Discoveries Fall 2010 by ULH webmaster

FALL 2010

DISCOVERIES

FACES OF CANCER

A publication of the

J A M E S G R A H A M BROWN CANCER CENTER

letter from the director Dear Friends, On the cover of this issue of Discoveries, you find portraits from the “Faces of Cancer” campaign developed by the Kentucky Cancer Program at the James Graham Brown Cancer Center (see story, page 9). These patients represent different hometowns, backgrounds, ages, interests, and cancer types; but they share a serious medical problem which has brought them to the Brown Cancer Center.

INSIDE THIS ISSUE...

These patients were all treated in the Brown Cancer Center’s multidisciplinary clinics. The distribution of our patients is very similar to the cancer prevalence rate in Kentucky: • 14 percent of Brown Cancer Center patients are treated for breast cancers, while 13 percent of Kentucky’s cancer patients have breast cancer; • 14 percent of our patients are treated for lung cancer, while 19 percent of Kentuckians with cancer have a lung-related diagnosis; • 13 percent of our patients have gastrointestinal cancer, while 9 percent of Kentuckians with cancer do. The list goes on. (See charts to the right.) The mission of the James Graham Brown Cancer Center is to help relieve the disproportionate pain and suffering borne by Kentuckians from cancer. In order to do this, it is our goal to generate new knowledge relating to the nature of cancer, and to create new and more effective approaches to prevention, diagnosis and therapy, while delivering medical advances with compassion and respect to cancer patients throughout our region.

IN THE NEWS page

Breast Care Accreditation

ARTICLES page

The Fight Within Our teams of clinical and research scientists work together every day to honor this mission, and become the “other” faces of cancer.

Not Your Grandfather’s Surgery

Trent Discoveries

page

Brown Cancer Center patient mix – 2008 Blood & Marrow Melanoma Lung

Discoveries Brown Cancer Center, 2nd Floor 529 S. Jackson Street Louisville, KY 40202 www.browncancercenter.org Editor Kathy Keadle Contributors Tom Fougerousse Diane Konzen Albert Leggett Marion Whelan Lauren Williams

Gastrointestinal Gynecologic

Head & Neck

KY Cancer Prevalence – American Cancer Society 2010 Blood & Marrow Melanoma

Discoveries is published for the friends, faculty and staff of the James Graham Brown Cancer Center.

GenitoUrinary

Breast

At the Brown Cancer Center, we believe in and invest in promising translational research, research which will make a difference for our patients within the forseeable future. For our scientists, the clinic as well as the laboratory is a place for discovery and collaboration.

Lung

Breast Genito-Urinary Gastrointestinal

Gynecologic

Over the last decade, we have invested millions of dollars making our clinics the most advanced and most comfortable treatment facilities in the country. At the same time, we have also invested millions more in our research programs, ensuring that our scientists and clinicians have every tool they require to work together effectively, efficiently and creatively. This dedication to work across disciplines is leading to the discovery of novel new treatments and important new information about the nature of tumors that can be exploited in clinical trials. In this work, we see our patients not only as individuals who need our service – although they are, and we are honored to serve. We see our patients as key partners in the ongoing quest to unlock the mysteries of cancer in ways that will allow us to minimize its devastating effects on our patients, our families and our communities. They are truly the heroes in the “battle against cancer.” I invite you to read on to learn more about the work of our physicians and scientists on behalf of cancer patients everywhere, and about a few of the patients who have been the beneficiaries of our efforts.

Donald M. Miller, MD, PhD Director of the James Graham Brown Cancer Center

Discoveries................

A publication of the

J A M E S G R A H A M BROWN CANCER CENTER

welcome... BROWN CANCER CENTER WELCOMES DR. SHIAO WOO, CHAIR OF RADIATION ONCOLOGY AT UofL Shiao Y. Woo, former professor of radiation oncology and section chief of the division of central nervous system and pediatric cancers at the University of Texas - MD Anderson Cancer Center, has been appointed endowed professor and chairman of the Department of Radiation Oncology at the University of Louisville School of Medicine. “Professor Woo is an internationally recognized authority on the treatment of brain, spinal cord and pediatric cancers and adds to the University of Louisville and the James Graham Brown Cancer Center’s strengths in the neurosciences,” said Edward Halperin, MD, Dean of the UofL School of Medicine. “He is superbly trained, has obtained extensive clinical and research experience at the world-class MD Anderson Cancer Center of Houston, is widely published and serves on the board of directors of the Pediatric Radiation Oncology Society. His selection as chair, following our naming of new chairs in the departments of neurology, biochemistry and medicine, is a clear demonstration of growing national recognition of our clinical programs.” Woo completed an internal medicine residency and obtained board certification in internal medicine in the United Kingdom. He subsequently completed a residency in pediatrics and a fellowship in pediatric and adolescent hematology-oncology at Georgetown University Hospital, and a residency in radiation therapy at Stanford University Medical Center. He is board certified in pediatrics, pediatric hematologyoncology and radiation oncology. He has served on the faculties of Georgetown University, Tufts University, Baylor College of Medicine and MD Anderson, where he has been a professor since 1996. Woo has served as residency director for the departments of radiation oncology at both MD Anderson and Baylor and he also was associate chairman for research at Baylor. Woo’s areas of clinical and research interest are tumors of the blood, bone, nervous system and soft tissue in children and adults. He has published more than 120 articles in peerreviewed journals and authored more than 20 book chapters. “I am excited to be joining the vibrant UofL medical and scientific community and I believe there will be many growth opportunities for the department clinically and academically over the coming years,” Woo said. “I am looking forward to collaborating with colleagues in our department and others to do our part to advance the field of cancer care and research at UofL and beyond.”

DR. JESSE ROMAN NAMED CHAIR FOR UofL DEPARTMENT OF MEDICINE Dr. Jesse Roman, formerly professor of medicine at Emory University in Atlanta, joined the University of Louisville as chairman of the Department of Medicine at the University of Louisville School of Medicine in September 2009. “When we sought a worthy successor to our longstanding Chairman of Medicine, Dr. Richard Redinger, I envisioned a physician-scholar-teacher of the first rank; someone with a commitment to the ideals of academic medicine,” Edward Halperin, MD, Dean of the UofL School of Medicine, said. “We have hired such a person.” “Search committee chairman Dr. Donald Miller, director of the James Graham Brown Cancer Center, committee vice-chair Dr. Kerri Remmel, and the entire search committee, evaluated an exceptional pool of candidates for this very important position within the School of Medicine.” Roman received his medical degree from the University of Puerto Rico School of Medicine. He completed his residency at the San Juan Veterans Affairs Medical Center. He then joined the Pulmonary and Critical Care Medicine Fellowship Program at Washington University School of Medicine in St. Louis. He joined the Emory faculty in 1991. During Roman’s seven-year tenure as division director at Emory, the division witnessed a dramatic growth in its faculty which doubled in size, expanded its fellowship program now funded by two NIH-sponsored institutional training grants, increased its research portfolio eight-fold and attracted several national multi-center awards, standardized medical critical care delivery at four hospitals, and established several new clinical-research enterprises in lung disorders. He has published extensively in the areas of lung tissue remodeling and inflammation and on the role of extracellular matrices in the control of lung resident cell functions and tumor cells. He is the author of more than 120 scientific writings and his work has been continuously funded by federal organizations. His national reputation is evidenced by his membership in VA and National Institutes of Health study sections. He has served on important committees of the American Thoracic Society and the American College of Chest Physicians. Roman serves as a member of the steering committee of the NIH-sponsored Idiopathic Pulmonary Fibrosis Clinical Research Network and the scientific advisory committee of the Pulmonary Fibrosis Foundation. Roman also serves as President of the Southern Society for Clinical Investigation. He is a member of the editorial board for Clinical and Translational Science, the Open Biology Journal and Chest.

FALL 2010

welcome... NEW FACULTY The Brown Cancer Center welcomes the following faculty members who have joined us in our efforts to improve the lives of people with cancer.

Doug Coldwell, MD Professor of Radiology, UofL Department of Diagnostic Radiology, Dr. Coldwell, a specialist in radioembolization, will work with multiple Brown Cancer Center clinics. Dr. Coldwell completed a clinical fellowship at MD Anderson Hospital and Tumor Institute. He received his MD from the University of Texas at Galveston, and completed his residency at the Milton S. Hershey Medical Center in Hershey, PA.

Glenda Callender, MD Assistant Professor of Surgery, UofL Division of Surgical Oncology, Brown Cancer Center Breast Multidisciplinary Team. Dr. Callender completed a Surgical Oncology and Endocrine fellowship at MD Anderson Hospital and Cancer Institute in Houston, TX. She received her MD from Harvard Medical School, and completed her surgical residency at the University of Chicago Medical Center.

Zhong-Bin Deng, PhD Instructor of Medicine, UofL Department of Medicine, Division of Oncology/Hematology, Brown Cancer Center Tumor Immunobiology Research Program. Dr. Deng completed a research fellowship at the University of Alabama at Birmingham. He received his PhD in Immunobiology at the School of Life Science, Soochow University, Suzhour, P.R. China, and his MS from the College of Animal Science and Veterinary Medicine, Yangzhou University, P.R. China.

Rajesh K. Sharma, PhD Instructor of Medicine, UofL Department of Medicine, Division of Oncology/Hematology, Brown Cancer Center Structural Biology Research Program. Dr. Sharma recently completed a research fellowship with UofL’s Institute for Cellular Therapeutics. He completed his PhD in Biotechnology at Banaras Hinu University, Varanasi, India, and his Master’s of Science at Jawaharial Nehru University in Delhi.

Victor van Berkel, MD Instructor of Surgery, UofL Division of Thoracic Surgery, Brown Cancer Center Lung Cancer Multidisciplinary Team. Dr. van Berkel completed his surgical fellowship at BarnesJewish Hospital. He received his MD from Washington University in St. Louis and completed his surgical residency at Massachusetts General Hospital.

Kavitha Yaddanapudi, PhD Instructor of Medicine, UofL Department of Medicine, Division of Oncology/Hematology, Brown Cancer Center Molecular Targets Research Program. Dr. Yaddanapudi completed a post-doctoral research fellowship at Columbia University’s Mailman School of Public Health prior to being named an Associate Research Scientist there. She completed her PhD in Biochemistry at the Indian Institute of Science, Bangalore, India, and her MS at Madurai Kamaraj University, Madurai, India.

Amy Quillo, MD Assistant Professor of Surgery, UofL Division of Surgical Oncology, Brown Cancer Center Breast Multidisciplinary team. Dr. Quillo completed a surgical fellowship in endocrine and breast surgery at the Mayo Clinic. In addition to leadership in breast surgery, she will be pursuing programmatic development in endocrine surgery. She received her MD at the University of Louisville School of Medicine and completed her surgical residency at UofL affiliated hospitals.

Rebecca Redman, MD Assistant Professor, UofL Department of Medicine, Division of Medical Oncology, Brown Cancer Center Gastrointestinal Multidisciplinary Team. Dr. Redman completed her fellowship in Hematology Oncology at Duke University. Dr. Redman received her MD from the University of Wisconsin, completed her residency at University of North Carolina Hospitals, and her fellowship in hematology/oncology at Duke University Medical Center.

Discoveries................

A publication of the

Top: Red & Black Ball event organizers Dani Porter; Marie Porter; Aimee Webb, PhD; Ellie Porter Billops; and Joy Billops enjoy a beautiful evening. Right: Charla Young, Steve St. Angelo and Kevin Shurn at the Red & Black Ball.

J A M E S G R A H A M BROWN CANCER CENTER

Brown Cancer Center GETS PRESTIGIOUS DISTINCTION IN BREAST CARE The University of Louisville’s James Graham Brown Cancer Center is the first center in Kentucky to be granted a full three-year accreditation by the National Accreditation Program for Breast Centers (NAPBC), a program administered by the American College of Surgeons. Accreditation by the NAPBC is given only to those centers that have voluntarily committed to provide the highest level of quality breast care and that undergo a rigorous evaluation process and review of their performance. Kentucky First Lady Jane Beshear took part in an announcement of the honor at a press briefing on Wednesday, Jan. 20, at the James Graham Brown Cancer Center’s Breast Care Center. UofL President James Ramsey was also on hand to celebrate the achievement. “This is terrific news for the women of Kentucky,” said Mrs. Beshear. “To have a breast care center in our state recognized as one of the top in the country no doubt provides a great deal of comfort and confidence in the minds of our people.” “This distinction represents an acknowledgment of the dedication shown by our many breast care clinicians, support staff, counselors and researchers to providing only the most outstanding and comprehensive care to our patients,” said Donald Miller, MD, PhD, director of the James Graham Brown

Cancer Center at UofL. “We are honored to be among the fine institutions nationwide that are NAPBC-accredited, and this distinction underscores and invigorates our commitment to our patients, now and in the future.” The distinction is given after a survey process during which centers must demonstrate compliance with 27 standards established by the NAPBC for treating women who are diagnosed with the full spectrum of breast diseases, from breast cancer to benign lesions that require medical evaluation for treatment options. Three standards critical for accreditation are strong breast program leadership, a multidisciplinary approach to disease evaluation and management, and a breast cancer conference program featuring active collaboration between individuals involved in all aspects of a breast patient’s care, to ensure that optimal treatment strategies are created in every individual case. Other standards cited include proficiency in clinical management, research, community outreach, professional education and quality improvement. The standards apply to all disciplines involved in breast care, including radiology, pathology, medical oncology, surgical oncology, radiation oncology, plastic surgery, genetics and nursing. UofL’s mobile mammography unit was noted as an effective tool for community outreach, and ongoing quality

“This is terrific news for the women of Kentucky. To have a breast care center in our state recognized as one of the top in the country no doubt provides a great deal of comfort and confidence in the minds of our people.”” Jane Beshear Kentucky’s First Lady improvement initiatives were cited in areas including medical oncology and radiation oncology. Use of minimally invasive biopsy techniques for diagnosis, and disease or patient-specific targeted therapies when appropriate, were noted as well. “NAPBC accreditation means a great deal to us because it is a recognition of our commitment to what’s at the heart of breast care,” said Barb Kruse, associate director of multidisciplinary clinics at the James Graham Brown Cancer Center. “And that is the patients.” ■

RED & BLACK BALL RAISES AWARENESS, FUNDS FOR CANCER EDUCATION More than 300 people celebrated cancer education and prevention at the 4th Annual Red & Black Ball – for the love of Harriett on February 13, 2010. Proceeds from the Red and Black Ball benefit the Harriett B. Porter Cancer Education and Outreach Programs to reduce cancer health disparities in the African American community. Several initiatives including cancer education, screening, patient support and many faith-based programs have been implemented. The 2010 Robin Award for Community Spirit was presented to Dr. Beverly Gaines-Phipps. More than a dozen dedicated sponsors, including presenting sponsor Superior Maintenance Co., and ruby sponsor E-On U.S., supported the 2010 event. Through event sponsorship, ticket sales and auctions, the Red & Black Ball netted more than $65,000.

Brenda Sweatt laughs with Representative Darryl Owens at the Red & Black Ball.

FALL 2010

advanced cancer therapeutics COLLABORATES WITH BCC RESEARCH SCIENTIST IN CANCER METABOLISM Advanced Cancer Therapeutics (ACT), a privately held company dedicated to bringing new anti-cancer therapies to market, signed an exclusive agreement to leverage the translational research expertise of Jason Chesney, MD, PhD, associate professor, department of medicine at the University of Louisville’s James Graham Brown Cancer Center, to identify new clinical candidates for the prevention and treatment of cancers against two key cancer metabolic targets. As part of this agreement, over the next twenty-four months, Dr. Chesney will work with ACT to further refine and advance the preclinical candidates and backup compounds against two exciting and novel cancer targets that are known as 6-phosphofructo-2-kinase/fructose2,6-biphosphatase 3 (PFKFB3) and Choline Kinase (CK), both key cancer metabolism targets identified by

most solid tumors including lung, breast, ovarian, brain and prostate cancers. ACT’s medicinal chemists have developed over 150 rationally designed, potent compound inhibitors that inhibit choline kinase enzymatic activity, cell proliferation and tumor growth in xenograft studies.

Dr. Chesney as essential for cancer cell growth. ACT previously obtained worldwide exclusive licenses from the Brown Cancer Center for these two cancer metabolic programs summarized below: ■ PFKFB3: High glucose consumption is commonly observed in cancer cells. As PFKFB3 is the enzyme involved in an irreversible step of glycolysis, ACT synthesized over 100 rationally designed inhibitors of this protein. Scientific evidence suggests that inhibitors of the PFKFB3 enzyme block glucose uptake in cancer cells therefore inhibiting cancer cells proliferation and tumor growth. ■ Choline Kinase: Choline Kinase, the enzyme responsible for the phosphorylation of choline into phosphocholine, is over expressed in

“Dr. Chesney has long been a thoughtleader in cancer metabolism and his research has always been high quality and cutting-edge,” said Randall Riggs, President & CEO of ACT. “We are delighted to collaborate with him as we move closer to selecting novel clinical candidates that may prove to be lifesaving therapeutics for cancer patients.” In addition, Dr. Chesney is the Associate Director for Translational Research and the Medical Director of the Clinical Trials Office at the Brown Cancer Center. ■

UofL RESEARCH BUILDING GETS HIGH MARKS FOR BEING GREEN

The building has received a Gold LEED (Leadership in Energy and Environmental Design) certification, one of the council’s highest designations.

2000. Businesses, schools, government agencies, stores and homes can apply for certification through the program, but must meet strict criteria before they can qualify for a certified, silver, gold or platinum rating.

Only 33 research buildings in the United States have earned the same certification, and UofL’s eight-level, 288,000-square-foot building located just behind the James Graham Brown Cancer Center at 505 S. Hancock St. is believed to be the largest, said Stephen Cotton, assistant director of university planning, design and construction.

UofL’s building earned a total of 41 LEED credits, two more than the 39 credits needed to achieve a Gold rating, Cotton said.

The use of energy-saving natural light was a key factor in designing the $143 million, state-funded biomedical research facility, which opened in October. A reflective roof keeps heating costs down while special louvers and light shelves control the amount of sun entering the building. Another system in the building turns off electric lights when they aren’t being used.

The Clinical and Translational Research building is home to approximately 90 principal investigators and their teams, mostly conducting cancer research. The building also houses core laboratories including flow cytometry, microarray, advanced diagnostic imaging services and tumor bank to facilitate this work.

Condensed water from the air conditioner is used to irrigate the building’s landscaping, and built-in showers and bicycle racks make it easier for employees to avoid driving to work.

A large statue honoring the support of Kosair Charities was also installed in the courtyard in front of the CRT building to honor the group’s $12 million, four-year commitment to the facility and the pediatric oncology-related research that will go on inside.

The University of Louisville's Clinical and Translational Research (CTR) Building has received a top rating from the U.S. Green Building Council, a non-profit agency based in Washington that promotes sustainability in building design, construction and operation.

Dr. Larry Cook, Executive Vice President for Health Affairs (l) and Dr. James Ramsey, UofL President (r), give a tour of the LEED Certified Clinical and Translational Research building.

The U.S. Green Building Council established the LEED rating system in

Discoveries................

A publication of the

J A M E S G R A H A M BROWN CANCER CENTER

$3.15 million grant FROM HELMSLEY CHARITABLE TRUST WILL SUPPORT BCC RESEARCH PROGRAM IN OWENSBORO

Funding from the National Institutes of Health will help the University of Louisville develop, implement and evaluate an interdisciplinary oncology palliative care education program.

A $3.15 million grant from the Leona M. and Harry B. Helmsley Charitable Trust to support the UofL James Graham Brown Cancer Center and cancer research taking place in Owensboro will be used to create an endowed faculty position for a nationally recognized researcher in plant-based pharmaceuticals, as well as two new faculty positions to expand and enhance the research program. The grant will be matched with state “Bucks for Brains” funding to bring more than $4.5 million to the Owensboro Cancer Research Program (OCRP).

"Palliative care is now viewed as much more than end-of-life care. It focuses on ongoing quality of life and well-being and is integral to the treatment of cancer patients from time of diagnosis throughout the trajectory of the illness," said Mark Pfeifer, MD, chief medical officer for UofL Health Care and principal investigator on this project.

The grant was celebrated at a media event held August 5, 2010, in Owensboro. The OCRP is devoted to unlocking the potential of plant-made pharmaceuticals. The research and drug development program takes advantage of the natural products and agricultural industries in the Owensboro region to address diseases impacting the area, especially those that are tobacco-related. Ultimately, the partnership’s goal is to create less expensive drugs for cancer prevention and treatment. “We are excited to see the fine work of the James Graham Brown Cancer Center and Owensboro Medical Health System expand through this public/private initiative,” noted John Codey, trustee of the Helmsley Charitable Trust. “The promise of plant-based pharmaceuticals and vaccines to dramatically improve healthcare at reduced cost is both exciting and critically important.” The tobacco-based process involves inserting genes needed for drug development into the tobacco genome. The leaves are then harvested, processed and purified to derive a key ingredient. Projects underway at OCRP include the development of a plant-based vaccine to prevent HIV; the development of a second-generation cervical cancer vaccine grown in tobacco plants in order to make it affordable to millions of women worldwide; understanding how changes in the calcium-signaling pathway of stem cells impacts the

NIH GIVES MORE THAN $1.5 MILLION FOR INTERDISCIPLINARY ONCOLOGY PALLIATIVE CARE EDUCATION PROGRAM

Helmsley Charitable Trust Chairman John Codey

development and continued growth of lung cancer cells; and determining whether the interaction of the heavy metal cadmium with tobacco-derived carcinogens contributes to the development of lung cancer in smokers. “Plant-based pharmaceutical systems have a number of advantages,” said Dr. Donald Miller, director of the James Graham Brown Cancer Center. “The costs for starting materials are low, which translates into a lower production cost. The materials are readily available, meaning that we are able to increase production levels relatively quickly. Additionally, plant-based therapies have fewer issues with potential contamination than those utilizing other materials such as animal or human pathogens.” UofL President James Ramsey attended the celebratory event in Owensboro. “When we established this program in partnership with Owensboro Medical Health System in 2006, we envisioned other significant organizations joining us in our effort to create and develop novel approaches to preventing and treating cancer,” Dr. Ramsey said. “This gift from the Helmsley Charitable Trust moves our vision forward and is recognition for the importance of the work taking place here.” ■

"Almost every family has or will face a loved one needing cancer care, including curative treatment, symptom control and end-of-life care," he said. "Patients and families need the united services of physicians, nurses, chaplains and social workers, and there is a real need for health professionals to be educated in an interdisciplinary manner to prepare them for the real-world team environments they experience once they are in practice." The multidisciplinary team working on the program will have representatives from the schools of medicine, nursing and social work and from the clinical pastoral education programs of three Louisville hospitals. "We are all doing great work and are dedicated to the patients…. If we are able to work more seamlessly together, drawing on each other's capabilities more fluidly, we will be able to offer even better care to patients," said Terry Singer, dean of the Kent School of Social Work. NIH will pay the grant over five years. The team will devote the first year to the design of an innovative and integrated oncology palliative care curriculum that will include eight learning activities, and it will be required for all third-year medical students, third- and fourth-year nursing students, master's level social work students and clinical pastoral education residents. "The receipt of this grant is a great distinction for UofL," said Larry Cook, MD, executive vice president for health affairs at UofL's Health Sciences Center. "It's important to note that our faculty came up with this idea right here at UofL and won this funding through a highly competitive process."

FALL 2010

BCC LAUNCHES NEW PATIENT PROGRAM The Brown Cancer Center’s clinical mission is dedicated to treating the whole patient, not merely the cancer itself. With that in mind, the Brown Cancer Center recently introduced the utilization of a new Patient Navigation Program. This program is offered to assist cancer center patients and their families throughout their treatment process.

Ms. Jones and trained volunteer navigators help patients connect with any needed support, such as nutritional guidance, chaplaincy services, counseling or social work. The team also helps locate and direct patients to the many other services and support that may help patients, their caregivers and families deal with cancer diagnoses. Laura Jones (left), Patient Navigator, and Dr. Donald Miller (right), BCC Medical Director, with Mr. David Klein (center). Mr. Klein is the donor for the Patient Navigator position.

Laura Jones, the program’s first Patient Navigator, is responsible for helping patients and their families find, organize and use the numerous resources, treatment services and support services available to them. David Klein, cancer survivor, generously donated the funds that have been used to create the Patient Navigator position. “Mr. Klein believes in building relationships between patients and their navigators,” said Ms. Jones. “He wants patients to have navigators in the Brown Cancer Center who can help with information and resources.”

BCC receives accreditation WITH COMMENDATION FROM THE COMMISSION ON CANCER Dr. Donald M. Miller, director of UofL’s James Graham Brown Cancer Center, announced in July that the facility received a Three-Year Accreditation with Commendation from the Commission on Cancer (CoC), the group’s highest level of accreditation possible. “We are pleased that the CoC has recognized and endorsed our commitment to quality care, ongoing improvement, and public accountability for the care and services we provide,” Miller said. “The Brown Cancer Center continues to serve as a unique cancer care, research and support resource for the region.” The Brown received accreditation with commendation as a Teaching Hospital Cancer Program – the only such program in the region – following an onsite evaluation by a physician surveyor. The award recognized excellence in the areas of cancer committee leadership, cancer data management, clinical services, research, community outreach, and quality improvement. According to the CoC, only 42 percent of cancer centers in the U.S. receive three-year accreditation with commendation.

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Less than a year ago, the Brown also became the first center in Kentucky to receive CoC accreditation as a breast care center. Established in 1922 by the American College of Surgeons (ACS), the CoC is a consortium of professional organizations dedicated to improving survival rates and quality of life for cancer patients through standard-setting, prevention, research, education, and the monitoring of comprehensive, quality care. According to Mary Wilson, CTR, the team leader for cancer registry, the center has maintained its accreditation status for more than 20 years. “We report to the CoC on an ongoing basis in real time on the status of all of our programs, and they can send a surveyor at any time, so we are in a constant state of readiness,” Wilson explained. “I am extraordinarily confident in and proud of our cancer care, research, and outreach programs. When the surveyor arrives, we simply say, ‘Welcome!’” ■

A publication of the

According to the ACS, receiving care at a CoC-accredited program ensures that a patient will have access to: ■ Comprehensive care, including a range of state-of-the-art services and equipment ■ A multispecialty, team approach to the best treatment options ■ Information about ongoing clinical trials and new treatment options ■ Access to cancer-related information, education and support ■ A cancer registry that collects data on type and stage of cancers and treatment results and offers lifelong patient follow-up ■ Ongoing monitoring and improvement of care ■ Quality care close to home

J A M E S G R A H A M BROWN CANCER CENTER

KCP update Faces of Cancer recently appeared at the 2010 Kentucky State Fair.

FACES OF CANCER Cancer survivors across Kentucky are sharing their experiences through Faces of Cancer, a project of the Kentucky Cancer Program. Regional offices are creating photographic essays featuring local people for exhibition in hospitals, banks, galleries, churches, and other venues. In reflection of Kentucky’s diverse population, the project features individuals of many different ages, races, socioeconomic classes, and cancer types. Faces of Cancer travels throughout the district and opens in each community with a ceremony featuring patient

testimonials of survival; remarks by physicians and local officials; an unveiling of the pictures; and a special reception. Photographers have generously donated their time and talents to make the project a reality. Faces of Cancer debuted in Louisville at the annual Cancer Survivor Celebration at the James Graham Brown Cancer Center. Survivors who have participated in the project view Faces of Cancer as an opportunity to share inspirational thoughts to encourage newly diagnosed

patients and to honor health care providers. Faces of Cancer recently appeared at the 2010 Kentucky State Fair where cancer survivors were invited to sign a banner depicting the faces and to share their personal stories. Two Faces of Cancer books have been published and a new one will be released in the spring for the James Graham Brown Cancer.

TREATING TOBACCO USE AND DEPENDENCE IN KENTUCKY HOSPITALS An innovative project is underway in select Kentucky hospitals for treating tobacco use and dependence among in-patients. Under contract with the Kentucky Department for Public Health, the Kentucky Cancer Program has developed a toolkit for use by administrators, educators, and clinicians to develop a systems approach to addressing one of the state's most challenging public health concerns.

University of Louisville Hospital, University of Kentucky Medical Center, and St. Elizabeth’s Hospital in North Kentucky participated in the pilot project to create strategies for patient intervention. The program includes an online continuing education program, a video on Kentucky Tobacco Quit Line, and a video featuring comments from administrators like Jim Taylor and Kay Lloyd from University Hospital who address nicotine addiction in the hospital

setting and share their perspectives on web-based training for employees. Several hospitals in other communities are now being given the opportunity to evaluate the toolkit for final changes prior to a statewide distribution. The program is expected to be a valuable resource to hospitals as they prepare for impending changes in the Joint Commission’s requirements for tobacco cessation counseling.

HORSES AND HOPE AT THE WORLD’S CHAMPIONSHIP HORSE SHOW Thanks to a gift from the United Professional Horsemen’s Association Pink Ribbon Program, Horses and Hope was able to provide breast cancer education and mammograms to workers in the American Saddlebred industry

during the World’s Championship Horse Show, held in conjunction with the Kentucky State Fair, August 22-28, 2010. Horses and Hope, a partnership between Kentucky First Lady Jane Beshear and the Kentucky Cancer Program, the state mandated cancer control program housed at the James Graham Brown Cancer Center, aims to increase breast cancer awareness, education, screening and treatment referral among Kentucky’s horse industry workers and their families.

The United Professional Horsemen’s Association is an association of professional horsemen and horsewomen who united in 1968 to improve the horse show industry. “We’re so grateful to the UPHA for this gift which has allowed us to bring our program to other segments of the equine industry,” said Connie Sorrell, director of KCP. “We have many success stories of people who have been screened or treated as a result of Horses and Hope and we want to continue to expand the project to reach new groups because we really believe it makes a difference.”

FALL 2010

grateful patients honor a caregiver PHILANTHROPY STRIVING TO SUPPORT THE MARGIN OF EXCELLENCE Gifts have long been a financial foundation for the Brown Cancer Center and have helped the organization provide the best health care to patients. A new donation program has been created to help produce further contributions for the future – the Grateful Patients program. While continuing to seek financial assistance for the Brown Cancer Center, University Hospital will also be included in the Grateful Patients program. It has been built to give patients and families the opportunity to give back if they desire. Their financial gifts can acknowledge an exceptional experience or honor front line caregivers, who are the people saving and impacting lives.

them – to get them water, to talk to them or just to answer simple questions about parking or the cafeteria. Donations will provide support for: ■ Innovative opportunities to transform health care through science and research ■ Exceptional patient and family care ■ Community-based health care programs such as health screenings and educational events ■ Health care resources to the underserved ■ Physician-funded projects and programs to improve health care ■ Exceptional program-specific services

The Grateful Patients program is not just about money; if patients want to make a financial contribution, or honor a care giver we encourage that gesture. However, it is about us as an organization just being there for

Philanthropy helps to explore new treatment options that have worldwide impact and enable University Hospital and the Brown Cancer to provide the highest level of care. ■

For about 15 years I have had the honor to serve as a Trustee of the James Graham Brown Foundation and for almost 25 years as a member of the board of the University of Louisville’s James Graham Brown Cancer Center. I would like to share with you some observations I have made as a result of these positions. The progress of the James Graham Brown Cancer Center over the years is quite impressive. Over the past 30 years, the Brown Cancer Center has not only been a local treatment option for people in Louisville and throughout the state, but it has become a significant contributor to the biomedical research community. The center's strategic plan and the recruitment of new faculty have placed heavy emphasis on investigational areas that will lead to new approaches to prevention, diagnosis and treatment of cancer. This emphasis on translation is now paying off. Brown Cancer Center scientists have several novel cancer treatments in early phase clinical trials with more than a dozen others in preclinical stages. Importantly, there also has been a strong emphasis on prevention. A study on the use of berries to prevent lung cancer in high-risk individuals began in late 2006. The focus on "patient-oriented" research has created a collaborative environment in which both basic scientists and clinical

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The Development staff is eager to answer any questions about the Grateful Patients program. We can be contacted at 502-562-4651. This is a tremendous opportunity to create a non-traditional revenue stream to support those needs that support our mission of providing exceptional care.

investigators place a premium on work that will have an impact on cancer prevention and treatment.

Dear Colleagues:

Bill Kingston Director of Development, BCC

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The advances taking place in research and clinical care are attracting attention from philanthropic organizations throughout the nation. Most recently, the Helmsley Charitable Trust provided significant financial support of the Brown Cancer Center’s research efforts via the Owensboro Cancer Research Program. This program seeks to develop plant-based pharmaceuticals for the prevention, treatment and cure of various forms of cancer and other diseases that contribute to the development of cancers. Philanthropic support is necessary as the Center strives to attract more top researchers and physicians in the effort to earn Comprehensive Cancer Center designation from the National Cancer Institute. Our Cancer Center is well-positioned to continue its development into one of the pre-eminent cancer centers in the nation, if not the world. Almost 30 years ago, The Brown Foundation joined with community leaders to found the James Graham Brown Cancer Center, giving form to the vision of superior care for cancer patients here in Louisville. I believe the dreams of those founders is being achieved and continues to warrant our support. Yours in Service,

Bob Rounsavall Bob Rounsavall, III Member, Regional Cancer Center Corporation Board Trustee, University of Louisville

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the future of cancer research BCC METABOLOMICS RESEARCH OFFERS NEW INSIGHTS Any sports team functions best when teamwork is at play. Players pass the ball to one another to move it down the court or field and into the goal. So what happens when one super-performer with fancy footwork runs away with the ball? The rest of the team is left in the dust. And cancer in the body is a similar thing. Cancer cells are super-performers, they are able to grow and reproduce without knowing when to stop, or pass the ball to someone else. Unless we can get control of these rogue over-performers, we have a hard time preventing and controlling cancer’s growth. That’s where metabolomics comes in.

Metabolomics is defined broadly as a group of technologies applied to understanding how an organism differs between the healthy state and the diseased state, or how it responds to drug therapy, nutrition and other external influences. To understand this, a team of scientists and physicians in the James Graham Brown Cancer Center are looking at the process of metabolism within cells, in order to determine how they work, normal and cancerous. “Cancer isn’t a single disease, and even in the cancers of one organ, there are many subtypes that behave differently from one another, and are treated quite differently in the clinic,” said Andrew Lane, PhD, metabolomics team member and associate director of the Center for Regulatory and Environmental Analytical Metabolomics (CREAM), which is a partnership between the University of Louisville’s Department of Chemistry and the Brown Cancer Center. “Unfortunately there are many different ways for a normal cell to become cancerous, making individualized approaches more complex. Their metabolism provides a detailed readout

“There has not been great progress in lung cancer with respect to survival over the past several decades. We've had marginal gains. Metabolomics research is a whole new avenue that's only begun to be explored.” Michael Bousamra, MD Head of Thoracic Surgery

of what cells are doing and it is possible, using our methods, to determine the biochemical differences between say, a lung tumor and non-cancerous lung in the same individual. We expect these differences to reflect the specific molecular pathologies and thus guide optimal treatment strategies.”

The process begins None of the work being done by the metabolomics team would be possible without the patients who consent to participate in the studies by allowing their tissue to be analyzed. Patients like Teresa Secor, 42, a mother of three from Sellersburg, Ind., who came to see Michael Bousamra, MD, head of thoracic surgery at the Brown Cancer Center and member of the metabolomics team, with suspicious lesions in her left lung. “I developed ulcers in my stomach from taking ibuprofen after a hysterectomy and when they did a CT scan of my stomach, they saw some spots on my lung,” Secor said. A needle biopsy confirmed they were cancerous. “Dr. Bousamra asked me if I wanted to participate in the study, and explained that they would use my bloodwork and tissue samples for research, and that I’d get a substance intravenously during surgery that would help them when they looked at the tissue,” she said. “I had a lot of questions, but they were very patient with me and answered every one. I was okay with it. If I could help get us that much closer to better treatments or a cure, I wanted to be part of it.” “Metabolomics is a relatively understudied field in cancer and I’ve been very successful in recruiting patients into the study,” said Bousamra,

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who has recruited over 90 patients to this study. “They are basically consenting to allow their tissue to be studied after it is removed. When you think about the gains we can make by studying tumor metabolism, it’s easy to get excited.” While being prepped for surgery, Secor received a glucose solution, made up of carbon, hydrogen and oxygen, delivered intravenously. The glucose's carbon content, normally made up of six neutrons and six protons per atom – carbon-12 – is engineered to have one more neutron in each carbon atom, which makes it both heavy and magnetic. This "enriched" carbon-13, or c-13, serves as a “tracer,” a guide by which to follow the path of metabolism through cancerous and non-cancerous cells.

Technology speeds things along Once the patient’s tissue is removed, it travels to the lab, where CREAM members use sophisticated technology to compare the process of metabolism in the normal lung tissue to the tissue in the lung tumor. The tracers are heavier than the normal atom and are magnetic, and so they can easily be detected by mass spectrometry which weighs atoms, and nuclear magnetic resonance spectroscopy, which measures magnetism of atoms, giving the researchers a comprehensive profile of how the c-13 tracer was metabolized over a period of time, in cells, tissues or whole organisms. The technology has made a big difference in the speed at which the investigators can make their discoveries. “The technology we use was originally designed for application in the field of proteomics, the study of protein structure and function,” said Richard Higashi, PhD, associate director of mass spectrometry development at CREAM. “We hijacked the technology when we recognized the power it held to analyze our data. Ten years ago, it would have

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Teresa Fan, PhD, director of the Center for Regulatory and Environmental Analytical Metabolomics, and Richard Higashi, PhD, the center's associate director of mass spectrometry.

taken a dozen labs a dozen years to compile the information we’re now able to generate in just a few months.”

Center, have been working with Lane since the early 1980s studying the principles of metabolism.

The team compares what they find to specimens that have not been enriched by c-13 to make sure the labeled and unlabeled processes are the same, Higashi said.

“Metabolomics can be applied to anything that gets biochemically transformed,” Fan said, “and it is a great avocation to apply this to cancer cell research.”

“We can describe the metabolic pathways present in the lung cancer cell to get a sense of how it came to be, and compare that against the same patient’s normal tissue,” he said.

Recent publications in peer-reviewed journals have demonstrated important findings and given clues to the process of development of non-small-cell lung cancer, the most common type of the disease. One study described a mechanism of action in lung cancer cells that could be valuable for determining which early stage cases of the disease might be sensitive to a particular chemotherapy and which might not.

The promise of metabolomics Senior team members Higashi and Teresa Fan, PhD, director of CREAM, who both have joint UofL appointments in chemistry and at the Brown Cancer

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“We’re at the tip of the iceberg,” Fan said. “By comparing the normal versus cancerous cells in the same patient, we’re really understanding what lung cancer is and the data are very rich.” Said Bousamra, “There has not been great progress in lung cancer with respect to survival over the past several decades. We’ve had marginal gains. Metabolomics research is a whole new avenue that’s only begun to be explored.”

An opportunity for collaboration As part of the move toward collaboration between investigators at UofL and the University of Kentucky, the metabolomics team has joined forces with Rolf Craven, PhD, at UK and submitted a proposal for funding for a collaborative project. “Dr. Craven is studying signaling pathways that allow tumor cells to spread and survive outside of their normal environment and they identified a protein that is induced in cancer and has been implicated in tumor formation,” Fan said. “We saw Dr. Craven’s poster at the UofL / UK Lung Cancer Summit last fall and recognized that this protein might play an important role in lung cancer metabolism.” She said, “We looked at our data and found that in some of our patients, this protein was, in fact, overexpressed. We found an opportunity for collaboration which was the purpose, of course, of the Summit and which really drives the whole field of cancer research forward more quickly.” Opportunities to speed discovery are especially important to patients like Teresa Secor. “Being a part of this research was my way of fighting back against my cancer because it was something I could say ‘yes’ to,” she said. “I’m going to help

them, I pray, get an answer. I’m putting my piece into the puzzle, and I hope my piece helps put it all together.”

Lung cancer and beyond Based on their work with lung cancer, the metabolomics team has turned their attention to breast cancer as well, using the same approach.

FACES OF CANCER ”There is always hope...even when you think there is no hope.” Janice Fulton Lung Cancer Clarksville, IN

The researchers say that breast cancer is both a good scientific model and a very important target because it’s the leading cancer in women. Because breast cancer usually appears in one breast while the other breast remains healthy, it’s a natural model for using a patient as her own control. “We think of our work as directed serendipity,” Higashi said. “We design experiments with the idea that we’ll enhance our chances of stumbling across something that could change the landscape of cancer treatment and prevention.” Metabolomics, he said, is a huge advancement for the field of cancer research. It is playing a role in translational research, with Brown Cancer Center members Jason Chesney, MD, PhD, Brian Clem, PhD, Sucheta Telang, MD, and others using metabolomics to study the efficacy of possible drug compounds, identified the computer-based drug discovery system led by John Trent, PhD. Compounds such as one that is potentially effective in targeting the enzyme that makes phosphocholine, a molecule found to be more abundant in tumors than in the surrounding non-cancerous tissue. The biotechnology firm Advanced Cancer Therapeutics (ACT) has invested in this project, another step toward the

potential development of a more effective therapy for lung and other cancers. “All of the answers to our questions about cancer are in those tissue samples,” said Higashi. “It’s up to us to make sense of it all so we can truly realize one of the missions of this place, which is to create the knowledge to heal.” ■

Patient-based metabolomics studies require the coordinated efforts of many people, and the team wishes to acknowledge the unsung contributions of nursing and clinical staff and the study volunteers, as well as the financial support of the Kentucky Lung Cancer Program, the National Science Foundation, the Kentucky EPSCoR Program, the National Institutes of Health, and local sources including the Robert W. Rounsavall, Jr. Family Foundation and the Drive Cancer Out Campaign.

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the fight within DR. JUN YAN FINDS WAYS TO TRAIN THE BODY TO FIGHT CANCER MORE EFFECTIVELY

The enthusiasm and passion Jun Yan, MD, PhD has for his work is obvious from the moment he begins to discuss it. Dr. Yan is a scientist in the Tumor Immunobiology program, whose goal is to understand the role of the immune system and inflammation in the development and progression of cancer, and to harness the power of the immune system to develop novel immune-based therapies and vaccines against all types of cancer. “We need to understand how these tumors escape from immune system attack,” Dr. Yan explains. “Conversely, we need to establish some approaches that can augment or trigger the immune system to recognize tumor cells and eventually eradicate this devastating disease.” Specifically, Dr. Yan’s research focuses on tumor immunotherapy mediated by anti-tumor antibodies that bind to tumors and activate complement, and which have been shown to be enhanced by co-administration of yeast-derived beta-glucan.

“We found that antibody therapy alone is not very effective, but they can work when administered with an activating agent,” Dr. Yan explains. “Today, nine antibody therapies are now approved. The culture has changed.”

and translational research program, and I was intrigued by the opportunities and strong leadership here.”

After his fellowship, Dr. Yan joined the research faculty at Yale University, but received a call from Dr. Ross three years later.

“Jun had been very involved with the use of beta glucan as a cancer immunotherapy modality that is completely novel and important,” said Donald M. Miller, MD, PhD, Brown Cancer Center director. “His work has had and will continue to have terribly important implications down the road.”

“He asked me to return to Louisville again,” Dr. Yan remembers. “The cancer center was developing a strong clinical

The leadership was just as enthusiastic about Dr. Yan’s return.

“With this approach, we are essentially educating the immune system by marking the tumor as ‘other’ rather than ‘self,’ equipping the body to fight the disease more effectively.” Jun Yan, MD, PhD Tumor Immunobiology Program

“With this approach, we are essentially educating the immune system by marking the tumor as ‘other’ rather than ‘self,’ equipping the body to fight the disease more effectively.”

Circular Path Dr. Yan first began his work at the Brown Cancer Center in the late 1990s when he came to Louisville for his postdoctoral fellowship with the University of Louisville’s division of experimental immunology and immunopathology in the department of pathology. His mentor was Gordon Ross, PhD, and the two developed a professional rapport that would set the stage for years of fruitful collaboration. During that time, Dr. Yan completed work in which indigenous beta glucan was used to mimic pathogen through co-administration with antibodies – an unusual approach at the time.

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FACES OF CANCER 2010 JULEP BALL SCIENTISTS OF THE YEAR

”We’re not promised tomorrow so live like it’s your last day.”

Numerous volunteers, sponsors, celebrity guests and cancer center staff have worked together since 2005 to donate more than $1.2 million through a Derby-eve gala to the James Graham Brown Cancer Center. At the 2009 event, the new name “Julep Ball,” was introduced to more than 1,000 guests and volunteers.

David Howard Hodgkin’s Lymphoma Louisville

The Julep Ball, presented by Southern Wine & Spirits, remains a major component of the Brown Cancer Center’s annual fundraising and awareness campaigns, funding critical early stage cancer research and providing patient support services to thousands of cancer patients from across the country.

Hit the Ground Running Upon his return, Dr. Yan worked diligently to improve the therapeutic efficacy of the new therapies in a variety of tumor types, including breast, lung, colon, and liver, as well as lymphoma. His work showed that the most promise was shown in the treatment of lymphoma, colon, breast and lung cancers. The research work conducted in the laboratory was spotlighted by the NIH as “significant.”

The Ball also gives the cancer center an opportunity to recognize scientist(s) whose accomplishments are particularly noteworthy. The 2010 Julep Ball Scientist of the Year Award was presented to Hari Bodduluri, PhD, (right) UofL Professor of Microbiology and Immunology, and leader of the Brown Cancer Center’s Tumor Immunobiology Program; and Jun Yan, MD, PhD, (left) UofL Associate Professor of Medicine, and scientist in the Tumor Immunobiology Program.

With pre-clinical work complete, two Phase I trials were completed in 2007-08 to test the toxicity in both single dose and multiple/escalating dose treatments. Trials revealed the therapy to have an extraordinarily safe profile. “We can infuse this polysaccharide and re-educate the immune cells and those cells can be primed and activated to eradicate cancer,” Dr. Yan says. “It has been almost 15 years, and this polysaccharide is now in Phase II clinical trial.” Working with Egan-based pharmaceutical company BioThera, the UofL licensed therapy is being tested in multiple centers in the Far East, with initial results presented at the December 2009 ASCO meeting. Dr. Yan and his colleagues are not taking time to celebrate the recognition, however. “A second approach we now use in the lab is to study whether we can increase the body’s immune cells – so we’ve developed a tumor vaccine,” Dr. Yan says. “Basically the tumor vaccine will augment anti-tumor immune cells and those cells serve as surgeons. They can go to the field and remove the cancer cells.”

Dr. Jun Yan runs his lab in the Clinical and Translational Research Building. According to Dr. Yan, the success is due in large part to the research environment at the Brown Cancer Center. “I think that we are very fortunate to work in the Brown Cancer Center because this environment provides us all the infrastructure and all the necessary collaborations. All my colleagues worked together as a team to bring this drug from bench to now – eventually – to the bedside.” ■

The goal of the Tumor Immunobiology Program is to understand the role of the immune system and inflammation in the development and progression of cancer, and to harness the power of the immune system to develop novel immune-based therapies and vaccines against all types of cancer. The program has 21 members who come from a wide variety of disciplines ranging from basic immunology to structural biology and molecular imaging. This breadth is a major strength of the program and allows its members to address complex and technically challenging projects. Drs. Bodduluri and Yan are working on multiple projects, including basic research that is leading to development of novel vaccines for cancers and infectious diseases.

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a collaborative spirit JASON CHESNEY LEADS BCC’S TRANSLATION RESEARCH EFFORTS healthy immune systems, are a major obstacle to cancer therapies, particularly cancer immunotherapies and vaccines. Metastatic melanoma tumors, in particular, are especially resistant to these therapies.

Sitting in his office in UofL’s brand new Clinical and Translational Research Building overlooking the James Graham Brown Cancer Center and the entire Health Sciences Center, Jason Chesney, MD, PhD, discusses the multi-center Phase II clinical trial for which he serves as Principal Investigator.

“We saw a presentation at the SSCI about work with ONTAK – a drug that was already on the market – targeted for T cell lymphoma,” Dr. Chesney remembers. “It sparked the question, ‘Would it kill regulatory T cells?’ Could we use this drug to boost immunity against cancer and increase effectiveness of vaccines?”

“We will include up to 15 cancer centers,” he explains. “We currently have nine, including MD Anderson and the University of Chicago, with the Brown Cancer Center serving as the lead.” His current leadership role over a randomized, multi-center 80 patient trial began with an idea that he developed along with Donald Miller, MD, PhD, Brown Cancer Center Director, at the 2005 Southern Society for Clinical Investigation (SSCI) meeting in New Orleans.

When he returned to Louisville, Dr. Chesney wrote the protocol for a study of 16 patients from the Brown’s multidisciplinary melanoma clinic. “The company and government funding sources were initially skeptical,” notes Dr. Chesney. “Luckily at the Brown, lack of external funding doesn’t automatically squash an idea that may have merit.”

Regulatory T cells, while crucial to

According to Dr. Miller, “We have been able to use philanthropy to fund projects like this. We believe that the important advances will come from work that may not be of interest to the usual funding sources. The Brown Foundation support,

“It has been particularly gratifying to be a part of the process of researchers working closely with clinicians.” Jason Chesney, MD, PhD Associate Director for Translational Research

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KLCRP, Human Medical Improvement Fund, and others have allowed us to fund selective promising approaches – although not all of them work out as well as the ONTAK study.” The Brown Cancer Center funded the Phase II trial, including specimen collection and all administration. In fact, the Brown Cancer Center’s Clinical Trial Office has a staff of more than 20 that manage scores of trials, educate patients, and manage regulatory requirements. “It really is a testament to the role of philanthropy in leading-edge research,” Dr. Chesney continues. “Because donors believe in what we’re doing, we can fund initial work, have the necessary team to support creative clinical ideas, and gather critical data to get external funding sources on board – ultimately benefiting patients.”

Collaborative Spirit This environment of scientific collaboration and freedom is exactly what wooed Dr. Chesney to Louisville from Cornell University in New York, which was, he thought, a “perfect situation.” Dr. Chesney first visited the Brown in 2001 when he was invited to give a talk on an enzyme involved in sugar metabolism in cancer cells that he had discovered. He was invited back to give another presentation in 2002, when Dr. Miller and cancer center deputy director John Eaton, PhD, approached him to consider running his lab at the Brown. “At first I thought, ‘Not a chance!’” Dr. Chesney remembers. “My apartment in New York was right across the street from my lab. I believed that it didn’t get any better than that.”

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“Luckily at the Brown, lack of external funding doesn’t automatically squash an idea that may have merit.” Jason Chesney, MD, PhD Associate Director for Translational Research

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“Then as I listened to them (Drs. Miller and Eaton) and thought about the opportunity they were offering, I realized that this was the chance of a lifetime.” Dr. Chesney moved into his first lab in the newly dedicated Delia B. Baxter Biomedical Research Building in 2003, winning his first independent grant in 2003-04. “It was obvious that he was an extremely talented young scientist,” Dr. Miller said. “We were VERY luck to get him to come here.” Today, Dr. Chesney is associate director for translational research and medical director of the clinical trials office, which runs more than 80 therapeutic trials at any given time.

“We have built the clinical and research programs around translational research, that is the measure of success,” Dr. Miller explains. “The clinicians and scientists are friends and in some cases, as in the case of Jason, they are the same.” “It has been particularly gratifying to be a part of the process of researchers working closely with clinicians,” Dr. Chesney says. “These two groups are trained completely differently and think completely differently – but there is amazing synergy when they work together. To conduct effective translational research, that synergy is absolutely essential.”

Promising Results The collaboration between lab and clinic was evident throughout the initial ONTAK trial.

Of the initial 16 patients from the Brown’s melanoma clinic, five patients experienced regression of melanoma metastases, one of which experienced a near complete response. While 30 percent of all patients saw clinical benefit from the therapy, 66 percent of patients who received treatment prior to chemotherapy received significant benefit. Mary Ann Rasku, then a technician in Dr. Chesney’s lab, confirmed that ONTAK depleted the regulatory T cells and activated immunity specific for melanoma, and was first author of the 2008 paper announcing the results published in the Journal of Translation Medicine. “Mary Ann has just started her third year

FACES OF CANCER ”To those battling melanoma, I would say to keep your faith in God and the Brown Cancer Center, and they will pull you through.” Tom Freeman Melanoma Westport

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at the University of Louisville Medical School,” Dr. Chesney said, “and I hope that she will pursue an academic career in translational oncology once she completes her medical degree.” The paper written by Ms. Rasku and the team was selected by the journal for the 2007-2008 “Bedside to Bench Award.” According to journal editors, the study “exemplifies the journey of ‘Translational Medicine’ between laboratory and the clinic and provides an excellent basis for further studies of T cell depleting agents and their efficacy in cancer patients.” With the promising early data in hand, Eisai, the pharmaceutical company behind ONTAK, committed to initiate pre-clinical work to confirm the findings

in mice – a key step to advancing to clinical trials in humans. That work led to the $12 million Phase II trial, directed by Dr. Chesney, that is currently underway. The goal is to identify a correlation between the depletion of T cells with response rate, and time vaccine treatment when the regulatory T cells are depleted. “Melanoma is a gateway to immunotherapies for all types of cancer,” Dr. Chesney explains. “We may be able to combine this therapy with cancer-specific vaccines to dramatically improve their effectiveness and the body’s ability to fight cancer.”

In fact, Dr. Chesney is already working on a protocol for non-small cell lung cancer, one of three new targets that are likely next steps for the treatment. In the mean time, his work is considered a shining example of the potential of translational clinical research among university and cancer center leaders. “Translational research is a cycle,” Dr. Chesney says. “This research came from the bedside to the bench and back again. The cycle feeds scientific creativity that ultimately means a better life for cancer patients.” ■

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not your grandfather’s surgery “3D,” “HD,” AND “DUAL-CONTROL” ARE MORE THAN TERMS FOR GAMING SYSTEMS

Twenty-five years ago, businesses relied on typewriters, carbon paper, and calculators. FAX machines and small, stand-alone computers with word processors were new to the scene, but showing promise as potential time-savers. Today, of course, smaller, faster, more powerful computers connected by high-speed fiber optics have completely changed the way we conduct business and live our lives. The same evolution can be seen in surgery. Twenty-five years ago, most surgeries were performed through “open” incisions that required long hospital stays, risked morbidity, and resulted in significant scarring. While laparoscopic and other minimally invasive techniques were introduced through the 1990s, there were still drawbacks, including the awkwardness of the instrumentation, working in a three-dimensional space with only a two-dimensional image for a guide, and

the exaggeration of hand tremors and small movements that could be catastrophic in micro-surgical situations. Before 2000, surgical robotics was little more than a medical curiosity. Today, however, robotic surgery is gaining momentum and proving to be a reliable alternative to open surgery for many procedures. Surgeons at the James Graham Brown Cancer Center have offered surgical alternatives with the da Vinci Si surgical system since its installation at University of Louisville Hospital in the fall of 2009. Along with 3D HD visualization that is now standard in such units, the University Hospital unit is the only one in the area, and one of only a few in the country, to feature dual controls – allowing two surgeons to work simultaneously on complex cases. Daniel Metzinger, MD, a Brown Cancer Center gynecologic surgeon, emphasizes that the dual control technology “provides surgeons with enhanced ability to take our

multidisciplinary collaborative approach into the operating room.”

Patients seeking advances at Brown Clinics Less than a decade ago, one of the most debilitating common procedures was the hysterectomy or any surgery of the pelvis. In 2009, Shera McCandless was among the first patients to benefit from the new technology at the Brown. Following a diagnosis of a particularly aggressive cervical cancer, Brown Cancer Center surgeon Lynn Parker, MD was able to remove the cancerous tissues effectively while allowing Ms. McCandless to return home the following day. Just a few years ago, recovery from this type of surgery would have been measured in weeks rather than days. “I feel lucky that this was available,” Ms. McCandless said three months after her procedure. “I was sold when I learned that I wouldn’t have to take a whole month to do nothing after surgery.” The surgeons of the Brown’s Gynecologic Oncology Clinic, including Drs. Metzinger, Parker, and Michael Milam, MD, agree. “With the da Vinci we’re seeing improved patient recovery, shorter hospital stays, less scarring and better overall outcomes,” Dr. Milam said. The same can be said of patients in the Brown’s Head and Neck Clinic. When Jerry Stephens complained of a sore throat and earache that wouldn’t go away, his family physician prescribed antibiotics. Two weeks later, something still wasn’t right, Stephens said. “The antibiotics weren’t working,” he said. “I went to get a second opinion.”

Drs. Lynn Parker, Daniel Metzinger, and Michael Milam visit with patient Shera McCandless during a post-operative visit.

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That second opinion was a potential life-saver; an otolaryngologist discovered cancerous lesions in his throat near his voice box.

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The University Hospital unit is the only one in the area, and one of only a few in the country, to feature dual controls - allowing two surgeons to work simultaneously on complex cases.

In April 2010 at University of Louisville Hospital, UofL surgeons Jeffrey Bumpous, MD and Kevin Potts, MD teamed up to complete the first da Vinci TransOral Robotic Surgery (TORS) in the state of Kentucky and surrounding region. They were able to remove the cancerous tissue with no major incisions. According to Dr. Bumpous, leader of the head and neck multidisciplinary team, “The da Vinci puts the camera at the site of the cancer and gives us the ability to see everything. It ultimately results in better outcomes for our patients.” Jeffery Jorden, colorectal surgeon at the Brown Cancer Center, draws the connection of better outcomes directly to the enhancements the da Vinci provides his own surgical technique. “The biggest advantage in colorectal surgery can be seen when performing anastomosis of the intestine,” Dr. Jorden explained. “The removal of hand tremors combined with the 3D HD imaging allow for a higher level of precision.”

Future is Bright, and in the Future Robotic surgery is growing and rapidly

expanding to new treatment areas. Scores of studies have been conducted and more are underway to quantify the benefits and risks of robot-assisted procedures. (See http://www.da vincisurgery.com/clinical-evidence/ for more information on clinical studies.) It will take surgical pioneers and visionary teachers such as those found at the University of Louisville and at academic medical centers across the country to make the most of the technological breakthroughs. “As with any relatively new technique or procedure, there is a learning curve, and it is important that things progress in an orderly fashion with a lot of time spent to train residents, fellows, and practicing surgeons to use minimally invasive techniques safely and effectively,” said Kelly McMasters, MD, chair of the UofL department of surgery. “As a surgical community we must continue to

study and measure outcomes of these techniques to ensure the highest possible quality of care for our patients.” To date, University of Louisville surgeons in four Brown Cancer Center multidisciplinary clinics are offering patients the benefits of robot-assisted surgery. While not all cancers or tumor sites allow for the use of the da Vinci, the patients who are currently reaping the benefits are grateful. ■

FACES OF CANCER ”The Brown Cancer Center gave me a will with the help of God to live.” Lettie Standard Cervical Cancer Louisville

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powerful computer grid VALUABLE RESOURCE FOR CANCER CENTER COLLABORATORS SEARCHING FOR NOVEL THERAPIES FOR CANCER “Borrowing” the resources of school computers when they are not in use by students is a win-win proposition for the James Graham Brown Cancer Center and schools in the coal counties of Kentucky. Researcher John Trent and collaborators are able to scan millions of compounds to determine whether they may be effective in fighting cancer, and the students in the schools get brand new computers, all part of a partnership between the BCC and the Kentucky Dataseam Initiative, a non-profit organization that harnesses unused computing

power in more than 50 school districts. When scientists in the BCC identify potential targets for drug discovery – cellular areas that may be particularly vulnerable because their structure and function is well-understood – the next step is to find drugs that might serve as the means of attack. The search process requires the screening of vast libraries of molecular compounds, drug substances that have already been created. Some of these libraries contain millions of compounds. The process is comparable

to looking for a specific puzzle piece in a box that contains 10 million puzzle pieces that look more or less the same. The computer grid allows John Trent, PhD, an associate professor of medicine and director of molecular modeling at the BCC, to shorten the time required to sort through potential compounds from years to days. It has helped the Brown Cancer Center build a promising drug pipeline for new cancer therapies. “The school computers were an amazing untapped resource,” Trent said. “Plus, Apple computers that are so popular in schools are based on the Unix or Linux computing platform, which is similar to the supercomputers in my lab, as well as many others. So it makes the system easier to use for us.” Recently, 68 UofL faculty members received Clinical and Translational Science Pilot Grant Program awards for various projects, and several of these awards went to BCC members who are working with Trent to advance the search for more effective treatments for cancer. The Clinical and Translational Science Pilot Grant Program is a state-funded effort to support clinical and translational research at the University of Louisville.

The computer grid allows John Trent, PhD, associate professor of medicine and director of molecular modeling at the Brown, to shorten the time required to sort through potential compounds from years to days.

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One of those investigators is Chi Li, assistant professor of medicine and pharmacology and toxicology, who is working to identify compounds that might stimulate a protein called Bax, which can initiate cell death, a natural process that is impaired as cancer cells grow and proliferate. Li and his team are using the computer grid to scan compounds that might activate Bax and lead to cell death, which may someday lead to better drug treatments for cancer.

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“We identified 69 potentially useful compounds and have acquired 32 for further testing,” said Li. Further work will determine whether the compounds can help Bax do its job and they will be tested in human tumor cells. Robert Mitchell, associate professor of biochemistry and molecular biology, is working with Trent on a project aimed at developing better drugs to starve a lung tumor’s blood supply by choking the blood vessels which feed it. “Our lab recently discovered an inhibitor of a tumor-associated angiogenesis, or blood vessel growth, and we did this using the computational grid as a tool,” said Mitchell. “Now, we’re continuing this work by attempting to optimize or fine tune the potency of this inhibitor, so that it targets not only one growth factor but two, debilitating a tumor’s ability to feed and re-generate itself.” Mitchell predicts that by creating a one-two punch, he and his team can create a much stronger anti-angiogenic agent than is currently available. In partnership with Hari Bodduluri, professor of microbiology and immunology, Trent is working on another project which focuses on metastasis, the spread of cancer to distant sites in the body, which is responsible for a significant part of cancer-related illness and death. This project makes use of the computer grid to scan for compounds that have specific

FACES OF CANCER ”Laugh a lot and be happy.” Jennifer Ziegler AML Leukemia Louisville

The Kentucky House of Representatives honored Dr. John Trent for winning Apple Computer’s 2008 National Science Innovator Award. As director of molecular modeling at the James Graham Brown Cancer Center, Dr. Trent and 14 key scientists are discovering new treatments for deadly cancers.

anti-metastatic properties. “The target we’ve found, which we’ll now hopefully discover compounds to combat, has been implicated in the growth and spread of several types of cancer, including basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, melanoma, ovarian, kidney, liver, breast, colon, lung, pancreatic and prostate cancers,” Trent said. “So this has widespread potential.” Another project, in partnership with Brad Chaires, professor of medicine and the James Graham Brown Chair in cancer biophysics, focuses on G-quadruplex DNA, unusual four-stranded structures that play a role in protecting chromosomes from damage, making

John Trent receives Apple Computer's Science Innovator Award.

them a potentially important player in cancer development. “Small molecules that can selectively recognize G-quadruplexes represent a highly promising new avenue for cancer chemotherapy,” Chaires said. “We have already discovered three compounds, using the computational grid, that are promising leads for therapeutic agents, and we are now moving onto preclinical studies that are the next steps toward moving these compounds from bench to bedside.” Other projects with additional collaborators have similar goals – to take an identified drug target and try to find existing compounds that may have efficacy against it, in order to make a “match” and advance the field of cancer therapeutics. “This is a very promising tool to help us develop life-saving drugs and treatments faster,” Trent said. ■ FALL 2010

JAMES GRAHAM BROWN CANCER CENTER

NON-PROFIT ORG US POSTAGE PAID LOUISVILLE, KY PERMIT NO 879

529 South Jackson Street Louisville, KY 40202

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mark your calendar... 11/17

Kentucky Cancer Program/American Cancer Society Cancer Support Group Meeting – Brown Cancer Resource Center

WHAT MAKES THE BROWN CANCER CENTER DIFFERENT?

11/21

Horses and Hope Day – Churchill Downs – 502-852-6318

1/13

Kentucky African Americans Against Cancer Volunteer Program and 20 Year Celebration – The Olmstead – 502-852-6318

The James Graham Brown Cancer Center at the University of Louisville is an academic cancer center. Our physician-scientists are on the forefront of cancer treatment discoveries, and they bring this knowledge to patient treatment and care.

1/29

3rd Annual Multidisciplinary Thoracic Oncology Conference: Ongoing Developments and the Latest Advances in Lung Cancer – Clinical and Translational Research Building http://uofl.me/thoracic10

2/12

Red & Black Ball – for the love of Harriett – Grand Ballroom, Galt House Hotel & Suites – 502-562-8021

2/25

Kentucky Cancer Program Breast Cancer Survivor Weekend Retreat – Homewood Suites Hurstbourne Lane 502-852-6318

3/4

Dress in Blue Day for Colon Cancer Screening Awareness

5/5

Kentucky Cancer Program Cancer Survivor’s Day – Brown Cancer Center

5/6

Horses and Hope at the Kentucky Oaks Pink Out – Churchill Downs

5/6

The Julep Ball – Grand Ballroom, Galt House Hotel & Suites www.julepball.org

Our mission is to generate new knowledge relating to the nature of cancer, and to create new and more effective approaches to prevention, diagnosis and therapy, while delivering medical advances with compassion and respect to cancer patients throughout our region. How can I donate? You may make a tax-deductible gift by visiting www.browncancercenter.org. To learn more about how you can support the work of the James Graham Brown Cancer Center, please contact Bill Kingston, Director of Development, at 502-562-4642 or jwilliam.kingston@louisville.edu.

For more information about any of these events, please call 502-562-8021. Or, visit www.browncancercenter.org for additional information regarding all upcoming events and classes at the Brown Cancer Resource Center.