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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.
Citation preview
A publication of the J A M E S G R A H A M BROWN CANCER CENTER
FALL 2010
DISCOVERIES
FACESOF
CANCER
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 CancerCenter (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 themto the Brown Cancer Center.
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, while13 percent of Kentucky’s cancer patients have breast cancer;
• 14 percent of our patients are treated for lung cancer, while 19 percent of Kentuckianswith cancer have a lung-related diagnosis;
• 13 percent of our patients have gastrointestinal cancer, while 9 percent of Kentuckianswith cancer do.
The list goes on. (See charts to the right.)
The mission of the James Graham Brown Cancer Centeris to help relieve the disproportionate pain and sufferingborne by Kentuckians from cancer. In order to do this,it is our goal to generate new knowledge relating to thenature of cancer, and to create new and more effectiveapproaches to prevention, diagnosis and therapy, whiledelivering medical advances with compassion and respectto cancer patients throughout our region.
Our teams of clinical and research scientists work togetherevery day to honor this mission, and become the “other”faces of cancer.
At the Brown Cancer Center, we believe in and invest inpromising translational research, research which will makea difference for our patients within the forseeable future.For our scientists, the clinic as well as the laboratory is aplace for discovery and collaboration.
Over the last decade, we have invested millions of dollars making our clinics the mostadvanced 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 scientistsand clinicians have every tool they require to work together effectively, efficientlyand creatively.
This dedication to work across disciplines is leading to the discovery of novel new treatmentsand important new information about the nature of tumors that can be exploited in clinicaltrials. In this work, we see our patients not only as individuals who need our service – althoughthey are, and we are honored to serve. We see our patients as key partners in the ongoingquest to unlock the mysteries of cancer in ways that will allow us to minimize its devastatingeffects 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 behalfof cancer patients everywhere, and about a few of the patients who have been the beneficiariesof our efforts.
Donald M. Miller, MD, PhDDirector of the James Graham Brown Cancer Center
2A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
Discoveries is publishedfor the friends, faculty andstaff of the James GrahamBrown Cancer Center.
DiscoveriesBrown Cancer Center, 2nd Floor529 S. Jackson StreetLouisville, KY 40202www.browncancercenter.org
EditorKathy Keadle
ContributorsTom FougerousseDiane KonzenAlbert LeggettMarion WhelanLauren Williams
letter from the director
INSIDE THIS ISSUE...
page
IN THE NEWS
Breast Care Accreditation
ARTICLES
The Fight Within
Not Your Grandfather’s Surgery
Trent Discoveries
14page
20page
22page
5
Brown Cancer Centerpatient mix – 2008
BreastGenito-Urinary
Gastro-intestinal
Gynecologic
Head& Neck
Lung
Melanoma
Blood & Marrow
KY Cancer Prevalence – AmericanCancer Society 2010
Lung
Gynecologic
Gastro-intestinal
Genito-Urinary
BreastMelanoma
Blood & Marrow
3FALL 2010
welcome...
Shiao Y. Woo, former professor of radiationoncology and section chief of the division ofcentral nervous system and pediatric cancersat the University of Texas - MD AndersonCancer Center, has been appointed endowedprofessor and chairman of the Department ofRadiation Oncology at the University ofLouisville School of Medicine.
“Professor Woo is an internationally recognized authority on thetreatment of brain, spinal cord and pediatric cancers and addsto the University of Louisville and the James Graham BrownCancer Center’s strengths in the neurosciences,” said EdwardHalperin, MD, Dean of the UofL School of Medicine.
“He is superbly trained, has obtained extensive clinical andresearch experience at the world-class MD Anderson CancerCenter of Houston, is widely published and serves on theboard of directors of the Pediatric Radiation Oncology Society.His selection as chair, following our naming of new chairs in thedepartments of neurology, biochemistry and medicine, is aclear demonstration of growing national recognition of ourclinical programs.”
Woo completed an internal medicine residency and obtainedboard certification in internal medicine in the United Kingdom.He subsequently completed a residency in pediatrics and afellowship in pediatric and adolescent hematology-oncologyat Georgetown University Hospital, and a residency in radiationtherapy at Stanford University Medical Center.
He is board certified in pediatrics, pediatric hematology-oncology and radiation oncology. He has served on the facultiesof Georgetown University, Tufts University, Baylor College ofMedicine and MD Anderson, where he has been a professorsince 1996. Woo has served as residency director for thedepartments of radiation oncology at both MD Andersonand Baylor and he also was associate chairman for researchat Baylor.
Woo’s areas of clinical and research interest are tumors of theblood, bone, nervous system and soft tissue in children andadults. He has published more than 120 articles in peer-reviewed journals and authored more than 20 book chapters.
“I am excited to be joining the vibrant UofL medical andscientific community and I believe there will be many growthopportunities for the department clinically and academicallyover the coming years,” Woo said. “I am looking forward tocollaborating with colleagues in our department and othersto do our part to advance the field of cancer care and researchat UofL and beyond.”
BROWN CANCER CENTERWELCOMES DR. SHIAO WOO, CHAIROF RADIATION ONCOLOGY AT UofL
Dr. Jesse Roman, formerly professor ofmedicine at Emory University in Atlanta,joined the University of Louisville as chairmanof the Department of Medicine at theUniversity of Louisville School of Medicine inSeptember 2009.
“When we sought a worthy successor toour longstanding Chairman of Medicine,
Dr. Richard Redinger, I envisioned a physician-scholar-teacherof the first rank; someone with a commitment to the ideals ofacademic medicine,” Edward Halperin, MD, Dean of the UofLSchool of Medicine, said. “We have hired such a person.”
“Search committee chairman Dr. Donald Miller, director ofthe James Graham Brown Cancer Center, committee vice-chairDr. Kerri Remmel, and the entire search committee, evaluatedan exceptional pool of candidates for this very importantposition within the School of Medicine.”
Roman received his medical degree from the University ofPuerto Rico School of Medicine. He completed his residencyat the San Juan Veterans Affairs Medical Center. He then joinedthe Pulmonary and Critical Care Medicine Fellowship Programat 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 whichdoubled in size, expanded its fellowship program now fundedby two NIH-sponsored institutional training grants, increased itsresearch portfolio eight-fold and attracted several nationalmulti-center awards, standardized medical critical care deliveryat four hospitals, and established several new clinical-researchenterprises in lung disorders.
He has published extensively in the areas of lung tissue remod-eling and inflammation and on the role of extracellular matricesin the control of lung resident cell functions and tumor cells.He is the author of more than 120 scientific writings and hiswork has been continuously funded by federal organizations.His national reputation is evidenced by his membership in VAand National Institutes of Health study sections. He has servedon important committees of the American Thoracic Society andthe American College of Chest Physicians.
Roman serves as a member of the steering committee of theNIH-sponsored Idiopathic Pulmonary Fibrosis Clinical ResearchNetwork and the scientific advisory committee of the PulmonaryFibrosis Foundation. Roman also serves as President of theSouthern Society for Clinical Investigation. He is a member ofthe editorial board for Clinical and Translational Science, theOpen Biology Journal and Chest.
DR. JESSE ROMAN NAMED CHAIR FORUofL DEPARTMENT OF MEDICINE
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welcome...
The Brown Cancer Center welcomes the following facultymembers who have joined us in our efforts to improvethe lives of people with cancer.
Doug Coldwell, MDProfessor of Radiology, UofL Department of DiagnosticRadiology, Dr. Coldwell, a specialist in radioembolization, willwork with multiple Brown Cancer Center clinics. Dr. Coldwellcompleted a clinical fellowship at MD Anderson Hospital andTumor Institute. He received his MD from the University of Texasat Galveston, and completed his residency at the Milton S.Hershey Medical Center in Hershey, PA.
Glenda Callender, MDAssistant Professor of Surgery, UofL Division of SurgicalOncology, Brown Cancer Center Breast Multidisciplinary Team.Dr. Callender completed a Surgical Oncology and Endocrinefellowship at MD Anderson Hospital and Cancer Institute inHouston, TX. She received her MD from Harvard MedicalSchool, and completed her surgical residency at the Universityof Chicago Medical Center.
Zhong-Bin Deng, PhDInstructor of Medicine, UofL Department of Medicine, Divisionof Oncology/Hematology, Brown Cancer Center TumorImmunobiology Research Program. Dr. Deng completed aresearch fellowship at the University of Alabama at Birmingham.He received his PhD in Immunobiology at the School of LifeScience, Soochow University, Suzhour, P.R. China, and his MSfrom the College of Animal Science and Veterinary Medicine,Yangzhou University, P.R. China.
Amy Quillo, MDAssistant Professor of Surgery, UofL Division of SurgicalOncology, Brown Cancer Center Breast Multidisciplinary team.Dr. Quillo completed a surgical fellowship in endocrine andbreast surgery at the Mayo Clinic. In addition to leadership inbreast surgery, she will be pursuing programmatic developmentin endocrine surgery. She received her MD at the University ofLouisville School of Medicine and completed her surgicalresidency at UofL affiliated hospitals.
Rebecca Redman, MDAssistant Professor, UofL Department of Medicine, Division ofMedical Oncology, Brown Cancer Center GastrointestinalMultidisciplinary Team. Dr. Redman completed her fellowshipin Hematology Oncology at Duke University. Dr. Redmanreceived her MD from the University of Wisconsin, completedher residency at University of North Carolina Hospitals,and her fellowship in hematology/oncology at Duke UniversityMedical Center.
NEW FACULTY
Rajesh K. Sharma, PhDInstructor of Medicine, UofL Department of Medicine, Divisionof Oncology/Hematology, Brown Cancer Center StructuralBiology Research Program. Dr. Sharma recently completeda research fellowship with UofL’s Institute for CellularTherapeutics. He completed his PhD in Biotechnology atBanaras Hinu University, Varanasi, India, and his Master’s ofScience at Jawaharial Nehru University in Delhi.
Victor van Berkel, MDInstructor of Surgery, UofL Division of Thoracic Surgery, BrownCancer Center Lung Cancer Multidisciplinary Team.Dr. van Berkel completed his surgical fellowship at Barnes-Jewish Hospital. He received his MD from WashingtonUniversity in St. Louis and completed his surgical residencyat Massachusetts General Hospital.
Kavitha Yaddanapudi, PhDInstructor of Medicine, UofL Department of Medicine, Divisionof Oncology/Hematology, Brown Cancer Center MolecularTargets Research Program. Dr. Yaddanapudi completed apost-doctoral research fellowship at Columbia University’sMailman School of Public Health prior to being named anAssociate Research Scientist there. She completed her PhD inBiochemistry at the Indian Institute of Science, Bangalore,India, and her MS at Madurai Kamaraj University,Madurai, India.
Top: Red & Black Ball event organizersDani Porter; Marie Porter; Aimee Webb, PhD;Ellie Porter Billops; and Joy Billops enjoy abeautiful evening.
Right: Charla Young, Steve St. Angelo and KevinShurn at the Red & Black Ball.
More than 300 people celebrated cancer education and prevention at the 4th AnnualRed & 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 andOutreach Programs to reduce cancer health disparities in the African American community.Several initiatives including cancer education, screening, patient support and many faith-basedprograms have been implemented. The 2010 Robin Award for Community Spirit was presentedto 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 salesand auctions, the Red & Black Ball netted more than $65,000.
RED & BLACK BALL RAISES AWARENESS,FUNDS FOR CANCER EDUCATION
Brown Cancer CenterGETS PRESTIGIOUS DISTINCTION IN BREAST CARE
Brenda Sweatt laughs with Representative Darryl Owensat the Red & Black Ball.
5FALL 2010
“This is terrific news for thewomen of Kentucky. To have abreast care center in our staterecognized as one of the top inthe country no doubt providesa great deal of comfort andconfidence in the minds ofour people.””
Jane BeshearKentucky’s First Lady
The University of Louisville’s JamesGraham Brown Cancer Center is thefirst center in Kentucky to be granted afull three-year accreditation by theNational Accreditation Program forBreast Centers (NAPBC), a programadministered by the American College ofSurgeons. Accreditation by the NAPBC isgiven only to those centers that havevoluntarily committed to provide thehighest level of quality breast care andthat undergo a rigorous evaluationprocess and review of their performance.
Kentucky First Lady Jane Beshear tookpart in an announcement of the honor ata press briefing on Wednesday, Jan. 20,at the James Graham Brown CancerCenter’s Breast Care Center. UofLPresident James Ramsey was also onhand to celebrate the achievement.
“This is terrific news for the women ofKentucky,” said Mrs. Beshear. “To have abreast care center in our state recognizedas one of the top in the country nodoubt provides a great deal of comfortand confidence in the minds ofour people.”
“This distinction represents an acknow-ledgment of the dedication shown byour many breast care clinicians, supportstaff, counselors and researchers toproviding only the most outstandingand comprehensive care to our patients,”said Donald Miller, MD, PhD,director of the James Graham Brown
Cancer Center at UofL. “We are honoredto be among the fine institutions nation-wide that are NAPBC-accredited, and thisdistinction underscores and invigoratesour commitment to our patients, nowand in the future.”
The distinction is given after a surveyprocess during which centers mustdemonstrate compliance with27 standards established by the NAPBCfor treating women who are diagnosedwith the full spectrum of breast diseases,from breast cancer to benign lesions thatrequire medical evaluation for treatmentoptions. Three standards critical foraccreditation are strong breast programleadership, a multidisciplinary approachto disease evaluation and management,and a breast cancer conference programfeaturing active collaboration betweenindividuals involved in all aspects of abreast patient’s care, to ensure thatoptimal treatment strategies are createdin every individual case.
Other standards cited include proficiencyin clinical management, research,community outreach, professionaleducation and quality improvement.The standards apply to all disciplinesinvolved in breast care, includingradiology, pathology, medical oncology,surgical oncology, radiation oncology,plastic surgery, genetics and nursing.UofL’s mobile mammography unit wasnoted as an effective tool for communityoutreach, and ongoing quality
improvement initiatives were cited inareas including medical oncology andradiation oncology. Use of minimallyinvasive biopsy techniques for diagnosis,and disease or patient-specific targetedtherapies when appropriate, were notedas well.
“NAPBC accreditation means a great dealto us because it is a recognition of ourcommitment to what’s at the heart ofbreast care,” said Barb Kruse, associatedirector of multidisciplinary clinics at theJames Graham Brown Cancer Center.“And that is the patients.” �
6A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
Advanced Cancer Therapeutics (ACT),a privately held company dedicated tobringing new anti-cancer therapies tomarket, signed an exclusive agreementto leverage the translational researchexpertise of Jason Chesney, MD, PhD,associate professor, department ofmedicine at the University of Louisville’sJames Graham Brown Cancer Center, toidentify new clinical candidates for theprevention and treatment of cancersagainst two key cancer metabolic targets.
As part of this agreement, over the nexttwenty-four months, Dr. Chesney willwork with ACT to further refine andadvance the preclinical candidates andbackup compounds against two excitingand novel cancer targets that are knownas 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) andCholine Kinase (CK), both key cancermetabolism targets identified by
Dr. Chesney as essential for cancercell growth.
ACT previously obtained worldwideexclusive licenses from the Brown CancerCenter for these two cancer metabolicprograms summarized below:
� PFKFB3: High glucose consumption iscommonly observed in cancer cells.As PFKFB3 is the enzyme involved inan irreversible step of glycolysis, ACTsynthesized over 100 rationallydesigned inhibitors of this protein.Scientific evidence suggests thatinhibitors of the PFKFB3 enzymeblock glucose uptake in cancer cellstherefore inhibiting cancer cellsproliferation and tumor growth.
� Choline Kinase: Choline Kinase,the enzyme responsible for thephosphorylation of choline intophosphocholine, is over expressed in
most solid tumors including lung,breast, ovarian, brain and prostatecancers. ACT’s medicinal chemistshave developed over 150 rationallydesigned, potent compound inhibitorsthat inhibit choline kinase enzymaticactivity, cell proliferation and tumorgrowth in xenograft studies.
“Dr. Chesney has long been a thought-leader in cancer metabolism and hisresearch has always been high qualityand cutting-edge,” said Randall Riggs,President & CEO of ACT. “We aredelighted to collaborate with him aswe move closer to selecting novelclinical candidates that may proveto be lifesaving therapeutics for cancerpatients.”
In addition, Dr. Chesney is the AssociateDirector for Translational Research andthe Medical Director of the Clinical TrialsOffice at the Brown Cancer Center. �
advanced cancer therapeuticsCOLLABORATES WITH BCC RESEARCH SCIENTIST IN CANCER METABOLISM
The University of Louisville's Clinical and Translational Research (CTR)Building has received a top rating from the U.S. Green BuildingCouncil, a non-profit agency based in Washington that promotessustainability in building design, construction and operation.
The building has received a Gold LEED (Leadership in Energy andEnvironmental Design) certification, one of the council’s highestdesignations.
Only 33 research buildings in the United States have earned the samecertification, and UofL’s eight-level, 288,000-square-foot buildinglocated just behind the James Graham Brown Cancer Center at 505 S.Hancock St. is believed to be the largest, said Stephen Cotton, assistantdirector of university planning, design and construction.
The use of energy-saving natural light was a key factor in designingthe $143 million, state-funded biomedical research facility, whichopened in October. A reflective roof keeps heating costs down whilespecial louvers and light shelves control the amount of sun enteringthe building. Another system in the building turns off electric lightswhen they aren’t being used.
Condensed water from the air conditioner is used to irrigate thebuilding’s landscaping, and built-in showers and bicycle racks makeit easier for employees to avoid driving to work.
The U.S. Green Building Council established the LEED rating system in
2000. Businesses, schools,government agencies, storesand homes can apply forcertification through theprogram, but must meetstrict criteria before they canqualify for a certified, silver,gold or platinum rating.
UofL’s building earned atotal of 41 LEED credits,two more than the 39credits needed to achievea Gold rating, Cotton said.
The Clinical and TranslationalResearch building is home toapproximately 90 principal investigators and their teams, mostlyconducting cancer research. The building also houses core laboratoriesincluding flow cytometry, microarray, advanced diagnostic imagingservices and tumor bank to facilitate this work.
A large statue honoring the support of Kosair Charities was alsoinstalled in the courtyard in front of the CRT building to honor thegroup’s $12 million, four-year commitment to the facility andthe pediatric oncology-related research that will go on inside.
UofL RESEARCH BUILDING GETS HIGH MARKS FOR BEING GREEN
Dr. Larry Cook, Executive Vice President for HealthAffairs (l) and Dr. James Ramsey, UofL President (r),give a tour of the LEED Certified Clinical andTranslational Research building.
7FALL 2010
Funding from the National Institutes ofHealth will help the University of Louisvilledevelop, implement and evaluate aninterdisciplinary oncology palliative careeducation program.
"Palliative care is now viewed as much morethan end-of-life care. It focuses on ongoingquality of life and well-being and is integralto the treatment of cancer patients fromtime of diagnosis throughout the trajectoryof the illness," said Mark Pfeifer, MD, chiefmedical officer for UofL Health Care andprincipal investigator on this project.
"Almost every family has or will face a lovedone needing cancer care, including curativetreatment, symptom control and end-of-lifecare," he said. "Patients and families needthe united services of physicians, nurses,chaplains and social workers, and there isa real need for health professionals to beeducated in an interdisciplinary mannerto prepare them for the real-world teamenvironments they experience once theyare in practice."
The multidisciplinary team working on theprogram will have representatives from theschools of medicine, nursing and social workand from the clinical pastoral educationprograms of three Louisville hospitals.
"We are all doing great work and arededicated to the patients…. If we are ableto work more seamlessly together, drawingon each other's capabilities more fluidly,we will be able to offer even better care topatients," said Terry Singer, dean of theKent School of Social Work.
NIH will pay the grant over five years.
The team will devote the first year to thedesign of an innovative and integratedoncology palliative care curriculum thatwill include eight learning activities, andit will be required for all third-year medicalstudents, third- and fourth-year nursingstudents, master's level social work studentsand clinical pastoral education residents.
"The receipt of this grant is a greatdistinction for UofL," said Larry Cook, MD,executive vice president for health affairsat UofL's Health Sciences Center. "It'simportant to note that our faculty cameup with this idea right here at UofL andwon this funding through a highlycompetitive process."
NIH GIVES MORE THAN$1.5 MILLION FORINTERDISCIPLINARYONCOLOGY PALLIATIVECARE EDUCATION PROGRAM
A $3.15 million grant from the Leona M.and Harry B. Helmsley CharitableTrust to support the UofL James GrahamBrown Cancer Center and cancerresearch taking place in Owensboro willbe used to create an endowed facultyposition for a nationally recognizedresearcher in plant-based pharmaceuti-cals, as well as two new faculty positionsto expand and enhance the researchprogram. The grant will be matchedwith state “Bucks for Brains” funding tobring more than $4.5 million to theOwensboro Cancer ResearchProgram (OCRP).
The grant was celebrated at a mediaevent held August 5, 2010, inOwensboro.
The OCRP is devoted to unlocking thepotential of plant-made pharmaceuticals.The research and drug developmentprogram takes advantage of the naturalproducts and agricultural industriesin the Owensboro region to addressdiseases impacting the area, especiallythose that are tobacco-related.Ultimately, the partnership’s goal is tocreate less expensive drugs for cancerprevention and treatment.
“We are excited to see the fine work ofthe James Graham Brown Cancer Centerand Owensboro Medical Health Systemexpand through this public/privateinitiative,” noted John Codey, trusteeof the Helmsley Charitable Trust. “Thepromise of plant-based pharmaceuticalsand vaccines to dramatically improvehealthcare at reduced cost is bothexciting and critically important.”
The tobacco-based process involvesinserting genes needed for drugdevelopment into the tobacco genome.The leaves are then harvested, processedand purified to derive a key ingredient.
Projects underway at OCRP include thedevelopment of a plant-based vaccineto prevent HIV; the development of asecond-generation cervical cancervaccine grown in tobacco plants inorder to make it affordable to millionsof women worldwide; understandinghow changes in the calcium-signalingpathway of stem cells impacts the
development and continued growth oflung cancer cells; and determiningwhether the interaction of the heavymetal cadmium with tobacco-derivedcarcinogens contributes to thedevelopment of lung cancer in smokers.
“Plant-based pharmaceutical systemshave a number of advantages,” saidDr. Donald Miller, director of theJames Graham Brown Cancer Center.“The costs for starting materials are low,which translates into a lower productioncost. The materials are readily available,meaning that we are able to increaseproduction levels relatively quickly.Additionally, plant-based therapies havefewer issues with potential contamina-tion than those utilizing other materialssuch as animal or human pathogens.”
UofL President James Ramsey attend-ed the celebratory event in Owensboro.
“When we established this program inpartnership with Owensboro MedicalHealth System in 2006, we envisionedother significant organizations joining usin our effort to create and develop novelapproaches to preventing and treatingcancer,” Dr. Ramsey said. “This gift fromthe Helmsley Charitable Trust moves ourvision forward and is recognition forthe importance of the work takingplace here.” �
$3.15 million grantFROM HELMSLEY CHARITABLE TRUST WILL SUPPORTBCC RESEARCH PROGRAM IN OWENSBORO
Helmsley Charitable Trust Chairman John Codey
Dr. Donald M. Miller, director of UofL’sJames Graham Brown Cancer Center,announced in July that the facilityreceived a Three-Year Accreditation withCommendation from the Commission onCancer (CoC), the group’s highest levelof accreditation possible.
“We are pleased that the CoC has recog-nized and endorsed our commitment toquality care, ongoing improvement, andpublic accountability for the care andservices we provide,” Miller said. “TheBrown Cancer Center continues to serveas a unique cancer care, research andsupport resource for the region.”
The Brown received accreditation withcommendation as a Teaching HospitalCancer Program – the only such programin the region – following an onsiteevaluation by a physician surveyor.The award recognized excellence in theareas of cancer committee leadership,cancer data management, clinicalservices, research, community outreach,and quality improvement. According tothe CoC, only 42 percent of cancercenters in the U.S. receive three-yearaccreditation with commendation.
Less than a year ago, the Brown alsobecame the first center in Kentucky toreceive CoC accreditation as a breast carecenter.
Established in 1922 by the AmericanCollege of Surgeons (ACS), the CoC is aconsortium of professional organizationsdedicated to improving survival ratesand quality of life for cancer patientsthrough standard-setting, prevention,research, education, and the monitoringof comprehensive, quality care.
According to Mary Wilson, CTR, theteam leader for cancer registry, thecenter has maintained its accreditationstatus for more than 20 years.
“We report to the CoC on an ongoingbasis in real time on the status of all ofour programs, and they can send asurveyor at any time, so we are in aconstant state of readiness,” Wilsonexplained. “I am extraordinarilyconfident in and proud of our cancercare, research, and outreach programs.When the surveyor arrives, we simplysay, ‘Welcome!’” �
BCC receives accreditationWITH COMMENDATION FROM THE COMMISSION ON CANCER
According to the ACS, receiving care ata CoC-accredited program ensuresthat a patient will have access to:
� Comprehensive care, includinga range of state-of-the-artservices and equipment
� A multispecialty, teamapproach to the besttreatment options
� Information about ongoingclinical trials and newtreatment options
� Access to cancer-relatedinformation, educationand support
� A cancer registry that collectsdata on type and stage ofcancers and treatment resultsand offers lifelong patientfollow-up
� Ongoing monitoring andimprovement of care
� Quality care close to home
The Brown Cancer Center’s clinical mission is dedicated to treating thewhole patient, not merely the cancer itself.
With that in mind, the Brown Cancer Center recently introduced theutilization of a new Patient Navigation Program. This program isoffered to assist cancer center patients and their families throughouttheir treatment process.
Laura Jones, the program’s first Patient Navigator, is responsiblefor helping patients and their families find, organize and use thenumerous resources, treatment services and support servicesavailable to them.
David Klein, cancer survivor, generously donated the funds thathave been used to create the Patient Navigator position.
“Mr. Klein believes in building relationships between patientsand their navigators,” said Ms. Jones. “He wants patients tohave navigators in the Brown Cancer Center who can help withinformation and resources.”
Ms. Jones and trained volunteer navigators help patients connect withany needed support, such as nutritional guidance, chaplaincy services,counseling or social work. The team also helps locate and directpatients to the many other services and support that may helppatients, their caregivers and families deal with cancer diagnoses.
BCC LAUNCHES NEW PATIENT PROGRAM
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.
8A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
KCP update
Cancer survivors across Kentucky aresharing their experiences throughFaces of Cancer, a project of theKentucky Cancer Program. Regionaloffices are creating photographic essaysfeaturing local people for exhibition inhospitals, banks, galleries, churches, andother venues. In reflection of Kentucky’sdiverse population, the project featuresindividuals of many different ages, races,socioeconomic classes, and cancer types.
Faces of Cancer travels throughout thedistrict and opens in each communitywith a ceremony featuring patient
testimonials of survival; remarks byphysicians and local officials;an unveiling of the pictures; anda special reception. Photographershave generously donated their timeand talents to make the project a reality.Faces of Cancer debuted in Louisville atthe annual Cancer Survivor Celebrationat the James Graham Brown CancerCenter.
Survivors who have participated inthe project view Faces of Cancer as anopportunity to share inspirationalthoughts to encourage newly diagnosed
patients and to honor health careproviders. Faces of Cancer recentlyappeared at the 2010 Kentucky State Fairwhere cancer survivors were invited tosign a banner depicting the faces and toshare their personal stories. Two Faces ofCancer books have been published and anew one will be released in the springfor the James Graham Brown Cancer.
FACES OF CANCER
An innovative project is underway inselect Kentucky hospitals for treatingtobacco use and dependence amongin-patients. Under contract with theKentucky Department for Public Health,the Kentucky Cancer Program hasdeveloped a toolkit for use byadministrators, educators, and cliniciansto develop a systems approach toaddressing one of the state's mostchallenging public health concerns.
University of Louisville Hospital,University of Kentucky Medical Center,and St. Elizabeth’s Hospital in NorthKentucky participated in the pilotproject to create strategies for patientintervention. The program includes anonline continuing education program, avideo on Kentucky Tobacco Quit Line,and a video featuring comments fromadministrators like Jim Taylor and KayLloyd from University Hospital whoaddress nicotine addiction in the hospital
setting and share their perspectives onweb-based training for employees.
Several hospitals in other communitiesare now being given the opportunity toevaluate the toolkit for final changesprior to a statewide distribution. Theprogram is expected to be a valuableresource to hospitals as they preparefor impending changes in the JointCommission’s requirements for tobaccocessation counseling.
TREATING TOBACCO USE AND DEPENDENCE IN KENTUCKY HOSPITALS
HORSES AND HOPE AT THE WORLD’S CHAMPIONSHIP HORSE SHOW
Thanks to a gift from the UnitedProfessional Horsemen’s AssociationPink Ribbon Program, Horses andHope was able to provide breast cancereducation and mammograms to workersin the American Saddlebred industry
during the World’s Championship HorseShow, held in conjunction with theKentucky State Fair, August 22-28, 2010.
Horses and Hope, a partnershipbetween Kentucky First Lady JaneBeshear and the Kentucky CancerProgram, the state mandated cancercontrol program housed at the JamesGraham Brown Cancer Center, aimsto increase breast cancer awareness,education, screening and treatmentreferral among Kentucky’s horseindustry workers and their families.
The United Professional Horsemen’sAssociation is an association ofprofessional horsemen and horsewomenwho united in 1968 to improve the horseshow industry.
“We’re so grateful to the UPHA for thisgift which has allowed us to bring ourprogram to other segments of the equineindustry,” said Connie Sorrell, directorof KCP. “We have many success storiesof people who have been screened ortreated as a result of Horses and Hopeand we want to continue to expand theproject to reach new groups because wereally believe it makes a difference.”
9FALL 2010
Faces of Cancer recently appeared at the 2010 Kentucky State Fair.
The Development staff is eager toanswer any questions about theGrateful Patients program. We canbe contacted at 502-562-4651.This is a tremendous opportunity tocreate a non-traditional revenue streamto support those needs that support ourmission of providing exceptional care.
Bill KingstonDirector ofDevelopment, BCC
10A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
Dear Colleagues:
For about 15 years I have had the honor toserve as a Trustee of the James Graham BrownFoundation and for almost 25 years as amember of the board of the University ofLouisville’s James Graham Brown CancerCenter. I would like to share with you someobservations I have made as a result of thesepositions.
The progress of the James Graham Brown Cancer Center over the yearsis quite impressive. Over the past 30 years, the Brown Cancer Centerhas not only been a local treatment option for people in Louisville andthroughout the state, but it has become a significant contributor to thebiomedical research community.
The center's strategic plan and the recruitment of new faculty haveplaced heavy emphasis on investigational areas that will lead tonew approaches to prevention, diagnosis and treatment of cancer.This emphasis on translation is now paying off. Brown Cancer Centerscientists have several novel cancer treatments in early phase clinicaltrials with more than a dozen others in preclinical stages. Importantly,there also has been a strong emphasis on prevention. A study on theuse of berries to prevent lung cancer in high-risk individuals began inlate 2006. The focus on "patient-oriented" research has created acollaborative environment in which both basic scientists and clinical
investigators place a premium on work that will have an impact oncancer prevention and treatment.
The advances taking place in research and clinical care are attractingattention from philanthropic organizations throughout the nation.Most recently, the Helmsley Charitable Trust provided significantfinancial support of the Brown Cancer Center’s research efforts via theOwensboro Cancer Research Program. This program seeks to developplant-based pharmaceuticals for the prevention, treatment and cureof various forms of cancer and other diseases that contribute to thedevelopment of cancers. Philanthropic support is necessary as theCenter strives to attract more top researchers and physicians in theeffort to earn Comprehensive Cancer Center designation from theNational Cancer Institute.
Our Cancer Center is well-positioned to continue its development intoone of the pre-eminent cancer centers in the nation, if not the world.Almost 30 years ago, The Brown Foundation joined with communityleaders to found the James Graham Brown Cancer Center, giving formto the vision of superior care for cancer patients here in Louisville.I believe the dreams of those founders is being achieved and continuesto warrant our support.
Yours in Service, Bob RounsavallBob Rounsavall, IIIMember, Regional Cancer Center Corporation BoardTrustee, University of Louisville
grateful patients honor a caregiverPHILANTHROPY STRIVING TO SUPPORT THE MARGIN OF EXCELLENCE
Gifts have long been a financialfoundation for the Brown Cancer Centerand have helped the organizationprovide the best health care to patients.A new donation program has beencreated to help produce furthercontributions for the future – theGrateful Patients program.
While continuing to seek financialassistance for the Brown Cancer Center,University Hospital will also be includedin the Grateful Patients program.It has been built to give patients andfamilies the opportunity to give back ifthey desire. Their financial gifts canacknowledge an exceptional experienceor honor front line caregivers, who arethe people saving and impacting lives.
The Grateful Patients program is notjust about money; if patients want tomake a financial contribution, orhonor a care giver we encourage thatgesture. However, it is about us as anorganization just being there for
them – to get them water, to talk tothem or just to answer simple questionsabout parking or the cafeteria.
Donations will provide support for:
� Innovative opportunities to transformhealth care through science andresearch
� Exceptional patient and family care
� Community-based health careprograms such as health screeningsand educational events
� Health care resources to theunderserved
� Physician-funded projects andprograms to improve health care
� Exceptional program-specific services
Philanthropy helps to explore newtreatment options that have worldwideimpact and enable University Hospitaland the Brown Cancer to provide thehighest level of care. �
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 AndrewLane, 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
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 beginsNone 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,
the future of cancer researchBCC METABOLOMICS RESEARCH OFFERS NEW INSIGHTS
“There has not been great progressin lung cancer with respect tosurvival over the past severaldecades. We've had marginal gains.Metabolomics research is a wholenew avenue that's only begun tobe explored.”
Michael Bousamra, MDHead of Thoracic Surgery
11FALL 2010
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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 con-
tent, 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 speedsthings alongOnce 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 RichardHigashi, PhD, associate director of massspectrometry development at CREAM.
“We hijacked the technology when we
recognized the power it held to analyze
our data. Ten years ago, it would have
taken a dozen labs a dozen years to
compile the information we’re now able
to generate in just a few months.”
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.
“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.
The promise of metabolomicsSenior team members Higashi and
Teresa Fan, PhD, director of CREAM,
who both have joint UofL appointments
in chemistry and at the Brown Cancer
Center, have been working with Lane
since the early 1980s studying the
principles of metabolism.
“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.”
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.
Teresa Fan, PhD, director of the Center for Regulatory and EnvironmentalAnalytical Metabolomics, and Richard Higashi, PhD, the center's associatedirector of mass spectrometry.
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.
13FALL 2010
“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 opportunityfor collaborationAs part of the move toward collaboration
between investigators at UofL and the
University of Kentucky, the metabolomics
team has joined forces with RolfCraven, 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 cancerand beyondBased on their work
with lung cancer, the
metabolomics team has
turned their attention
to breast cancer as
well, using the same
approach.
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, SuchetaTelang, 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. Compoundssuch 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.” �
FACES OF CANCER
”There is alwayshope...even whenyou think there isno hope.”
Janice FultonLung CancerClarksville, IN
The enthusiasm and passion Jun Yan,MD, PhD has for his work is obviousfrom the moment he begins to discuss it.
Dr. Yan is a scientist in the TumorImmunobiology program, whose goalis to understand the role of the immunesystem and inflammation in thedevelopment and progression of cancer,and to harness the power of the immunesystem to develop novel immune-basedtherapies and vaccines against all typesof cancer.
“We need to understand how thesetumors escape from immune systemattack,” Dr. Yan explains. “Conversely,we need to establish some approachesthat can augment or trigger the immunesystem to recognize tumor cells andeventually eradicate this devastatingdisease.”
Specifically, Dr. Yan’s research focuseson tumor immunotherapy mediated byanti-tumor antibodies that bind totumors and activate complement, andwhich have been shown to be enhancedby co-administration of yeast-derivedbeta-glucan.
“With this approach, we are essentiallyeducating the immune system bymarking the tumor as ‘other’ rather than‘self,’ equipping the body to fight thedisease more effectively.”
Circular PathDr. Yan first began his work at the BrownCancer Center in the late 1990s when hecame to Louisville for his postdoctoralfellowship with the University ofLouisville’s division of experimentalimmunology and immunopathology inthe department of pathology. His mentorwas Gordon Ross, PhD, and the twodeveloped a professional rapport thatwould set the stage for years of fruitfulcollaboration.
During that time, Dr. Yan completedwork in which indigenous beta glucanwas used to mimic pathogen throughco-administration with antibodies – anunusual approach at the time.
“We found that antibody therapy aloneis not very effective, but they can workwhen administered with an activatingagent,” Dr. Yan explains. “Today, nineantibody therapies are now approved.The culture has changed.”
After his fellowship, Dr. Yan joined theresearch faculty at Yale University, butreceived a call from Dr. Ross three yearslater.
“He asked me to return to Louisvilleagain,” Dr. Yan remembers. “The cancercenter was developing a strong clinical
and translational research program, andI was intrigued by the opportunities andstrong leadership here.”
The leadership was just as enthusiasticabout Dr. Yan’s return.
“Jun had been very involved with theuse of beta glucan as a cancerimmunotherapy modality that iscompletely novel and important,” saidDonald M. Miller, MD, PhD, BrownCancer Center director. “His work hashad and will continue to have terriblyimportant implications down the road.”
14A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
“With this approach, we are essentially educatingthe immune system by marking the tumor as ‘other’rather than ‘self,’ equipping the body to fight thedisease more effectively.”
Jun Yan, MD, PhDTumor Immunobiology Program
the fight withinDR. JUN YAN FINDS WAYS TO TRAIN THE BODY TO FIGHT CANCER MORE EFFECTIVELY
Hit the Ground RunningUpon his return, Dr. Yan workeddiligently to improve the therapeuticefficacy of the new therapies in a varietyof tumor types, including breast, lung,colon, and liver, as well as lymphoma.His work showed that the most promisewas shown in the treatment oflymphoma, colon, breast and lungcancers. The research work conductedin the laboratory was spotlighted by theNIH as “significant.”
With pre-clinical work complete, twoPhase I trials were completed in 2007-08to test the toxicity in both single doseand multiple/escalating dose treatments.Trials revealed the therapy to have anextraordinarily safe profile.
“We can infuse this polysaccharide andre-educate the immune cells and thosecells can be primed and activated toeradicate cancer,” Dr. Yan says. “It hasbeen almost 15 years, and this polysac-charide is now in Phase II clinical trial.”
Working with Egan-based pharmaceuti-cal company BioThera, the UofL licensedtherapy is being tested in multiplecenters in the Far East, with initial resultspresented at the December 2009 ASCOmeeting.
Dr. Yan and his colleagues are not takingtime to celebrate the recognition,however.
“A second approach we now use in thelab is to study whether we can increasethe body’s immune cells – so we’vedeveloped a tumor vaccine,” Dr. Yansays. “Basically the tumor vaccine willaugment anti-tumor immune cells andthose cells serve as surgeons. They cango to the field and remove the cancercells.”
According to Dr. Yan, the success is duein large part to the research environ-ment at the Brown Cancer Center.
“I think that we are very fortunate towork in the Brown Cancer Centerbecause this environment provides us allthe infrastructure and all the necessarycollaborations. All my colleagues workedtogether as a team to bring this drugfrom bench to now – eventually – to thebedside.” �
15FALL 2010
Numerous volunteers, sponsors, celebrityguests and cancer center staff have workedtogether since 2005 to donate more than$1.2 million through a Derby-eve gala tothe James Graham Brown Cancer Center.At the 2009 event, the new name“Julep Ball,” was introduced to morethan 1,000 guests and volunteers.
The Julep Ball, presented by SouthernWine & Spirits, remains a major componentof the Brown Cancer Center’s annualfundraising and awareness campaigns,funding critical early stage cancer researchand providing patient support services tothousands of cancer patients from acrossthe country.
The Ball also gives the cancer center anopportunity to recognize scientist(s)whose accomplishments are particularlynoteworthy.
The 2010 Julep Ball Scientist ofthe Year Award was presented toHari Bodduluri, PhD, (right) UofLProfessor of Microbiology and Immunology,and leader of the Brown Cancer Center’sTumor Immunobiology Program; andJun Yan, MD, PhD, (left) UofL AssociateProfessor of Medicine, and scientist in theTumor Immunobiology Program.
The goal of the Tumor ImmunobiologyProgram is to understand the role of theimmune system and inflammation in thedevelopment and progression of cancer,and to harness the power of the immunesystem to develop novel immune-basedtherapies and vaccines against all typesof cancer.
The program has 21 members who comefrom a wide variety of disciplines rangingfrom basic immunology to structuralbiology and molecular imaging. Thisbreadth is a major strength of the programand allows its members to address complexand technically challenging projects.
Drs. Bodduluri and Yan are working onmultiple projects, including basic researchthat is leading to development of novelvaccines for cancers and infectious diseases.
2010 JULEP BALLSCIENTISTS OF THE YEAR
FACES OF CANCER
”We’re not promisedtomorrow so live likeit’s your last day.”
David HowardHodgkin’s LymphomaLouisville
Dr. Jun Yan runs his lab in theClinical and Translational ResearchBuilding.
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-centerPhase II clinical trial for which he serves
as Principal Investigator.
“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.
Regulatory T cells, while crucial to
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.
“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?”
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.”
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 fund-
ing sources. The Brown
Foundation support,
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 SpiritThis 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, approachedhim 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.”
a collaborative spiritJASON CHESNEY LEADS BCC’S TRANSLATION RESEARCH EFFORTS
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“It has been particularly gratifying tobe a part of the process of researchersworking closely with clinicians.”
Jason Chesney, MD, PhDAssociate Director for Translational Research
17FALL 2010
“Luckily at the Brown, lack of externalfunding doesn’t automatically squash an ideathat may have merit.”
Jason Chesney, MD, PhDAssociate 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 work-
ing closely with clinicians,” Dr. Chesney
says. “These two groups are trained
completely differently and think com-
pletely differently – but there is amazing
synergy when they work together. To
conduct effective translational research,
that synergy is absolutely essential.”
Promising ResultsThe 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 battlingmelanoma, I wouldsay to keep your faithin God and the BrownCancer Center, and theywill pull you through.”
Tom FreemanMelanomaWestport
19FALL 2010
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 immunother-
apies 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.” �
Twenty-five years ago, businesses reliedon typewriters, carbon paper, andcalculators. FAX machines and small,stand-alone computers with wordprocessors were new to the scene,but showing promise as potentialtime-savers.
Today, of course, smaller, faster, morepowerful computers connected byhigh-speed fiber optics have completelychanged the way we conduct businessand live our lives.
The same evolution can be seen insurgery.
Twenty-five years ago, most surgerieswere performed through “open”incisions that required long hospitalstays, risked morbidity, and resulted insignificant scarring.
While laparoscopic and other minimallyinvasive techniques were introducedthrough the 1990s, there were stilldrawbacks, including the awkwardnessof the instrumentation, working in athree-dimensional space with only atwo-dimensional image for a guide, and
the exaggeration of hand tremors andsmall movements that could becatastrophic in micro-surgical situations.
Before 2000, surgical robotics was littlemore than a medical curiosity. Today,however, robotic surgery is gainingmomentum and proving to be a reliablealternative to open surgery for manyprocedures.
Surgeons at the James Graham BrownCancer Center have offered surgical alter-natives with the da Vinci Si surgicalsystem since its installation at Universityof Louisville Hospital in the fall of 2009.
Along with 3D HD visualization thatis now standard in such units, theUniversity Hospital unit is the only onein the area, and one of only a few in thecountry, to feature dual controls – allow-ing two surgeons to work simultaneouslyon complex cases.
Daniel Metzinger, MD, a BrownCancer Center gynecologic surgeon,emphasizes that the dual controltechnology “provides surgeons withenhanced ability to take our
multidisciplinary collaborativeapproach into the operating room.”
Patients seeking advances atBrown ClinicsLess than a decade ago, one of the mostdebilitating common procedures was thehysterectomy or any surgery of thepelvis.
In 2009, Shera McCandless was amongthe first patients to benefit from the newtechnology at the Brown. Following adiagnosis of a particularly aggressivecervical cancer, Brown Cancer Centersurgeon Lynn Parker, MD was able toremove the cancerous tissues effectivelywhile allowing Ms. McCandless to returnhome the following day. Just a few yearsago, recovery from this type of surgerywould have been measured in weeksrather than days.
“I feel lucky that this was available,”Ms. McCandless said three months afterher procedure. “I was sold when Ilearned that I wouldn’t have to takea whole month to do nothing aftersurgery.”
The surgeons of the Brown’sGynecologic Oncology Clinic, includingDrs. Metzinger, Parker, and MichaelMilam, MD, agree.
“With the da Vinci we’re seeingimproved patient recovery, shorterhospital stays, less scarring and betteroverall outcomes,” Dr. Milam said.
The same can be said of patients in theBrown’s Head and Neck Clinic.
When Jerry Stephens complained of asore throat and earache that wouldn’t goaway, his family physician prescribedantibiotics. Two weeks later, somethingstill wasn’t right, Stephens said.
“The antibiotics weren’t working,” hesaid. “I went to get a second opinion.”
That second opinion was a potentiallife-saver; an otolaryngologist discoveredcancerous lesions in his throat near hisvoice box.
20A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
not your grandfather’s surgery“3D,” “HD,” AND “DUAL-CONTROL” ARE MORE THAN TERMS FOR GAMING SYSTEMS
Drs. Lynn Parker, Daniel Metzinger, and Michael Milam visit with patientShera McCandless during a post-operative visit.
The University Hospital unit is theonly one in the area, and one ofonly a few in the country, to featuredual controls - allowing twosurgeons to work simultaneouslyon complex cases.
21FALL 2010
In April 2010 at University of LouisvilleHospital, UofL surgeons JeffreyBumpous, MD and Kevin Potts, MDteamed up to complete the first da VinciTransOral Robotic Surgery (TORS) in thestate of Kentucky and surroundingregion. They were able to remove thecancerous tissue with no major incisions.
According to Dr. Bumpous, leader of thehead and neck multidisciplinary team,“The da Vinci puts the camera at the siteof the cancer and gives us the ability tosee everything. It ultimately results inbetter outcomes for our patients.”
Jeffery Jorden, colorectal surgeon atthe Brown Cancer Center, draws theconnection of better outcomes directly tothe enhancements the da Vinci provideshis own surgical technique.
“The biggest advantage in colorectalsurgery can be seen when performinganastomosis of the intestine,” Dr. Jordenexplained. “The removal of hand tremorscombined with the 3D HD imagingallow for a higher level of precision.”
Future is Bright,and in the FutureRobotic surgery is growing and rapidly
expanding to new treatment areas.Scores of studies have been conductedand more are underway to quantify thebenefits and risks of robot-assistedprocedures. (See http://www.davincisurgery.com/clinical-evidence/for more information on clinical studies.)
It will take surgical pioneers andvisionary teachers such as those foundat the University of Louisville and atacademic medical centers acrossthe country to make the most of thetechnological breakthroughs.
“As with any relatively newtechnique or procedure,there is a learning curve,and it is important thatthings progress in anorderly fashion with alot of time spent to trainresidents, fellows, andpracticing surgeons touse minimally invasivetechniques safelyand effectively,” saidKelly McMasters, MD,chair of the UofLdepartment of surgery.“As a surgical communitywe must continue to
study and measure outcomes of thesetechniques to ensure the highest possiblequality of care for our patients.”
To date, University of Louisville surgeonsin four Brown Cancer Center multidisci-plinary clinics are offering patients thebenefits of robot-assisted surgery. Whilenot all cancers or tumor sites allow forthe use of the da Vinci, the patients whoare currently reaping the benefits aregrateful. �
FACES OF CANCER
”The Brown CancerCenter gave me a willwith the help of Godto live.”
Lettie StandardCervical CancerLouisville
“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 organi-
zation 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.
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.
22A publication of the J A M E S G R A H A M BROWN CANCER CENTERDiscoveries................
powerful computer gridVALUABLE RESOURCE FOR CANCER CENTER COLLABORATORSSEARCHING FOR NOVEL THERAPIES FOR CANCER
The computer grid allows John Trent, PhD,associate professor of medicine and directorof molecular modeling at the Brown, toshorten the time required to sort throughpotential compounds from years to days.
23FALL 2010
“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 ofbiochemistry 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
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
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. �
The Kentucky House ofRepresentatives honoredDr. John Trent for winning AppleComputer’s 2008 National ScienceInnovator Award. As director ofmolecular modeling at the JamesGraham Brown Cancer Center,Dr. Trent and 14 key scientists arediscovering new treatments fordeadly cancers.
John Trent receives Apple Computer'sScience Innovator Award.
FACES OF CANCER
”Laugh a lot andbe happy.”
Jennifer ZieglerAML LeukemiaLouisville
J A M E S G R A H A MBROWN CANCER CENTER529 South Jackson StreetLouisville, KY 40202
NON-PROFIT ORGUS POSTAGE
PAIDLOUISVILLE, KYPERMIT NO 879
mark your calendar...WHAT MAKES THE BROWNCANCER CENTER DIFFERENT?
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.
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 502-562-4642or [email protected].
w w w . b r o w n c a n c e r c e n t e r . o r g
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.
11/17 Kentucky Cancer Program/American Cancer Society CancerSupport Group Meeting – Brown Cancer Resource Center
11/21 Horses and Hope Day – Churchill Downs – 502-852-6318
1/13 Kentucky African Americans Against Cancer Volunteer Programand 20 Year Celebration – The Olmstead – 502-852-6318
1/29 3rd Annual Multidisciplinary Thoracic Oncology Conference:Ongoing Developments and the Latest Advances inLung Cancer – Clinical and Translational Research Buildinghttp://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 SurvivorWeekend Retreat – Homewood Suites Hurstbourne Lane502-852-6318
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 & Suiteswww.julepball.org