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Applied Biotechnology, Bioengineering, Cancer, Genetics, Research, Stanford News

Minuscule DNA ring tricks tumors into revealing their presence

Minuscule DNA ring tricks tumors into revealing their presence

cool minicirclesAn animal study just published in Proceedings of the National Academy of Sciences shows how, in the not-distant future, doctors may be able to not only detect tumors early in humans, but also monitor the effectiveness of cancer drugs in real time, guide clinical trials of new drugs, and even screen entire populations of symptom-free people for nascent tumors that could have otherwise slipped under the radar.

The potential is huge. And the principal investigator, Sam Gambhir, MD, PhD, is credible: He chairs Stanford’s radiology department, directs the Canary Center at Stanford for Cancer Early Detection and has authored or co-authored nearly 600 peer-reviewed research publications.

From my news release about the study:

Imagine: You pop a pill into your mouth and swallow it. It dissolves, releasing tiny particles that are absorbed and cause only cancerous cells to secrete a specific protein into your bloodstream. Two days from now, a finger-prick blood sample will expose whether you’ve got cancer and even give a rough idea of its extent. That’s a highly futuristic concept. But its realization may be only years, not decades, away.

The key to early cancer detection lies in finding valid biomarkers: substances whose presence in a person’s blood or urine flags a probable tumor. (High blood levels of the molecule known as PSA, for example, can signify prostate cancer.) But although various tumor types indeed secrete characteristic substances into the blood, these same substances typically are made in healthy tissues, too, albeit usually in smaller amounts. So a positive test result for, say, PSA doesn’t necessarily mean the person has cancer. Contrariwise, a small tumor just may not secrete enough of the trademark substance to be detectable.

Gambhir’s team appears to have found a way to force any of numerous tumor types to produce a biomarker whose presence in the blood unambiguously signifies cancer, because no adult tissues – cancerous or otherwise – would normally be making it. This particular substance is a protein naturally present in human embryos as they’re forming and developing, but absent in adults.

The scientists designed a genetic construct, called a DNA minicircle, that contains a single gene coding for the telltale substance. DNA minicircles are tiny, artificial, single-stranded DNA rings about 4,000 nucleotides in circumference – roughly one-millionth as long as the strand that you’d get if you stretched the DNA in all 23 chromosomes of the human genome end to end.

Gambhir and his colleagues rigged their minicircles so that this sole gene would be “turned on” only inside cancer cells. (For more details on how to do this, please see my release.) They injected the minicircles into mice who had small tumors and mice who didn’t. Within 48 hours, a simple blood test indicated the presence of the biomarker in the blood of mice with tumors, but not in the blood of the tumor-free mice.The bigger the tumor volume, the more of the biomarker in the blood.

The technique will likely apply to a broad range of cancers, and can possibly be modified to help pinpoint budding tumors’ location in the body.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, Nanoparticles home in on human tumors growing in mice’s brains, increase accuracy of surgical removal and Nanomedicine moves one step closer to reality
Photo by Jim Strommer

Aging, Chronic Disease, In the News, Media, Neuroscience, Women's Health

Science Friday explores women’s heightened risk for Alzheimer’s

Science Friday explores women's heightened risk for Alzheimer's

More than two-thirds of the Americans living with Alzheimer’s are women — some like the character Alice in the movie “Still Alice,” who suffers from an early onset form of the disease.

Science Friday tackled that topic Friday, with guests Michael Greicius, MD, MPH, associate professor of neurology and director of the Stanford Center for Memory Disorders, and Roberta Diaz Brinton, PhD, professor of pharmacology at the University of Southern California. The two quickly disputed the belief that more women get Alzheimer’s disease because they live longer.

“The way women age puts them at risk,” Brinton said. As they transition through menopause, some women develop cognitive symptoms such as insomnia, depression and short-term memory loss, leaving them at greater risk for Alzheimer’s, she explained.

Women who have a form of a gene called APOE-e4 are particularly at risk, although it doesn’t seem to affect men, Greicius said. The gene interacts with estrogen.

Scientists are continuing to decipher the link between estrogen and Alzheimer’s and the possibility of hormone therapies, as well as the connection — if any — between pregnancy and Alzheimer’s risk, the scientists told listeners.

The 18-minute segment is available here.

Previously: Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice, The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius, Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men and The toll of Alzheimer’s on caretakers

Aging, Cancer, Emergency Medicine, Medical Education, Pregnancy, Stanford News

Stanford Medicine magazine reports on time’s intersection with health

Stanford Medicine magazine reports on time's intersection with health

Why is it that giant tortoises typically live for 100 years but humans in the United States are lucky to make it past 80? And why does the life of an African killifish zip past in a matter of months?

I’ve often mused about the variability of life spans and I figure pretty much everyone else has too. But while editing the new issue of Stanford Medicine magazine’s special report on time and health, “Life time: The long and short of it,” I learned that serious scientists believe the limits are not set in stone.

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics Anne Brunet, PhD, in “The Time of Your Life,” an article on the science of life spans. My first thought was, wow! Then I wondered if some day humans could live like the “immortal jellyfish,” which reverts back to its polyp state, matures and reverts again, ad infinitum. Now that would be interesting.

Also covered in the issue:

  • “Hacking the Biological Clock”: An article on attempts to co-opt the body’s timekeepers to treat cancer, ease jetlag and reverse learning disabilities.
  • “Time Lines”: A Q&A with bestselling author and physician Abraham Verghese, MD, on the timeless rituals of medicine. (The digital edition includes audio of an interview with Verghese.)
  • “Tick Tock”: A blow-by-blow account of the air-ambulance rescue of an injured toddler.
  • “Before I Go”: An essay about the nature of time from a young neurosurgeon who is now living with an advanced form of lung cancer. (The neurosurgeon, Paul Kalanithi, MD, is featured in the video above, and our digital edition also includes audio of an interview with him.)

The issue also includes a story about the danger-fraught birth of an unusual set of triplets and an excerpt from the new biography of Nobel Prize-winning Stanford biochemist Paul Berg, PhD, describing the sticky situation he found himself in graduate school.

Previously Stanford Medicine magazine traverses the immune system, Stanford Medicine magazine opens up the world of surgery and Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions.

Scope Announcements, Stanford News

100,000 followers for @StanfordMed

100,000 followers for @StanfordMed

Twitter 100K mark - 560v2

Over the weekend, we reached a milestone on Twitter: Our @StanfordMed feed now has 100,000 followers. We’re happy to be followed by so many people (it seems like just yesterday that we were feeling giddy over the 50,000 mark), and we hope you’ll consider following us if you don’t already.

And as a reminder, you can also read about the latest news and developments on the school’s Facebook page, and you can now read Scope stories via Flipboard.

Previously: Introducing the Scope magazine on Flipboard50,000 Twitter followers – and countingFive thousand blog entries – and counting and Introducing the @ScopeMedBlog Twitter feed

Cancer, Imaging, In the News, Research, Technology

Stanford instructor called out for his innovative – and beautiful – imaging work

Stanford instructor called out for his innovative - and beautiful - imaging work

breast cancer cells

I’ll skip the name word play – it’s just too obvious – but I won’t skip Michael Angelo’s work. Angelo, MD, a pathology instructor at Stanford, developed a new imaging technique that labels antibodies with metallic elements, then uses an ion beam to scan the tissue, revealing up to 100 proteins at once in a single cancer cell.

This technique, called multiplexed ion beam imaging, or MIBI, captured the attention of the National Institutes of Health, which featured Angelo in its NIH Director’s Blog this week. The images are lovely to look at, but also quite useful to learn more about tissue types.

Here’s Angelo describing the image above:

Angelo used MIBI to analyze a human breast tumor sample for nine proteins simultaneously—each protein stained with an antibody tagged with a metal reporter. Six of the nine proteins are illustrated here. The subpopulation of cells that are positive for three proteins often used to guide breast cancer treatment (estrogen receptor a, progesterone receptor, Ki-67) have yellow nuclei, while aqua marks the nuclei of another group of cells that’s positive for only two of the proteins (estrogen receptor a, progesterone receptor). In the membrane and cytoplasmic regions of the cell, red indicates actin, blue indicates vimentin, which is a protein associated with highly aggressive tumors, and the green is E-cadherin, which is expressed at lower levels in rapidly growing tumors than in less aggressive ones.

Taken together, such “multi-dimensional” information on the types and amounts of proteins in a patient’s tumor sample may give oncologists a clearer idea of how quickly that tumor is growing and which types of treatments may work best for that particular patient.  It also shows dramatically how much heterogeneity is present in a group of breast cancer cells that would have appeared identical by less sophisticated methods.

Angelo was given a NIH Director’s Early Independence Award last fall, and he’s ramping up his investigations of breast cancer.

Cancer, Patient Care

Bone marrow transplantation: The ultimate exercise in matchmaking

Bone marrow transplantation: The ultimate exercise in matchmaking

candy heart - smallStanford Blood Center is home to one of the top human leukocyte antigen (HLA) histocompatibility laboratories in the country. While the center is best known for supplying blood products to hospitals, SBC’s HLA lab supports the success of hundreds of bone marrow transplants administered at Stanford Health Care by providing and developing tests to determine donor and recipient organ compatibility.

What Is Bone Marrow?

Bone marrow is in the center of the bone and contains hematopoietic stem cells (HSC). These cells are immature cells that can grow into red blood cells, white blood cells or platelets, which serve the following purposes in the body:

  • Red blood cells carry oxygen throughout the body
  • White blood cells help fight infections
  • Platelets help control bleeding

When bone marrow is damaged or destroyed, it can no longer make normal blood cells and a stem cell transplant (bone marrow transplant) is required.

Bone Marrow Transplantation

A bone marrow transplant is the process of replacing unhealthy HSC with healthy ones in order to restart hematopoiesis, the process of generating red blood cells, white blood cells, and platelets.

Patients requiring a bone marrow transplant are often being treated for one of the following:

Patients requiring a bone marrow transplant are often being treated for one of the following:

  • Blood cancers like leukemia
  • Diseases which result in bone marrow failure like aplastic anemia
  • Other immune system diseases

In some cases, the patient will receive an autologous transplant where the stem cells come from the patient’s own blood or bone marrow, which would need to have been drawn and stored prior to the patient becoming ill.

When a patient receives stem cells from another person, it’s called an allogeneic transplant. When conducting an allogeneic transplant, it’s of the utmost importance that the donor and patient’s immune systems are closely matched; otherwise the patient will either reject the healthy donor HSC or the donor cells can attack the patient. The latter scenario is called graft-versus-host disease, and can be fatal in some cases.

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Medical Education, Patient Care, Stanford News

Stanford student earns national recognition for research on medical communication

Stanford student earns national recognition for research on medical communication

scope photo winning poster

Stanford medical student Genna Braverman, a member of the 2013 entering class, recently won “best poster” at the national meeting of the Society of Teachers of Family Medicine. The poster visually represented a qualitative analysis of nearly 800 written student reflections collected over the past seven years, describing communication challenges the students encountered when learning how to practice family medicine.

When I talked recently with Braverman about her work, she emphasized that it can be quite a challenge to convey qualitative work in a visually compelling, streamlined manner. But the subject matter is something she’s always been interested in – interpersonal dynamics, the doctor-patient relationship, and communication issues were on her mind before medical school, and her interest intensified after she took courses in bioethics at Stanford.

Braverman enjoys a close relationship with her adviser, Erika Schillinger, MD, who she called an “amazing, inspiring mentor.” Her interest was piqued after listening to Schillinger speak, and confirmed when they met and she learned of all their overlapping interests. Schillinger mentioned a large dataset of student reflections she was interested in analyzing, and Braverman thought the project sounded like just what she was hoping to spend her summer and fall working on.

About the findings, she told me, “In the written reflections, students overwhelmingly wrote about communication challenges that related to working with patients and their families, and the main themes we found were challenges in exchanging verbal information, navigating emotionally charged situations, and negotiating the terms of the encounter.”

The poster represents only a portion of the entire research project’s findings. In addition to these written responses, there was data collected afterwards from focus groups, in which the researchers found an interesting divergence. “Many, many more students discussed challenges communicating with other members of the healthcare team (particularly with their attending physicians) in the context of an evaluative environment,” Braverman said.

So what do these results suggest should be done? Currently, communication curricula focus on the content and process of the medical interview, while psychodynamic factors – including those aspects of the encounter that are emotionally charged or conflicting – receive less time and energy. Schillinger is very interested in curricular reform early in medical school, and this research suggests that the sizable communications curriculum in the first two years should be reevaluated. Particular areas of interest might be agenda setting, use of interpreters, and time management

In her career, Braverman hopes to combine patient care, teaching, and research, and so she’s pursuing academic medicine. She told me: “I find the variety of work appealing… I want a chance to work with patients directly but also to help advance the field. Teaching is very important to me.”

In addition to her adviser, she said her teachers Sylvia Bereknyei, DrPH, and Janine Bruce, MD, were instrumental in pushing her to earn this recognition.

Photo courtesy of Genna Braverman

Aging, Genetics, In the News, Mental Health, Neuroscience, Research, Women's Health

Are women at greater risk for Alzheimer’s? Stanford expert to discuss on today’s Science Friday

Are women at greater risk for Alzheimer’s? Stanford expert to discuss on today's Science Friday

2187905205_158290644d_zConfession: I named my parents’ cat (who died recently) Watson after listening to Ira Flatow interview James Watson, PhD, while driving cross country with my dad in 2000. Both before and after the all-critical cat-name-inspiring program, Science Friday has been a part of my Friday as often as I can squeeze it in.

So I was happy to hear that today’s program (which airs locally from 11 a.m. to 1 p.m. on KQED) will feature Stanford’s Michael Greicius, MD, MPH. He’ll be talking about Alzheimer’s disease and why the disease affects men and women differently.

Greicius, medical director of the Stanford Center for Memory Disorders, has worked with the gene variant known as ApoE4 – the largest single genetic risk factor for Alzheimer’s, particularly for women. Last spring, he published a study showing that healthy ApoE4-positive women were twice as likely to contract the disease as their ApoE4-negative counterparts.

Greicius is expected to be on in the second hour, from 12 to 1 p.m. Pacific time.

Previously: Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice, Examining the potential of creating new synapses in old or damaged brains, The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men
Photo by *Ann Gordon

Events, Science, Science Policy, Stanford News, Technology

The challenge – and opportunity – of regulating new ideas in science and technology

The challenge – and opportunity – of regulating new ideas in science and technology

running image

Innovation in science and technology holds promise to improve our lives. But disruptive business models, do-it-yourself medical devices, and open platforms also introduce corporate and personal risks. How can the public stay safe from unknown consequences as a company’s product or service matures? In a recent panel co-sponsored by Stanford’s Rock Center for Corporate Governance and Center for Law and the Biosciences, experts in law, business, and ethics discussed what happens when science and technology outrun the law.

Talk of drones, app-based car services, and music-sharing technologies teased out key issues currently disrupting legal paradigms. But biomedical science took center stage. “Health is more regulated than any other [area]” said panelist Hank Greely, JD, the Deane F. and Kate Edelman Johnson Professor of Law and director of the Center for Law and the Biosciences. He characterized the FDA’s processes as useful in slowing innovation in the health space but noted that rigorous pre-market regulation “won’t work in most parts of the economy.”

What happens when regulation is beyond reach? Greely noted that even if the FDA could limit an entrepreneurial company, it couldn’t conquer the DIY market. He referenced a procedure known as transcranial direct current stimulation, which, by applying electrodes to the head, can feel like “Adderall through a wire” or alter a person’s mood according to placement. A transmitting device is so simple to make, Greely said, “the hardest part will be finding an open Radio Shack.”

Moderator Dan Siciliano, JD, faculty director of the Rock Center and professor of the practice of law, asked the panelists which under-regulated technologies they found frightening. Vapor cigarettes, answered Eleanor Lacey, JD, for luring youth through fruit flavors and targeting them through advertising channels prohibited for regular cigarettes. (As previously reported on Scope, the FDA announced last spring that it would regulate the sale, but not marketing, of e-cigarettes.)

Lacey, vice president, general counsel and secretary of SurveyMonkey, discussed regulation issues involving health information that is transmitted on the company’s platform, where users own their data. She pointed to instances of users creating surveys on which respondents shared HIPAA-protected information, admitted suicidal thoughts, or confessed to crimes. The company cooperates with law enforcement in a very narrow set of sensitive situations but also upholds neutrality of the user-owned space and the user right to control the content: “You don’t want us to be able to shut it down,” Lacey said.

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CDC, Chronic Disease, Events, In the News, Patient Care, Research

Stanford expert to discuss systemic exertion intolerance disease (formerly chronic fatigue syndrome) during public call

Stanford expert to discuss systemic exertion intolerance disease (formerly chronic fatigue syndrome) during public call

telephone-158190_640Chronic fatigue syndrome is not only real, but it also has a new name: “systemic exertion intolerance disease” (SEID). The weeks-old name change was heralded by an Institute of Medicine report, which was reviewed by Stanford’s José Montoya, MD.

Montoya will discuss the disease, the name change, and some of Stanford’s work on SEID, in a “patient-centered” conference call sponsored by the CDC on Monday afternoon. He’ll be joined by the CDC’s Elizabeth Unger, PhD, MD, chief of the chronic viral diseases branch.

The public is welcome to join in, and listeners will be able to submit questions during the conference call, which begins at noon Pacific time.

More details, including the call-in number, can be found on the CDC’s website.

Previously: Chronic fatigue syndrome gets more respect (and a new name), Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed, Unbroken: A chronic fatigue syndrome patient’s long road to recovery and Patients’ reaction to ME/CFS coverage in Stanford Medicine magazine
Photo by OpenClips

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