UPMC Physician Resources

Key Oncoprotein Found in Merkel Cell Carcinoma

PITTSBURGH, Aug. 15, 2011 – Researchers at the University of Pittsburgh Cancer Institute (UPCI) have identified the oncoprotein that allows a common and usually harmless virus to transform healthy cells into a rare but deadly skin cancer called Merkel Cell Carcinoma (MCC). Their findings, published today in the Journal of Clinical Investigation, could improve diagnosis for MCC and may help in understanding how other cancers arise.

Three years ago, Yuan Chang, M.D., and Patrick S. Moore, M.D., M.P.H., in the Cancer Virology Program at UPCI, discovered a new human cancer virus, called Merkel Cell polyomavirus (MCV), that causes most cases of MCC. But until now, it was not clear how the virus triggered cancer development.

To figure that out, lead author Masahiro Shuda, Ph.D., UPCI research associate, and the team systematically examined the viral proteins that might trigger cancer cell growth. After establishing human MCC cell lines, the scientists learned that knocking out a viral protein called “small tumor protein,” or sT, stopped the cancer cells from replicating. When they introduced sT into healthy cells in the lab, the cells took on the characteristics of cancer cells.

“This was a surprise because the viral sT proteins from other similar viruses that cause cancers in laboratory animals do not directly increase cancer activity in cells,” Dr. Shuda said. “Once we found this, we had to next understand the biological mechanisms that make MCV sT a cancer-causing protein, or oncoprotein.”

The MCV sT triggers a cellular process called “cap-dependent translation” that allows certain cellular oncoproteins to be made, Dr. Moore explained. Although the cancers caused by MCV are rare, the virus is important because it helps scientists pinpoint cell pathways that are key to more common cancers. These cancers also might activate cap-dependent translation through a DNA mutation rather than through a virus infection. 

In related studies recently published by the team in Emerging Infectious Diseases, MCV was shown to normally infect four out of five healthy adults, where it remains a silent resident in skin cells without causing any symptoms. Only when specific mutations occur in the DNA of the virus―for example, by ultraviolet light exposure―does it have potential to cause cancer. The researchers are now working to identify new agents to target MCC cancer cells that may be more active and less toxic.

MCV is the first virus in the family of polyomaviruses shown to cause human cancer, but six other polyomaviruses have recently been discovered as inapparent infections of people, and scientists are actively seeking to find out if they are additional, cancer-causing viruses as well. MCV is the second human cancer virus found by the Chang-Moore laboratory, which previously also discovered the virus causing Kaposi’s sarcoma – the most common cancer among AIDS patients.  

Other co-authors are Hyun Jin Kwun, Ph.D., and Huichen Fung, Ph.D., both of the Cancer Virology Program. The research was funded by the National Institutes of Health, the American Cancer Society and UPCI. Dr. Chang is an American Cancer Society Professor of pathology, and Dr.  Moore is an American Cancer Society Professor of microbiology and molecular genetics, Pitt School of Medicine.

Pitt Team Finds A Molecular Pathway That Can Lead to Inflammation in Asthma

PITTSBURGH, Aug. 8, 2011  Researchers at the University of Pittsburgh School of Medicine have identified a molecular pathway that helps explain how an enzyme elevated in asthma patients can lead to increased mucus production and inflammation that is characteristic of the lung condition. Their findings, reported online in this week’s Proceedings of the National Academy of Sciences, reveal unique interactions between biological molecules that could be targeted to develop new asthma treatments.

An enzyme called epithelial 15-lipoxygenase 1 (15LO1) metabolizes fatty acids to produce an eicosanoid known as 15 hydroxyeicosaetetranoic acid (15 HETE) and is elevated in the cells that line the lungs of asthma patients, explained Sally E. Wenzel, M.D., professor of medicine, Pitt School of Medicine, and director of the Asthma Institute at UPMC and Pitt School of Medicine. Her team showed in 2009 that the enzyme plays a role in mucus production.

“In this project, we found out 15 HETE is conjugated to a common phospholipid,” she said. “That complex, called 15HETE-PE, and 15LO1 behave as signaling molecules that appear to have a powerful influence on airway inflammation.”

By examining lung cells obtained by bronchoscopy from 65 people with asthma, the researchers found that both 15LO1 and 15HETE-PE displace an inhibitory protein called PEBP1 from its bond with another protein called Raf-1, which when freed can lead to activation of extracellular signal-regulated kinase(ERK). Activated ERK is commonly observed in the epithelial, or lung lining, cells in asthma, but until now the reason for that was not understood.

“This is an important study as it directly explores the important role of 15-lipoxygenase 1 in the airway epithelial cells of patients with asthma, which immediately establishes the relevance to human disease,” said Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine, UPSOM.

Other experiments showed that knocking down 15LO1 decreased the dissociation of Raf-1 from PEBP1, which in turn reduced ERK activation. The pathway ultimately influences the production of factors involved in inflammation and mucus production.

“These results show us on both a molecular and mechanistic level and as mirrored by fresh cells from the patients themselves that the epithelial cells of people with asthma are very different from those that don’t have it,” Dr. Wenzel said. “It also gives us a potential treatment strategy: If we can prevent Raf-1 displacement, we might have a way of stopping the downstream consequences that lead to asthma.”

Co-authors include Jinming Zhao, Ph.D., Silvana Balzar, M.D., Claudette M. St. Croix, Ph.D., and John B. Trudeau, B.S., of UPSOM and the Asthma Institute; and Valerie B. O’Donnell Ph.D., of Cardiff University, United Kingdom. The study was funded by the National Institutes of Health and the American Heart Association.

Leading Lung Cancer Researcher Named to Key Posts at Pitt and University of Pittsburgh Cancer Institute

PITTSBURGH, July 25, 2011 – Mark A. Socinski, M.D., a leading expert in lung cancer research, has been appointed director of the Lung Cancer Section of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine, co-director of the UPMC Center for Excellence in Lung Cancer and co-director of the Lung and Thoracic Malignancies Program at the University of Pittsburgh Cancer Institute (UPCI).

Dr. Socinski joins Pitt and UPCI on Sept. 1. He will be the first member of Pitt’s Department of Medicine faculty to have a joint appointment as professor of surgery in the Department of Cardiothoracic Surgery.

“Mark represents the perfect blend of translational and clinical expertise so necessary for the advancement of lung cancer care, research and education at our institution, and for transforming our center of excellence in lung cancer into one of the pre-eminent programs in the country,” said Nancy E. Davidson, M.D., director of UPCI and UPMC Cancer Centers.

Dr. Socinski is an internationally renowned expert in the development of novel chemotherapy agents and treatment strategies for advanced non-small cell lung cancer and small cell lung cancer. He has played a leading role in developing aggressive and innovative combined-modality approaches to treat patients with locally advanced non-small cell lung cancer, and he is at the forefront of integrating novel targeted agents with cytoxic chemotherapy regimens. Most recently, his clinical research has focused on incorporating personalized medicine and the use of molecular biomarkers in the treatment of lung cancer.

Dr. Socinski received his B.A. in zoology, M.S. in pathology and M.D. from the University of Vermont. He completed his residency training in internal medicine at the Beth Israel Hospital, Harvard Medical School, and completed training in medical oncology at the Dana Farber Cancer Center, Harvard Medical School. Dr. Socinski joined the faculty of the Medical Center Hospital of Vermont and University of Vermont in 1989 and was then recruited to the University of North Carolina at Chapel Hill and the Lineberger Comprehensive Cancer Center in 1995, where he currently serves as professor of medicine in the Division of Hematology-Oncology and director of the Multidisciplinary Thoracic Oncology Program.

He has served as an active member of several leading cancer organizations, including the American Society of Clinical Oncology, International Society for the Study of Lung Cancer and the American College of Chest Physicians. He co-chairs the National Cancer Institute Thoracic Malignancy Steering Committee.

Children’s Hospital of Pittsburgh of UPMC/Pitt Esteemed Infectious Disease Clinician/Researcher To Be Awarded Carol Ann Craumer Endowed Chair for Pediatric Research

PITTSBURGH, July 19, 2011 Toni Darville, M.D., chief of the Division of Infectious Diseases at Children’s Hospital of Pittsburgh of UPMC, will be awarded the Carol Ann Craumer Endowed Chair for Pediatric Research in an installation ceremony Monday, July 25.

The Carol Ann Craumer Endowed Chair for Pediatric Research was established in 1998 to recognize outstanding leaders in pediatric research and to provide resources for research innovations that could directly influence medical care for children.

Dr. Darville, professor of pediatrics and immunology, University of Pittsburgh School of Medicine, is one of the world’s leading researchers on the immunological mechanisms for damage to the female reproductive tract caused by Chlamydia trachomatis. Chlamydia, the most frequently reported sexually transmitted disease in the United States and a major global public health target, causes infertility and is believed to play a role in preterm labor and complications in premature infants.

“This endowed chair is a testament to Dr. Darville’s significant accomplishments as a physician and scientist in the area of infectious diseases,” said David H. Perlmutter, M.D., physician-in-chief and scientific director at Children’s, and the Vira I. Heinz Professor and Chair of the Department of Pediatrics, University of Pittsburgh School of Medicine. “Her research already has greatly expanded our understanding of this devastating disease and has outstanding potential to lead to novel vaccine strategies for prevention. Toni also is a wonderful mentor, whose energy and enthusiasm for uncovering the causes of childhood diseases and new treatments has had a transformational effect at Children’s Hospital.”

For the last 16 years, Dr. Darville has received research funding from the National Institutes of Health, and in 1998 she received the Pediatric Infectious Diseases Society’s Young Investigator Award. Her research has been featured in numerous journals, including Immunity, Journal of Biological Chemistry, Journal of Immunology and PLoS Pathogens. She is a member of the Society for Pediatric Research, the American Society for Microbiology and the American Association of Immunologists, and has been recognized many times during her career by medical students and residents as an outstanding teacher. 

In November 2009, together with a team of researchers from the Pitt School of Medicine, Dr. Darville established the UPMC Sexually Transmitted Infections Cooperative Research Center, which competed successfully for a $12.5 million, five-year grant from the National Institute of Allergy and Infectious Diseases. Scientists at the center focus their research, based at Children’s Hospital, Magee-Womens Research Institute and the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine, on the prevention of female reproductive tract complications caused by sexually transmitted infections. The research projects are aimed at developing new therapies to treat bacterial infections of the female upper genital tract that produce pelvic inflammatory disease (PID). Each year in the United States, it is estimated that more than 1 million women experience an episode of acute PID. More than 100,000 women become infertile each year as a result of PID, and a large proportion of the ectopic pregnancies that occur every year are due to PID complications.

The Carol Ann Craumer Endowed Chair in Pediatric Research was established in June 2000 from a bequest from the William and Eleanor Craumer Trust. The fund was established in the name of Carol Ann, their daughter, who contracted polio in August 1953. During the fall of that year, she was admitted to Children’s where she was confined to an iron lung and then passed away in April 1954.

Pitt Study: Esophageal Cancer Risk Higher in Medically Treated GERD Patients with Fewest Symptoms

PITTSBURGH, July 18, 2011 – Medically treated patients with mild or no symptoms of  gastroesophageal reflux disease (GERD) are at higher risk for developing esophageal cancer than those with severe GERD symptoms, according to a University of Pittsburgh study published in the current issue of Archives of Surgery.

Many patients who develop adenocarcinoma, a common form of esophageal cancer, are unaware that they have Barrett’s esophagus – a change in the cells lining the esophagus often due to repeated stomach acid exposure. In some cases, Barrett’s esophagus develops into esophageal cancer. 

“Typically, patients with severe GERD symptoms are screened for Barrett’s esophagus, but those with mild or absent symptoms are not. Unfortunately, many patients who develop adenocarcinoma don’t know that they have Barrett’s esophagus until it has transformed into cancer and become advanced, leading to obstruction,” said principal investigator Blair A. Jobe, M.D., professor and director of esophageal research and esophageal diagnostics and therapeutic endoscopy, Department of Cardiothoracic Surgery, Pitt School of Medicine.

The study included 769 GERD patients who presented for their first upper endoscopy, in which a flexible endoscopic camera is guided through the esophagus and stomach to look for tissue changes. Participants were separated into three groups: patients who were referred for upper endoscopy for any clinical indication regardless of symptoms; patients with typical GERD symptoms, such as heartburn, regurgitation and difficulty swallowing; and patients with atypical GERD symptoms, such as hoarseness, throat-clearing, mucus, coughing and a lump sensation in the throat.

All study participants underwent endoscopy and completed questionnaires and a detailed medication history. Endoscopy revealed that 122 of these patients, or 15.9 percent, had Barrett’s esophagus or adenocarcinoma. Patients who were adequately managing their GERD symptoms with proton pump inhibitors (PPIs) were 61 percent more likely to have Barrett’s esophagus or adenocarcinoma if they reported no severe GERD symptoms, compared to patients taking PPIs who reported severe symptoms. Patients with severe GERD symptoms often experienced irritation or swelling of the esophagus, but that was associated with decreased odds of having esophageal cancer.  

“Our research indicates that even patients without severe symptoms may benefit from Barrett’s esophagus screening,” Dr. Jobe noted.  “If GERD patients are screened early enough, there is a better chance that Barrett’s esophagus can be identified before it becomes cancerous,” he stated. “We are learning that the chronic and long-term use of PPIs may not be entirely without consequences and may lead to more insidious problems such as calcium malabsorption or cause one to be asymptomatic in the face of continued esophageal injury from GERD.” 

Dr. Jobe and his Pitt colleagues have established the Barrett’s Esophagus Risk Consortium (BERC), in which primary care patients are being screened with in-office, small-caliber, unsedated endoscopy in an attempt to better understand risk factors for the condition as well as lower the threshold for screening. The multicenter effort is funded by the National Institutes of Health.

Study co-authors include Katie S. Nason, M.D., M.P.H.,  Omar Awais, M.D., Matthew J. Schuchert, M.D., and James D. Luketich, M.D., all from Pitt; and Promporn Paula Wichienkuer, M.D., M.P.H., Robert W. O’Rourke, M.D., John G. Hunter, M.D., and Cynthia D. Morris, Ph.D., M.P.H., all from Oregon Health and Science University.

The study was funded by the Robert Anthony McHugh Research Fund for the Prevention and Early Detection of Esophageal Cancer, David Gold and Irene Blumenkrantz Esophageal Cancer Research Fund, the Sampson Family Endowed Chair, the UPMC Heart, Lung and Esophageal Surgery Institute, the American Surgical Association Foundation Fellowship Award and grants from the National Institutes of Health.

Pitt Researchers Find New Way to Classify Post-Cardiac Arrest Patients

Pitt Researchers Find New Way to Classify Post-Cardiac Arrest Patients, Improving Ability to Predict Outcomes

PITTSBURGH, July 11, 2011 – A new method for scoring the severity of illness for patients after cardiac arrest may help to predict their outcomes, according to researchers at the University of Pittsburgh School of Medicine. Most importantly, their findings, published in the early online version of Resuscitation, also show that none of the severity categories rules out the potential for a patient’s recovery.

“Traditionally, we have used historical or event-related information, such as initial cardiac rhythm or whether someone witnessed the collapse, to categorize these patients upon arrival at the hospital,” said Jon C. Rittenberger, M.D., lead author and assistant professor of emergency medicine. “Unfortunately, more than 10 percent of the time, such information is unavailable, which limits our ability to tailor therapies, counsel families about prognosis or select patients for clinical trials.”   

Cardiac arrest is the most common cause of death in North America, resulting in approximately 350,000 deaths each year.

The researchers looked at retrospective data for more than 450 post-cardiac arrest patients treated at UPMC Presbyterian between January 2005 and December 2009. Both in-hospital and out-of-hospital cardiac arrests were included. In 2007, the hospital implemented a multi-disciplinary post-cardiac arrest care plan, including therapeutic hypothermia, or cooling of patients to minimize brain damage.

Four distinct categories of illness severity were identified based on a combination of neurological and cardiopulmonary dysfunction during the first few hours after restoration of a patient’s spontaneous circulation. The researchers looked at rates of survival, neurologic outcomes and development of multiple organ failure for patients in each category, and found wide variations among the groups.

“Now, objective data available to the clinician at the bedside during initial evaluation may provide a better way of predicting outcomes and guiding the decisions of families and clinicians. We found that the category of illness severity had a stronger association with survival and good outcomes than did such historically used factors as initial rhythm of arrest or where it happened,” said Dr. Rittenberger.  “Our results indicate that illness severity should be carefully measured and accounted for in future studies of therapies for these patients.”

Co-authors of the study include Samuel A. Tisherman, M.D., Margo B. Holm, Ph.D., Francis X. Guyette, M.D., M.P.H., and Clifton W. Callaway, M.D., Ph.D., all of the University of Pittsburgh.

The research was supported by a grant from the National Center for Research Resources. Dr. Rittenberger is also supported by an unrestricted grant from the National Association of EMS Physicians/Zoll EMS Resuscitation Research Fellowship.

UPMC Palliative Care Program Recognized With Circle of Life Honor

PITTSBURGH, July 11, 2011 UPMC today was recognized for its innovative program that improves the care of patients near the end of life or with life-threatening conditions with a Circle of Life Citation of Honor from the American Hospital Association (AHA). The Circle of Life Award celebrates programs across the nation that have made great strides in palliative and end-of-life care.

A team of health care professionals work together as part of UPMC’s palliative care program to provide comfort to patients near the end of life. The program integrates family support with inpatient, outpatient and home care. 

“It’s a great honor for UPMC’s palliative care program to be honored with this citation,” said Robert Arnold, M.D., chief medical officer, UPMC Palliative and Supportive Institute. “Our goal is to help people with serious illness maintain the best quality of life possible, whether it be through managing pain, providing support to their families or facilitating conversations about the kind of care they expect.”

UPMC was selected by leaders in medicine, nursing, social work, ethics and health administration. The committee focused on innovative programs that respect patient goals and preferences, provide comprehensive care, acknowledge and address the family or caregivers’ concerns and needs, and build systems and mechanisms of support to continue the program for future patients and caregivers.

This is the 12th year for the Circle of Life Award. The 2011 awards are supported, in part, by the California HealthCare Foundation and the Archstone Foundation, based in Oakland, Calif. Major sponsors are the American Hospital Association, the Catholic Health Association, National Consensus Project for Quality Palliative Care and the National Hospice and Palliative Care Organization and the National Hospice Foundation. The American Academy of Hospice and Palliative Medicine and the National Association of Social Workers are Circle of Life co-sponsors. The Circle of Life Award is a program administered by the Health Research & Educational Trust.

“A patient needing palliative or end-of-life care faces difficult challenges that must be addressed with skill and unique expertise,” said AHA president and CEO, Rich Umbdenstock. “These winners exemplify what the health care field is striving for: compassionate care for patients and families at all times. These innovative programs serve as guiding lights for others on this path.”

For more information on the Circle of Life Award, visit www.aha.org/circleoflife.

UPMC is Only Health System Named ‘Most Wired’ for 13 Consecutive Years

PITTSBURGH, July 11, 2011 – For the 13th consecutive year, UPMC has been named one of the 100 “Most Wired” health systems in the country, the only organization to earn that distinction, according to Hospitals & Health Networks, the journal of the American Hospital Association (AHA).

UPMC also is one of the winners of the 2011 Most Wired Innovator Awards for its development of eVisits, a Web-based system for providing secure “electronic housecalls” to patients. This pioneering approach to health care is available to patients of most UPMC primary care physicians and provides a safe, convenient and cost-effective alternative to in-person visits or phone calls for more than 20 conditions. eVisits, using physician-created, structured questionnaires, are integrated into UPMC’s extensive electronic medical records (EMRs) to ensure continuity of patient care.

The awards will be presented at the 2011 Health Forum and AHA Leadership Summit in San Diego, July 17 to 19.

“UPMC is a long-time leader in adopting, developing and commercializing smart technology that improves care for patients. We are honored to be consistently recognized for these achievements by Hospitals & Health Networks and proud of the dedicated team of clinicians and technologists at UPMC who have made this possible,” said Daniel Drawbaugh, chief information officer of UPMC.

The 13th annual Most Wired Survey and Benchmarking Study included more than 1,300 hospitals and health systems across the country and measured the use of technology in clinical quality and safety, business and administrative functions, and ambulatory and community services.

Over the past five years, UPMC has invested more than $1.3 billion in technology to support clinical excellence and administrative efficiency as it creates new models of accountable care. UPMC is one of the nation’s earliest and most sophisticated users of EMRs. Children’s Hospital of Pittsburgh of UPMC in 2009 was the first pediatric facility in the nation to achieve HIMSS Stage 7 status for its virtually paperless environment and the most comprehensive use of EMRs, while seven other UPMC hospitals are Stage 6, as measured by HIMSS Analytics, a subsidiary of the Healthcare Information and Management Systems Society.

Last year, UPMC ranked fifth in the InformationWeek500, a list of the nation’s top technology innovators across all industries, and also was honored with the Healthcare Innovation Award for creating a system that allows radiologists and physicians to access imaging studies from across UPMC to better care for patients.

UPMC Opens New Specialty Clinic for Smokers, Offers Early Screenings That Could Save Lives

PITTSBURGH, July 7, 2011 – UPMC has established a new specialty clinic that will offer early lung cancer screening using low-dose helical CT scanning, a technique that was proven in a national trial to reduce deaths because tumors were detected early when treatment is more effective.

The Lung Nodule Clinic, located on the fourth floor of Falk Clinic in Oakland, is intended to screen current and former heavy smokers, said Christopher Faber, M.D., medical director of the UPMC Comprehensive Lung Center. Smoking remains the leading cause of lung cancer, the most common cancer in adults. 

“Patients will be evaluated to see if they are candidates for the screening test,” explained Dr. Faber. “If they are, they will participate in a one-hour, eight-person, group-educational session led by a nurse coordinator, followed by a low-dose helical CT scan.” 

A low-dose helical CT scan, also referred to as spiral CT, uses X-rays to obtain a multiple-image scan of the entire chest during a 7 to 15 second breath-hold. Patients will be strongly encouraged to quit smoking during the educational session, which will include smoking cessation information. Results of the CT scan will be sent to the patient and their primary care physician. 

This new fee-for-service clinic grew out of the findings of the National Cancer Institute’s National Lung Screening Trial, a randomized national trial that involved more than 53,000 current and former heavy smokers ages 55 to 74 and compared the effects of two screening procedures for lung cancer ― low-dose helical CT scans and standard chest X-ray ― on lung cancer mortality. The study found 20 percent fewer lung cancer deaths and a 7 percent reduction in overall mortality among the trial participants who were screened with low-dose helical CT. 

“The results of this study are very important, suggesting that many Americans who smoke should not only quit smoking, but also undergo lung cancer screening, both of which will reduce lung cancer mortality rates, said Mark Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine.

The lung screening program currently is not covered by insurance. The out-of-pocket fee of $200 includes the nurse coordinator-led class, CT scan and valet parking.

University of Pittsburgh Cancer Institute Again Earns Elite Comprehensive Cancer Center Status from National Cancer Institute

PITTSBURGH, July 7, 2011 – The National Cancer Institute (NCI) has renewed the University of Pittsburgh Cancer Institute’s (UPCI) status as a “Comprehensive Cancer Center,” the highest distinction it grants. With this designation comes national and international recognition that UPCI is a center of excellence in basic and clinical research, prevention and control programs, and population sciences, as well as a vital part of the region for cancer education and outreach.

“This renewal differentiates UPCI as a national leader in cancer research and care,” said Nancy E. Davidson, M.D., director of UPCI and UPMC Cancer Centers. “As one of only 40 centers in the country with this elite designation, our patients can be confident they receive the very best care possible, including superior patient education, access to the most up-to-date screening technologies and cutting-edge treatment options.”

In October, UPCI celebrated the successful renewal of its Cancer Center Support Grant from the NCI. The grant supports UPCI’s broad range of clinical, research and educational programs and its mission to lessen the burden of cancer for people throughout Western Pennsylvania and beyond. The grant renewal, a review of the quality of UPCI’s research and clinical care, was the first step in UPCI’s designation renewal. The second step evaluated UPCI’s programs in patient education, community service and community outreach.

“The renewal of our core grant was vital because it confirms the exceptional work happening inside the Cancer Institute,” said Dr. Davidson. “The renewal of our comprehensive status, however, is equally important because it recognizes our role in the community. An NCI-designated comprehensive cancer center should be an integral part of the fabric of the community, and our commitment to the community is as strong as our dedication to finding cures for this disease.”

Established in 1985, UPCI received its designation as an NCI-designated Comprehensive Cancer Center in 1989 and has retained this distinction since then.

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