CHAPEL HILL, NC - The article "Two-faced proteins? Proteins that both hinder and spur cancer progression may not be as uncommon as previously thought" written by Jef Akst and published in the January  2011  issue of The Scientist quotes UNC Lineberger members James Bear, PhD, and Ned Sharpless, MD.

Dr. Bear is an associate professor of Cell and Development Biology. Dr. Sharpless is an associate professor of medicine and genetics and associate director for Translational Research at UNC Lineberger.

Read article.

In a paper that appeared online last week in the journal Pigment Cell & Melanoma Research, a team of UNC researchers tested whether DNA methylation profiling could be accomplished on melanoma and mole tissues that had been preserved in fixatives for typical pathology examination after biopsy. They found that results on tissues prepared in this way were reliable and DNA methylation distinguished malignant melanomas from non-malignant moles.

Melanoma is one of the only forms of cancer that is still on the rise and is the most common form of cancer in young adults. The incidence of melanoma in women under age 30 has increased more than 50 percent since 1980.

“When melanoma is diagnosed early, the prognosis is good. However, once it spreads, it is very difficult to treat. Melanomas and moles can appear similar on the skin and under the microscope making diagnosis of some melanomas difficult. That’s why we wanted to determine whether a test for DNA methylation is feasible as a tool for diagnosis,” added Nancy Thomas, MD, PhD, professor of dermatology and a member of UNC Lineberger Comprehensive Cancer Center.

Kathleen Conway Dorsey, Ph.D, added, “We are very excited because, with this study, we have shown that this type of testing is feasible and that it has the potential to reliably distinguish between melanoma and benign skin lesions. Devising a molecular test that could aid in the early specific diagnosis of melanoma could have significant benefit for patients.” Conway is assistant research professor of epidemiology at UNC’s Gillings School of Global Public Health and a member of UNC Lineberger Comprehensive Cancer Center.

The team’s research pinpointed sites on 22 genes that have significantly different methylation levels between melanomas and non-melanoma lesions, as well as 12 locations that are highly predictive of melanoma. According to Thomas, another goal of the team is to develop a DNA-methylation test for melanoma tumor DNA that is shed into the bloodstream and that can serve as a measure for disease activity.

“If this test can be developed, it opens the door to diagnose recurrence early and initiate treatment while tumors are more likely to respond to treatment. It would also give us another way to monitor patients for response to treatment and help us better optimize treatments for each patient,” Thomas noted.

Other members of the research team include Sharon Edmiston, BS, Zakaria Khondker, MStat, Pamela Groben, MD, clinical professor of pathology & Laboratory Medicine, Xin Zhou, PhD, Pei Fen Kuan, PhD, research assistant professor of biostatistics, Honglin Hao, Craig Carson, PhD, and David Ollila, MD, associate professor of surgery, all at UNC-Chapel Hill. The team also included Haitao Chu, MD, PhD, of the University of Minnesota and Marianne Berwick, PhD, MPH, of the University of New Mexico.

The research was funded by the National Cancer Institute and a UNC Lineberger Pilot Grant.

The enzyme, known as Rad18, detects a protein called DNA polymerase eta (Pol eta) and accompanies it to the sites of sunlight-induced DNA damage, enabling accurate repair. When Pol eta is not present, alternative error-prone polymerases take its place – a process that leads to DNA mutations often found in cancer cells.

In one known example, faulty DNA repair due to Pol eta- deficiency is responsible for the genetic disease xeroderma pigmentosum-variant, which makes patients extremely susceptible to skin cancers caused by exposure to sunlight. However, scientists did not know how the cells selected the correct DNA Polymerase for error-free repair of each type of DNA damage.

“We found that the mechanism that promotes the ‘chaperone’ enzyme to recruit Pol eta to sites of DNA damage is managed by another signaling protein termed ‘Cdc7’ which we know is essential to normal regulation of the cellular lifecycle,” said lead author Cyrus Vaziri, PhD, who is an associate professor of pathology and laboratory medicine and member of UNC Lineberger Comprehensive Cancer Center. Thus cells employ Cdc7 to ensure accurate DNA repair during the stage of their lifecycle that is most vulnerable to cancer-causing mutations.

The study was published in November in the Journal of Cell Biology.

According to Vaziri, the dual role that Cdc7 plays in the cell lifecycle and DNA repair offers a promising target for potential cancer therapies.

“We know that cancer cells have high levels of Cdc7 activity and can evade some DNA-damaging therapies such as cis-Platinum through Rad18 and Pol eta activity. We may be able to target this pathway in platinum-resistant tumors to prevent DNA repair and enhance cancer cell killing by platinating agents,” he said.

Other members of the research team include Komaraiah Palle, PhD from UNC’s Department of Pathology and Laboratory Medicine, Tovah Day, PhD, Laura Barkley, PhD, and Ying Zou, PhD, from Boston University, Naoko Kakusho, PhD, and Hisao Masai, PhD, from the Genome Dynamics Project at the Tokyo Metropolitan Institute of Medical Science, Satoshi Tateishi, PhD, from Kumamoto University, Japan, and Alain Verreault, PhD, from the Universite de Montreal, Canada.

The research was funded by grants from the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

Long periods of such reflux can change the cells lining the esophagus, making them appear more like intestinal cells than esophageal cells. These cellular changes can also be a precursor to cancer. As in most cancers, early identification of these pre-cancerous cells often leads to better outcomes for patients. Barrett’s esophagus afflicts more than one percent of the U.S. population, with most patients above the age of 50.

The new system involves the use of a tiny light source at the tip of an endoscope. Physicians shine short bursts of this light at locations of suspected disease along the lining of the esophagus, known as the epithelium. In particular, they are trying to spot characteristic changes within the cells.

"By interpreting the way the light scatters after we shine it at a location on the tissue surface, we can the spot the tell-tales signs of cells that are changing from their healthy, normal state to those that may become cancerous," said Neil Terry, a PhD student working in the laboratory of Adam Wax , associate professor of biomedical engineering at Duke’s Pratt School of Engineering , who developed the device.

The team published their findings in the January 2011 issue of the journal Gastroenterology .

"Specifically, the nuclei of pre-cancerous cells are larger than typical cell nuclei, and the light scatters back from them in a characteristic manner," Terry continued. "When we compared the findings from our system with an actual review by pathologists, we found they correlated in 86 percent of the samples."

UNC gastroenterologist Nicholas Shaheen, MD, MPH conducted the preliminary clinical trial of the device on 46 patients with Barrett’s esophagus. Shaheen is a professor in the UNC School of Medicine and the UNC Gillings School of Global Public Health and director of UNC’s Center for Esophageal Diseases and Swallowing .

"Currently, we take many random tissue samples from areas we where we think abnormal cells may be located," Shaheen said. "This new system may make our biopsies smarter and more targeted. Early detection is crucial, because the cure rate for esophageal cancer that is caught early is quite high, while the cure rate for advanced disease is dismal, with a 15 percent survival rate after five years."

The technology that Wax and his team developed for cancer detection is known as angle-resolved low coherence interferometry (a/LCI) . In this process, light is shined into a cell and sensors capture and analyze the light as it is reflected back. The technique is able to separate the unique patterns of the nucleus from the other parts of the cell and provide representations of its changes in shape in real time.

"This optical approach of sampling allows us to cover more tissue sites in less time, and has the potential to significantly improve our ability to spot and monitor these pre-cancerous cells," Wax said. "This type of approach could be used to improve and perhaps one day supplant the physical biopsies currently being used."

Wax pointed out that since approximately 85 percent of all cancers begin within the layers of the epithelium in various parts of the body, he believes that the new system could also work in such cancers as those of the colon, trachea, cervix or bladder.

The research was supported by the National Institutes of Health, the National Science Foundation and Oncoscope, Inc. , a company founded in 2006 by Wax based on the Duke technology. Wax has a financial interest in the company, and Terry is a consultant.

Oncoscope plans a clinical trial of the system for Food and Drug Administration premarket approval (PMA), and Wax said there could be a commercially available device as early as 2012.

CHAPEL HILL, N.C. - Six University of North Carolina at Chapel Hill faculty members have been named fellows of the American Association for the Advancement of Science.

The association, the world's largest general scientific society, elects fellows to recognize their efforts toward advancing science applications that are considered scientifically or socially distinguished.

The six new fellows are biologist Kerry S. Bloom, Ph.D.; anthropologist Paul W. Leslie, Ph.D.; chemist Wenbin Lin, Ph.D.; computer scientist Dinesh Manocha, Ph.D.; geneticist and psychiatrist Patrick F. Sullivan, M.D.; and physicist John F. Wilkerson, Ph.D.

Bloom was recognized for his research using yeast cells, which has led to insights into how chromosomes work and the mechanics and dynamics of cell division. He is Thad L. Beyle Distinguished Professor of Biology in the College of Arts and Sciences and a member of the Lineberger Center.

Leslie was recognized for his contributions to demographic, social, health and environmental modeling of human populations living in arid and semi-arid environments in East Africa. He is an anthropology professor and department chair in the college.

Lin was recognized for his contributions to the field of inorganic chemistry, including nanoparticle imaging agents and anticancer drugs. He is a chemistry professor in the college and in the UNC Eshelman School of Pharmacy, as well as a member of the Lineberger Center.

Manocha was recognized for his theoretical and practical contributions to geometric computing, and strong applications to computer graphics, robotics and parallel computing. He is Phi Delta Theta/Matthew Mason Distinguished Professor in the computer science department in the college.

Sullivan was recognized for his contributions to understanding the genetics of schizophrenia, smoking behavior and major depression. He is Ray M. Hayworth and Family Distinguished Professor of Psychiatry and professor of genetics in the UNC School of Medicine, adjunct professor of epidemiology in the UNC Gillings School of Global Public Health, and a member of the Lineberger Center and the Carolina Center for Genome Sciences.

Wilkerson was recognized for his leadership of experimental efforts to understand the fundamental properties of the neutrino and neutron. He is John R. and Louise S. Parker Distinguished Professor in the physics and astronomy department in the college.

The six are among 503 scientists awarded the honor this year. New fellows will be presented with a certificate and a rosette pin at the association's annual meeting in Washington, D.C., in February.

For more information and a database of current fellows, go to:
http://www.aaas.org/aboutaaas/fellows/

Photos:

Bloom: http://bit.ly/eoqBNx
Leslie: http://bit.ly/grCIrv
Lin: http://bit.ly/dPcxuK
Manocha: http://bit.ly/ijbxRK
Sullivan: http://bit.ly/iiOGWh
Wilkerson: http://bit.ly/hrOD54

News Services contact: Patric Lane , (919) 962-8596

AAAS contact: Katharine Zambon , (202) 326-6434

The program will feature talks by physician/scientists and a patient’s parents on topics ranging from indoor tanning to clinical trials and from genetic testing to psychosocial support for melanoma patients.

David Ollila, MD, is the UNC spokesperson for the event.  “We are proud to partner with the Melanoma Research Foundation to sponsor this educational event for patients and families. While the number of melanoma cases in the US is increasing annually, research and treatment are advancing, and this symposium is the place to learn about the progress being made.”

Ollila is professor of surgery, co-leader of the UNC Multidisciplinary Melanoma Program, and a member of UNC Lineberger Comprehensive Cancer Center. Nancy Thomas, MD, PhD, is program co-leader, a speaker for the event and a member of UNC Lineberger.

Participants must register for the program by February 18 and may sign up either by calling (800) 673-1290 or by visiting: http://www.melanoma.org/get-involved/unc-chapel-hill-melanoma-patient-day.

These are the types of public health questions that defy a quick fix and the answers being sought by the first six projects funded under the Health E NC (Health for Everyone in North Carolina) grants program. The program provides pilot funding in support of the University Cancer Research Fund’s strategic goal of optimizing cancer outcomes in North Carolina.

Projects were selected through a competitive review process that included a national group of experts. Projects were prioritized for funding that emphasize breakthrough innovation and excellence in behavioral research; collaborative, cross-disciplinary approaches; potential for generating additional external funding from peer-reviewed sources; and real and tangible impact on the health of North Carolinians. The projects focus on areas of the state where cancers, and in particular breast, lung and colorectal cancers, are common and place a burden on the health of North Carolinians.

“We challenged UNC Lineberger members from both the Gillings School of Global Public Health and the School of Medicine to design forward-looking projects focused on the state’s biggest needs. We then asked a group of national experts in the field to select the best. The result will be to put outstanding ideas to the test in North Carolina communities,” said Shelley Earp, MD, UNC Lineberger’s director.

Current projects include:

• Healthy Stores, Healthy Communities
• Circles of Care: Supporting African Americans with Cancer
• Partnering with N.C. Community Colleges to Prevent Cancer Among Students, Employees and Community Residents
• Meeting the Needs of Cancer Survivors in North Carolina: Assessing and Improving the Medicaid Medical Home Model
• Improving Colorectal Cancer Screening in N.C. Medicaid Beneficiaries
• Addressing Cancer Disparities by Studying Issues of Coverage, Convergence & Cost in Multiple Settings

About Health-E-NC

Health-E-NC is a statewide effort to improve cancer outcomes for the diseases that hit North Carolina’s citizens the hardest. Sponsored by UNC Lineberger Comprehensive Cancer Center and the University Cancer Research fund, Health-E-NC is aimed at finding out what really works in the areas of cancer prevention, detection, diagnosis, treatment and survivorship and helping to spread the latest and best evidence-based cancer information to health care providers and advocacy groups as well as cancer patients, their families and survivors. For more information, visit: www.health-e-nc.org/home.do

About the University Cancer Research Fund:

The University Cancer Research Fund was created by the N.C. General Assembly with the mission to ensure that future generations of North Carolinians will develop cancer less often and live longer and better when they do. Research creates new knowledge, turns that knowledge into innovative treatment, screening, and prevention, and then assures delivery of innovations across the state – that research is the key unlocking the doors to a new and better future. The UCRF is helping make that research possible.

In their ongoing quest to better understand racial disparities in breast cancer prognosis, a team led by Robert Millikan, DVM, MPH, PhD, has analyzed tissue from 1149 invasive breast cancer patients (518 African American and 631 White) who are participants in the Carolina Breast Cancer Study (CBCS). The CBCS is a longstanding population-based study of breast cancer risk and behavior that focuses on young and African American women. Their findings were published December 15, 2010 in the journal Clinical Cancer Research.

“Our data show that basal-like breast cancer is an equally aggressive disease in African American women and white women. In addition, African American women had worse outcomes no matter what kind of breast cancer they developed, suggesting that other factors such as disparities in access to care and treatment, for example for the more common subtypes of breast cancer like luminal A breast cancer, also contribute to the higher breast cancer mortality observed in African American women,” said study co-author Charles M. Perou, PhD, professor of Genetics and Pathology.

The team classified their tumors into four subtypes: luminal A, luminal B, basal-like (also known as triple-negative) and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2+/ER-) and compared long-term survival outcomes.

The team found that breast cancer mortality was highest for patients with HER2+/ER- and basal-like breast cancers. African Americans had higher breast-cancer specific mortality than whites in all subtypes of breast cancer, with the statistically significant difference was in the most common subtype, Luminal A. In this subtype, which typically has the best prognosis, African American women had a statistically significantly worse survival than white women. “Based on these data, I am not sure we can identify a truly good prognosis subtype in African-American women, and we need to find out why” said study co-author Lisa Carey, MD, “these are treatable cancers, and whether women are getting the right drugs or getting the right care, or if there are other fundamental differences in the cancers themselves we should know about is why we have studies like the CBCS ongoing.”

“This study underlines the importance of our previous recommendation that African American women, and all breast cancer patients, need the best possible diagnostic workups – including tumor typing, and access to the latest clinical trials,” said Robert Millikan, DVM, MPH, PhD, principal investigator of the CBCS.

“This study also showed the worst prognosis for patients with HER2+/ER- breast cancer, but was completed before the introduction of the drug trastuzumab and other targeted drugs used to treat HER2-positive breast cancers,” noted Lisa Carey, MD, “New, promising therapies are being introduced at a rapid rate and both patients and physicians should take steps to ensure that they have the latest information.”

The CBCS is a population-based case-control study that enrolls women with breast cancer from 24 counties in North Carolina as cases and an equal number of women without breast cancer as controls. Women who consent to the study are interviewed about their health histories and their tumor tissue is collected. The study relies on extensive cooperation from all of the women who agree to participate, their physicians and pathologists, as well as a large number of hospitals in North Carolina.

Participants are selected from a list of newly diagnosed breast cancer patients provided by the North Carolina Central Cancer Registry (NCCCR), which identifies and registers all new cancer diagnoses in the state. All participants are selected through a scientific randomization process and thus no volunteers are accepted.

In addition to Millikan, who is a professor of epidemiology at UNC Gillings School of Public Health and a member of UNC Lineberger Comprehensive Cancer Center, study authors include Katie O’Brien, Stephen Cole, Chiu-Kit Tse, Charles M. Perou, PhD, and Lisa A. Carey, M.D.

The team also included William D. Foulkes, MD, of McGill University in Montreal and Joseph Geradts, MD, of Duke University.

This research was funded by the University Cancer Research Fund, the National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer, UNC Lineberger Comprehensive Cancer Center Core Grant, a training grant from the National Institutes of Health and the Turner Family Cancer Research Fund.

However, a new study from the University of North Carolina at Chapel Hill suggests that African-American men delay going to the doctor because they do not trust the health-care system, rather than because they feel the need to display their masculinity.

“Men’s concepts of what it means to be a ‘real’ man are generally shaped by traditional masculine role norms, which encourage men to be extremely self-reliant and these norms often affect their health behavior,” said Wizdom Powell Hammond, PhD, assistant professor of health behavior and health education at the UNC Gillings School of Global Public Health and a member of UNC’s Lineberger Comprehensive Cancer Center. “We’ve seen in other studies that men with strong commitment to traditional masculine role norms delay health care because they don’t want to seem weak.

“But this study shows that the opposite may be true for African-American men,” Hammond said. “Their delays in getting routine check-ups are attributable more to medical mistrust. Their beliefs about masculinity may not always have a negative impact on their use of health care.”

Hammond’s study, “Masculinity, Medical Mistrust and Preventive Health Services Delays Among Community-Dwelling African-American Men,” appears in the December 2010 issue of the Journal of General Internal Medicine.

The study was based on surveys of 610 African-American men, aged 20 and older, recruited primarily in barbershops in the North, South, Midwest and West regions of the U.S. The authors adjusted for possible differences in age, education, income, health insurance, health status and access to a regular physician.

Men with a stronger commitment to traditional masculine role norms were 23 percent less likely to delay blood pressure screening and 38 percent less likely to delay getting their cholesterol checked than men with a weaker commitment to such norms, the research found. On the other hand, men who reported being highly mistrustful of the medical system were more than twice as likely to delay routine check-ups and cholesterol screenings and three times more likely to delay having their blood pressure checked by a physician or health-care professional than men who were less mistrustful.

“What we found is that mistrust of the medical system accounts for delays in using health care, especially among older African-American men,” Hammond said. “The survey results indicated that African-American men consider preventive medical services, like getting their blood pressure and cholesterol levels checked, as a demonstration of masculinity, rather than a denial of it.”

Previous studies have shown that, among adults, men are less likely than women to use preventive health services and wait longer after symptom onset before seeking care. This underuse of preventative services coincides with shorter life spans and more preventable deaths among men than women.

Compared to non-Hispanic white men, Hammond said, African-American men go less often for   preventive health visits, are less likely to know their cholesterol levels, have poorer blood pressure control and face greater illness and premature death from conditions that usually respond well to treatments if caught in early stages.

“To improve the health of African American men, we should consider addressing why they lack trust in the health-care system and its providers,” Hammond said. “Health-care providers and public health professionals also might consider leveraging traditional masculine self-reliance in interventions and clinical encounters as a way to empower African American men to ‘seize control’ of their health. This gendered, patient-centered approach could shift power balances, perhaps inspiring greater health-care system trust among African-American men.”

Other authors of the study are Giselle Corbie-Smith, PhD, associate professor of social medicine and epidemiology in the UNC Gillings School of Global Public Health and the UNC School of Medicine; Derrick Matthews, PhD candidate, and Amma Agyemang, research associate, both in the public health school’s health behavior and health education department; and Dinushika Mohottige, student in the UNC School of Medicine.

The study is available at http://www.springerlink.com/content/3902p42334k62v58/ (subscription required).

UNC Men’s Health Lab website: http://www.menshealthlab.org

Media note: Hammond can be reached at (919) 962-9802 or email

Gillings School of Global Public Health contact: Ramona DuBose, (919) 966-7467, email

News Services contact: Patric Lane, (919) 962-8596, email

The research reinforces hopes that a related decision by the U.S. Food and Drug Administration last month will lead to fewer cases and deaths from anal cancer.

Until now, HPV vaccine was approved only for protection against cervical cancer and genital warts in females, and for genital warts in males.

However, the FDA recently approved the HPV vaccine, Gardasil, to prevent anal cancer and associated precancerous lesions due to the virus in both males and females aged 9 to 26.

The UNC findings, published earlier by researchers at the Gillings School of Global Public Health and the Lineberger Comprehensive Cancer Center, found that men are more open to getting HPV vaccine when it is described as also preventing HPV-related cancers, including anal cancer, as opposed to preventing genital warts alone. Researchers surveyed a national sample of more than 600 men aged 18-59 and asked about their willingness to get vaccinated. Sixty percent wanted the cancer-preventing vaccine, compared to 42 percent when the vaccine was depicted as only protecting against warts. The study, “Does framing human papillomavirus vaccine as preventing cancer in men increase vaccine acceptability?” appeared in the August 2010 issue of the journal Cancer Epidemiology, Biomarkers & Prevention.

Annie-Laurie McRee, a UNC doctoral student and lead author of the study, said the researchers hope their findings and the new FDA approval will promote HPV vaccination in boys and young men. “Now that HPV vaccine is indicated for cancer prevention in males, it’s important for health-care providers and public health professionals to be aware of these findings,” she said. “Being able to promote the cancer prevention benefits of vaccination is especially important, in part because people perceive cancer to be more severe than other HPV-related diseases like warts.”

The vaccine can potentially protect young men from strains of the virus that cause about 90 percent of anal cancers, as well as several other cancers and genital warts. However, few adolescent boys and young men in the United States who are eligible for the vaccine have initiated the three-dose vaccination series.

“The FDA made a critical public health decision,” said Noel T. Brewer, PhD, senior investigator on the study, UNC Lineberger member and associate professor of health behavior and health education in the public health school. “Now that HPV vaccine can prevent anal cancer, I believe it will motivate men to get the vaccine and decrease cancer deaths.”

Along with Brewer and McRee, other study co-authors were Paul L. Reiter, a postdoctoral fellow at the UNC Lineberger Comprehensive Cancer Center, and Kim Chantala, a research data analyst in the UNC Gillings School of Global Public Health.

Funding for the research came from the Investigator-Initiated Studies Program of Merck & Co. Inc., an HPV vaccine maker; the American Cancer Society; and the Cancer Control Education Program at the UNC Lineberger Comprehensive Cancer Center.

For more information, visit http://www.unc.edu/~ntbrewer/hpv.htm .

Note: Brewer can be reached at (919) 966-3282 or by email .

FDA announcement: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm237941.htm

Study link (subscription required): http://cebp.aacrjournals.org/content/19/8/1937.abstract

About 75% of people with low-grade brain tumors and 20% of people with acute myeloid leukemia have a mutated version of a gene known as IDH. IDH helps cells metabolize, or eat, food. "We now know that IDH represents the most frequently mutated metabolic gene in human cancer. And that changes the landscape of cancer research in metabolism quite a lot," said Yue Xiong, PhD, William R. Kenan Jr. professor of biochemistry and biophysics at the UNC Lineberger Comprehensive Cancer Center.

Xiong and collaborators at UNC, the University of California San Diego, and the Shanghai Medical College of Fudan University in China discovered that the IDH mutation sets off a battle inside cells between two metabolites, small molecules produced by metabolic enzymes. On the good side—the side that leads to normal cell growth—is a molecule called α-KG. On the bad side—the side that leads to cancer—is a molecule called 2-HG.

The researchers discovered that cells with the IDH mutation produce less α-KG and more 2-HG than normal cells. 2-HG then outcompetes α-KG, disabling a whole family of enzymes that depend on α-KG to do their jobs in the cell. Normal cell functions break down, contributing to the development of cancer.

Two of the affected enzymes are also involved in controlling gene expression, so if 2-HG wins the battle, it can also activate other genes that lead to cancer growth.

Bolstering α-KG to help fight 2-HG could offer a new treatment option for patients with the mutation. "α-KG is a natural product of the body. So we know we can survive it, we know it's not toxic. That gives us a window of opportunity," said Xiong.

"In terms of future therapeutic interventions for IDH-mutated tumors, there are two directions we could go," Xiong said. "One is developing a drug that inhibits the ability of the mutant enzyme from producing 2-HG. Another is to somehow provide α-KG back to the patients with mutated IDH to battle 2-HG."

Such therapies would help only those cancer patients with IDH mutations. "We no longer believe there will be a single silver bullet, a drug to treat and cure all types of cancers," Xiong said. "Instead, we are looking into the therapeutic treatment of individual types of cancer. Therefore, a specific agent that is targeting a very specific event such as tumor with mutated IDH now becomes much more valuable."

In 2010, more than 13,000 people died from brain and other nervous system cancers, and more than 20,000 died from leukemia. A drug that helps even a portion of patients with these cancers can still affect a lot of people, said Xiong.

Research collaborators included Yi Zhang, Kenan distinguished professor of biochemistry and biophysics at UNC and an investigator of the Howard Hughes Medical Institute, Stephen Frye of the UNC Eshelman School of Pharmacy, Kun-Liang Guan of the University of California San Diego, and Shi-min Zhao and students at Shanghai Medical College of Fudan University

Media contacts:
Les Lang , (919) 966-9366
Tom Hughes , (919) 966-6047

Tina Shaban, BSN, RN, OCN, event organizer and manager, CCSP Patient and Family Resource Center explains, "Our staff had noted that many patients and family members were not prepared for the cold weather, wearing only several shirts instead of outer wear, a borrowed coat that was too big or too small, or a blanket wrapped like a shawl. This drive shows the deep commitment and compassion our staff feels for the patients and families under their care."

Distribution of coats will continue through the end of January. Additional WARM winter coats can be dropped off at The Patient and Family Resource Center, N.C. Cancer Hospital, Main Lobby Level. For additional information, please contact the Resource Center at 919-843-0680.

CHAPEL HILL, N.C. - The National Cancer Institute estimates that more than 43,000 Americans were diagnosed with pancreatic cancer last year and more than 36,000 died from the disease. Despite advances in genetic science showing that the Ras oncogene is mutated in virtually all pancreatic cancers, scientists have been frustrated by the complexity of the signaling pathways in humans, which make it difficult to pinpoint potential therapeutic targets.

In a study published today in the Cell Press journal Developmental Cell, a team of researchers led by Channing Der, PhD, Distinguished Professor of Pharmacology at UNC-Chapel Hill, took a step back to a simpler organism – a common roundworm – and made a discovery about how the Ras oncogene chooses a signaling pathway and how the consequences of that choice play out in cellular development – a key issue in cancer, which is characterized by uncontrolled cell growth.

Der, who is also a member of UNC Lineberger Comprehensive Cancer Center, explains, “In humans the cell signaling pathways are very complex; there are more than 20 different downstream partners beyond the two proteins we study – Raf and RalGEF – that Ras can choose to interact with. In C. elegans, there is only one of each protein. That made it easier for us to identify how Ras chooses a partner to ‘dance’ with and what are the critical events in the subsequent cell development that promote cancer.”

“We found an elegant mechanism by which Ras switches partners and showed that the choice leads to very different fates for the cell. Now we can go back to the human pancreatic cancer cell and ask whether similar mechanisms are at work in determining how Ras causes pancreatic cancer,” he adds.

Scientists often study simpler organisms to tease out genetic and cellular activity that might be almost impossible to map in humans. “Worms’ cells actually share a great deal of functional overlap with human cells. However, while there may be one mechanism in a simple organism like a worm, there are multiple mechanisms at work in humans. It’s a great thing for us as people, because there is a great deal of redundancy in our biological systems that helps them self-repair and function better, but it makes it a lot harder to study what’s going on at a basic level,” Der notes.

“If this signaling works in a similar way in humans, the C. elegans model may be very powerful for helping us find new therapeutic targets for pancreatic cancer,” he concludes.

In addition to Der, the team included graduate student Tanya Zand, and Assistant Professor David Reiner, PhD, both of UNC’s Department of Pharmacology.

The project was supported by the National Institutes of Health.

Kirsten Rieth, a technical project manager at RTI International, was the 500th enrollee. “I decided to take part in the trial to help move the science forward,” she explains. Rieth has a background in science and at RTI is involved in moving research from the laboratory setting to commercial application.  “I believe that tailored treatment is the right way to go. People are all different, and medicines that work for some may not work for others.  This trial may help move us toward being able to prescribe the right medicine for each individual.”

William Irvin, MD, assistant professor of medicine and trial principal investigator says, “Both Dr. Howard McLeod and I were recruited to UNC with UCRF funding. We are glad to be able to offer this trial, also funded by the UCRF, to women across North Carolina.”

McLeod, PharmD, is the Eshelman Distinguished Professor in the UNC School of Pharmacy, and director of the UNC Institute for Pharmacogenomics and Individualized Therapy (IPIT).

Irvin explains, “With Dr. McLeod’s expertise in pharmacogenomics and Dr. Lisa Carey’s and my expertise in breast cancer, we were able to develop a trial that evaluates the impact of genotype-driven dosing of tamoxifen on drug concentrations in the blood and the impact of this strategy on patients’ quality of life. The UCRF funding allowed us to include a larger number of participants, thus giving more statistical significance to our results.

“The next steps for us to study will be the effect of other genetic differences in the body’s ability to metabolize tamoxifen and the whether genotype-driven dosing of tamoxifen helps improve breast cancer outcomes.”

Lisa Carey, MD, associate professor of medicine and medical director of the UNC Breast Center, and a mentor to Dr. Irvin, says, “The future of medicine lies in individualized therapy, which up to now has focused on characteristics of the tumor.  But we know that much of the time how well our drugs work has as much to do with the makeup of the person as with the makeup of the tumor.  This trial’s focus on matching the right dose to the right patient is how we all want to practice medicine.”

Irvin explains the science behind the study, “Tamoxifen is an excellent drug for personalized medicine, because there are already two FDA-approved doses, and we know a great deal about how it is metabolized.  The body has a gene that is responsible for converting tamoxifen to its active form.  There are several different versions of this gene; some are very active, some are less so.”

The study consisted of a blood draw that will allow UNC scientists to determine which of these genes an individual patient has.  If she has one of the less active versions of the gene, her tamoxifen dose will be increased to the higher FDA approved dose, and the after a few months, the active metabolite concentrations will be checked to see if changing the dose of tamoxifen can overcome having a less active form of the gene.”

“To date, evidence of efficacy for antidepressant drugs has been modest,” says Ryan Raddin, MD, hematology oncology fellow, and principal investigator of the trial. “In this pilot study, we will explore whether the medications, citalopram and mirtazapine, are efficacious in cancer patients. Additionally, our unique study design will seek to mirror clinical practice by tailoring the medication to individual symptoms.”

“Studying depression in patients with cancer is particularly important,” explains Donald Rosenstein, MD, trial co-principal investigator, professor of psychiatry and director of the UNC Lineberger Comprehensive Cancer Support Program. “Some studies have shown that as many as 40 percent of cancer patients have major depressive disorder. Depression can be detected by a symptom inventory or screening tests. Poorly controlled depression affects both quality of life and adherence to cancer treatment.”

Study scientists will recruit 52 cancer patients being treated at UNC for the nine-week trial. All study participants will receive standard psychosocial support and will receive mirtazapine, citalopram or placebo, based on their presenting symptom profile and random assignment. The study is a double-blind trial, meaning that neither the patients nor the trial leaders will know to which arm of the study a patient has been assigned until the conclusion of the trial.

“This is the first investigator-initiated interventional trial of the Supportive Care Program at UNC,” says, Stephen Bernard, MD, professor of medicine, co-director of the UNC Palliative Care Program and the physician in charge of the UNC Supportive Care Consultation Service and Clinic. “An interdisciplinary team of experts from oncology, supportive care, pharmacy, psychiatry, nursing and biostatistics is conducting the trial. “

Funding for this pilot study is provided in part by a grant from the University Cancer Research Fund. “If this pilot study proves efficacy for these drugs, we hope to develop a larger study involving more patients and more institutions,” says Raddin.

For more information about this trial, email the research coordinator or call 919- 966-2044.

The UNC Center received its first Reynolds grant in 2003 to train students, residents, and community physicians in geriatric care.

"As our population ages, 40-50 percent of specialists’ patients will be older," explains Jan Busby-Whitehead, MD, professor of medicine, director of the UNC Center for Aging and Health and principal investigator. "These patients have complex needs due to the number of chronic conditions they have and the number of medicines they take.

"This grant will allow us to train specialists in emergency medicine, physical medicine and rehabilitation, hematology and oncology, trauma and critical care surgery, and the hospital medicine service in critical issues of geriatric care and geriatric syndromes such as dementia, physiology of aging, and geriatric assessments.  They, in turn, will provide training to their peers, residents and fellows."

UNC is one of 10 institutions nationwide to receive a grant.

"Just as the pediatrics specialty addresses the issues specific to children, so does the geriatrics specialty address the special issues facing older patients," Busby-Whitehead said.

Co-principal investigators are Ellen Roberts, PhD, MPH, associate professor of medicine, Center for Aging and Health; Hyman Muss, MD, professor of medicine and director, UNC Lineberger Comprehensive Cancer Center geriatric oncology program; and Phillip Boysen, MD, UNC School of Medicine executive associate dean of graduate medical education and professor of anesthesiology.

Other UNC faculty leaders on the grant are Kevin Biese, MD, assistant professor of emergency medicine and residency program director; Elizabeth Dreesen, MD, assistant professor of surgery and associate chief of trauma surgery; Cherri Hobgood, MD, associate professor of emergency medicine; Michael Lee, MD, MHA, professor and chair of physical medicine and rehabilitation; Allen Lyles, MD, associate professor of internal medicine and pediatrics, section chief for inpatient education and practice, and associate director of the internal medicine residency program; Anthony Meyer, MD, PhD, professor and chair of surgery; Paul Ossman, MD, MPH, assistant professor of medicine; Donald Rosenstein, MD, professor of psychiatry and leader of the UNC Lineberger Comprehensive Cancer Support Program; Renae Stafford, MD, MPH, assistant professor of surgery and director of surgical critical care; and Paul Thananopavarn, MD, assistant professor of physical medicine and rehabilitation.

The Donald W. Reynolds Foundation is a national philanthropic organization founded in 1954 by the late media entrepreneur for whom it is named. Headquartered in Las Vegas, it is one of the 50 largest private foundations in the United States.

The Aging and Quality of Life program was conceived by the Foundation in response to a growing consensus that physicians lack adequate training to meet the increasing needs of the frail elderly patient. Such patients typically suffer from multiple, interactive physical and psychosocial conditions – both acute and chronic – that compromise their capacity to function in daily life and lessen their independence.

The new discovery – outlined in a study appearing in the online Early Edition of the Proceedings of the National Academy of Sciences during the week of Jan. 10, 2011 – also could lead to more effective treatments for life threatening medical conditions such as cancer.

University of North Carolina at Chapel Hill researchers used technology known as PRINT (Particle Replication in Non-wetting Templates) to produce very soft hydrogel particles that mimic the size, shape and flexibility of red blood cells, allowing the particles to circulate in the body for extended periods of time.

Tests of the particles' ability to perform functions such as transporting oxygen or carrying therapeutic drugs have not been conducted, and they do not remain in the cardiovascular system as long as real red blood cells.

However, the researchers believe the findings – especially regarding flexibility – are significant because red blood cells naturally deform in order to pass through microscopic pores in organs and narrow blood vessels. Over their 120-day lifespan, real cells gradually become stiffer and eventually are filtered out of circulation when they can no longer deform enough to pass through pores in the spleen. To date, attempts to create effective red blood cell mimics have been limited because the particles tend to be quickly filtered out of circulation due to their inflexibility.

Beyond moving closer to producing fully synthetic blood, the findings could affect approaches to treating cancer. Cancer cells are softer than healthy cells, enabling them to lodge in different places in the body, leading to the disease's spread. Particles loaded with cancer-fighting medicines that can remain in circulation longer may open the door to more aggressive treatment approaches.

"Creating particles for extended circulation in the blood stream has been a significant challenge in the development of drug delivery systems from the beginning," said Joseph DeSimone, Ph.D., the study's co-lead investigator, Chancellor's Eminent Professor of Chemistry in UNC's College of Arts and Sciences, a member of UNC's Lineberger Comprehensive Cancer Center and William R. Kenan Jr. Distinguished Professor of Chemical Engineering at N.C. State University. "Although we will have to consider particle deformability along with other parameters when we study the behavior of particles in the human body, we believe this study represents a real game changer for the future of nanomedicine."

Chad Mirkin, Ph.D., George B. Rathmann Professor of Chemistry at Northwestern University, said the ability to mimic the natural processes of a body for medicinal purposes has been a long-standing but evasive goal for researchers. "These findings are significant since the ability to reproducibly synthesize micron-scale particles with tunable deformability that can move through the body unrestricted as do red blood cells, opens the door to a new frontier in treating disease," said Mirkin, who also is a member of President Obama's Council of Advisors on Science and Technology and director of Northwestern's International Institute for Nanotechnology.

UNC researchers designed the hydrogel material for the study to make particles of varying stiffness. Then, using PRINT technology — a technique invented in DeSimone's lab to produce nanoparticles with control over size, shape and chemistry — they created molds, which were filled with the hydrogel solution and processed to produce thousands of red blood cell-like discs, each a mere 6 micrometers in diameter.

The team then tested the particles to determine their ability to circulate in the body without being filtered out by various organs. When tested in mice, the more flexible particles lasted 30 times longer than stiffer ones: the least flexible particles disappeared from circulation with a half-life of 2.88 hours, compared to 93.29 hours for the most flexible ones. Stiffness also influenced where particles eventually ended up: more rigid particles tended to lodge in the lungs, but the more flexible particles did not; instead, they were removed by the spleen, the organ that typically removes old real red blood cells.

Watch Video

The study, "Using Mechano-biological Mimicry of Red Blood Cells to Extend Circulation Times of Hydrogel Microparticles," was led by Timothy Merkel, a graduate student in DeSimone's lab, and DeSimone. The research was made possible through a federal American Recovery and Reinvestment Act stimulus grant provided by the National Heart, Lung and Blood Institute, part of the National Institutes of Health (NIH). Support was also provided by the National Science Foundation, the Carolina Center for Cancer Nanotechnology Excellence, the NIH Pioneer Award Program and Liquidia Technologies, a privately held nanotechnology company developing vaccines and therapeutics based on the PRINT particle technology. DeSimone co-founded the company, which holds an exclusive license to the PRINT technology from UNC.

Other UNC student, faculty and staff researchers who contributed to the study are Kevin P. Herlihy and Farrell R. Kersey from the chemistry department; Mary Napier and J. Christopher Luft from the Carolina Center for Cancer Nanotechnology Excellence; Andrew Z. Wang from the Lineberger Center; Adam R. Shields from the physics department; Huali Wu and William C. Zamboni from the Institute for Pharmacogenomics and Individualized Therapy at the Eshelman School of Pharmacy; and James E. Bear and Stephen W. Jones from the cell and developmental biology department in the School of Medicine.

The study is an example of the type of research that supports the Innovate@Carolina Roadmap, UNC's plan to help Carolina become a world leader in launching university-born ideas for the good of society. To learn more about the roadmap, visit innovate.unc.edu .

The work was performed in collaboration with W.R. Kenan, Jr. Distinguished Professor, Jenny Ting, PhD. First author, Sean Gregory, MS, a graduate student in UNC’s Department of Microbiology and Immunology played a critical role in this work.

The virus-produced protein, called a homolog, binds to the cellular protein that normally triggers an inflammatory response, a key immune system weapon for fighting viral infection. However, the homolog lacks a key part of the cellular protein that triggers the inflammation process. Inflammasome activation leads to the production of proinflammatory cytokines and eventual cell death.

Damania compares the homolog’s action to what can happen when completing a jigsaw puzzle. “Sometimes there will be a piece that ‘almost’ fits into an available space, but because it’s not an exact fit, leaving it there will keep you from completing the puzzle. The viral homolog gums up the works, preventing the formation of a large complex called the inflammasome, and keeping the cell’s immune response from deploying.”

According to Damania, a cell’s response to a viral invader is to commit suicide. The cells die rather than spread the virus, which uses the cell by hijacking its genetic machinery to produce more virus. Kaposi sarcoma virus’ ability to evade the body’s immune system helps it lie dormant and persist in the body over a lifetime.

Both researchers are members of UNC Lineberger Comprehensive Cancer Center. Dr. Damania studies the Kaposi’s sarcoma virus, which is known to cause certain types of human cancer, because it can infect cells and lie dormant without triggering cellular death. Virus-infected cells then proliferate, and can give rise to cancer.

Damania and Ting’s research collaborators include Sean Gregory, M.S., Beckley Davis, PhD, John West, PhD, and Debra Taxman, PhD, all of UNC Lineberger and the UNC Department of Microbiology and Immunology. Damania is also a member of the UNC Center for AIDS Research. Dr. Ting is the co-Director of the Inflammatory Disease Institute and Director of the Center for Translational Immunology. The team also included collaborators, John Reed, MD, and Shu-ichi Matsuzawa, PhD, both of the Sanford-Burnham Medical Research Institute in La Jolla, California.

The research was supported by the US National Institutes of Health, the University Cancer Research Fund, the American Heart Association, the Burroughs Wellcome Fund, and the Crohn’s & Colitis Foundation of America. Damania is a Leukemia & Lymphoma Society Scholar and Burroughs Wellcome Fund Investigator in Infectious Disease.

Becoming tobacco-free is one of the most important things cancer patients can do to improve their health. People tend to be familiar with the link between smoking and lung cancer. However, many patients may not know that smoking causes 30% of all cancer deaths and has been associated with many different kinds of cancer including bladder, cervical, esophageal, kidney, laryngeal, lung, oral, pancreatic, stomach, and colorectal cancer as well as leukemia. Continuing to smoke can interfere with cancer treatment and recovery, causing delayed healing and increasing risk of infections and complications. By quitting all tobacco use, patients can improve their health, reduce their chances of getting cancer again, protect loved ones from secondhand smoke, and save money.

While many patients want to quit, some find it very difficult to do this on their own. The combination of cessation medication and counseling is the most effective treatment and cancer patients who receive treatment within three months of diagnosis have higher quit rates. With pilot year funding from the University Cancer Research Fund, the N.C. Cancer Hospital Nicotine Dependence Program (NCCH NDP) began providing on-site tobacco use treatment for N.C. Cancer Hospital patients in March 2009. As of December 1, 2010, the program has logged more than 200 referrals and nearly 1,000 patient contacts. The program is directed by Dr. Adam Goldstein, a nationally recognized expert in the field of tobacco use treatment and research, and staffed by certified tobacco treatment specialists and pharmacists.

The NCCH NDP provides evidence-based treatment to help patients achieve their goal of becoming tobacco free. During the first appointment, program participants work with their tobacco treatment specialist to make a quit plan. The plan may include medicines to help with quitting, discussion of triggers and strategies to cope with them, suggestions for changing thoughts and behaviors related to tobacco use, and additional resources such as the NC Quitline fax referral. Participants then receive regular follow-up in person or by phone to support them through their quitting process.

According to NCCH NDP Program Manager Katie Patsakham, “Cancer treatment provides a unique opportunity for patients who use tobacco. They are being counseled by their physicians about the importance of quitting. They spend a significant amount of time in medical facilities that are tobacco-free. Most importantly, the fact that they are coming to the NCCH on a regular basis provides us with many opportunities to develop relationships, problem solve, and provide encouragement. Many patients have tried to quit before but they have not experienced the level of service we can provide. “

NCCH providers and patients are fortunate in that very few cancer centers across the nation provide this level of expertise in helping patients overcome nicotine addiction. More than 80 clinicians and staff members have been involved with the program so far. In a recent survey, providers were overwhelmingly enthusiastic when asked about ease of patient referral, quality of services, and their overall satisfaction with the program. According to Dr. Mark Weissler, Chief of the Division of Head and Neck Surgery, "Tobacco abuse is a major cause of head and neck cancer.  Our patients struggle with their addiction and many continue to use tobacco products even after the development of a head and neck cancer.  The Nicotine Dependence Program has been a real boon to our practice and a real help to our patients in their fight against this deadly addiction.”

It’s never too late to quit. For more information about the program, please email Katie Patsakham or call her at 919-445-5358.

Richard Goldberg, MD, physician in chief of North Carolina Cancer Hospital and associate director of UNC Lineberger Comprehensive Cancer Center, said, "The leadership of Dr. Rosenstein is critical to UNC as we enhance and expand programs to address the range of issues that our patients and their families face with a diagnosis of cancer. His expertise at the national level of building effective psychiatric health programs will provide UNC with the direction needed to develop outstanding services, research initiatives, and training and collaborative services."

In describing the new UNC Comprehensive Cancer Support Program, Rosenstein explained that it will include several educational, clinical and research services. "Each of these components will address different needs of cancer patients, their families and the clinicians who care for them. The program is being designed to minimize the many challenges cancer patients face."

"Our outreach efforts will be critical to fulfilling our mission to serve North Carolina and will foster collaborations between UNC and North Carolina community-based oncologists." Rosenstein said.

Shelton Earp, MD, director of UNC Lineberger Comprehensive Cancer Center, said, "We were able to attract Don Rosenstein with the support from the University Cancer Research Fund and the Fund's vision to expand and enhance clinical care for the citizens of North Carolina. Dr. Rosenstein will create a research program to evaluate the best practices for comprehensive patient support."

Rosenstein has been at NIH for 17 years. He earned his undergraduate degree in psychology from Wesleyan University in Middletown, CT, his medical degree from Northwestern University School of Medicine, and completed his residency training in psychiatry at Yale University. Some of his recent awards include the NIH Director’s Award and the NIMH Director's Career Award for Significant Scientific Achievement.

Dr. Rosenstein talks about his work with cancer patients - Watch video

By specifically measuring the activity level of a small subset of the 20,000 plus genes that may be “turned on” or “turned off” within each tumor, the test can give patients a more accurate picture of how their disease might progress, researchers say.

Designed by a multi-institutional team of scientists, the relatively simple test was specifically designed to be performed using equipment present in many hospital laboratories, an advantage over other recently developed genomic tests that require more sophisticated technology and expertise.

“Here we have developed a method that can be used in the everyday clinic and has the potential to benefit all breast cancer patients,” said study co-author Charles Perou, PhD, associate professor of genetics and pathology in the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. “Based on the genomics of a tumor, we can make good predictions about how a patient might do, but we can also define predictive markers that tell us which drugs to give patients.”

A report of the study appears in the Feb. 9 (Monday) online issue of the Journal of Clinical Oncology.

One in eight women in the United States will receive a diagnosis of breast cancer in their lifetime. The disease occurs when mutations accumulate in critical genes — such as those that control cell growth and division or the repair of damaged DNA — allowing cells to grow and divide uncontrollably to form a tumor. The specific genetic changes in these tumor cells determine in large part how aggressively the cancer will behave.

A major focus of Perou’s research is to provide more biological information that can be mobilized in the fight against breast cancer. He and his colleagues used DNA microarrays or “gene chips” to scan the thousands of genes within tumor samples taken from breast cancer patients. They found that the samples could be classified into five biologic groups or subtypes – Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like – and that each group had a specific genomic signature corresponding to distinct disease outcomes. The researchers then honed in on a small subset of 50 genes that can still identify these biologic groups as robustly as the original list of thousands of genes.

In this study, Perou and his colleagues modified their approach to measure the activity levels of those 50 genes using a technology called RT-PCR. Then, using a separate set of 761 patients, they validated the test’s ability to predict patients’ actual outcomes. The researchers also showed – using another group of 133 patients – that the test was able to predict response to a common chemotherapy regimen. Clinical trials are currently being conducted to confirm the study’s results in even larger numbers of patients.

“Here we’ve demonstrated that this test can predict the likelihood a patient will relapse and can define the biologic subtype of their tumor – pieces of information that together could be used to make treatment decisions,” Perou said. “We also found that patients in just two groups actually benefited from the chemotherapy regimen we studied, whereas the patients in the other three groups showed a much lower response rate. The idea is for clinicians to use this knowledge to help determine what drugs a patient should get and should not get.”

The multi-center study was led by researchers at UNC’s Lineberger Comprehensive Cancer Center; the University of Utah Huntsman Cancer Institute, Salt Lake City; and Washington University Siteman Cancer Center, St. Louis, Mo. Along with Perou, co-authors include Matthew Ellis, MD, associate professor of medicine, Washington University School of Medicine; and Philip S. Bernard, MD, assistant professor of pathology and medical director of Huntsman’s molecular pathology laboratory. Study co-authors from Perou’s laboratory at UNC include Joel S. Parker, the lead author and graduate student; Xiaping He, research associate; and Zhiyuan Hu, former postdoctoral fellow and current director of UNC pathology-genomics laboratory. UNC College of Arts and Sciences statistics professors Andrew B. Nobel, PhD, and J.S. Marron, PhD, who is also Amos Hawley Distinguished Professor of Biostatistics in the UNC Gillings School of Global Public Health, also contributed to the study.  Laboratories at the University of Utah, the University of British Columbia and Washington University contributed to the study as well.

Perou is one of the inventors of the test and has patents pending for the technology described in this news release. Along with colleagues at the Huntsman Cancer Institute and Siteman Cancer Center, he is a partner in the company, University Genomics, which is working to commercialize the test.

The research was supported by the National Institutes of Health.

Watch a video of Dr. Perou talking about this study.

Stuart Gold, MD, professor of pediatrics and chief of the division of pediatric hematology/oncology, said, “Dr. Kasow is a wonderful addition to our bone marrow transplant program. With the experience she brings from St. Jude she will be an incredible asset to the growth of our program.

“Dr. Kasow, along with pediatric transplant physician Jennifer Jaroscak, nurse practitioner Cammie Moore, and bone marrow transplant coordinator Sam Sharf complete an experienced team to care for these very complex children and offer them the most up to date and state of the art transplant regimens and the best of personalized care.”

Richard Goldberg, MD, physician in chief of the North Carolina Cancer Hospital and associate director of UNC Lineberger Comprehensive Cancer Center, said, "Attracting Dr Kasow to North Carolina is a great asset for our pediatric patients who need bone marrow transplants. The University Cancer Research Fund has made it possible to bring physician scientists of her caliber to UNC so that best medical practices can be delivered and developed right here."

Kasow earned her undergraduate degree from the University of Florida in Gainesville, FL, and her DO degree from the West Virginia School of Osteopathic Medicine in Lewisburg, WV. She completed a residency in pediatrics at Columbus Children’s Hospital in Columbus, OH and fellowships in pediatric hematology-oncology and bone marrow transplantation at St. Jude Children’s Research Hospital. She was honored by St. Jude in 2008 as the Outstanding Physician of the Year.

February 3, 2009 Tour

January 22, 2009 Tour

Muss said, “Our objective for the Geriatric Oncology Program will be to ensure the highest quality of oncologic care for older patients while factoring in the patient's functional status and other non-cancer illnesses. The program will develop clinical trials integrating prevention, treatment, quality of life, and translational research focused on older patients with cancer. Additionally, the program will develop educational programs for students, house staff, fellows, and faculty concerning aging and cancer to insure the development of research and clinical programs dedicated to advancing cancer care for older patients.”

“In addition to being a master clinician Hy Muss is a national leader in geriatric and breast oncology research,” said Richard Goldberg, MD, UNC Lineberger associate director of clinical research and physician in chief of the NC Cancer Hospital. “As our population ages, the need for oncology programs that are centered upon addressing the issues of this growing population is enormous. Cancer is more common in older adults, and Dr. Muss’ expertise will guide UNC’s research and clinical care to help us address issues facing our older patients with cancer.”

Shelley Earp, MD, director of UNC Lineberger Comprehensive Cancer Center, said, “Simply put, Hy Muss is a national treasure. His clinical research accomplishments are outstanding, but are frankly secondary to his skills as a doctor, teacher, and colleague. We are thrilled that the University Cancer Research Fund has allowed us to bring Hy back to North Carolina to start the new, much needed Geriatric Oncology effort.”

Muss earned his undergraduate cum laude degree in chemistry from Lafayette College in Easton, PA and his medical degree from the State University of New York Downstate Medical Center in Brooklyn, NY. He completed his internship, residency and a research fellowship at Peter Bent Brigham Hospital in Boston, MA. He was honored for his military service in Vietnam with a Bronze Star.

He serves on the Board of Directors for the American Society of Clinical Oncology Foundation and for the Cancer and Leukemia Group B (CALGB) Cooperative Group, and on the editorial boards of several publications including, Oncology, The Breast Journal, and CURE.

Watch a video interview with Dr. Muss.

A new study, published in the May 14 issue of the New England Journal of Medicine, shows that chemotherapy in addition to the surgery or surgery and radiation improves survival among older women.

The study was conducted with 600 women through the National Cancer Institute clinical trials cooperative Cancer and Leukemia Group B.

“This study is important because it is among the first several trials specifically targeted to older women with early-stage breast cancer and shows that chemotherapy can make a difference,” said Hyman Muss, MD, professor of medicine at the University of North Carolina at Chapel Hill and a member of UNC Lineberger Comprehensive Cancer Center, and corresponding author on the study.

The study compared a combination of chemotherapy drugs – the standard treatment – to a single drug in patients with early-stage breast cancer aged 65 and older. The combination therapy provided significantly better outcomes than a single drug treatment.

Similar studies involving women younger than 70 years of age have also shown that combination therapies provide better outcomes.

For this trial, the standard chemotherapy consisted of either cyclophosphamide, methotrexate, and fluouracil (CMF) or doxorubicin plus cyclophosphamide. The single drug was the oral drug, capecitabine.

Because patients often prefer oral to intravenous chemotherapy, a new effective oral agent for multi-drug treatment would be useful in treating older women with breast cancer. But the study showed that patients who were randomly assigned to capecitabine were twice as likely to have a relapse, and at three-years after completing therapy, the rate of relapse-free survival was 68 percent in the capecitabine group versus 85 percent in the standard-chemotherapy group.

The multi-institution trial included faculty from UNC Lineberger and Duke University, as well as clinical trials cooperative groups and institutions across the US and Canada.

Check out WRAL's coverage of this story.

Allbritton moved to UNC from the University of California at Irvine, and Lawrence from the Albert Einstein College of Medicine in New York.

They decided to come to UNC for similar reasons – a top-notch chemistry department that meshed well with their interests, an outstanding medical school, and a first-rate cancer center. Both of them are members of UNC Lineberger Comprehensive Cancer Center in addition to their appointment in the College of Arts and Sciences and both were looking for research partners. Allbritton notes, “Most of my work is very interdisciplinary and depends on high quality collaborations with clinicians and basic biomedical scientists.”

Soon after their arrival, they realized that their research interests overlapped. Although they were aware of each other’s work, “It was the first time we had ever met,” said Lawrence, who in addition to his appointment in Chemistry is a Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy . “We have very similar interests but bring to the table different tools to attack the biological problems that interest us. Nancy really knows how to manipulate and design analytical chemistry technology in a way that goes beyond the frontiers of science. I do the same thing, but at the molecular level.”

Allbritton asked Lawrence to discuss a possible collaboration over lunch, which he accepted, joking, “How could I say no when she was paying?”  For her part, Allbritton is happy that a simple lunch ‘bribed’ Lawrence to participate in a scientific collaboration that is now paying huge dividends, thanks to an investment by the University Cancer Research Fund (UCRF).

They both credit UCRF with providing the opportunity to turn that lunch conversation into a reality. They asked themselves, “Wouldn’t it be great not only to tell whether a patient has cancer (or that it has returned) with a simple blood test, but also to be able to tell that patient which combination of cancer drugs will work? In short, we could know in six hours rather than six months whether a particular drug regimen will be effective.” The pair went on to invent a tool to do just that for leukemia – the first target of their research.

Once they proved their concept, this dynamic duo faced a disagreement over where to next test their strategy. “Nancy felt we should turn our attention to breast cancer, whereas I felt prostate cancer rated a higher priority,” Lawrence noted (with tongue firmly in cheek). Their agreement to disagree resulted in two successful NIH grant proposals, with Lawrence taking the lead on the prostate cancer grant and Allbritton leading the breast cancer grant – totaling almost $5 million over the next five years.

“While breast and prostate cancer are very different in many ways, both are nearly impossible to treat after they have metastasized,” said Lawrence.

“The UCRF funding really jump-started the collaboration,” says Allbritton. But the scientists hope that the return on this investment will be much greater than the sum of their NIH grants. Their goal: to give clinicians another weapon in the early-detection arsenal and a tool to create personalized treatment for many different cancers.

UNC Lineberger physicians and scientists are teaming with them to realize this goal. Breast cancer experts, Channing Der, PhD and Jen Jen Yeh, MD and prostate cancer expert Young Whang, MD, PhD are collaborating on the grants.

Study co-author Richard M. Goldberg, MD, says, “Unfortunately, our research team did not find any improvement in disease-free survival when bevacizumab was used with the current state-of-the-art chemotherapy – 6 months of fluorouracil and oxaliplatin.”

The National Surgical Adjuvant Breast and Bowel Project trial analyzed more than 2600 patients over the course of almost three years. Patients were randomly assigned to the experimental or control arm of the trial and, overall, the two groups were comparable in terms of demographics and disease profile.

“While we saw a slight, transient effect in patients who were less than 15 months from their initial diagnosis and treatment, the long-term survival benefit was insignificant. Therefore we do not recommend the use of bevacizumab for this particular group of patients,” said Goldberg, who is associate director for clinical research at UNC Lineberger Comprehensive Cancer Center and Physician-in-Chief of the N.C. Cancer Hospital.

“It is disappointing when a treatment that clearly helps some patients does not work in another group, but we know that cancer is a diverse group of many diseases and these clinical trials help us further define those differences, helping us make progress toward more tailored therapies,” he added.

Other institutions involved in this multicenter trial include the University of Pittsburgh and Allegheny General Hospital, University of Florida and Florida Cancer Specialists, Helen F. Graham Cancer Center at Christiana Care, Newark, DE, Southeast Cancer Control Consortium – Community Clinical Oncology Program (CCOP), Goldsboro, NC, Atlanta Cancer Care Regional CCOP, Kaiser Permanente Northern California, All-Ireland Cooperative Oncology Research Group and Kaiser Permanente Midtown I in Denver, CO.

The research was supported by the Public Health Service, National Cancer Institute and Department of Health and Human Services.

The company, G-Zero Therapeutics, is also commercializing a high potential marker of molecular age measured from a patient blood sample, which could assist physicians in making more informed treatment-management decisions.

The Qualifying Therapeutic Discovery Project (QTDP) is designed to provide grants or tax credits, as determined by the Department of Health and Human Services, to qualified biotechnology companies employing fewer than 250 people.  The companies must demonstrate reasonable potential to develop new therapies to treat cancers or chronic diseases with unmet medical needs; reduce long-term health care costs in the U.S.; or significantly advance the goal of curing cancer.

“G-Zero is a great example of innovation at Carolina,” said Shelley Earp, MD, director of UNC Lineberger Comprehensive Cancer Center.

“The core findings on which G-Zero was founded were based on discoveries from Dr. Sharpless’ laboratories and licensed by UNC to create the company.  As this grant shows, there is significant potential to develop therapies that could help thousands of cancer patients avoid significant side effects from cancer treatment.

The research projects leading to discoveries licensed by G-Zero were partially supported by an Innovative Pilot Project award from the University Cancer Research Fund.  The company also has benefited from working with Carolina KickStart, according to Sharpless.  The market for G-Zero’s services may ultimately be in the billions of dollars.

The QTDP grant defrays small business expenses incurred in 2009 and 2010, and is designed to help promote the business’ growth.

The work of G-Zero Therapeutics supports the Innovate@Carolina Roadmap, UNC’s plan to help Carolina become a world leader in launching university-born ideas for the good of society. To learn more about the roadmap, visit innovate.unc.edu .