National Cancer Institute Reviews the UCCCC s Comprehensive Cancer Center Status The University of Chicago Medicine Comprehensive

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1 Spring 2013 National Cancer Institute Reviews the UCCCC s Comprehensive Cancer Center Status The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) completed a successful review for a 5-year P30 Cancer Center Support Grant (CCSG) and was recommended for renewal as a Comprehensive Cancer Center by the National Cancer Institute (NCI). The UCCCC is one of only 41 Comprehensive Cancer Centers nationwide, and one of only two in Illinois, to have earned this prestigious status. The designation represents the highest mark of excellence in basic, clinical, and population research, and an institution s dedication to developing more effective treatments for cancer. The outstanding work of our Cancer Center is central to our missions of research, education, and advanced clinical care to improve the options and outcomes of patients diagnosed with cancer and to prevent these diseases, said Everett Vokes, MD, John E. Ultmann Professor of Medicine and Radiation Oncology, chair of the Department of Medicine. When the National Cancer Act was signed into law in 1971, the NCI created a Cancer Centers Program to support the work of centers that excel at making scientific discoveries and applying them to new approaches to cancer prevention, diagnosis, and treatment. Although individual investigators at these institutions receive grant support for specific research projects, the funding provided by the CCSG extends their capability through the provision of the necessary infrastructure, and, as a result, maximizes productivity. For example, a large portion of the CCSG at the UCCCC sustains core facilities, which are shared research resources that house stateof-the-art technologies and expertise that investigators could not otherwise afford. The grant also supports the UCCCC s strategic leadership to coordinate and promote the growth of research programs and initiatives, as well as to recruit new faculty. Additionally, the CCSG provides pilot project funding, which allows investigators to develop some of their newest ideas and generate the preliminary results needed to apply for national grant funding. To qualify for the CCSG award and accompanying Under Dr. Le Beau s leadership, the UCCCC fosters truly multidisciplinary research, providing an outstanding platform for new cancer discoveries. NCI designation, institutions must successfully meet rigorous competitive standards associated with scientific and organizational merit. Centers are evaluated on the innovativeness and impact of their research in clinical, basic, translational, and population sciences. In addition, the following six essential characteristics are assessed: facilities; organizational capabilities; transdisciplinary collaboration and coordination; cancer focus; institutional commitment; and the center director. The UCCCC received accolades in numerous areas, including its innovative research on epidemiology and the genetic basis of cancer, the molecular mechanisms of transformation, tumor immunology, hematological malignant diseases, and imaging sciences, as well as its innovative clinical trials portfolio and exceptional pharmacogenomics research. The UCCCC devoted one full year in preparation of the CCSG grant, which concluded with a site visit that showcased the past 5 years of research for the NCI review committee. At this most recent review, the UCCCC was awarded its best score, and was rated as exceptional-outstanding. The areas that received particular recognition were institutional commitment and transdisciplinary collaboration and coordination, according to UCCCC Director Michelle M. Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine. For a center of our size, we have a remarkable number of multi-investigator grants, which highlights the collaborative nature of our faculty and how they bring unique skills to push the field of cancer research forward as a team, she said. Under Dr. Le Beau s leadership, the UCCCC fosters truly multidisciplinary research, providing an outstanding platform for new cancer discoveries, said Habibul Ahsan, MBBS, MMedSc, Louis Block Professor of Health Studies, Medicine, and Human Genetics, and associate director for population research. The UCCCC s successful competitive grant review and recommendation for re-designation as a Comprehensive Cancer Center is a testament of its achievement. Habibul Ahsan, MBBS, MMedSc UCCCC Director Michelle M. Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine, and UCCCC Associate Director for Population Research Habibul Ahsan, MBBS, MMedSc, Louis Block Professor of Health Studies, Medicine, and Human Genetics. Michelle M. Le Beau, PhD From the Director In this issue, we are delighted to report on some exciting developments that have occurred at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC). In the early winter, the National Cancer Institute (NCI) recommended renewal of our designation as a Comprehensive Cancer Center, a title shared by only 41 centers in the nation. This status distinguishes the UCCCC as a center with the highest level of scientific excellence in our efforts to translate laboratory discoveries into prevention and treatment strategies to reduce the devastating effects of cancer. I am tremendously grateful for the hard work and accomplishments of our staff and physicians and physician-scientists. After many months of preparation, we were not only recommended for renewal of our Cancer Center Support Grant and comprehensive status, but we garnered the highest score in our history from the NCI. In February, after 3 years of construction, our brand-new flagship hospital opened its doors to patients. The Center for Care and Discovery provides state-ofthe-art cancer care to patients in an environment that fosters close collaborations between our clinicians and researchers. The hospital houses some of the most sophisticated medical technology and diagnostic tools available, and its flexible design allows for the integration of emerging technologies and future innovations. The new facility expands our ability to deliver comprehensive cancer care to residents of the Chicago area and surrounding communities. Inside this issue, you will also learn about the discovery of a new gene that contributes to acute myeloid leukemia, as well as the development of a new approach that may soon improve the success of radiation therapy. We also relay the stories of one parent s efforts to expand pediatric cancer research in Illinois and the importance of peer support to help survivors cope during their cancer journey. Regards, Michelle M. Le Beau, PhD Director, The University of Chicago Medicine Comprehensive Cancer Center; Arthur and Marian Edelstein Professor of Medicine

2 Pathways to Discovery UCCCC Researchers Pinpoint Tumor Suppressor Gene Involved in Acute Myeloid Leukemia Researchers at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) have identified a gene that contributes to the development of acute myeloid leukemia (AML). This pivotal finding follows 40 years of University of Chicago research that has slowly unraveled the genetic basis of leukemia. In 1973, Janet Rowley, PhD, Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics and Cell Biology, and Human Genetics, was examining the DNA of leukemia cells and observed that one copy of chromosome 7 was missing. She deduced that one out of the more than 1,000 genes found on chromosome 7 could possibly be responsible for keeping the growth of leukemia cells in check. The search for a tumor suppressor gene continued among Dr. Rowley s colleagues at the University of Chicago. In the 1990s, Michelle M. Le Beau, PhD, UCCCC director and the Arthur and Marian Edelstein Professor of Medicine, used a high-resolution technique called fluorescence in situ hybridization (FISH) to define the segment of chromosome 7 that was commonly deleted. She narrowed the region of interest to about 50 genes. Most recently, in 2009, Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology (IGSB), and his research team harnessed advanced technology to further Megan McNerney, MD, PhD, instructor of pathology, and Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology. map the genes. Specifically, they used single nucleotide polymorphism (SNP) arrays to detect variations in the genes, as well as next-generation sequencing to analyze gene expression at high sensitivity. Because these techniques generate an overwhelming amount of information, Dr. White teamed with IGSB Director of Informatics Robert Grossman, PhD, to develop a large computing infrastructure that could meet the processing and storage demands of the biological data being generated. The analyses indicated that the CUX1 gene was the most significantly differentially expressed gene in cells that had lost chromosome 7. Interestingly, the researchers also identified a CUX1 fusion transcript, in other words, part of CUX1 fused to another gene. They hypothesized that this disruption in CUX1 may contribute to the growth of abnormal blood cells, a hallmark of AML. Next, the researchers tested the gene s activity in the fruit fly. When they knocked out the CUX1 gene, some of the fruit flies developed leukemia. Collaborating with John Cunningham, MD, professor of pediatrics, the investigators carried out similar studies in mice and again observed that deficient levels of CUX1 contributed to abnormal growth of blood cells. They described their findings in an article 1 published in the February 7 issue of Blood, the American Society of Hematology s journal. The first author of the paper, Megan McNerney, MD, PhD, instructor of pathology and fellow in Dr. White s laboratory, said, This is a uniquely University of Chicago story, starting with findings from Janet Rowley and continuing over the years with an excellent group of clinicians and scientists using different technologies who worked collaboratively on myeloid leukemias. She added that further studies that reveal how CUX1 regulates other genes will help find a potential pathway that can be targeted with drugs. 1 This study was supported by the Cancer Research Foundation, the Leukemia & Lymphoma Society, the Chicago 1000 Cancer Genomes Project, and grants CA and CA40046 from the National Cancer Institute of the National Institutes of Health. Town Hall Meeting Fosters Discussions to Shape Cancer Disparities Education The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) has partnered with the largest minority-serving institution in the Midwest, Chicago State University (CSU), to develop a new cancer disparities concentration within the CSU s Master of Public Health (MPH) program and the University of Chicago Pritzker School of Medicine (PSOM). A town hall meeting was held in January on the University of Chicago campus to gather feedback and generate content for the curriculum that will prepare students for addressing cancer disparities in the Southside community. A 4-year National Cancer Institute grant is funding this effort, known as the Chicago Southside Cancer Disparities Initiative 1. The principal investigator is Karen E. Kim, MD, professor of medicine and director of the UCCCC s Office of Community Engagement and Cancer Disparities. Dr. Kim led the discussion at the town hall meeting where nearly 40 faculty, students, and health professionals from PSOM gave their input on curriculum development. Two additional town hall meetings will take place this spring at CSU and in the Southside community to gather more information about the community s needs and the capacity for cancer disparities research, outreach, and education. 1 This project is being supported by grant numbers CA and CA from the National Cancer Institute of the National Institutes of Health. Students and faculty from the University of Chicago Pritzker School of Medicine discuss planning a curriculum that will prepare students for addressing cancer disparities in the Southside community. Open Cancer Clinical Trials Patient enrollment is under way for more than 350 clinical trials at The University of Chicago Medicine Comprehensive Cancer Center. A few of our newly launched clinical trials include: n Compassionate use of veliparib for treatment of refractory fallopian tube/ ovarian cancer Gini Fleming, MD, principal investigator. n A Phase II study evaluating the efficacy and tolerability of everolimus in combination with trastuzumab and vinorelbine in the treatment of progressive HER2-positive breast cancer brain metastases Rita Nanda, MD, principal investigator. n A Phase II study of sunitinib in recurrent, refractory, or progressive high grade glioma and ependymoma tumors in pediatric and young adult patients Charles Rubin, MD, principal investigator. n TPF induction chemotherapy and veliparib a Phase I/Randomized Phase II study in patients with locoregionally advanced squamous cell carcinoma of the head and neck Jonas De Souza, MD, principal investigator. To learn more about these or any other UCCCC clinical trial, call toll-free for adult clinical trials or for pediatric clinical trials, or go to and click on Search Clinical Trials in the blue box. Pathways to Pathways to Discovery is a quarterly publication of The University of Chicago Medicine Comprehensive Cancer Center. Spring 2013, Volume 8, Number 2 The University of Chicago Medicine 5841 S. Maryland Ave., MC1140, H212 Chicago, IL Phone: Fax: by The University of Chicago Medicine Comprehensive Cancer Center. All rights reserved. Executive Editor and Writer Hoyee Leong, PhD managing editor and Writer Jane Kollmer Editorial Advisors Michelle M. Le Beau, PhD Marcy A. List, PhD Graphic Designer Adam Indyk Printing G Thomas Partners LLC Photos Lois Bernstein Photography Serena Dawn Boggs David Christopher Lloyd DeGrane Diane Ostrega Bruce Powell C. Saville Photography Cancer Program ranked #15 in nation and #1 in Illinois by U.S. News & World Report. Follow us for news, events, and other interesting information. 2

3 At the Forefront of Discovery Expanding Childhood Cancer Research in Illinois (from left) Illinois District 4 Representative Cynthia Soto, the Lutarewych family, and John Cunningham, MD, professor of pediatrics. Illinois taxpayers now have the option to contribute to childhood cancer research, thanks to the dedicated efforts of the mother of a pediatric cancer survivor. Today, advances in research and treatment have led to an 80% cure rate for pediatric cancers. However, the small percentage of national funds allotted to pediatric cancer research is declining, and cancer remains the number one disease-related cause of death for children. Laura Lutarewych knows firsthand about the importance of pediatric cancer research because her daughter was treated for leukemia at the University of Chicago Medicine Comer Children s Hospital. Now in full remission, 5-year-old Atia is the inspiration behind Laura s charity, Atia s Project Ladybug Fund, the Chicago chapter of the nonprofit organization founded by reality television star Dina Manzo to support families and children dealing with childhood cancer. The group delivers Comfort Baskets filled with thoughtful necessities to families at Comer. Although Project Ladybug has provided resources to individual families, Laura wanted to raise money for pediatric cancer on a larger scale. Last year, opportunity knocked when she learned that childhood cancer research is not among the funds that taxpayers can make charitable donations to on Schedule G of the state income tax return. With sponsorship from Illinois District 4 Representative Cynthia Soto, Laura appealed to lawmakers in Springfield and received overwhelming support. In August 2012, Governor Pat Quinn passed legislation adding the Childhood Cancer Research Fund to the state s income tax program. With this change, academic centers throughout Illinois can apply for state funds to advance the study of pediatric cancers. The primary hope is that we find a cure but, in the meantime, we need to find better therapies that spare survivors from side effects, Laura said, referencing the complex and long-term health issues faced by childhood cancer survivors, such as infertility, heart disease, and secondary cancers. Professor of Pediatrics John Cunningham, MD, said, Given that our pediatric cancer research program has over 50 people who are focused on understanding the basis of pediatric cancer and developing new therapies, we re very excited about the opportunities that these additional resources will create. He is also chief of the Section of Pediatric Hematology/Oncology and the vice-chair for research in the Department of Pediatrics. In the current funding climate, these state funds are critical for supporting, maintaining, and enhancing pediatric cancer research. (from left) John Cunningham, MD, professor of pediatrics, Dina Manzo, founder of Project Ladybug and reality TV star, and 5-year-old pediatric cancer survivor Atia Lutarewych with her mother Laura, brother Asher, and father Steve. A New Kitchen for Comer Patients and Families In December, a ribbon-cutting ceremony was held to dedicate the newly remodeled family kitchen on the pediatric oncology floor at the University of Chicago Medicine Comer Children s Hospital. The kitchen was remodeled to provide a warm, welcoming retreat where patients, their families, and guests can escape, recharge, and congregate. The project was funded by Atia s Project Ladybug Fund, a charity run by Laura Lutarewych, the mother of a little girl named Atia, who was treated at Comer for leukemia. Laura said, As we all know, the kitchen is the heart of the home, and when a child battles cancer, often the hospital becomes the family s new home. Renovations made to the kitchen space include: new pendant lighting above the island, new side lamps beside the couch, new flooring, new paint colors, new bar stools, a new couch, new end tables, new art work, a new clock, a new flat-screen TV, and more. Gala Held to Light the Way to a Cure for Cancer The University of Chicago Cancer Research Foundation Auxiliary Board (UCCRFAB) held its annual dinner in February at the Michigan Shores Club in Wilmette and raised almost $160,000, the highest amount in the event's history. More than 200 people attended the gala, which featured dinner, dancing, and a live and silent auction. The UCCRFAB is dedicated to raising funds to aid in the prevention and cure of cancer. For the second year, it is supporting the work of clinician scientists Jill de Jong, MD, PhD, assistant professor of pediatrics, Peter O Donnell, MD, assistant professor of medicine, and Michael Spiotto, MD, PhD, assistant professor of radiation and cellular oncology. The emcee was NBC5 News anchor Rob Stafford, and the auctioneer was Alyssa Quinlan. (from left to right) Michael Spiotto, MD, PhD, Jill de Jong, MD, PhD, UCCRFAB President Annette Hickman, UCCCC Director Michelle Le Beau, PhD, and UCCRF Executive Director Mary Ellen Connellan. Members of the UCCRFAB. (from left to right) Midge Wegener, Julie Sullivan, Magda Springuel, and Georgia Heisinger chaired the auction and benefit. 3

4 Pathways to Discovery State-of-the-Art Hospital Expands Cancer Care at the UCCCC In February, the University of Chicago Medicine Center for Care and Discovery (CCD) welcomed its first patients. The 10-story hospital for the future delivers complex specialty care with a focus on cancer, gastrointestinal disease, neuroscience, advanced surgery, and medical imaging. With an entire floor devoted solely to cancer, patients from the Chicago area and beyond have access to customized care provided by experts at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC). It is really exciting for us to have a modern, sophisticated hospital with leadingedge technology where our exceptional doctors and talented researchers can make discoveries that accelerate the pace of medicine, said Michelle M. Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine and UCCCC director. The new hospital is committed not only to providing innovative care, but also to enhancing the patient experience. Its 240 inpatient rooms are all private and spacious, with sweeping views of the Chicago skyline and UChicago campus. The capability of providing state-ofthe-art cancer care in a patient- and familycentered environment is tremendously exciting, said Walter Stadler, MD, Fred C. Buffett Professor of Medicine & Surgery and interim chief of the Section of Hematology/Oncology. Collaboration The hospital connects by walkway bridges to Comer Children s Hospital and the outpatient Duchossois Center for Advanced Medicine (DCAM), and is strategically located across the street from the Gordon Center for Integrative Science and the Knapp Center for Biomedical Discovery, The new Center for Care and Discovery. two dedicated research facilities housing the basic science laboratories of UCCCC researchers. The close proximity of the buildings facilitates the translation of scientific discoveries into life-saving treatments. Unlike most hospitals, the spacious CCD houses specialists side-by-side in a collaborative environment. The ability to have clinicians from multiple fields sharing resources and working in the same place toward a common purpose is unique to our new hospital, said Chair and Professor of Radiology David Paushter, MD. Collaborations are often as easy as walking down the hall. Technology Clinicians in the new hospital utilize sophisticated technologies and the most advanced diagnostic tools available, such as surgical robots to treat prostate cancer more precisely and procedural rooms that are outfitted with leading-edge imaging equipment. These rooms feature CT (computed tomography) techniques that obtain images from many angles, enabling imageguided procedures that are faster and more comfortable for the patient. For example, a two-part treatment interventional radiology approach for liver cancer that involves embolization of the tumor s blood vessels using chemotherapy combined with radiofrequency ablation of the tumor can now be performed in the same room. In addition, two neurointerventional biplane suites allow expanded capability for the non-invasive treatment of strokes, brain aneurysms, and tumors by the neurointerventional team. Procedural rooms are also equipped with monitors that integrate multiple inputs of data, such as the patient s radiologic images and tumor cytology reports. Seeing all the information on one screen makes the procedure much more efficient, said Irving Waxman, MD, professor of medicine. Piloted at DCAM for the past 2 years, this technology is now the standard of care at the CCD. At many medical centers, Dr. Waxman added, integration is an afterthought. In addition to technology that streamlines medical procedures, the new hospital also functions as a state-of-the-art platform for teaching the next generation of cancer surgeons. Students at the Pritzker School of Medicine can watch procedures via the hospital s video streaming and teleconferencing capabilities. The hospital is set up to integrate our clinical and research excellence with our teaching, said Mitchell C. Posner, MD, Thomas D. Jones Professor of Surgery. Future The CCD was designed to accommodate innovations and changing medical needs for decades to come. New cancer interventions will be based on ever-advancing technologies, such as high-intensity frequency ultrasound, which uses sound waves to treat tumor masses. Aytekin Oto, MD, professor of radiology and surgery, and colleagues have been investigating the technology as a potential treatment for prostate cancer, in addition to the current offering of laser ablation of prostate cancer guided by MRI (magnetic resonance imaging). Over time, the technology may be incorporated into practice at the CCD. Also likely in the future are hybrid procedures in which surgeons operate on a patient from both an endoscopic and traditional surgery approach. Dr. Waxman said such minimally invasive procedures could spare tissue and provide better outcomes for patients with cancer. The CCD is one of few hospitals with operating rooms that are set up for such procedures. The CCD is very progressive in terms of planning for the innovations that lie ahead, he said. A New Age of Radiation Therapy Nearly half of all cancer patients receive radiation therapy, yet why some patients benefit but others do not remains poorly understood. A team of scientists at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) hope to improve the success of radiation therapy by studying how cancer cells respond to radiation. Stephen Kron, MD, PhD, professor of molecular genetics and cell biology, has been collaborating for over a decade with Ralph Weichselbaum, MD, professor of radiation and cellular oncology, to advance new concepts in radiation therapy. Senescent Cells Dr. Weichselbaum and his colleagues had recently shown that patients whose cancer has begun to spread often respond well to treating the metastasis with a few, high doses of radiation therapy. At the same time, Dr. Kron was studying radiation using microscopy to follow chromosome damage and repair. Working together, they found that high radiation doses cause DNA damage that cannot be repaired. As a result, cancer cells stop dividing and instead age prematurely. Whether aging the cells in a tumor is a good idea or not continues to be controversial. Although the aged, senescent cells can no longer divide, there is concern that they may create inflammation that accelerates the recovery and growth of nearby cancer cells. A Cancer Vaccine Drs. Kron and Weichselbaum hypothesized that if they could selectively age cells within a tumor but manage the inflammatory signal, the radiation might bolster antitumor immunity rather than enhance cancer growth. They found that treating cancer cells concurrently with poly-adp ribose polymerase (PARP) inhibitors and radiation not only promotes senescence, but modulates inflammation so that the cells adopt the properties of a vaccine. Injected into mice, the senescent cells activated an anti-tumor immune response. The vaccine prevented new tumors and slowed the growth of existing tumors. Most Stephen Kron, MD, PhD, professor of molecular genetics and cell biology exciting, inoculating the vaccine and then treating the tumor with radiation had dramatic effects, apparently curing the mice. Dr. Kron said, Our studies indicate that the advantage of using PARP inhibitors to enhance the effects of radiation therapy may result from both intensifying the damage to the cancer cells, as well as stimulating the host s immune system to recognize the tumor as a foreign invader. These observations fit well with an emerging trend where patients receiving radiation therapy are also treated with drugs and vaccines meant to activate the patient s immune response. Kron and Weichselbaum envision applying their new insights by using a patient s own cancer cells to form a senescent cell vaccine. They hope to dramatically improve the benefits of radiation therapy, particularly in patients whose cancer has recurred and spread. Our hunt-and-kill idea combining the new immune stimulating drugs and perhaps our vaccine with image-guided radiotherapy to tackle metastasis could be quite powerful, said Dr. Weichselbaum. We have submitted grants in the hopes that we will be able to investigate these concepts further and progress to clinical trials in the near future. A Conversation With Stephen Kron, MD, PhD Professor of Molecular Genetics and Cell Biology If you were not a scientist, what would your profession be? Other options have come up along the way, but nothing has struck my fancy other than maybe trying science in another country. My friend at the University of Bordeaux has it pretty good! What is the most rewarding part of your job? As a mentor, I get to help students become successful. It more than makes up for getting only half as much done as if I could just tell them what to do. Is there a professional goal that you have not yet accomplished? Any goals I ve set and actually accomplished were just too realistic for me to know at the time. Where have you been that you feel everyone should go? An ocean beach on a windy day with no one else in sight. If you had one piece of advice for someone considering your field, what would it be? Think twice, then think again. It s too easy to confuse a love for learning about discoveries with a desire to join the struggle to make them. Who inspires you? I try hard to be someone my mentors would be proud of. Where would you like to go on your next vacation? My wife Beth and I still have a long list of wine regions we hope to visit or return to. What is your favorite way to relax? Changing out of work clothes, starting on cooking our dinner, and the first glass of wine for the evening. What was the last book you read? Maybe Kitchen Confidential, a few years ago? 4

5 Member News & updates 1 Effective Jan. 1, Walter Stadler, MD, Fred C. Buffet Professor of Medicine and Associate Dean for Clinical Research, assumed the role of Interim Chief of the Section of Hematology/Oncology in the Department of Medicine. He took over the position after the departure of Richard L. Schilsky, MD, professor of medicine, who is now serving as the inaugural chief medical officer for the American Society of Clinical Oncology. 2 The American Cancer Society has presented Yu-Ying He, PhD, assistant professor of medicine, with a Research Scholar Award. This 4-year award supports investigator-initiated projects across the cancer research continuum. Dr. He s research will explore the molecular mechanisms of skin carcinogenesis in organ transplant recipients. She is studying how Cyclosporin A, an immunosuppressive drug used to prevent rejection following organ transplantation, increases the risk for skin cancer by inhibiting the repair of and the response to DNA damage from ultraviolet B (UVB) exposure, and promoting cell survival and growth. 3 Michael R. Bishop, MD, has been appointed professor of medicine and director of the hematopoietic stem cell transplant program at the University of Chicago Medicine, effective November 15. Dr. Bishop is an authority on the use of stem cell transplantation as a treatment for lymphoma, leukemia, and multiple myeloma. 4 Victoria Villaflor, MD, was promoted to associate professor of medicine. Her research aims to understand the clinical and molecular characteristics of upper aerodigestive tract malignancies. She is an expert in novel cancer therapies and is also involved in the development of molecularly targeted agents for the treatment of these cancers. 5 Bakhtiar Yamini, MD, was promoted to associate professor of surgery. In addition to his clinical work, Dr. Yamini studies cellular DNA damage response and the treatment of malignant brain tumors in children and adults. 6 Karen E. Kim, MD, was promoted to professor of medicine. Her research interests include chemoprevention and screening for populations at high risk for colorectal cancer. As the director for the UCCCC Office of Community Engagement and Cancer Disparities, Dr. Kim is developing culturally adapted awareness and screening programs for underserved and minority populations in the UCM surrounding communities. 7 Glenn Randall, PhD, was promoted to associate professor of microbiology. His laboratory investigates the roles of virus-host interactions in replication and pathogenesis, focusing on the hepatitis C virus. 8 Samuel Volchenboum, MD, PhD, assistant professor of pediatrics, has received $40,000 from the University of Chicago Office of Technology and Intellectual Property s Innovation Fund to improve the efficiency of clinical trials. The Innovation Fund, which supports proof-of-concept projects, will allow Dr. Volchenboum to build a prototype webbased system that will generate clinical trial protocols, streamline the process of opening studies at treatment centers, 1 integrate studies with electronic medical records, issue work orders, and automatically create the reports required by hospitals, pharmaceutical companies, and the U.S. Food and Drug Administration. A book co-edited by Patrick La Riviere, PhD, associate professor of radiology, was published by Taylor & Francis in December. Emerging Imaging Technologies in Medicine surveys emerging technologies that have potential clinical use in the future. 9 Anna Di Rienzo, PhD, professor of human genetics, has been elected to the board of directors for the Genetics Society of America. She will serve a 3-year term. 10 Chuan He, PhD, professor of chemistry, was selected to receive a $400,000 grant from Gabrielle s Angel Foundation for Cancer Research through its new Collaborative Research grant program. Working with Ari Melnick, MD, of Weill Cornell Medical College, and Ross Levine, MD, of Memorial Sloan-Kettering Cancer Center, Dr. He is searching for the molecular basis of acute myeloid leukemia and developing targeted therapies to help patients. 11 Kay Macleod, PhD, associate professor in the Ben May Department for Cancer Research, was named as a senior editor of the American Association for Cancer Research s journal, Molecular Cancer Research. At the Forefront of Discovery The Cancer Research Foundation has awarded Young Investigator Awards to five scientists at the University of Chicago, all of whom are UCCCC members. The awards are designed to nurture young scientists in the pursuit of independent hypotheses and to enable them to develop the preliminary data necessary to successfully compete for major research grants. The awardees and their research proposals are as follows: Jane Churpek, MD, assistant professor of medicine, Characterizing the Contribution of Mutations in Cancer Predisposition Genes to Therapy-related Myeloid Neoplasms James L. LaBelle, MD, PhD, assistant professor of pediatrics, Defining the Mechanism and Therapeutic Targets of BIM BH3-Mediated Cell Death in Diffuse Large B-cell Lymphoma 12 Hongtao Liu, MD, PhD, instructor of medicine, Prophylactic Donor Lymphocyte Infusion after T Cell Depleted Allogeneic Stem Cell Transplant in High-Risk Patients with Hematologic Malignancies 13 Manish Sharma, MD, assistant professor of medicine, Disease Progression Models for Biomarkers and Patient-Reported Outcomes in Cancer Patients 14 Fabrice Smieliauskas, PhD, assistant professor of health studies, Off-Label Drug Use in Oncology: Policy, Unintended Consequences, and Comparative Effectiveness Four UCCCC members received funds from the American Cancer Society Institutional Research Grant, which was awarded to the institution to provide seed money for newly independent investigators for pilot projects. The awardees and their research proposals are as follows: 15 Alexander Langerman, MD, assistant professor of surgery, Patient Centered Treatment Decisions in Oropharyngeal Cancer 16 Aasim Padela, MD, MSc, assistant professor of medicine, The Influence of Religious Concepts and Values upon the Decision to Pursue Breast Cancer Screening among American Muslims (Dr. Padela also received the 2012 Ibn Sina Award from the Compassionate Care Network for his contributions to the field of Islamic medical ethics.) 17 Gordana Raca, MD, PhD, assistant professor of medicine, Genomic Profiling of Myeloid Sarcoma Fabrice Smieliauskas, PhD, assistant professor of health studies, Off-Label Drug Use in Oncology: Policy and Unintended Consequences for Clinical Research

6 Pathways to Discovery Research Highlights The following represent some of the research accomplishments of UCCCC members published November 2012 January MicroRNA-30c Sensitizes Breast Cancer Cells to Chemotherapy Researchers identify a new micro-rna that regulates chemotherapy response in breast cancer. Micro-RNAs are small RNA molecules that influence gene expression. The molecular mechanisms underlying chemotherapy resistance are poorly understood. Geoffrey Greene, PhD, Virginia and D.K. Ludwig Professor of the Ben May Department for Cancer Research, Olufunmilayo Olopade, MBBS, FACP, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, Eileen Dolan, PhD, professor of medicine, and colleagues including Huiping Liu, MD, PhD, demonstrated that microrna-30c, a prognostic biomarker for breast cancer, sensitized breast cancer tumors in animals to various chemotherapeutic drugs. Their research also defined the micrornamediated signaling network responsible for regulating chemoresistance. These findings will help facilitate the development of novel therapeutic strategies to combat chemoresistance in breast cancer. (Bockhorn et al., Nat Commun 4:1393, 2013) This study was supported by The University of Chicago Cancer Research Foundation Women s Board, National Institutes of Health (NIH) T90 Regenerative Medicine Training Program (DK ); Department of Defense Breast Cancer Research Program (W81XWH ); Paul Calabresi K12 Award (1K12CA ); National Cancer Institute (K99 CA ); the Chicago Fellows Program at the University of Chicago; the University of Chicago Clinical and Translational Science Award (UL1 RR024999); The University of Chicago Medicine Comprehensive Cancer Center Pilot Project Funds; BSD Imaging Research Institute Pilot Research Projects Using Animal Imaging; UCMC/ Northshore Collaborative Funds; a Segal Grant and the Virginia and D. K. Ludwig Fund; funds from the Sociedad Española de Oncología Médica (SEOM); the Breast SPORE at University of North Carolina (5-P50 CA ); NIH grants 1R21 CA159066, R21 CA139278, U54 CA126524, and P01 CA139490; the Pharmacogenetics of Anticancer Agents Research Group (UO1 GM61393); the Breast Cancer Research Foundation; the Breast SPORE (P50 CA ); the Doris Duke Charitable Foundation; and the Cancer Center Support Grant (CA014599). Researchers Define How a Signaling Complex Regulates Cell Death A new study reveals how the IκB kinase complex (IKK) prevents cell death. IKK is a key regulator of inflammation, immune responses, and tumorigenesis. Anning Lin, PhD, professor of the Ben May Department for Cancer Research, and colleagues studied the signaling mechanisms by which IKK regulates programmed cell death, known as apoptosis. The researchers discovered that IKK inhibits tumor necrosis factor (TNF-α)-stimulated apoptosis by at least two distinct mechanisms involving activation of a survival factor, NF-κB, and inhibition of a proapoptotic protein, BAD. These results change the prevailing paradigm of how IKK regulates apoptosis, which for the past 15 years was thought to function only through NF-κB. Since directly targeting IKK or NF-κB will have severe side-effects in clinic, the new finding may provide novel strategies in combating cancer and other diseases. (Yan et al., Cell 152:304-15, 2013) This work was supported by the National Basic Research Program of China (2012CB910801), National Natural Science Foundation of China ( ), Chinese Academy of Sciences (SIBS2010CSP001), and National Institutes of Health grant numbers CA100460, CA128114, and GM Genetic Variation Contributes to Ethnic Disparities in Neuroblastoma A team of UCCCC investigators identified a genetic variation that contributes to ethnic disparities in high-risk neuroblastoma and survival. African American patients with neuroblastoma have a higher prevalence of highrisk disease and poor survival compared with white patients. To identify genetic variants that may account for this observation, the researchers examined DNA from more than 2700 children diagnosed with neuroblastoma who were enrolled in a Children s Oncology Group clinical trial. They found that a genetic variant within the sperm associated antigen 16 (SPAG16) gene was associated with high-risk disease in patients of both African and European ancestry. Results from this study emphasize the role of genetic variation in predicting disease outcome in patients with neuroblastoma. Susan Cohn, MD, professor of pediatrics, Nancy Cox, PhD, professor of medicine, M. Eileen Dolan, PhD, professor of medicine, Navin Pinto, MD, instructor of pediatrics, and colleagues including Eric Gamazon, PhD, were among the study authors. (Gamazon et al., J Natl Cancer Inst 105:302-9, 2013) This work was supported by the National Institutes of Health grant numbers U01 GM61393, R01 MH090937, U01 HG005773, R01 MH090937, and R01 CA078545; Alex s Lemonade Stand; Children s Neuroblastoma Cancer Foundation; Elise Anderson Fund; Neuroblastoma Children s Cancer Society; Little Heroes Cancer Research Foundation; St. Baldrick s Foundation; and the Cancer Research Foundation. Researchers Identify Gene Involved in Hormone Therapy-Resistant Prostate Cancer Elevated expression levels of the embryonic stem cell regulator, Sox2, lead to prostate cancer relapse after hormone therapy. Androgen deprivation therapy is the mainstay of prostate cancer treatment, yet cancer relapse is a significant problem due to the growth of hormone therapy-resistant prostate cancer cells. Donald Vander Griend, PhD, assistant professor of surgery, Russell Szmulewitz, MD, assistant professor of medicine, and colleagues discovered that elevated expression levels of Sox2 result from loss of androgen receptor-mediated repression during hormone therapy and subsequently lead to cancer re-growth and metastasis of prostate cancer cells. Inhibiting the function of Sox2 has the potential to aid in the treatment of prostate cancer and prevent relapse after hormone therapy. (Kregel et al., PLoS One 8:e53701, 2013) This work was supported by a Pilot Award from the National Cancer Institute (P50 CA090386); SPORE in Prostate Cancer at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the University of Chicago Medicine Comprehensive Cancer Center; an American Cancer Society Institutional Research Grant (ACS-IRG, #IRG ); Cancer Center Support Grant (P30 CA14599); The Brinson Foundation; the Alvin Baum Family Fund; the University of Chicago Cancer Research Foundation Women s Board; an HHMI: Med-into-Grad Fellowship ( ); a Cancer Biology Training Grant (T32-CA09594); and an Immunology Training Grant (AI ). MicroRNA-495 Functions as a Tumor Suppressor in Leukemia New research shows that microrna-495 acts as a tumor suppressor by targeting leukemia-related genes in acute myeloid leukemia (AML) with mixed lineage leukemia (MLL) rearrangements. Jianjun Chen, PhD, assistant professor of medicine, and colleagues demonstrated that the expression of microrna-495 is significantly lower in MLL-rearranged AML compared with non-mll-rearranged AML and normal tissue samples. Forced expression of microrna-495 inhibited leukemogenesis by preventing expression of the PBX3 and MEIS1 genes. These results broaden our understanding of the mechanisms underlying MLLrearranged leukemia, a disease associated with poor survival, and facilitate the development of new therapeutic strategies. Additional UCCCC researchers involved in the study include Janet Rowley, MD, DSc, Blum-Riese Distinguished Service Professor of Medicine, UCCCC Director Michelle Le Beau, PhD, Arthur and Marian Edelstein Professor of Medicine, Richard A. Larson, MD, professor of medicine, and Sandeep Gurbuxani, MBBS, PhD, assistant professor of pathology. (Jiang et al., Proc Natl Acad Sci USA 109: , 2012) This work was supported by the National Institutes of Health grant numbers R01 CA127277, R01 CA Sub-Award, P01 CA40046, and P30 CA Cancer Center Support Grant (CCSG); a Leukemia and Lymphoma Society Translational Research Grant; an American Cancer Society Research Scholar grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Fidelity Foundation; the University of Chicago Committee on Cancer Biology Fellowship Program; a Leukemia and Lymphoma Society Special Fellowship; and Gabrielle s Angel Foundation for Cancer Research. Molecular Profile of Head and Neck Cancer Predicts Sensitivity to Chemotherapy Researchers find that a specific mutation in squamous cell carcinoma of the head and neck (SCCHN) predicts sensitivity to gefitinib, a chemotherapeutic agent that targets the epidermal growth factor receptor (EGFR). The majority of patients with SCCHN who undergo therapy with EGFR inhibitors become resistant to treatment over time. Ezra Cohen, MD, associate professor of medicine, Tanguy Seiwert, MD, assistant professor of medicine, Olufunmilayo Olopade, MBBS, FACP, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, and colleagues evaluated the sensitivity of SCCHN cell lines to the EGFR inhibitor gefitinib. They found that cells harboring mutations that result in constitutively active AKT, a downstream signaling protein, were resistant to treatment. Although these results need to be validated in tumor tissue, the findings may potentially help refine patient selection and treatment decisions for SCCHN. (Young et al., Mol Oncol published online ahead of print, November 2012) This work was supported by an ASCO Career Development Award and National Institutes of Health CTSA award (UL1 RR024999). CT Imaging Predicts Prognosis in Patients with Mesothelioma A new study shows that changes in disease volume from CT scans collected during treatment are associated with survival in patients with malignant pleural mesothelioma. Samuel Armato, PhD, associate professor of radiology, Hedy Kindler, MD, associate professor of medicine, and colleagues obtained serial CT scans during the course of standard chemotherapy for 81 patients. They showed that increases in disease volume, extracted by segmentation using a semiautomated process, predicted poor patient survival and were associated with clinical factors, including disease histology. These results demonstrate that continuous measurements of disease volume are prognostically significant in patients with mesothelioma. This study is complementary to the team s work on correlating CT measurements of tumor thickness with patient survival (Labby et al., J Thorac Oncol 7: , 2012 and Labby et al., Ann Oncol published online ahead of print, November 2012) This work was supported by the University of Chicago Medicine Comprehensive Cancer Center; the Raine Medical Research Foundation; the US National Institutes of Health grant numbers T32 EB and R01 CA102085; the Simmons Mesothelioma Foundation; the Kazan Law Firm s Charitable Foundation; the National Health and Medical Research Council, Australia; and the Cancer Council Western Australia. 6

7 At the Forefront of Discovery Drawing Strength from Cancer Survivors Amalia Rigoni of Olympia Fields thought life was going well until she was diagnosed with breast cancer. Under the mentorship of a breast cancer survivor, combined with world-class treatment from experts at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC), she faced her disease with courage and determination. She would later use her experience to help others overcome the shock and confusion of a cancer diagnosis. Dodging a Bullet In 2000, Amalia noticed a thickening in her right breast, but her mammogram results appeared normal. She still felt something was wrong, so she sought advice from the medical director at the insurance company where she worked. He advised her to insist on undergoing a fine-needle aspiration biopsy to investigate the suspicious tissue. As someone who worked in health insurance, I was used to advocating for people; now it was my turn, she said. This time, Amalia got an answer. At 42, she had advanced breast cancer. Although the news changed her world instantly, she Having the support of other survivors often helps cancer patients process the emotions and navigate through the health system. Amalia Rigoni felt she had dodged a bullet. She wondered what would have happened if the cancer was not discovered. While she was still reeling from the news, she received a call from Joyce, her brother s coworker and a breast cancer survivor, who offered support during her journey. Amalia had many decisions to make, so she sought a second opinion from the UCCCC. Seeing that a team of multidisciplinary specialists discussed her case, she knew she was in good hands. As scared as I was in the beginning about breast cancer, when I got to the [UCCCC], it was like the weight was lifted off my shoulders, Amalia recalled. She had surgery to remove the tumor and 10 cancerous lymph nodes. She also underwent chemotherapy and radiation therapy, followed by anti-estrogen therapy. Helping Others Thirteen years later, Amalia is still cancerfree. Amalia is a shining example of a young patient with high-risk cancer who was treated aggressively and has done great, said Nora Jaskowiak, MD, associate professor of surgery, who cared for Amalia, along with Gini Fleming, MD, professor of medicine. She beat a poor prognosis. Amalia said she was able to get through breast cancer because of Joyce, her doctors, her loved ones, and other survivors. She became passionate about helping women realize that a diagnosis of breast cancer is not an automatic death sentence. In 2003, she joined the Y-ME National Breast Cancer Organization as a bilingual outreach educator and hotline coordinator. Having the support of other survivors Amalia Rigoni is a 13-year survivor of breast cancer. often helps cancer patients process the emotions and navigate through the health system, Amalia said. My experiences with the thousands of women I have spoken with on the hotline and met in person have helped me understand that advocacy is the best weapon we have to fight this disease until a cure is found. Focus on: Core Facilities Facility Supports Development of New Immune-Based Therapies for Cancer Immunotherapy, which harnesses the patient s immune system to fight disease, provides a promising avenue for effective cancer treatments. However, many of these new treatments require specialized testing, as well as special expertise and facilities for manufacturing. At the University of Chicago Medicine Comprehensive Cancer Center (UCCCC), investigators interested in conducting novel immunotherapy clinical trials can take advantage of the unique services provided by the Human Immunologic Monitoring-current Good Manufacturing Practice (HIMcGMP) Facility. The HIM-cGMP Facility manufactures clinical-grade immunotherapy products, including cell-based cancer vaccines that boost a patient s immune response against their tumor. These products are made in a special clean room environment where the air quality is regulated and staff are required to dress in sterile gowns. A major role of the Facility is to ensure compliance with U.S. Food and Drug Administration regulations known as current Good Manufacturing Practices (cgmps) on safety, identity, purity, and strength of the manufactured products being administered to patients. Using cells as drugs follows similar safety requirements as pharmaceuticals, but the challenges are different, said Amittha Wickrema, PhD, associate professor of medicine and scientific co-director of the HIM-cGMP Facility. The Facility also helps researchers perform assays, including analyses of cytokines in serum, and gene expression analyses in tumor biopsies, to measure the immune response induced by various therapeutic interventions in patients participating in clinical trials. The specialized analyses for these studies benefit from interfacing with other UCCCC shared core facilities, such as the Genomics Core Facility, the Cytometry and Antibody Technology Facility, and Human Tissue Resource Center, to analyze and correlate the data with clinical outcomes. This information helps determine, for example, the optimal dose of a vaccine needed to elicit the appropriate immune response. There are a lot of questions to ask within the framework of personalized medicine, said HIM-cGMP Facility Scientific Co-Director Thomas F. Gajewski, MD, PhD, professor of pathology and medicine. We are always searching for biomarkers that can tell us which patients respond to which therapy and if they don t, then why not. A suited-up technician prepares a peptide vaccine for melanoma patients in the HIM-cGMP Facility. The Facility also offers customized assistance to investigators who are interested in translating their laboratory ideas into clinical research protocols. To date, immunotherapy trials have been explored in melanoma, pancreatic cancer, leukemia, prostate cancer, and kidney cancer. Dr. Gajewski said the portfolio is expanding. He added that the recruitment of a national expert, Michael Bishop, MD, professor of medicine, to lead the University of Chicago Medicine hematopoietic stem cell transplant program will result in novel treatments for lymphoma, leukemia, and multiple myeloma. One of Dr. Bishop s research interests is to find ways to enhance immune effects of transplanted cells against cancer. By manufacturing therapeutic cancer vaccines and measuring biological responses, the HIM-cGMP Facility plays a central role in developing new targeted immunotherapeutics for cancer. UCCRF Associates Board Holds Annual Ball in the Style of Gatsby The University of Chicago Cancer Research Foundation (UCCRF) Associates Board held its annual fundraising event in March. More than 250 people attended the Gatsby Gala at Room 1520 in Chicago. The evening featured cocktails, appetizers, dancing, and a silent auction, raising nearly $49,000 to support cancer research at the UCCCC. The UCCRF Associates Board is an organization of young philanthropists dedicated to raising the funds necessary to aid in the prevention and cure of cancer. Christine Castro, Natalie Platt, and Mallory DeHaven Laurel Buchi-Fotre, Carrie Leman, Palmer Conti, Gwendolyn Smith, Danielle Quivey, and Allisha Benjamin Gala co-chairs Stephanie Werner, Margaux Harrold, Ruthie Neumeier, and Associates Board President Katherine Crouch Gala attendees were dressed up in 1920s fashion. 7

8 Pathways to Discovery UCCRF Women s Board Supports the Early Work of Talented Cancer Researchers The University of Chicago Cancer Research Foundation (UCCRF) Women s Board has raised over $14 million to support cancer research at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) since it was founded in The Women s Board is one of the UCCRF s three fundraising boards. The Board consists of 73 women from a wide range of ages and geographical locations who volunteer their time and generosity for the various fundraising events that take place throughout the year. What makes us different from other organizations is that our funds go solely for research, said Women s Board President and melanoma survivor Jill Pollock. Most members have been personally affected or touched by cancer, and they are interested in the research aspect. Some of the Board s fundraising initiatives include the Chicago Hunter Derby, a world-class equestrian competition, and the Annual Appeal mailing. In the past, they hosted the Dream Home Preview at the Merchandise Mart, featuring rooms decorated by Chicago s top designers. The annual Grand Auction and gala is the largest fundraising effort of the Women s Board, raising $700,000 in Featured in publications such as Town and Country magazine and with sponsors that have included Verdura and Ralph Lauren, this perennially sold-out gala is considered to be one of the finest charity events in the country. Pollock said one of the Board s goals for the coming years is to gradually increase its membership and identify new ways of raising funds in advance of the Grand Auction s 50th anniversary celebration in Philanthropic support serves as a significant source of funding to researchers at the UCCCC who need seed money to start their projects. Funds provided by the Women s Board have enabled new scientists to generate enough research data to compete for federal research grant funding. We look to support projects that would not otherwise have funding, said Pollock. This is the investigator who needs $20,000 or $30,000 just to get their idea started. The Board has been a longtime supporter of research by new faculty in the Ben May Department for Cancer Research, which was created by Nobel Laureate Dr. Charles Huggins, a pioneer in hormonal therapy for prostate cancer. Researchers have continued to build on Dr. Huggins s work in basic cancer biology research. For example, Professor Geoffrey Greene, PhD, has made great progress in understanding the molecular mechanisms underlying the promotion of breast cancer by estrogen and targeting the estrogen receptor protein for the treatment and prevention of breast cancer. The Women s Board has also supported the Committee on Cancer Biology, which is training our future generation of cancer researchers. In addition, the Board has invested in several shared research Jill Pollock, UCCRF Women s Board facilities that provide President UCCCC researchers with leading-edge technologies and expertise to perform innovative research and drug discovery, including the Human Tissue Resource Center, which collects, stores, and distributes research-quality human biospecimens. The dedication and support of the Women s Board has been instrumental in advancing UCCCC laboratory research which is essential for guiding the development of personalized and more effective cancer prevention and treatment strategies. save the dates! The University of Chicago Cancer Research Foundation (UCCRF) presents a list of upcoming fundraising events: Women s Board Chicago Hunter Derby Sunday, September 8, 2013 Annali Farm, Antioch UCCCC and UCCRF Shubitz Prize Recognition Dinner Monday, October 7, 2013 The University of Chicago Gleacher Center Women s Board Grand Auction Saturday, November 9, 2013 Four Seasons Hotel For more information, please contact Pathways to Spring 2013 In this issue 1 The UCCCC is recommended for renewal as a Comprehensive Cancer Center by the National Cancer Institute. 2 Researchers identify a gene that contributes to acute myeloid leukemia. 3 A parent takes steps to expand funding for childhood cancer research in Illinois. 4 Experts collaborate to advance the field of radiation therapy. The University of Chicago Medicine 5841 S. Maryland Ave., MC1140 H212 Chicago, IL The new Center for Care and Discovery provides state-of-theart cancer care. 7 A breast cancer survivor helps others overcome the shock and confusion of a cancer diagnosis. Support cancer research through the UCCRF: /donations

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