New approach may benefit second-most common breast cancer

The second-most common type of breast cancer is a very different disease than the most common and appears to be a good candidate for a personalized approach to treatment, according to research conducted by a multidisciplinary team led by University of Pittsburgh Cancer Institute (UPCI) scientists.

Invasive lobular carcinoma, which is characterized by a unique growth pattern in breast tissue that fails to form a lump, has distinct genetic markers that indicate there may be benefits from drug therapies beyond those typically prescribed for the more common invasive ductal carcinoma.

The study results were published in Cancer Research.

Patients with invasive lobular carcinoma typically are treated through surgical removal of the cancer, followed by chemotherapy or hormone therapy or both, usually with the estrogen-mimicking drug tamoxifen or estrogen-lowering aromatase inhibitors, the same as patients with invasive ductal carcinoma.

Senior author on the study was Steffi Oesterreich, faculty member in pharmacology and chemical biology in the School of Medicine and director of education at the Women’s Cancer Research Center. “Recent analyses have shown that a subset of patients with lobular carcinoma receive less benefit from adjuvant tamoxifen than patients with ductal carcinoma,” Oesterreich said. “Our study, the largest of its kind, indicates an issue with the estrogen receptors inside lobular carcinoma cells and points to a potential target for drug therapy in future clinical trials, which we are developing.”

The UPCI study included collaborations across multiple disciplines, ranging from biostatistics and biomedical informatics to pathology and human genetics, in order to produce results with the potential for rapid translation into clinical therapies.

Said lead author Matthew Sikora, a post-doctoral associate in Oesterreich’s department: “In addition to its potential clinical implications, the study highlights the need for more and better models mimicking invasive lobular cancer that can be used for laboratory studies.

“Because lobular carcinomas account for only 10 to 15 percent of breast cancers, while ductal carcinomas make up nearly 80 percent, lobular carcinomas are a less attractive option for laboratory study,” said Sikora.

“However, 30,000 women in the U.S. are diagnosed with lobular carcinoma every year, so there is a great need for further study of this disease.”

The other Pitt co-authors were Kristine L. Cooper, Amir Bahreini, Soumya Luthra, Uma Chandran, Nancy E. Davidson and David J. Dabbs. Two researchers from the University of Utah also contributed to the study.

This research was supported by the Breast Cancer Research Foundation, the Noreen Fraser Foundation, the Department of Defense breast cancer research program fellowship and Era of Hope Scholar Award and the Pennsylvania Department of Health.

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Grants fund multiple Brain Institute projects

With $1.75 million from the DSF Charitable Foundation, University of Pittsburgh Brain Institute (UPBI) researchers will begin to establish a NeuroDiscovery Center, akin to a Bell Labs for neuroscience, and hunt for new drugs for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Huntington’s and Parkinson’s diseases.

Thanks to another $1.8 million DSF gift, another team of neuroscientists and clinicians will explore the application of a new imaging technology to traumatic brain injury, particularly in wounded veterans of the U.S. armed forces.

UPBI, also recently established, will enable investigators to perform high-risk, high-impact neuroscience. Scientific director Peter Strick, chair of neurobiology in the School of Medicine, will use a $750,000 gift from the DSF Charitable Foundation to create the NeuroDiscovery Center’s pilot fund that will support especially innovative basic and translational research.

Strick said: “Often, it is an investigator with the boldest idea who holds the key to the next great discovery. DSF Charitable Foundation’s generosity will make it possible for UPBI researchers to freely explore challenging scientific questions that can lead to important discoveries and lay the foundation for the therapeutic advances of the future.”

He noted that Bell Laboratories provided a unique research environment in which a diverse group of scientists were brought together and given the resources that led to landmark successes, including the development of radio astronomy, the transistor, the laser, information theory, several new computer languages and seven Nobel Prizes.

“Many of the world’s renowned neuroscientists are here at Pitt, and the Brain Institute will foster their ability to collaborate with experts across disciplines, including computer science, mathematics and bioengineering, as well as medicine and neurobiology,” Strick said. “This wealth of knowledge and experience presents a rare opportunity to conduct powerful, influential science.”

A three-year, $1 million gift from the DSF Charitable Foundation will fund another project in the Brain Institute’s NeuroDiscovery Center. Principal investigators Robert Friedlander, chair of neurological surgery, and J. Timothy Greenamyre,  neurology faculty member and director of the Pittsburgh Institute for Neurodegenerative Diseases, will look for drugs that can affect the function of mitochondria, the so-called powerhouses of cells.

Said Friedlander: “Research conducted here and elsewhere has shown us that mitochondria are key regulators of programmed cell death, which is a critical factor in neurodegenerative diseases such as ALS. If we can protect mitochondria, we might be able to delay symptom progression and extend life just as we have done in animal models of ALS, Huntington’s and Parkinson’s disease.”

The DSF Charitable Foundation also is providing $1.8 million over three years to support the study of an innovative brain imaging technology called high-definition fiber tracking (HDFT) for veterans of the U.S. military who have sustained traumatic brain injuries (TBI).

The HDFT project will be led by Walter Schneider, faculty member in psychology, neurological surgery and radiology and a senior scientist at Pitt’s Learning Research and Development Center, and David Okonkwo, neurological surgery faculty member and director of the brain trauma program. It aims to reveal damage to the fiber tracts, or cables, of the brain just as X-rays indicate broken bones.

Said Okonkwo: “Conventional imaging techniques are not able to show these injuries, so it’s harder to diagnose, treat or monitor them. HDFT has the potential to identify TBI quickly and accurately, which could in turn influence therapy and recovery.”

In addition to HDFT scans, participants in the research project will receive a toolkit that includes material to carry out targeted therapies, mobile technology to support ongoing monitoring and other treatment aids.

The DSF Charitable Foundation also made a gift of $100,000 to the Mark A. Nordenberg Scholarship Fund.

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Neuromuscular Research Lab begins Air Force work

Marking the fifth ongoing research site at a Department of Defense installation, the University recently launched a Warrior Human Performance Research Center to conduct performance-optimization and injury-prevention research at Air Force Special Operations Command (AFSOC) at Hurlburt Field, Fla., as part of a three-year, $3 million study.

The new site brings this eight-year-old program to a third branch of the United States military, the Air Force, with ongoing sites at Naval Special Warfare SEALs bases at Little Creek, Va.; Stennis Space Center, Miss., and Coronado, Calif. and the Army Special Operations post at Fort Bragg, N.C.

Noted Scott Lephart, director of the Neuromuscular Research Lab overseeing this program and chair of sports medicine and nutrition in the School of Health and Rehabilitation Sciences (SHRS): “The funding is in place to begin working soon with the Marine Corps Forces Special Operations Command in Camp Lejeune, N.C. This final piece is very important because it completes our support to all four Special Operations Forces components and enables us to fully support the needs of the U.S. Special Operations Command’s priority operation called the ‘Preservation of the Force and Families Task Force.’”

The Warrior Human Performance Research Centers help to design physical-training programs to improve individual performance and reduce injury. They have shown success in limiting training, combat and recreation injuries; enhancing force readiness by maximizing the effects of training to reduce fatigue and optimize performance, and prolonging the operation life as well as enhancing the quality of life after service. For instance, the inaugural center, at Fort Campbell, Ky., with the 101st Airborne, implemented a specific training program that reduced overuse injuries by 25.4 percent, lower-extremity injuries by 17.5 percent and acute injuries by 15.9 percent.

Said Timothy Sell, faculty in the SHRS Department of Sports Medicine and Nutrition and principal investigator on the AFSOC research with the Department of Defense: “The lab at Hurlburt is functionally identical to our other labs. The research model is the same, too. What’s different is the operator, and our research model has adaptability to be specific to each military group and each group of operators.”

There are four different operators at AFSOC versus, say, a Navy SEAL, although the Navy SEAL has duties in different areas. The AFSOC operators are pararescue, combat controllers, combat weathermen and Tactical Air Control Party. These are battlefield airmen from helicopters and planes, yet they also carry out various ground duties such as counterterrorism deployment and remote airfield/air-traffic control — a function they performed in Haiti after the 2010 earthquake there. Pilots are not part of this human performance warrior study, which focuses on the 23rd Special Tactics Squadron.

“But each research project is unique,” Sell added, referring to the wide ranges of what they call task- and demand-analysis studies in these various Special Forces. “We go out in the field, observe the different operators, monitor them and observe the cardiovascular and musculoskeletal demands, and that tells us about each group.”

This research, Sell continued, hones in on the specific needs of each military segment of Special Forces and informs officials how to better train and prevent injuries among those groups.

The program began in 2005 under the concept of bringing sports medicine research and expertise to the military, and the Special Operations components have embraced these projects. One assistant professor and two research associates at each base lead research into regular demands on these soldiers. The three Pitt employees assigned to the Hurlburt Field site are faculty member Meleesa Wohleber and research associates Deirdre McFate and Andrew Simonson.

The Department of Defense designated $7.2 million in total grants to Pitt and SHRS for fiscal year 2013 and similar funding for 2014. In addition, the U.S. Special Operations Command has invited Pitt and the Neuromuscular Research Lab to become its applied scientific partner in support of Preservation of the Force and Families Task Force. This partnership is in the final stages of execution.

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Pittsburgh benchmarked in annual UCSUR report

The total population of southwestern Pennsylvania is slowly but steadily rising and the region’s economy continues to march forward on several broad fronts. Yet, the region’s level of diversity continues to lag behind that of comparable metropolitan areas, and ozone air pollution and the rate of people who smoke are issues of concern.

These are some of the findings in the recently released 2014 Pittsburgh Today & Tomorrow report. The annual report was conducted by Pittsburgh Today, part of the University Center for Social and Urban Research. It compares the Pittsburgh metropolitan statistical area with 14 U.S. metropolitan regions in 10 categories: arts, demography, education, economy, environment, health, housing, public safety, sustainability and transportation.

The benchmark regions are chosen based on a variety of overlapping similarities, including demographics and industrial mix. The benchmark regions are Boston, Charlotte, Cincinnati, Cleveland, Denver, Detroit, Indianapolis, Kansas City, Milwaukee, Minneapolis/St. Paul, Philadelphia, Richmond, St. Louis and Washington, D.C.

Also included in the 2014 Pittsburgh Today & Tomorrow report are articles focusing on important issues facing the region. Topics covered in the report’s articles include southwestern Pennsylvania’s immigration gap, public school absenteeism, efforts in the region to find a middle ground in the debate over Marcellus Shale drilling and environmental protection, and public transportation.

Additional data and statistics for southwestern Pennsylvania and the Pittsburgh metropolitan region are available on the Pittsburgh Today website.

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