Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

Fetal alcohol cardiac toxicity - in a dish

Alcohol-induced cardiac toxicity is usually studied in animal models; a cell-culture based approach could make it easier to study possible interventions more Read more

Fighting cancer with combinatorial imagination

Arbiser says he arrived at Tris-DBA-palladium by using his chemist’s imagination, in a “your chocolate landed in my peanut butter” kind of Read more

Heated, targeted chemotherapy helps abdominal cancers

Cancer of the colon, ovaries, appendix or other organs within the abdomen often spreads to the lining of the abdominal cavity. Experts call this condition peritoneal surface malignancy. Until recently, treatment options for this form of cancer only provided relief from symptoms.

Emory University Hospital is one of a few facilities nationwide to utilize a new combination therapy to slow or prevent recurrence of this cancer. Hyperthermic intraperitoneal chemoperfusion (HIPEC) is a procedure done immediately following surgery that delivers heated chemotherapy directly into the abdominal cavity where it can penetrate cancerous tissue. Heat at 42 C (107 F) destroys cancer cells and enhances the power of chemotherapy.

The term “intraperitoneal” means that the treatment is delivered to the abdominal cavity. “Hyperthermic chemoperfusion” means that the solution containing chemotherapy is heated to a temperature greater than normal body temperature.

Charles Staley, MD, chief of surgical oncology at the Emory Winship Cancer Institute, says by bathing the abdomen with heated chemotherapy immediately following surgery doctors can administer a higher dose of medication than would normally be tolerated by a patient if given intravenously – the traditional way chemotherapy is administered.

During surgery, Staley removes all visible tumors throughout the abdomen, a procedure known as cytoreductive surgery. Following surgery, while still in the operating room, Staley administers the new treatment, which takes about two hours. Recent studies show improved prognosis in patients treated with HIPEC after the cytoreductive surgery.

Illustration of heated chemo therapy

Illustration of heated, targeted chemotherapy

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New heart valve replacement option under study

A new option for heart valve replacement is under study at Emory University Hospital. Cardiologists at the Emory Heart & Vascular Center are conducting groundbreaking research to study a non-surgical treatment option for patients with severe aortic stenosis, a narrowing of the aortic valve opening that affects tens of thousands of people each year. It is most common among elderly patients over 70 years of age, but can surface earlier in life in those with rheumatic heart disease or congenital abnormalities of the valve. Patients often develop symptoms of chest pain, shortness of breath, fainting spells and heart failure.

Peter Block, MD

Peter Block, MD

Emory cardiologists, led by Peter Block, MD, FACC, professor of medicine, Emory School of Medicine, are performing percutaneous aortic valve replacement as part of a clinical trial, comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis. It provides a new way for doctors to treat patients who are too ill or frail to endure the traditional surgical approach. So far, 115 people have participated in the phase II clinical trial.

In this new procedure, doctors create a small incision in the groin or chest wall and then feed a wire mesh valve through a catheter and place it where the new valve is needed. The standard therapy, which has been used to treat aortic stenosis for more than 30 years, is to remove the diseased valve through open-heart surgery.

Block says the results seen so far in this clinical trial show great promise for this procedure. He says this is especially important since tens of thousands of Americans are diagnosed with failing valves each year and that number is expected to increase substantially in the coming years as baby boomers pass the age of 70.

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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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