University Times

New cancer therapy is patented

School of Medicine researchers have been awarded a patent for the development of a new DNA therapy for head and neck cancers. The therapy targets the epidermal growth factor receptor (EGFR), a protein found on the surface of many types of cancer cells that causes them to multiply.

Standard treatments for head and neck cancers often are ineffective and tend to have debilitating side effects, explained Jennifer R. Grandis, a faculty member in otolaryngology and pharmacology and director of the head and neck  program  at  the  University of Pittsburgh Cancer Institute.

The new treatment is based on a form of genetic therapy called “antisense,” or AS, in which a synthesized strand of DNA or RNA targets the EGFR genes within a tumor. The therapy blocks the production of a protein produced by the gene. According to Grandis, expectations were exceeded in a phase I study of the therapy that was designed primarily to determine the safety and potential toxicity of EGFR AS injections in patients with advanced head and neck cancers.

“Not only were the AS injections well tolerated, but tumors disappeared or shrank considerably in 29 percent of the patients,” said Grandis. “These results show that EGFR AS therapy has great potential as a safe, effective treatment.”

A phase II clinical trial evaluating the safety and efficacy of EGFR AS injections in combination with the drug cetuximab and radiation therapy soon will be open for eligible patients. According to Ethan Argiris, a faculty member in medicine and principal investigator of the trial, the study will enroll patients 70 years of age or older with advanced head and neck cancers who aren’t eligible for cisplatin, the chemotherapy often used to treat head and neck cancers.

Bigger striatum = better gaming

Researchers can predict your performance on a video game simply by measuring the volume of specific structures in your brain. A new study published in the journal Cerebral Cortex found that nearly a quarter of the variability in achievement seen among men and women trained on a new video game could be predicted by measuring the volume of three structures in their brains.

The study adds to the evidence that specific parts of the striatum, a collection of distinctive tissues tucked deep inside the cerebral cortex, profoundly influence a person’s ability to refine his or her motor skills, learn new procedures, develop useful strategies and adapt to a quickly changing environment.

“This is the first time that we’ve been able to take a real-world task like a video game and show that the size of specific brain regions is predictive of performance and learning rates on this video game,” said Pitt psychology faculty member Kirk Erickson, the study’s lead author.

Research has shown that expert video gamers outperform novices on many basic measures of attention and perception, but other studies have found that training novices on video games for 20 or more hours often yields no measurable cognitive benefit. These contradictory findings suggest that pre-existing differences in the brain might predict variability in learning rates, the authors wrote.

Animal studies that showed that the striatum becomes active during habit formation and skill acquisition led the researchers to explore whether the striatum might be related to human learning ability.

They focused on three brain structures: The caudate nucleus and the putamen in the dorsal striatum and the nucleus accumbens in the ventral striatum.

The caudate nucleus and putamen are involved in motor learning, but research has shown they also are important to the cognitive flexibility that allows one to shift quickly between tasks; the nucleus accumbens is known to process emotions associated with reward and punishment.

The researchers began with a basic question about these structures: Is bigger better?

Using magnetic resonance imaging to analyze the size of these brain regions in 39 healthy adults (aged 18-28; 10 of them male) who had spent less than three hours a week playing video games in the previous two years, they compared the volume of each brain structure with that of the brain as a whole.

Participants then were trained on one of two versions of Space Fortress, a video game that requires players to try to destroy a fortress without losing their own ship to one of several potential hazards.

Half of the study participants were asked to focus on maximizing their overall score in the game while also paying attention to the various components of the game. The other participants had to shift priorities periodically, improving their skills in one area for a period of time while also maximizing their success at the other tasks.

The latter approach, called variable-priority training, encourages the kind of flexibility in decision-making that often is required in daily life. Studies have shown that variable-priority training is more likely than other training methods to improve those skills people use every day.

The researchers found that players who had a larger nucleus accumbens did better than their counterparts in the early stages of the training period, regardless of their training group.

This made sense, Erickson said, because the nucleus accumbens is part of the brain’s reward center, and a person’s motivation for excelling at a video game includes the pleasure that results from achieving a specific goal. This sense of achievement and the emotional reward that accompanies it likely are highest in the earliest stages of learning, he said.

Players with a larger caudate nucleus and putamen did best on the variable-priority training and players in whom those structures were largest learned more and learned more quickly during the training period, he said.

“This study tells us a lot about how the brain works when it is trying to learn a complex task,” Erickson said. “We can use information about the brain to predict who is going to learn certain tasks at a more rapid rate.”

Such information might be useful in education, where longer training periods may be required for some students, or in treating disability or dementia, where information about the brain regions affected by injury or disease could lead to a better understanding of the skills that also might need attention, he said.

The study was funded by the Office of Naval Research.

Marketing to expert, novice consumers differs

Organizing products based on customers’ knowledge levels can improve consumers’ learning and their degree of satisfaction, according to a study co-authored by Cait Poynor, a faculty member in business administration in the Joseph M. Katz Graduate School of Business.

Expert consumers like to be surprised by unusual product presentation, while novices crave familiarity, she and a colleague from the University of South Carolina found in their work, “Smart Subcategories: How Assortment Formats Influence Consumer Learning and Satisfaction.” The paper is to be published in the June issue of Journal of Consumer Research; a preprint can be found at http://journals.uchicago.edu/jcr.

What works for one consumer may not work for another. The authors found that highly knowledgeable consumers liked being surprised by product formats; on the other hand, novice consumers had an easier time when familiar with product groupings.

“Results may explain why expert cooks love the chaos of farmer’s markets, whereas novice cooks find them overwhelming,” the authors state. “Or, for retail food stores, a gourmet grocery that caters to a more knowledgeable ‘foodie’ may build a happier, better-informed consumer base by presenting items in more novel and exotic formats (by season, optimal wine pairings or country of origin, for example), whereas retailers at the edge of a college campus may help their novice college-age shoppers most by grouping items in the most traditional formats — all fruits together, all coffee together, all bread together, etc.”

The study also found that highly knowledgeable consumers were “notoriously complacent” when it came to paying attention to product information: People who consider themselves experts in a domain generally breeze past potentially new and important information, while novices employ all of their cognitive capacity when making a purchase decision.

The data were collected from 123 undergraduate students who completed a two-part study as part of their course work. Both parts were carried out online where the presentation of information could be manipulated.

Students first were placed in two different groups based on their level of prior knowledge, then asked to make selections based upon information presented to them in various formats.

Researchers analyzed the students’ choices based upon an algorithm that assessed product learning and satisfaction.

According to the research, the way to establish the most satisfied and well-informed consumer can be determined only by considering consumer familiarity with product categories and their expectations about the retail environment.

Astro prof funded to study far-off galaxies

Physics and astronomy faculty member Jeffrey Newman was among 69 researchers chosen by peer review from among 1,750 applicants for the U.S. Department of Energy’s early career research program. The $85 million initiative is funded by the 2009 American Recovery and Reinvestment Act.

Newman, who studies the distant universe, will refine an algorithm he devised to improve calculations that measure the distance to the farthest visible galaxies.

The distance to a faraway galaxy is determined by measuring its redshift, or how its emitted light is stretched out by the universe’s expansion. These distances are vital in determining the nature of the as-yet undetected dark energy that appears to make up most of the universe’s mass and is causing it to expand faster over time.

But the redshift of the farthest, faintest visible galaxies can only be gauged with indirect calculations. Estimations off by a mere 0.5 percent would result in an incorrect answer to what dark energy may be.

Newman’s technique will be critical for future projects such as the Large Synoptic Survey Telescope (LSST), a 14-year effort involving 23 universities including Pitt. The powerful telescope will record how the sky changes from night to night, allowing for unprecedented study of elusive dark matter and dark energy, which has greater pull on the universe than dark matter.

Newman’s work on the LSST is essential in studying these cosmic components and for determining how far back in the universe’s history the telescope is looking for each galaxy observed.

Newman also is on the executive committee of the All-wavelength Extended Groth Strip International Survey, or AEGIS, a massive project involving nearly 100 researchers worldwide to map a distant region of the universe — the Extended Groth Strip — and document the past 10 billion years of galactic evolution with telescopes around the world and in space. Newman will use data from the AEGIS project to test and perfect his algorithm.

Dental school research funded

Two dental school faculty members recently received grants for their research.

• Mary Marazita, director of the Center for Craniofacial and Dental Genetics, vice chair of the Department of Oral Biology and associate dean of the Office of Research, was granted nearly $3 million from the National Institute of Dental and Craniofacial Research for her work on the genetics of cleft lip and palate.

Marazita’s research will focus on laying the groundwork to improve the ability to identify genes, genetic counseling in families with cleft lip and palate, and will eventually lead to improved therapies for these birth defects.

• Alexandre Vieira, a faculty member in the Department of Oral Biology and director of the University’s Dental Registry and DNA Repository, was awarded a $1.9 million grant from the National Institute of Dental and Craniofacial Research for his project on the genetics of caries, or cavities.

Vieira’s work will examine genes that control enamel formation, saliva function or composition, and immune response.

Art gives kids a visual voice

Identifying the public health and safety needs of children from low-income communities may be best accomplished through art, report Pitt researchers in the online issue of Progress in Community Health Partnerships: Research, Education and Action.

In their paper, available at www.upmc.com/MediaRelations/NewsReleases/2010/Documents/Yonas.pdf, researchers describe the success of Visual Voices, an arts-based program that engages community members as partners in research.

As an artist who specializes in painting, Michael Yonas, a faculty member in the School of Medicine’s Department of Family Medicine, created Visual Voices in 1993 to bring youth together in a common venue for artistic expression. He has conducted the program in nine cities across the United States.

The study was based on Visual Voices programs conducted with 22 children ages 8-15 in two low-income and predominantly African-American communities in Baltimore and Pittsburgh. During the sessions, participants created paintings and drawings to share their perceptions, both positive and negative, of community safety and violence, as well as their hopes for the future.

Afterward, they combined their individual art projects into two “visual voice” exhibits that were displayed publicly in each city.

Yonas and colleagues reviewed and coded themes represented in the artwork.

Factors that participants identified as important to safety included school and social networks — family, friends and the local community.

Places that they identified as unsafe were corner stores, streets and alleys with poor lighting and abandoned houses. Other contextual factors identified as unsafe were drugs, smoking, drinking, gambling, guns and violence.

“Community members are experts in their own lives much more so than those who reside outside their communities,” said Yonas. “Visual Voices helps incorporate residents’ unique expertise into the research process in a non-intrusive and fun way, and creates valuable data about their life experiences.”

“The heart of Visual Voices is to ask and listen,” said Jessica G. Burke, study co-author and faculty member in the Department of Behavioral Community Health Sciences in Pitt’s Graduate School of Public Health. “You need to first ask what it is people care about in order to develop public health interventions that are appropriate for specific communities.”

The project was funded by a grant from the Centers for Disease Control and Prevention to the Johns Hopkins Center for Injury Research and Policy.

Kimberly Rak of the Department of Behavioral and Community Health Sciences and anthropology was among other co-authors of the study.

Osteoporosis drug test begins

Endocrinologists at the School of Medicine and UPMC are launching a clinical trial of a new osteoporosis drug.

Participants will receive either teriparitide (Forteo), which already is FDA-approved for osteoporosis treatment, or an experimental agent called parathyroid hormone-related protein (PTHrP), explained principal investigator Mara Horwitz, a metabolic bone specialist at UPMC and faculty member in the medical school’s Division of Endocrinology and Metabolism.

“We are very eager to find out how this new drug compares to a therapy that is currently available,” Horwitz said. “Our previous studies suggest that it may increase bone density more dramatically with fewer side effects, but this is the first head-to-head comparison.”

On the cellular level, bone constantly is broken down and rebuilt in a process called resorption. In osteoporosis, this balancing act is off-kilter, leaving bones less dense and more vulnerable to fracture.

Many drugs, such as alendronate (Fosamax) and raloxifene (Evista), work by decreasing bone resorption. They can improve bone density by 2-10 percent over several years and reduce fractures, but many patients’ bone density already has been reduced by half by the time treatment begins.

Another kind of agent works by promoting the creation of new bone. Teriparitide, a form of naturally occurring parathyroid hormone, currently is the only FDA-approved anabolic or bone-building agent in the United States. The experimental drug PTHrP, another protein made naturally by the body, also is an anabolic agent and appears to be unique in its ability to stimulate bone formation without simultaneously increasing bone breakdown. Both drugs are given as daily injections.

“When we studied PTHrP several years ago in small numbers of postmenopausal women with osteoporosis, we found that bone density increased by nearly 5 percent after only three months of treatment, and even at the highest doses, the side effects were negligible,” said senior investigator Andrew F. Stewart, chief of the Division of Endocrinology and Metabolism, who also is a member of Osteotrophin, which holds the patent for PTHrP.

In findings recently published online in the Journal of Clinical Endocrinology and Metabolism, Horwitz, Stewart and colleagues identified the maximum tolerable dose and therapeutic window of PTHrP and showed that PTHrP, at the tolerable doses, stimulated bone formation after only three weeks of treatment.

Pitt co-authors of the paper included Mary Beth Tedesco, Adolfo Garcia-Ocana and Linda Prebehala of the Division of Endocrinology and Metabolism; Alessandro Bisello of the Department of Pharmacology and Chemical Biology, and Susan Sereika of the Graduate School of Public Health.

The research was funded by the National Institutes of Health and the University of Pittsburgh Clinical Translational Sciences Award.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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