ultrasonic waves created by objects as they expand and contract when warmed by electromagnetic energy (e.g., light and microwaves).

Here’s the really interesting part: Because everything expands and contracts when heated — but not at identical rates — this scanning tool could have medical applications as well. For example, blood vessels that sprout from cancerous tumors absorb heat differently than surrounding tissue. So, blood vessels radiating from tumors could appear as “ultrasound hotspots” when scanned with the tricorder device.

The team is working to make this device ready to detect the presence of tumors and other health anomalies sometime within the next decade or so.

Previously: Beam me up! Detecting disease with non-invasive technology and Tiny size, big impact: Ultrasound powers miniature medical implant
Photo by Joe Haupt

Behavioral Science, Imaging, Neuroscience, Stanford News

Decisions, decisions: How emotions alter our decisions

Decisions, decisions: How emotions alter our decisions

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is part of a series on what she learned. 

emotionWhen it comes to charitable giving, the cold hard facts suggest hanging on to our money. But people routinely give their support to environmental or other causes.

Nik Sawe, a graduate student in environmental resources, wanted to know why. So he put people in an MRI and recorded their brain activity while showing them photos of iconic spaces and proposed destructive uses of those spaces.

In my story I describe their findings:

As expected, iconic images activated a part of the brain’s reward pathway involved in anticipating good outcomes, like getting money or food, and images of destructive land uses triggered a part of the brain that is often associated with response to bad outcomes, like experiencing pain or losing money.

The people with the biggest negative response to land destruction were the most likely to give money. Sawe said, “My hunch is that people get outraged over the proposed negative actions of a third party and that’s what drives donation. It’s punitive.”

This negative emotion driving environmental donation is the opposite of what people find with donations to charities or orphans, Sawe pointed out. There, people who anticipate the warm glow of giving are most likely to give. But, as I write in the piece:

In each case, he said, it’s our emotions that often override the pure cost-benefit analysis that goes into deciding which cause to support.

Previously: Decisions, decisions: The way we express a decision alters the outcome and Decisions, decisions: How our decision making changes with age
Photo by Shutterstock

Cancer, Imaging, Public Health, Research

Tattoo ink may mimic cancer on PET-CT images, researchers warn

tatoo lady

The hit new crime thriller “Blindspot is about a mysterious woman, Jane Doe, who is covered in extensive full-body tattoos. If Jane Doe were a real woman who ever needed medical imaging, she might need to be concerned.

In a case report published recently in the journal Obstetrics & Gynecology, researchers found that extensive tattoos can mimic metastases on positron emission tomography (PET) fused with computed tomography (CT). PET-CT imaging is commonly used to detect cancer, determine whether the cancer has spread and guide treatment decisions. A false-positive finding can result in unnecessary or incorrect treatment.

Ramez N. Eskander, MD, an assistant professor of obstetrics and gynecology at UC Irvine, and his colleagues describe the case study of a 32-year-old woman with cervical cancer and extensive tattoos. The pre-operative PET-CT scan using fluorine-18-deoxyglucose confirmed that there was a large cervical cancer mass, but the scan also identified two ileac lymph nodes as suspicious for metastatic disease. However, final pathology showed extensive deposition of tattoo ink and no malignant cells in those ileac lymph nodes.

It’s believed that carbon particles in the tattoo pigment can migrate to the nearby lymph nodes through macrophages, using mechanisms similar to those seen in malignant melanoma. The researchers explain in their case report:

Our literature search yielded case reports describing the migration of tattoo ink to regional lymph nodes in patients with breast cancer, melanoma, testicular seminoma, and vulvar squamous cell carcinoma, making it difficult to differentiate grossly between the pigment and the metastatic disease, resulting in unnecessary treatment.

The authors warn other physicians to be aware of the possible effects of tattoo ink on PET-CT findings when formulating treatment plans, particularly for patients with extensive tattoos.

Jennifer Huber, PhD, is a science writer with extensive technical communications experience as an academic research scientist, freelance science journalist, and writing instructor. 

Previously: Stanford researcher discusses enhancing imaging methods with nanotechnology in NIH podcast and Stanford fellow addresses burden of cervical cancer in Mongolia
Photo by Paulo Guereta

Imaging, In the News, Microbiology, Stanford News

Stanford image takes big honors at 2015 Nikon Small World Photomicrography Competition

Stanford image takes big honors at 2015 Nikon Small World Photomicrography Competition


Small things seldom get big press, but once a year the microscopic world takes front and center stage at Nikon’s annual Small World Photomicrography Competition. This year, a Stanford Medicine team took second place in the competition, edging out more than 2,000 entries from 83 countries around the world.

Their award-winning photo is a cacophony of color that uses immunofluorescence to illuminate a mouse colon colonized with human microbiota.

Four Stanford researchers were responsible for this mosaic of microbes: photographer Kristen Earle, PhD; second-year graduate student Gabriel Billings; KC Huang, PhD, a bioengineer and microbiologist; and Justin Sonnenburg, PhD, a microbiologist and co-author of The Good Gut.

Earle told me she took this image while working on a study with Sonnenburg that explores how images, like this one, can help researchers count microbes and see how they’re organized in a cross-section of gut.

Previously: Why C. difficile-defanging mouse cure may work in people, tooDrugs for bugs: Industry seeks small molecules to target, tweak and tune up our gut microbes and Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?
Image courtesy of Kristen Earle, Gabriel Billings, KC Huang and Justin Sonnenburg

Chronic Disease, Imaging, Pediatrics, Research, Stanford News

Why chronic disease harms kids’ bone development — and what to do about it

Why chronic disease harms kids' bone development — and what to do about it

osteoporosis“Someone once told me listening to me talk is like drinking from a fire hose,” Mary Leonard, MD, said to me at the end of our recent 45-minute interview. I had precisely the opposite reaction: After I left her office at Stanford Hospital, I was so parched from our conversation I walked across the street, bought a bottle of water and downed the whole thing.

Leonard, a professor of pediatrics and of medicine, has a sense of urgency for a reason: She’s trying to make sure children with chronic diseases build as much bone as possible before puberty ends. Once that window closes, she and other researchers believe, it’s too late to do much about it. And the likely consequence of emerging from adolescence with inadequate bone mass is early osteoporosis.

“Kids with kidney disease are, even as children, fracturing more than you would expect,” Leonard said. “Kids with arthritis are fracturing more than you would expect.” Ditto those with congenital heart disease, organ or bone marrow transplants, inflammatory bowel disease, cerebral palsy, muscular dystrophy or a history of cancer. The culprits: inflammation, immobility, malnutrition, stunted growth, steroid treatment or a combination thereof.

Leonard’s work fits in perfectly with the most recent issue of Stanford Medicine, which is all about how early experiences can have far-reaching consequences for our health. As she says in my story about her research program:

We believe that once you go through puberty, you’re not getting that bone back. I feel like we’ve described and described the problem, and now we need to do clinical trials to see what we can do to improve bone health in these patients. We just want to make sure they go into adulthood with the best, strongest skeleton possible — with bones to last a lifetime.

Leonard has several ideas about what would help — exercise interventions, medications, more aggressive treatment of the underlying condition at younger ages — and state-of-the-art imaging equipment with which to assess them. “We’re on the cusp,” she told me with excitement, “of transitioning from describing and describing to actually doing something.”

Previously: Stanford Medicine magazine tells why a healthy childhood matters, Pediatric nephrologist Mary Leonard discusses bone health in children with chronic diseases at Childx and Pediatrics group issues new recommendations for building strong bones in kids
Photo by Sebastian Kaulitzki/Shutterstock

Imaging, Neuroscience, NIH, Research, Videos

Video reconstruction reveals stunning detail within a tiny section of brain

Video reconstruction reveals stunning detail within a tiny section of brain

Important discoveries in science are often called “big” breakthroughs, yet much of the information that makes these “aha” moments possible is found in the most diminutive of details. So it seems fitting that our first glimpse into the inner workings of the mammalian cerebral cortex arises from a tidbit of brain no bigger than a grain of sand.

For the first time, researchers have created a digital reconstruction of part of a mammalian cerebral cortex — the “rind” of the brain, about two to three dimes thick, that plays a central role in functions like memory, thought, language and consciousness.

This digitized rendering was created by NIH grantee Jeff Lichtman, MD, PhD, and his colleagues as part of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Francis Collins, MD, PhD, director of the National Institutes of Health, offers more details on how the film was made over on the NIH Director’s blog.

Previously: Exercise and your brain: Stanford research highlighted on NIH Director’s blogProcess that creates transparent brain named one of year’s top scientific discoveries and How CLARITY offers an unprecedented 3-D view of the brain’s neural structure

Cancer, Genetics, Imaging, Precision health, Research, Science, Stanford News

You know it when you see it: A precision health approach to diagnosing brain cancer

You know it when you see it: A precision health approach to diagnosing brain cancer

BurlIf you know which virus has made a person ill, as well as whether your patient responds better to drug A or drug B, you’re in a much better position to treat them. In the world of oncology, it’s often the genetic personality of the tumor itself that determines the best treatment protocol. A tumor with one set of gene variants may be susceptible to only one of several treatments. To decide which drug to prescribe, you’ve got to know your tumor.

In some cancers, such as skin cancer, it’s easy to physically examine the tumor and easy to take a biopsy to root out the tumor’s genetic secrets. But for cancers deep in the brain, a biopsy is problematic. And without knowing more about a brain tumor, it’s harder to guess the right treatment.

Now a team of researchers, led by Stanford’s Haruka Itakura, MD, and Olivier Gevaert, PhD, have distinguished three types of brain tumors. Each type is identifiable by their appearance in MRIs and predictably associated with specific molecular characteristics. Itakura and Gevaert report their work in today’s Science Translational Medicine.

Magnetic resonance imaging revealed three distinct kinds of glioblastoma brain tumors, each of which could be associated with a different probability of patient survival and a unique set of molecular signaling pathways. The work paves the way for more precise diagnosis, better targeted therapies and personalized treatment of GBM brain tumors.

Previously: Brain imaging, and the “image management” cells that make it possibleA century of brain imaging and When it comes to brain imaging, there’s nothing simple about it
Photo by Travis

Imaging, Microbiology, Stanford News

When bacteria swarm: H. pylori home in on our stomach cells

Imagine you’re thrown into wild ocean waters, battered by waves until you can’t tell which way is up. Your only chance of survival is to somehow sense the location of a rock outcropping and cling to it. Now factor in that the churning water is highly acidic and lethal – that’s the predicament facing Helicobacter pylori, a bacterium that makes its home in one out of every two human stomachs and, for an unfortunate 20 percent of its hosts, causes ulcers.

H. pyloris safe haven is our stomach’s lining with its protective mucus and nutrient-rich cells. New research from the lab of Stanford microbiologist Manuel Amieva, MD, PhD, published today in Cell Host & Microbe demonstrates that the bacteria are able to detect and home in on metabolic molecules released by human stomach cells. The behavior, captured in the video above, shows H. pylori swarming to a microscopic needle releasing either a solution collected from stomach cells or the molecule urea.

The corkscrew-shaped bacterium moves with the help of its tail-like flagella. The bundle of flagella spin in one direction to propel the bacteria forward. When they reverse the spin, said Amieva, the flagella become like helicopter blades, pulling H. pylori backwards.

Previous experiments have shown the bacteria swim away from acid and H. pylori is known to have four chemical sensing receptors. “But this is the first time we’ve observed in real time the bacteria swimming towards something,” said graduate student and lead author, Julie Huang, referring to the technique that allowed the lab to watch H. pylori’s swimming behavior directly.

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Imaging, Microbiology, Research, Science, Stanford News, Technology

3-D structure of key signaling protein and receptor revealed

3-D structure of key signaling protein and receptor revealed

Using ultra-bright X-rays at SLAC National Accelerator Laboratory, a team of international researchers has captured the 3-D structure of a key signaling protein and its receptor for the first time.

The discovery provides new insight into the functioning of a common cell receptor called a G protein-coupled receptor or GPCR. Researchers estimate this protein, and its relatives, are the targets of about 40 percent of pharmaceuticals. From a SLAC release:

“This work has tremendous therapeutic implications,” said Jeffrey Benovic, PhD, a biochemist who was not involved with the study. “The study is a critical first step and provides key insight into the structural interactions in these protein complexes.”

Specifically, the researchers were able to illuminate the structure of the GPCR bonded with a signaling protein called arrestin. Arrestins and G proteins both dock with the GPCRs, however, researchers had previously only examined a bonded G protein. G proteins are generally the “on” switch, while arrestins usually signal the GPCR to turn off:

Many of the available drugs that activate or deactivate GPCRs block both G proteins and arrestins from docking.

“The new paradigm in drug discovery is that you want to find this selective pathway – how to activate either the arrestin pathway or the G-protein pathway but not both — for a better effect,” said Eric Xu, PhD, a scientist at the Van Andel Research Institute in Michigan who led the experiment. The study notes that a wide range of drugs would likely be more effective and have fewer side effects with this selective activation.

Previously: Why Stanford Nobel Prize winner Brian Kobilka is a “tour de force of science”, Funding basic science leads to clinical discoveries, eventually and Video of Brian Kobilka’s Nobel lecture
Video by SLAC National Accelerator Laboratory

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