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.” �

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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.

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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

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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 jwilliam.kingston@louisville.edu.

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