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CancerResearchOFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

August 15 1993Volume 53 •¿�Number 16PP,3655-3847ISSN0008-5472 •¿�CNREA 8

WE FIND PATHS WHERE

OTHERS FAIL TO LOOK

f

At the Sandoz Cytokine Development Unit

(CDU), we are exploring new paths of research and

development and studying more options in disease

treatment than were ever thought possible. Using

the latest technology, the CDU is working to

develop these treatments rapidly, with the same

high-quality standards we have always upheld.

At the CDU, our commitment to research and

development is unsurpassed. Sandoz created the

©1992S.iiulii/ Pharmaceuticals Corporation

CDU as an independent unit, fueled by the

dedication of specialized personnel. These highly

skilled individuals have been brought together for a

common goal-to explore new paths of therapy.

CYTOKINE DEVELOPMENT UNIT

ORINO IM E W

s SANDOZ

CELL SIGNALLINGAND CANCERTREATMENT

Sponsored by:American Association for Cancer Research

European Organisation for Research and Treatment of Cancer(Pharmacokinetics and Metabolism Group)

British Association for Cancer Research

EORTC(RMVl)

December5-9,1993ElSanJuanHotel,SanJuan,PuertoRico

CONFERENCE CHAIRPERSONSGarthPowis/ Tucson,AZ

PaulWorkman/ Macclesfield,England

PROGRAM COMMITTEESaraA.Courtneidge/ Heidelberg,GermanyKatherineA.Kennedy/ Washington,DCHansH.Grunicke/ Innsbruck,Austria JohnS.Lazo/ Pittsburgh.PAJohnA.Hickman/ Manchester.England ThomasR.Tritton/ Burlington,VT

SCIENTIFIC PROGRAM

IntroductionGarth Powis/ Tucson.AZAllen I. ON«/ WestPoint.PA

TyrosineKinasesandInhibitorsLewis T. Williams / San Francisco.CAAlexander Levitzki / Jerusalem.IsraelAlex Matter / Basel,Switzerland

Serine/Threonme Kinases and InhibitorsPeterJ.Parker/ London,EnglandHansH.Grunicke/Innsbruck.Austria

GTPBindingProteinsAlan K. Hall / London.EnglandFrankMcCormick/ Richmond.CAJay Gibbs/ WestPoint,PA

DomainBindingandInhibitionSara A. Courtneidge/ Heidelberg,Germany

Lipid SignallingLewisC. Cantley/ Boston,MAAlan P. Kozikowski/ Rochester,MNPaulWorkman/ Macclesfield.EnglandGarth Powis/ Tucson,AZ

Application Deadline: September 7, 1993

Modulationof SignallinginCombinationChemotherapyThomasR. Tritton/ Burlington.VTJohn S. Lazo / Pittsburgh.PAStephenB. Howell/ LaJolla,CA

Signallingandthe CellCycleLaurentMeijer/ Roscoff,FranceCarolineDive/ Manchester.EnglandMichaelJ. Worin' Croton.CT

DorisL. Slate / PaloAlto,CAAdrianL. Harris/ Oxford,England

GeneTargetingStanleyT. Crooke Carlsbad.CAMichaelE. Hogan/ Houston,TX

SummaryPaulWorkman/ Macclesfield.England

Applicants are encouraged to submit abstractsfor poster presentation.

InformationandApplicationFormsAmerican Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483215-440-9300 215-440-9313 (FAX)

Keep upwith the latest developments in

CanœrRoseareThe Official Journal of the

American Association for Cancer Research

CancerResearch

January l W3VOUjr* 53 - Numtxx lPP1-207ISSNOOÛ&M7?. CNPTA

Carlo M. Croce, M.D., Editor-in-Chief

Subscribe to Cancer Research—the leading citation source of original studies in cancer researchand cancer-related biomédical science. Issuedsemimonthly, Cancer Research publishes 7,000pages of important research each year, includingthe following regular features:•¿�The most up-to-date articles in basic researchand clinical and epidemiological investigations byauthors from the United States and more than 20countries•¿�Perspectives in Cancer Research, in whichleading investigators explore contemporary andat times controversial topics•¿�Advances in Brief, a rapid communication category for short but definitive, highly significant reports•¿�Supplemental issues developed from symposiaon relevant subjects•¿�Proceedings of the American Association forCancer Research, a special annual issuethat offers stimulating new research ideas in abstractform

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CancerResearchThe MostHighly CitedJournalIn Its Field

AACR SPECIAL CONFERENCE INCANCER RESEARCH

MolecularApproachesto CancerImmunotherapy

November7-11,1993TheGroveParkInn,Asheville,NorthCarolina

CONFERENCE CHAIRPERSON

RalphA. Reisfeld/ LaJolla.CA

SCIENTIFIC PROGRAM

KeynoteAddressGiorgioTrinchieri/ Philadelphia,PA

MonoclonalAntibodiesfor TumorTherapyAlanN.Houghton/ NewYork,NYAlbertF.LoBuglio/ Birmingham,ALIra Pastan/ Bethesda,MDDavidA. Scheinberg/ NewYork,NY

Genetically Engineered AntibodiesStephenD.Gillies/ Lexington.MAJeffreySchlom/ Bethesda.MDRichardP.Junghans/ Boston,MASherieL. Morrison/ LosAngeles.CACliveWoodhouse/ MountainView,CA

Gene Therapy of CancerJamesJ. Mulé/ PaloAlto,CADrewM.Pardoll/ Baltimore,MDDavidT.Curiel/ ChapelHill,NCPatrickHwu/ Bethesda,MDElizabethJaffee/ Baltimore,MD

Cytokinesin TumorTherapyStevenGillis / Seattle,WARolandMertelsmann/ Freiburg,GermanyRonaldLevy/ Stanford,CATerryStrom/ Boston,MA

Tumor Antigens Recognized by T-CellsOliveraJ. Finn/ Pittsburgh,PAPerA. Peterson/ LaJolla,CAMartinA. Cheever/ Seattle,WAMichaelT. Lotze/ Pittsburgh,PA

Antibodies as ImmunogensSoldanoFerrone/ Valhalla.NYDorothéeHerlyn/ Philadelphia.PAKennethFoon/ Lexington,KYAlanN.Houghton/ NewYork,NY

Future of Cancer ImmunotherapyIsaiahJ. Fidler/ Houston,TXPaulM.Sondel/ Madison,WlIrwinD.Bernstein/ Seattle.WAEugenieS.Kleinerman/Houston,TX

Applicants are encouraged to submit abstractsfor poster presentation.

Information and Application Forms

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483

215-440-9300 215-440-9313 (FAX)

INTERACTIONS OFCANCER SUSCEPTIBILITY GENES

AND ENVIRONMENTAL CARCINOGENS

Joint Meeting Organized by theAmerican Association for Cancer Research (AACR)

and the International Agency for Research on Cancer (IARC)

November 9-13, 1993Lyon, France

CONFERENCE CHAIRPERSONSFrederickP. Li / Boston,USA

RuggeroMontesano/ Lyon,France

PROGRAM COMMITTEE

Kari K. Alitalo/ Helsinki,FinlandJ. Carl Barrett/ ResearchTrianglePark,USAValerieBeral/ Oxford,EnglandDirk Bootsma/ Rotterdam,The NetherlandsCurtisC. Harris/ Bethesda,USAHenryC. Pilot / Madison,USA

BruceA.J. Ponder/ Cambridge,EnglandCarmenSapienza/ LaJolla.USATakashiSugimura/ Tokyo,JapanLorenzoTomatis/ Lyon,FranceLeeW.Wattenberg/ Minneapolis,USAI. BernardWeinstein/ NewYork,USA

SCIENTIFIC PROGRAM

IntroductoryLecturesCurtisC. Harris/ Bethesda,USALorenzoTomatis/ Lyon,FranceLee W. Wattenberg/ Minneapolis,USAManfredF. Rajewsky/ Essen,Germany

GeneticInstabilityKariK.Alitalo/ Helsinki,FinlandT. Heidmann/ Paris,FranceTheaD.Tlsty/ ChapelHill,USA

ExperimentalModelsofGeneticSusceptibilityJ. CarlBarrett/ ResearchTrianglePark,USAHenryC.Pilot/ Madison,USABernardM.Mechler/ Heidelberg,Germany

DMADamageandRepairDirkBootsma/ Rotterdam,TheNetherlandsJohnM.Essigmann/ Cambridge,USAMulsuoSekiguchi/ Fukuoka,Japan

MechanismsofTransgenerationalCarcinogenesisCarmenSapienza/ LaJolla,USAUlrikeWinlersberger/ Vienna,AustriaDavidMalkin/ Toronto,CanadaChristopherJ. Kemp/ Glasgow,Scotland

HumanCancersFrederickP.Li/ Boston,USAValerieBeral/ Oxford,EnglandBruceA. J. Ponder/ Cambridge,EnglandNeilE.Caporaso/ Bethesda,USAGilbertM.Lenoir/ Lyon,France

Markersof IndividualExposureRuggeroMonlesano/ Lyon,FrancePeterA.Cerutti/ Epalinges,Switzerland

Opportunities for PreventionI. BernardWeinslein/ NewYork,USA

Applicants are encouraged to submit abstractsfor poster presentation.

Information and Application Forms

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483(215) 440-9300 (215) 440-9313 (FAX)

COVER LEGEND.

CancerResearch

We are pleased to present on the cover of this issue ofCancer Research the four winners of the three 1993 GeneralMotors Cancer Research Awards, two of whom, Drs. GianniBonadonna (upper left) and Bernard Fisher (lower left), werecorecipients of the Charles F. Kettering Prize. Consideringthe importance of their contributions, it is not surprising thatthe two were also corecipients of the Bristol-Myers SquibbAwards for 1993. Because of an unexpected problem inscheduling. Dr. Bonadonna was only mentioned briefly as acoawardee of the Bristol-Myers Squibb Prize in the coverlegend to the May 15, 1993 issue of the journal, which featuredBernard Fisher. However, Dr. Bonadonna was recognizedearlier in our April 1, 1992 issue as an American CancerSociety Medal of Honor awardee for 1991 and the recipientof the Rosenthal Award of the AACR in November 1982.

Working on opposite sides of the Atlantic, Drs. Bonadonnaand Fisher both made their major contributions to the alleviation of much of the suffering, disfigurement, and emotionalstress of radical mastectomy in human breast cancer. Dr.Bonadonna contributed benchmark developments in combination chemotherapy, now widely applied throughout theworld. His first combination, CMF(cyclophosphamide. meth-otrexate. and 5-fluorouracil), demonstrated significantlylonger survival rates of breast cancer over surgery alone.Improved combinations, such as ABVD (Adriamycin, bleo-mycin, vinblastine, and dacarbazine), were more effective inMOPP (mechlorethamine. Oncovin, procarbazine. and pred-nisolone)-resistant Hodgkin's disease. He has also shown more

recently (J. Gin. Oncol.. 7: 1380-1397. 1989; J. Nati. CancerInst, 82: 1539-1545, 1990) that primary (preventive) chemotherapy can be effective for conservative surgery in womenwho would otherwise be candidates for mastectomy.

After graduation from the Milan School of Medicine in1959 and postdoctoral experience at Sloan-Kettering, Dr.Bonadonna returned to the Milan Tumor Institute, where henow is Director of the Division of Medical Oncology. Asmentioned previously, he received the Rosenthal Award fromthe AACR in 1982.

Dr. Fisher, Distinguished Service Professor of the University of Pittsburgh and chairman of the National SurgicalAdjuvant Breast and Bowel Project, shares the 1993 KetteringPrize for a brilliant career, which showed that breast cancer

can be treatable with minimal surgery. He also contributedto the justification and popularity of adjuvant chemotherapywith minimal surgery, which has now become a key part ofbreast cancer treatment (Cancer Research cover legend. May15. 1993). His accomplishments have greatly minimized thephysical and emotional trauma of the patient subjected toradical mastectomy. Dr. Fisher is now involved in a projectentailing a massive tamoxifen prevention trial for breast cancer, which is under way in several hundred centers in theUnited States and Canada.

Carlo M. Croce, M.D.. (upper right). Director of the Jefferson Cancer Institute and of the Jefferson Cancer Center inPhiladelphia, PA, is receiving the Charles S. Mott prize foroutstanding achievements in unraveling the molecular mechanisms involved in the malignant transformation of cells ofthe immune system. In 20 years of research at the WistarInstitute and now as Director of the Jefferson Cancer Instituteof the Thomas Jefferson Medical College, he has identifiedseveral key chromosomal rearrangements leading to the activation of oncogenes responsible for leukemia and lymphoma.He has deciphered the molecular mechanisms of a number ofchromosomal translocations leading to Burkitt's lymphoma,

follicular lymphoma, mantle cell lymphoma. and acute lym-phocytic leukemia. In addition. Dr. Croce has shown theinvolvement of the genes for the T-cell receptors in therearrangements in T-cell neoplasms. Among his impressivelist of accomplishments in molecular genetics are the trans-location of the c-myc oncogene triggering Burkitt's lymphoma

and the discovery of the bcl-l and hcl-2 oncogenes involvedin certain low-grade leukemias and lymphomas. These probesfor two oncogenes are used for the diagnosing and monitoringof these neoplasms.

For his critical contributions to the molecular genetics ofhuman cancer, he was awarded an Outstanding Investigator-ship of the NIH in 1985. and this has been renewed in theamount of $15 million for the next 7 years. He lives in centercity Philadelphia with his 13-year-old son and is a collectorof art of Italian masters. Among his many outside activities,Dr. Croce is Editor-in-Chief of Cancer Research.

Hidesaburo Hanafusa, Ph.D. (lower right), of The Rockefeller University, New York, is being awarded the Alfred P.Sloan Prize for the discovery of the singular role of damagedcellular oncogenes in cancer. He discovered and characterizedthe crk oncogene from a tumor-causing chicken virus. Theprotein encoded by this oncogene has two molecular structures, SH-2 and SH-3. which are responsible for its oncogenicactivity and are also products of many human oncogenes.These proteins are involved in signal transduction, responsiblefor proper cell regulation. Dr. Hanafusa made the revolutionary discovery that the Rous virus, when stripped of its srconcogene, could still maintain its malignant property bypurloining the infected cells' own src oncogene. This extraor

dinary discovery conclusively demonstrated that oncogenesoccur generally as normal components of mammalian cellsuntil switched on to malignancy and are not confined to aninfecting virus. As stated by Peter Vogt, the 1991 Mott Prizewinner, "This early discovery by Dr. Hanafusa was a quantumleap for cancer research."

A recipient of the Clowes Award from the AACR in 1986,Dr. Hanafusa resides in New York City with his wife, TerukoInoue, a senior research associate at The Rockefeller University.

We are grateful to Molino & Associates, Inc., for thephotograph and much of the information presented in thislegend.

Sidney Weinhouse