Update on SIV remission studies

Recently presented insights on how an antibody used to treat intestinal diseases can suppress Read more

Granulins treasure not trash - potential FTD treatment strategy

Granulins are of interest to neuroscientists because mutations in the granulin gene cause frontotemporal dementia (FTD). However, the functions of granulins were previously Read more

Blood vessels and cardiac muscle cells off the shelf

How to steer induced pluripotent stem cells into becoming endothelial cells, which line blood Read more

Strategies to target cancer stem cells

A story in last Friday’s New York Times highlights research on “cancer stem cells”: a fraction of cells in a tumor that are especially resistant to chemotherapy and resemble the body’s non-cancerous stem cells in their ability to renew themselves.

The story describes work by a team at the Broad Institute, who reported in the journal Cell that they had identified compounds that specifically kill cancer stem cells. The hope is that compounds such as these could be combined with conventional treatments to more effectively eliminate cancers.

However, scientists disagree on whether the phenomenon of cancer stem cells extends to different kinds of cancer and what is the best way to target them. Previously not much was known about how to attack these cells.

Work at Emory’s Winship Cancer Institute has been tracking how some biomarkers in cancer cells resemble or differ from those found in stem cells. These markers may help researchers home in on the cancer stem cells.

 

Anticancer therapy must target more than one type of cell. TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor

If "cancer stem cells" play the critical roles some scientists think they do, anticancer therapy must target more than one type of cell. In this figure from Van Meir + Hadjipanayis' review, TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor cells.Â

 

 

In a recent review, Emory brain cancer specialists Erwin Van Meir and Costas Hadjipanayis write:

The “cancer stem cell” hypothesis has invigorated the neuro-oncology field with a breath of fresh thinking that may end up shaking the foundation of old dogmas, such as the widely held belief that glioblastoma tumors are incurable because of infiltrative disease. If the infiltrated cells are in fact differentiated tumor cells, their dissemination beyond the surgical boundary may not be the primary cause of tumor recurrence.

Van Meir, the editor of a new book on brain cancer, adds this comment:

Clearly a lot more work needs to be done to understand the precise cause of glioblastoma recurrence after surgery and chemotherapy and how to prevent it.  The possibility of developing therapeutics that can specifically target the brain cancer stem cells is an exciting new development but will have to proceed with caution to spare normal stem cells in the brain. Developing new imaging tools that can track cancer stem cells in the brain of treated patients is also an important objective and some of the Emory investigators are evaluating the use of nanoparticles to this purpose.

A new faculty member at Winship, Tracy-Ann Read, recently published her research on a molecule that could be used to identify “tumor-propagating cells” in medulloblastoma, a form of brain cancer. She says:

Although cancer stem cells have been identified in many different types of cancer, it is becoming increasingly clear that the properties of these cells may vary greatly among the different tumor types. It is unlikely that one  therapeutic agent will be able to target the cancer stem cells in for example all types brain tumors. Hence  much work still needs to be done in terms of analyzing the properties of these cells in each tumor type and identifying the genes that are responsible for their unique ability to propagate the tumors. 

Winship’s director Brian Leyland-Jones has also reported at the San Antonio Breast Cancer Symposium that molecules that distinguish a hard-to-treat form of breast cancer resemble those that maintain stem cells.

Nice round-up from Nature’s stem cell blog editor Monya Baker

Posted on by Quinn Eastman in Cancer Leave a comment

Leverage universities for growth of metro Atlanta

Emory University President James W. Wagner, PhD

Emory University President James W. Wagner, PhD

In an Aug. 12 opinion piece published in The Atlanta Journal-Constitution, Emory University President James W. Wagner, PhD, says that if Atlanta is to move forward, it must recognize the important role that its colleges and universities play and put them front and center in public and private economic development plans.

Wagner notes that colleges and universities like Emory create the human capital needed to advance the economic, social and cultural lifeblood of a community.

“Work in the area of sustainable development creates an opportunity for the production of new ideas that can be applied as far away as a remote village in Africa or as close as the crowded corridors of metro Atlanta,” says Wagner.

“Whether the goal is creating world-class facilities for the research and treatment of cancer in Atlanta or a healthier economic climate through sustainable development on another continent, America’s most successful communities have come to rely heavily on their universities and colleges to sustain economic and social progress.”

Visit AJC.com to read Wagner’s opinion piece on the impact that Emory and other colleges and universities have on the communities they serve and how they can help move the region and state forward.

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Childhood cancer treatment may raise diabetes risk

Cancer survivors who got radiation treatments as children have nearly twice the risk of developing diabetes as adults. That’s according to a study led by Emory and Children’s Healthcare of Atlanta pediatric oncologist Lillian R. Meacham, MD.

Lillian Meacham, MD

Lillian Meacham, MD

The study, published in the August 10/24 issue of Archives of Internal Medicine, compared rates of diabetes in nearly 8,600 childhood cancer survivors diagnosed between 1970 and 1986, and nearly 3,000 of their siblings who did not have cancer.

Children who were treated with total body radiation or abdominal radiation to fight off cancer appear to have higher diabetes risks later in life, regardless of whether they exercise regularly or maintain a normal weight.

After adjusting for other risk factors, including body mass index – a ratio of height and weight – Meacham and team found that childhood cancer survivors overall were 1.8 times more likely to have diabetes.

And the more radiation that was used, the greater the diabetes risk. For those treated with total body radiation — a treatment often used before bone marrow transplants to treat childhood leukemia — the diabetes risk was more than seven times greater.

More study is needed to understand how radiation could promote diabetes in cancer survivors, notes Meacham.

She says it is imperative that clinicians recognize this risk, screen for diabetes and pre-diabetes when appropriate, and approach survivors with aggressive risk-reducing strategies.

Meacham is a professor of pediatrics in the Emory School of Medicine and medical director of the Cancer Survivor Program with the AFLAC Cancer Center and Blood Disorders Services, Children’s Healthcare of Atlanta.

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Remembering Grace Crum Rollins

Grace Crum Rollins

Grace Crum Rollins

She was quiet and small in stature but firm in her beliefs. Grace Crum Rollins made good on her late husband’s promise of helping construct a building to house Emory’s School of Public Health. In 1994, the Grace Crum Rollins Building became the permanent home for the school that Emory named for her extraordinary family.

Mrs. Rollins, whose generosity led the Rollins School of Public Health to become one of the nation’s premier schools in its field, died on August 8 at age 98.

Dean James Curran says, “Essentially, the school would not be what it is today without her family. Our faculty, students, and alumni are part of her legacy.”

Grace Crum married O. Wayne Rollins during the Depression. They worked hard, lived simply, and never bought anything on credit. When Wayne was hospitalized for an appendectomy, Grace knitted to pay his bill.

Years later, Forbes magazine would count him among the nation’s greatest business leaders. In what is considered one of the first leveraged buyouts, Wayne bought Orkin Exterminating in 1964. The family’s business grew to encompass oil and gas services, security systems, and real estate.

Also in 1964, Wayne and Grace moved to Atlanta with their sons Randall and Gary. The couple became involved at Emory through the Candler School of Theology and Wayne’s role as a university trustee. With a lead gift to the School of Medicine, they enabled construction of the O. Wayne Rollins Research Center, doubling Emory’s laboratory space. Upon learning that the School of Public Health needed a building, Wayne volunteered his support but died unexpectedly in 1991. Less than a year after his death, Grace and her sons fulfilled his promise by contributing $10 million for construction.

The Rollins attend an Emory event

Wayne and Grace Rollins attend an Emory event

Other gifts followed, including a $50 million lead gift through the O. Wayne Rollins Foundation for a second public health building. The Claudia Nance Rollins Building, which is named for Wayne’s mother, will open in 2010 and more than double the physical size of the school.

The idea of creating the first public health building appealed to Wayne Rollins’ entrepreneurial spirit. With just 20 faculty and 500 graduates, it was a risky endeavor, Curran says.

“Mrs. Rollins kept that commitment” notes Curran. “Today the school has 200 faculty and more than 5,000 alumni in 90 countries.”

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Relocating central vision

Susan Primo, MD

Susan Primo, MD

The patients seen by Emory low vision specialist Susan Primo, OD, MPH, have already exhausted most of their treatment options. They’ve completed medication regimens or had surgery to slow advanced age-related macular degeneration (AMD), a leading cause of blindness in the elderly. But still they don’t see well.

That’s where Primo comes in. At the Emory Eye Center, she’s studying whether behavioral modifications can lead to a change in brain activity to maximize use of remaining vision.

In macular degeneration, the macula—a layer of tissue on the inside back wall of the eyeball—gradually deteriorates. That delicate tissue is responsible for visual acuity, particularly in the center of the retina. Central vision is needed for seeing small and vivid details such as words on a page or the color of a traffic light, which means it is vital for common daily tasks such as reading or driving.

In more than two decades of working with patients who are visually impaired, Primo realized that people typically use their peripheral vision to compensate for loss in central vision. Studies have shown that people with progressive central vision loss compensate by spontaneously adopting a preferred retinal location (PRL) that takes over responsibility for visual clarity.

Normal vision

Normal vision

Vision with macular degeneration

But Primo and Georgia Tech psychologist Eric Schumacher wanted to know whether using these peripheral regions causes a change in how the brain is organized. Armed with Schumacher’s expertise in functional magnetic resonance imaging (fMRI) and Primo’s clinical experience, the researchers did indeed discover continued activity in the part of the brain that maps to the macula. The brain scans of people with AMD who had developed their peripheral vision showed substantially more activity than those of people who had not developed a PRL. Their study appeared in the December 2008 edition of Restorative Neurology and Neuroscience.

In a current study, Primo and Schumacher are exploring whether occupational training and biofeedback can help people with AMD focus on using good retinal cells and in turn speed up the brain’s reorganization.

“Although others have tried to study this reorganization of macular degeneration before, no one, to our knowledge, has tried to influence it,” says Primo. “Yet it’s important to begin to come up with therapies, treatments, and technology to help patients begin to use their residual vision faster and better than they could before.”

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Aspirin may aid colorectal cancer survival

This week’s Journal of the American Medical Association (JAMA) reports on the potential benefits of aspirin following a colorectal cancer diagnosis.

Dr. Vincent Yang

Vincent Yang, MD, PhD

Emory digestive disease expert Vincent W. Yang, MD, PhD, professor and director of the Division of Digestive Diseases, Emory School of Medicine, comments on the new study:

A large body of evidence shows that regular aspirin use can reduce the formation of colorectal cancer. Aspirin inhibits the activity of an enzyme called cyclooxygenase-2, or COX-2, that is often over-expressed in colorectal cancer.

In the Aug. 12 issue of JAMA, a study led by Andrew Chan, MD, MPH, of the Harvard Medical School, shows that regular aspirin use reduces deaths in patients who had been diagnosed with colon cancer. The study includes two large, diverse groups of individuals who were followed for more than 20 years for various health-related issues.

The individuals who developed colorectal cancer during the follow–up period and had used aspirin regularly had a lower death rate than those patients who developed colon cancers and did not take aspirin. More importantly, the benefit patients received from regularly using aspirin was more apparent if their cancers were positive for COX-2.

The results of this new study are consistent with the earlier finding reported in medical journals about aspirin’s chemopreventive effect on colorectal cancer. However, it should be noted that this study is observational by nature and that regular aspirin use can result in significant toxicities.

To learn more about the routine use of aspirin as an adjunct treatment for colorectal cancer, studies that are blinded and randomized placebo-controlled are necessary. Such clinical trials have been conducted which proved that aspirin taken at 81 mg or 325 mg per day is effective in preventing the recurrence of colorectal adenomas (polyps) after they are removed during screening colonoscopy.

A similar clinical trial could be conducted to test the ability of aspirin to prevent colorectal cancer recurrence. Perhaps patients could first be classified based on the COX-2 levels in their tumors before being randomized into the trial. A potential outcome would be that patients with COX-2-positive tumors would receive more benefit from aspirin use than those with tumors that are COX-2-negative. Chan’s JAMA findings are a catalyst for further study.

Yang is also professor of hematology and oncology at Emory Winship Cancer Institute.

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Dog days of summer bring ozone challenges

Surviving the heat isn’t the only concern for people in Atlanta during the dog days of summer, the hottest time of the year in the northern hemisphere from early July to mid-August. During this time, ozone levels peak in most industrialized cities, and heavily populated areas tend to be more at risk for pollution, in part, because of increased emissions from cars, trucks and factories.

Cars on the road

Cars on the road

Cherry Wongtrakool, MD, specialist in pulmonary medicine, says pollution is generally broken down into ozone and particulate matter, but can also include carbon monoxide, sulfur dioxide, and nitrogen oxides. Particulate matter is complex and includes organic chemicals including acid, metals, dust, smoke and soil. It is often classified by size and particles less than 10 micrometers are included in the air quality index, a common measure of the air pollution level.

In addition to increasing symptoms of asthma and causing respiratory symptoms like cough and shortness of breath, Wongtrakool says pollution has been associated with cardiovascular and respiratory illnesses.

She notes that studies to date suggest long-term exposure may accelerate atherosclerosis, or hardening of the arteries. Larger population studies have also suggested there are associations between air pollution and increased risk for cancer, and air pollution and increased risk of death secondary to cardiopulmonary causes.

Wongtrakool, who is sssistant professor of medicine in the Division of Pulmonary, Allergy and Critical Care, Emory School of  Medicine, says if you live in a big city like Atlanta, you can reduce your exposure to air pollution by limiting your time in the car, remaining indoors during the hottest part of the day – typically afternoon and early evening – and reducing time spent doing outdoor activity, particularly activity requiring heavy exertion. People with underlying lung disease should avoid going out when the air quality index is poor, she advises.

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H1N1 flu clinical studies start at Emory today

Emory doctors discuss H1N1 studies

Emory doctors discuss H1N1 studies

Today Emory researchers began vaccinating volunteer participants in the first of several planned clinical trials of a new H1N1 vaccine. A morning press briefing attended by Atlanta and national media provided Emory a platform to inform the public.

The clinical trials are expected to gather critical information that will allow the National Institutes of Health to quickly evaluate the new vaccines to determine whether they are safe and effective in inducing protective immune responses. The results will help determine how to begin a fall 2009 pandemic flu vaccination program.

Emory began signing up several hundred interested volunteers about two weeks ago and has been screening the volunteers to make sure they fit certain criteria. Volunteers will receive their first vaccinations over the first week of the trial and will return several times over the course of nine weeks to receive additional vaccinations and blood tests.

H1N1 clinical trial volunteer

H1N1 clinical trial volunteer

The clinical trials are in a compressed timeframe because of the possible fall resurgence of pandemic H1N1 flu infections that may coincide with the circulation of seasonal flu strains.

The clinical trials are being conducted by the eight Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

For more information about the Emory flu clinical trials, call 877-424-HOPE (4673) for the adult and senior studies, or 404-727-4044 for the pediatric studies.

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Discerning a prelude to Alzheimer’s

Imagine that an elderly relative has been having difficulty remembering appointments and acquaintances’ names, or even what happened yesterday. Memory problems can be signs of mild cognitive impairment (MCI), a prelude to Alzheimer’s disease.

Scientists believe that the outward effects of the slow damage that comes from Alzheimer’s only show up after the damage has been accumulating for years. However, memory difficulties can also be the result of stress or another health problem. Patients thought to have MCI at an initial doctor’s visit sometimes improve later.

That’s why researchers at Emory’s Alzheimer’s Disease Research Center have been testing noninvasive imaging approaches to distinguishing MCI from healthy aging and Alzheimer’s. Their goal is to identify individuals at risk of developing Alzheimer’s, at a time when intervention can make a difference in how the disease progresses.

“We believe that imaging technology may help us find the signature changes in brain structure that are specific to MCI,” says Felicia Goldstein, PhD, associate professor of neurology.

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color), a white matter fiber bundle connecting left and right hemisphere as illustrated in the 3D rendering of the tractograph derived from DTI (B). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure. Courtesy of Hui Mao.

Two recent papers highlight the use of diffusion tensor imaging, an advanced form of magnetic resonance imaging.

The first paper was published by Brain Imaging and Behavior with Goldstein as first author, in collaboration with Hui Mao, PhD, associate professor of radiology, and ADRC colleagues.

It examines diffusion tensor imaging as a way to probe the integrity of the brain’s white matter, and compares it with tests of memory and behavior traditionally used to diagnose MCI and Alzheimer’s.

White matter appears white because of the density of axons, the signal-carrying cables allowing communication between different brain regions responsible for complicated tasks such as language and memory.

Diffusion tensor imaging allows researchers to see white matter by gauging the ability of water to diffuse in different directions, because a bundle of axons tends to restrict the movement of water in the brain.

Goldstein and her colleagues found that patients diagnosed with “amnestic” MCI showed greater loss of white matter integrity in a certain part of the brain — the medial temporal lobe – than cognitively normal controls of similar age. This loss of white matter was linked with poor recall of words and stories.

The second paper, with Liya Wang, PhD, a senior research associate in Mao’s laboratory as first author, was published by the American Journal of Neuroradiology in April. Here the authors try combining probing white matter integrity with a MRI measure of whether the brain has shrunk as a result of disease.

Combining the two methods improves the accuracy of MCI diagnosis with respect to either alone, the authors found.

Mao notes that Emory has been participating in a multi-center study called ADNI (Alzheimer’s Disease Neuroimaging Initiative). Diffusion tensor imaging is a relatively new technique and could add information to future large-scale Alzheimer’s imaging studies, he says.

The Dana Foundation’s BrainWorks newsletter had an article recently on Alzheimer’s and brain imaging.

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Making a joyful noise: Joey finds his ‘real voice’

Emory Voice Center patient Joey Finley

Emory Voice Center patient Joey Finley

Last year, seven-year-old Joey Finley sang Christmas carols for the first time in his life. For most parents, this would be uneventful, but for Joey’s mom, Melanie, it was a breakthrough.

Joey was literally silenced all these years because of a rare disease called recurrent respiratory papillomatosis (RRP). The disease allows tumors to grow in the respiratory tract, and is caused by the human papilloma virus (HPV). Currently there are 20,000 active cases in the United States.

Although the tumors mostly occur in the larynx on and around the vocal cords, these growths may spread downward and affect the trachea, bronchi and sometimes the lungs, obstructing breathing. RRP papillomas are the same tumors that cause cervical cancer. There is no cure for RRP. And left untreated, the lesions may grow and cause suffocation and death.

Initially, doctors confused Joey’s RRP symptoms with pediatric GERD or acid reflux disease. Since Joey was two months old, he’s been in and out of hospitals, OR’s and doctor’s offices, and had more than 60 surgeries to remove the tumors on his vocal chords.

RRP adversely affected Joey’s speech. He began compensating for the “frogs” as he called them, by using other vocal muscles to talk.

When Joey met Edie Hapner, PhD, a speech pathologist at the Emory Voice Center, she says he sounded “like a little old man.” His voice was very raspy like that of a 60-year-old smoker.

After several speech therapy sessions at the Emory Voice Center with Dr. Hapner, Joey is a normal sounding child. Joey now sings in the school chorus and takes gymnastics and swimming lessons. It’s hard to imagine these activities for a child that not so long ago had trouble breathing because of HPV tumors blocking his airways.

Read more about Joey’s journey to ‘find his voice’ and hear him speak in the new issue of Emory Health magazine.

Listen to Emory patient Karon Schindler recount her experience at the Voice Center.

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