`
`Proceedings
`
`MUCUSECC
`Cee retary
`
`flTT
`EttFea)
`
`Miltenyi Ex. 1014 Page1
`Volume 49 e April 2008
`
` -
`
`Translating the latest discoveries
`into cancer prevention and cures
`
`9
`
`3 5
`
`Aptil 12-16, 2008
`SrMCs
`Sem eTyaT
`ag
`CMEjointly sponsored by the Vanderbilt University School of Medicine
`andithe American Association for Cancer Research.
`
`Miltenyi Ex. 1014 Page 1
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`

`

`American Association for Cancer Research,Inc.
`
`Officers
`
`President sconancmmnasiomenaeeeneESWilliam N. Hait
`
`President-Elect ......:.:::cccstesecsssnasavssesavscsecertbatencenstenedtsossessansesensensRaymond N. DuBois
`
`TrCASULEN .oe.seescseeceeseesssescneesenseestsaeensnsaeeneeessseecesernessasensaveneneeaeanensBayard D. Clarkson
`
`Past Presidetitrecs sassansiscentsvesusiusraceansccrsusscssacsienerssoeurasnsensmsnecesseesoneesGeoffrey M. Wahl
`
`Chief Executive Officet....ccccescesssesseesereeseceessenrenseenearaeenauesensenaessseessaneeesMargaret Foti
`
`Board of Directors
`
`Until 2010
`Until 2009
`Until 2008
`Judy E. Garber
`James L. Abbruzzese
`Sara A. Courtneidge
`Susan D. Desmond-Hellmann—_Lucile L. Adams-Campbell—Joe W. Gray
`Scott W. Lowe
`Elizabeth H. Blackburn
`Daniel A. Haber
`John D. Potter
`David R. Parkinson
`V. Craig Jordan
`David Sidransky
`Helen M. Piwnica-Worms
`Eileen P. White
`
`Address inquiries to the Office of the American Association for Cancer Research, Inc. (AACR), 615 ChestnutStreet,
`17th Floor, Philadelphia, PA 19106-4404 [Telephone: (866) 423-3965; Fax: (215) 440-7228; E-mail:
`aacr@aacr.org].
`The Proceedings ofthe American Association for Cancer Research 1s printed for the AACR by Cadmus Professional
`Communications, Columbia, MD 21046. Volume 49 of the Proceedings ofthe American Association for Cancer
`Research (ISSN 0197-016X) succeeds Volume 48. The CD-ROM version of the Proceedings is includedin the
`benefits of membership for active and associate members andis provided to authorized registrants of the AACR
`Annual Meeting, Apri! 12-16, 2008. Print copies are available for advance order by members and advanceregistrants
`of the Annual Meeting; in addition, while supplies last, the print Proceedings may also be purchased at a price of
`$60.00 by contacting the AACR Subscription Office, 615 Chestnut Street, 17th Floor, Philadelphia, PA 19106-
`4404 [Telephone: (866) 423-3965; Fax: (215) 440-7228; E-mail: pubs@aacr.org]. Add $6.00 for shipping for orders
`outside the U.S. Expedited delivery rates are available upon request.
`
`The Proceedings ofthe American Association for Cancer Research is copyrighted © 2008 by the AACR.All rights
`reserved. Redistribution orresale of the Proceedings or of any materials in the Proceedings, whether in machine-
`readable, other electronic, or any other form, is prohibited. Reproduction for advertising or promotional purposes,
`or republication in any form, may be permitted only underlicense from the AACR. Anyreproduction, whether
`electronic or otherwise, of abstracts beyond that permitted by copyright law must be authorized in writing in
`advance by the AACR. Requests to reproduce abstractswill be considered on anindividual basis and permission may
`be granted contingent upon paymentof an appropriate fee. Reproduction requests mustinclude a brief description
`of intended use. Third parties should also obtain the approvalof the authors before corresponding with the AACR.
`Failure to comply with the foregoing restrictions and unauthorized duplication of any portion of these materials are
`a violation of applicable laws and may be subject to criminal prosecution andcivil penalties.
`Noresponsibility is accepted by the Editors, by the American Association for Cancer Research, Inc., or by Cadmus
`Professional Communications for the opinions expressed by the contributors herein.
`
`Miltenyi Ex. 1014 Page 2
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`Miltenyi Ex. 1014 Page 2
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`

`

`Proceedings of the American Association for Cancer Research
`AACR Annual Meeting 2008
`April 12-16, 2008 * San Diego Convention Center
`San Diego, California
`
`Abscracts are numbered from 1 through 5867; however, s¢veral numbers may be omitted in the sequence. Abstracts were received directly from the
`guthors by electronic submission. Every effort has been made to reproduce the content of the abstracts according to the electronic version
`gabmitted, except in certain instances where changes were made to comply with AACRstyle. The AACR does not assume any responsibility for
`proofreading or correcting anyscientific, grammatical, or typographical errors, nor does the AACR assumeresponsibility for errors in the
`conversion of customized software, newly released software, orspecial characters. No responsibility is assumed by the AACR, publisher and
`copyright ownerofthe Proceedings; by the Vanderbilt University School of Medicine; by Coe-Truman Technologies, providers of abstract
`managementsoftware and services; or by the meeting organizers for any injury and/or damage to persons or property as a matter of products
`liability, negligence or otherwise, or for any use or operation of any methods, products,instructions, or ideas contained in the material herein.
`Independentverification of diagnoses and drug dosages should be made byreaders or users of this information.
`
`Continuing Medical Education (CME) Information
`
`Accreditation Statement
`This activity has been planned and implemented in accordance with the Essential Areas andPolicies of the Accreditation Council for Continuing
`Medical Education (ACCME)through the joint sponsorship of the Vanderbilt University School of Medicine (VSOM) and the American
`Association for Cancer Research (AACR). VSOMis accredited by the ACCMEto provide continuing medical education for physicians.
`
`Credit Designation Statement
`Vanderbilt School of Medicine designates this educational activity for a maximum of 47.25 AMA PRA Category I Credit(s)™.
`Physicians should only claim credit commensurate with the extentof their participation in the activity.
`2008 AACR Annual Meeting Statement of Educational Need, Target Audience, and Learning Objectives
`Advances in technology, progress in prevention, and rapid developmentsin thefield oftranslational cancer medicine have led to the increasing
`importanceoffostering dynamiccollaborations amongphysicians andclinician-scientists. These collaborationswill assist in gaining greater
`understanding andinsight into the significant contributions oflaboratory research to drug development and patientcare; to the design and conduct
`of clinical research protocols; to the epidemiological implications of cancer incidence; and to the immediatetranslation ofthe findings of laboratory
`research for the benefit of improving care and quality oflife of the cancer patient.
`
`This Annual Meeting is directed towardsscientists and clinicians engagedin all aspects ofclinical investigations pertaining to human cancer as well
`as the scientific disciplines of cellular, molecular, and tumorbiology; carcinogenesis; chemistry; developmental biology and stem cells;
`endocrinology; epidemiology and biostatistics; experimental/molecular therapeutics; immunology; radiobiology/radiation oncology; imaging; and
`prevention and survivorship research.
`
`After participating in this CMEactivity, physicians should beable to:
`
`* Demonstrate a clear understandingofthelatest research findingsin all areas of cancer research and how thesefindings will impact future
`decision making in the detection, diagnosis, prognosis, treatment, and prevention of cancer;.
`:
`* Translate how the integration of information from the basic, translational, and clinical sciences applies to the development of new drugs, and
`clinical researchtrials;
`Employ technological advancesto accelerate the research progress, improveearly detection and screening options, which will ultimately extend
`patients’ lives and improve their quality oflife;
`Formulate new strategies and forge collaborations that will further scientific and clinical research efforts towards the prevention, diagnosis, early
`detection, and treatment of cancer
`Evaluate the use of biomarkers and other indicators to better treat patients in this era of personalized medicine, and to make recommendations
`for clinical trials;
`Interpret scientific advances that increase understanding of cancer biology and pathogenesis.
`
`Disclosure Statement
`It is the policy ofVSOM thatthe information presented at VSOM-sponsored CMEactivities will be unbiased and based on scientific evidence. To
`help participants make judgments aboutthe presence of bias, VSOM and the AACRwill provide information that Program Committee members,
`speakers, and abstract presenters have disclosed aboutfinancial relationships they have with commercial entities that produce or market products or
`Services related to the content of chis CMEactivity. This disclosure information will be made available in the Proceedings Supplementofthis
`Meeting. In addition, off-label and investigational uses will be identified when mentioned.
`
`Claiming CME Credit
`Individuals wishing to receive AMA PRA Category I Credit(s) ™for their attendance at this conference should obtain a CME Information Kit,
`Which includes the Request for CME Credit form, from the CME Booth at the Annual Meeting or by writing to cme@aact-org. This form must be
`completed and returned to the CME Booth or the Office of CMEby April 25, 2008. All CME certificates will be available electronically from
`SOM following the meeting. Please visit www.cme.vanderbilt.edu for more information on how to obtain a certificate.
`
`Questions about CME?
`Please contact the AACR Office of CMEat (215) 440-9300 or cme@aacr.org.
`
`Next Annual Meeting:April 18-22, 2009, Denver, Colorado Miltenyi Ex. 1014 Page3
`
`Miltenyi Ex. 1014 Page 3
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`

`

`2008 Annual Meeting of the
`American Association for Cancer Research
`San Diego, California ¢ April 12-16, 2008
`Volume 49 © April 2008
`
`Table of Contents
`
`Session Title
`
`Page
`
`SessionTitle
`
`Page
`
`Cellular and Molecular Biology (CB)
`
`Stress Responses ....scscsecsseeeeeeeeeeseeceeeseneeneeeseseerareetnssavenenass435
`
`Epigenetic Alterations in Cancer: Causes and
`
`Basic Aspects of Gene Regulation in Cancer... 570
`
`Consequences.sisavalsustnmanncncenmancia dates ass 1
`
`Cell Surface Receptors in Cancer Initiation
`
`Epigenetic Profilingisccesssesssievcasassnntionenuacientanne tiepmaenieveieees7
`
`and Progression.....cccccsescescesecteeserensessersenesesenereaes 595
`
`Gene Regulation and Promoter Studies -.....ccsceeeereseesees 14
`
`Mechanisms Underlying Epigenetic Alterations
`
`Growth Control: Gene Regulation...cece eee21
`
`In. Cancel sscinisentecesnsesccnseneneannsmuanranacesnanaganeuneereenenganene 598
`
`Oncogenic Receptor Pathways 0.0...27
`
`Gell Cycle 1 sssssisstsnsccsareninxessonsencviancasansenniensasiissuensovennennte613
`
`Post-translational Control of Gene Expression and
`
`Epigenetic Therapy ssciniviniiuatncniviniiniemtannenentsy.618
`
`Gene Slleneingsinccamnnsimmonninmnmmnacnauds 34
`
`Epigenetics of Cancer: Clinical Implications.......see623
`
`Somatic Genetic Approaches to Cancer Gene
`
`Experimental ‘Therapy: Lesissisneveeenosiecssxenmnonrarannanns 630
`
`ToeHELAEATIOl cpesaxscsonesmmenssencnensamiennecancannaniiiaatanaabiend 41
`
`Experimental Therapy 2sscccesvesnreonseinenenssapeasaneanaaensnnns+4636
`
`Computational Systems Biology Applications
`
`Metabolism of Canice tecsuississaveaisesavoxesosesonosasxavanonsesxiurien 643
`
`and Resorcessssiseiessaratiesasyaiceenetiareiersveseneaivecia ite 185
`
`Signal Transduction and Therapeutics.cscseseserensenessen650
`
`Death Receptor and XIAP Antagonist Induced Apoptosis191
`
`Tumor Suppressor Pathways «.ccccssscnscressssereecrssstseereesseesnees656
`
`DYNA Danae aiid. Repair: seccrsennnonnnrernstionneetcinemnnerantenta 197
`
`Anticancer Therapies Targeting Autophagy,
`
`Signaling Pathways That Regulate Gene Expression......... 201
`
`Proteasome, and Survivin ...cseseecseteeccseeeeeeesteesseteeneetes 796
`
`Therapeutic Implications of Oncogenic Pathways1 ........ 208
`
`Apoptotic. Signaling :sisissnsninnnnanisaisenaneiirensioncarsanniniven 803
`
`Translational and Functional Genomics ....cceesseerereeeees 213
`
`Modulators of Tumor Cell Growth .....eccceseceeseeececeeeetees 809
`
`Programmed Cell Death in Tumorigenesis and Therapy..363
`
`Nuclear Signaling Pathwaysexcaanimnuinieieniainaeee 816
`
`Therapeutic Implications of Gene Regulatory
`
`Protein Kinases.......ccccccccceecessseesenececesessenetseeseeeteentetssneee BL
`
`Mechaitisittswcincscrstniccnemmveineiantmuaniimmanan 366
`
`Receptor Function, Signaling Methodology.......ceceuee 828
`
`Bioinformatics and Computational Molecular Biology ....385
`
`Signaling in Lung and Brain Tumorigenesis....00.00ccc00. 834
`
`Cancer Genomics 1: Genomic Profiling I SEER391
`
`Small G Proteins, Lipid Signaling, and mTOR................ 841
`
`Cancer Genomics 2: GenomicProfiling TL... cee397
`
`TumorProgression and Markers ......:sscsesssrsessseseessesenenees 847
`
`Cancer Genomics 3: Genomic Profiling IID ...cccccessereers404
`
`Interrogation of Cancer Genomes....cesesesenenenersenareeees 981
`
`DNADamageand Hypoxia: Regulators of
`
`Molecular Subtyping and Classification of Tumors:
`
`Gene Expression oo. eecsenerscsessecserseseetnenesneseanenenes410
`
`Biological and Clinical Implications«1... 984
`
`New Oncogene and Tumor Suppressor Pathways.............416
`
`Cell Cycle 2 sasssssasssssssssusaesnssacssscsiascaxicisacceiccationvbase 1004
`
`Novel Biomarkers for Tumor Detection and Progression .422
`
`p53, Telomerase, and Semescence..scesercreeverrvertseereersvnenres428
`
`Clinical and Biological Implications of Aberrant
`Miltenyi Ex. 1014 Page 4
`Gene EXpression spcamsscssevsnsossnsaensoencncaneninennnnies 009
`
`Miltenyi Ex. 1014 Page 4
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`

`

`Page
`Session Title
`Epigenetically Altered Oncogenes and Tumor Suppressor
`
`Session Title
`
`Page
`
`TUMOL VACCINES occ cess eeeeeeereeteeneeeneesesiaetsseseseserseaseneens 670
`
`GENESsnncieneteene Geese oeunaaneiananens LOG
`
`Molecular Predictors of Drug Sensitivity and Resistance..853
`
`Epigenetically Altered Pathways .....-ssssssesssresssessrsssrsnsesnes 1023
`
`Novel Assays and Technologies ssssxsssec avemucanatnaesscnansis 861
`
`Genome Instability: sensiassensimnccnonsmeuneroncsennenmenenmnenee 1027
`
`Molecular Signatures and Proteomic Biomarkers........... 1053
`
`Metabolic Approaches to Cancer vic cssscsesenerenenen 1032
`
`Phase II and III Clinical Trials 1; Gastrointestinal,
`
`Regulation of Bcl-2 and Caspases for Cancer Therapy...1039
`
`Pancreatic, Head and Neck, and Melanoma........... 1060
`
`Regulatory Genes as Targets for Therapy.....ssceesneeees 1046
`
`Phase II and III Clinical Trials 2: Genitourinary,
`
`Autophagy, Metabolic Stress, and Tumorigenesis.,......... 1173
`
`Gynecological, Breast, and Cachexia.......scsseessees 1065
`
`Therapeutic Implications of Oncogenic Pathways2 ......1176
`
`Molecular Markers for Cancer Diagnosis and
`
`Cancer Genomics 4: MicroRNA Profiling Lo... 1195
`
`Determination of Patient Outcomes....ccccceeces 1179
`
`Cancer Genomics 5: MicroRNA Profiling TH] ...........0...1202
`
`Novel Genomic Approaches, Drugs, Targets,
`
`Gell CyGlé: 3S nvrensnconesseetanenenmntenensstaennernessuenrstsesnerretonnster 1208
`
`anid, Strategtesivcricisnvnannemmnmnmnmeanemens 1182
`
`Cytokine and TGE-B Signaling.......ccscesssesseeeeeerens 1212
`
`Molecular Coxrelates 9 ysnensmomeerSeonancorernnnasenestoe 1303
`
`Emerging Techuologies): snnausmnnainesrnmenenncanses 1220
`
`Phase II and III Clinical Trials 3: Blood, Lung,
`
`Integration of Omics Technologies.....,...sseeseeeerieeee 1226
`
`Brain/CNS, and Sarcoma.....ccccscsscscssssteteessseeeseees 1311
`
`Signal Transduction in Breast Cancer,......:ssseserenereee L232
`
`Prognostic Biomarkers 2ecscnenmmrmmntinnmunamncesss 1316
`
`Signaling Pathways 1 ssmssianskeicnaccemmnngmieamnasreceenaeions 1239
`
`Signaling Pathways 2 sssissaivesssexsnsorsietasensinaiseassacsntens 1245
`
`Immunology (IM)
`
`Transcription Factors s.sesmcaicmiitensiansnnecieniats 1251
`
`Immune Biology / Tumor Microenvironment.......cseeses 56
`
`DNA Repair and Mutagenesis ......s:sccssesesesseessneseeeeseees 1372
`
`Tumor Immunobiology c.ceccseseesesssssscescecerecscseenesacnenee238
`
`Intracellular Signaling and Growth Control... 1375
`
`Immune Modulation 1 cesscssscscscsesceesvesessvenssensenssaeseeeseveeee 400
`
`Oncogenic and Tumor Suppressor Pathways... 1377
`
`Tumor Microenvironment py srreentersesscszempersnremessannett yin’ 583
`
`TUMOE VACHS Lisnsecrnoter eencezeniennrsnneticeweemapemninennnter 673
`
`Clinical Research (CL)
`
`Immune Modulation 2 siisceississsscsesnvessscnvensneessseceaveenn sens 897
`
`Phase I Clinical Trials and Clinical Pharmacology 1/
`
`Adoptive Cell Therapy wacsaniniinencannnrnmnmemuning, 1099
`
`Novel Trial Desighs...scsssssssessessssssssteussesssnessnseeen47
`
`Developmental Immunotherapy «...-scesscssesereseresneeseseesee 1188
`
`Phase I Clinical Trials and Clinical Pharmacology 2 .......... 52
`
`Tumor Vaccines 2 ....sccseseseescseerseeteenseerneeseneenenerererareseeeees 1258
`
`Biomarkers for Diagnosis and Detection...220
`
`Prognostic Biomarkers 1 ...c.sessssssssessecsesescseeeseeeeneeseeenenees 227
`
`TumorBiology (TB)
`
`Radiation Oncology....ssssessssessseeeseessseessnesesneeeenesssies234
`
`Antiangiogenesis apc ee eae il Gcgaye)2.
`
`Antibodies and Immunotherapy «..c.sscsecsseesecseeesessseeeneens 501
`
`Cell Surface and Signaling Changes Impacting Tumor
`
`Molecular Correlates L.essssessesssssssessssssuessssvesessescnssneensesssee 508
`
`Development and Progression ...ss.ssseecseenensreeceteeaneees 68
`
`Molecular Correlates Qissvssacansvvossonetasssscihevssrssnsucisatssiuiscu 515
`
`Genetic Modifiers of Metastasis .........cssssssssescesseeeresessenees 74
`
`Clinical Immunotherapy, ..ssssssecsesssssseesssrssseersseseseessereee OO
`Novel Drug Targets, Agents, and Mechanisms...........000662
`
`Inhibition of Angiogenesis and Targets for Inhibition........ 81
`
`siiesien88
`New Models for Studying Metastasis ..........
`MiltenyiEx. 1014 Page 5
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`Miltenyi Ex. 1014 Page 5
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`

`

`Session Title
`
`Page
`
`SessionTitle
`
`Page
`
`Radlosensitizing Agents: csscncsceusensnresanneaneneasdcnvagreveerexceietive 93
`
`Imagingin Preclinical and Clinical Therapeutics...........++ 880
`
`Tumor/HostInteractions, Angiogenesis,
`
`Pediatric Cancer’ Sisgrteesmerenmnsceses vcmmaueniaactacccvneteernmiens 885
`
`and Metastasis -...cccecserscssscesessessenecssccocesssnvvavevscerasees 101
`
`Stem Cells in the Central Nervous System..........0eeesee 892
`
`Endothelial Cell Activation and Signaling in
`
`HostInfluences on TumorProgression wesc999
`
`“DUNTIOTIBOTES15 as cascencanssacsanucimecemeremcutimanstnereeua se mesusanics252
`
`Radiation Biology and Experimental Radiotherapeutics. 1002
`
`Inhibition of Angiogenesis 1 .......cc:sessesssesesssseseseesensseareees259
`
`Expression Profiling and Biomarkers of Tumor Growth.1069
`
`Deoveases atid Protease Inbibitioticncecmapemncsemaee 267
`
`Imaging Tumors and the Tumor Microenvironment......1076
`
`‘Targeting Cancer Metastasis for Therapeutic
`
`Molecular Determinants of Tumor Susceptibility and
`
`Intervention a... cccceesseeseeseceenserceeeeeeseseeteeseseneneenenes 274
`
`PEGSTESSION scsncncesisennenemermennemeeesmneae 1081
`
`Therapies Affecting Tumor Progression.......:::+:++ses+++++++++-280
`
`Stem Cells in the Gastrointestinal and
`
`Molecular Basis for Organ-specific Metastasis........0.000++ 378
`
`Genitourinary Tracts sssussssesccseassovvsvesnesceiianneasszanees 1088
`
`Pediatric Cancer ]ov.cicccecesecsesseseccesreveccnscesseesersssetsesessees 382,
`
`Therapeutic and Radiation Responsiveness
`
`Pancreatic Cancer: Molecular Determinants.....cccceccce0000e.456
`
`of Stem Cells sagsiseansccacsasteicatssaasaseaaistieinnticesneeans 1093
`
`Role of Integrins and Extracellular Matrix in Tumor
`
`Generation and Maintenance of Cancer Stem Cells....... 1192
`
`PROSTESSION sesegeenTiieieiieR specks ndactan sp ooteeurisannonneverinivat’ 459
`
`Chemokine/Chemokine Receptors and
`
`Signaling Molecules Affecting Tumor Cell Mobility,
`
`Myeclomonocytic Cells svccccnnesssncusmvannnanscaariesiiiies 1265
`
`Invasion, and Metastasis sccssesssrescessesies ces svesiceteoeeneees 466
`
`Epithelial-Mesenchymal Transition sessssssssssessscsnessessnees1 272
`
`Stem Cells in Hormone-Dependent Cancers: Breast,
`
`Inflammation and Metastasis ......sssssecseseseseseessneereneseseee 1278
`
`Prostate, and, Ovarian acisazsrcesistssnescdhciancsnrereenecareseeeeey472
`
`SOT O81 rc onsen enosensitt Meaemrmmacmmammunsencscresna ite iS monanunll 1285
`
`Tumor Hypoxia, HIF-1 Inhibition w....ccccscsseseseeseseseersens479
`
`Endothelial Progenitors: Induction of Angiogenesis....... 1390
`
`Genes Regulating Cancer Metastasis .....cccsssssscsecessereess 587
`
`New Animal Models to Study Cancetn...sccscescsesssereereeeese 1 393
`
`Inhibition of Angiogenesis 2: New Targets
`
`ancl, Resistance’ savcgasiwsteisssusaiceteaiccnnannanacamianems590
`
`Prevention Research (PR)
`
`New Targets for the Therapy of Metastasis........cccccescseees 610
`
`Cancer Prevention. 1] -sarcuuscocmanecumummnarcenrrensecucy wn 108
`
`Cell Adhesion and Cytoskeleton.......cccccccsscssesssseeseseseeeee 681
`Genetically Engineered Models to Study Breast and Prostate
`
`Preclinical Prevention Studies: Biomarkers
`
`and Preventioncasaessscaeiisiesiciaeccai tii eiacsevnceveserseeiwense 115
`
`Cancers and Cell Responses to Treatment............2..+ 686
`
`Cancer Prevention 2 .0......ccccceescscesseserseeesnsensevensensuveseaacnes291
`
`New Models 1: Gastrointestinal, Liver, Skin, Squamous Cell
`
`Biomarkers in Cancer Prevention........ccccccccsesscessvtsesesears 375
`
`Careinoma, and, Neurofibronia..xssesccaxardunmeuneanes 693
`
`Ganeét Prevention 3 wassenswecmisweumnitinnietseailbveelciessecs493
`
`New Models 2: Leukemia, Mammary, Ovarian, Lung, and
`
`Cancer Prevention A. casasnsinawivaicevsiidiciiataerstecssacnerseensnees?21
`
`Renal Cancer ...ccccccccsecsesssesssecsesesseseceseetvsssassesececesenes 700
`
`Cancer Prevenitiont :5 2c. ...asseasecensiiansenvitiverwiwelantlscovensiie es 902
`
`Pediatric Cancer 2...cccccccccesssssessesscesenevenscasecsessesssecacesegnas 708
`
`Chemopreventive Strategiesscsuaissnsousvivarsassaielsacasineaniiinnali997
`
`Determinants of Metastasis ......cc...::-sccssssssesssesseseuvserennennas 868
`
`Cancer Preverition 6 sssmissswssvsnsscaraieescitceatig einarcasavacdiens 1106
`
`Environmental and Microenvironmental Impact
`
`Cancer Prevention 7 sasigseeiisasissasiisadagi secstrssnscsnsnesecarennvn 1298
`
`on Tumor ProgressionncdccstisisnnnnianinanmananB79
`
`Miltenyi Ex. 1014 Page 6
`
`Miltenyi Ex. 1014 Page 6
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`

`

`SessionTitle
`Epidemiology (EP)
`
`Page
`
`SessionTitle
`
`Page
`
`New Modulators of Enzymes, DNA, and Protein
`
`Biomarkers of DNA Damage and Repair, Exposure,
`
`[niteractiO18sicivicassnuseerucisnreveenncccsaiuanunimeaneanaremanenan. 304
`
`and Phehotypé lecacekGnokot... 28m 122
`
`Chemical Aspects of Carcinogenesis ........::cscetseceseecseeeess 530
`
`Molecular Markers and Phenotypes.....:s:sssseesrereseceseeeseeees 129
`
`Proteomics Applied to Cancer Diagnosis
`
`Environmental, Occupational, and Drug Exposures........ 244
`
`and Treatment Semssyenrtventtalanennesernprenedeeerseeind one 574
`
`Biomarkers of DNA Damage and Repair, Exposure,
`
`Imaging Agents and Radiotherapeutics........s.s0sesesereeerene749
`
`and Phenotype 2 .issssssiesscovssvesesesvsesssoecaveronsevoarastvesee44]
`
`Structural, Biology vssusssciscsusssiccecsninosdcidastaunscoaivntiions755
`
`Genetic Epidemiology 1: Breast and Ovarian Cancer......449
`
`Proteomic TumorProfiling 1 .occccseseessssesseesesseaeeeen DIZ
`
`Diet, Physical Activity, and Body Mass Index............0+4728
`
`Proteomic Tumor Profiling: 2 ccsrecssedebersrerpnenenrsbecdee denver 937
`
`Genetic Epidemiology 2: Colon,Prostate,
`
`Drug Design and Deliveryierbescsssarscsranessrosensreraresneannnenoness 987
`
`and, Lung Canteen wonsnniaasnaninnnansat 735
`
`Chemical Aspects of Cancer: Targeting, Discovery, Delivery,
`
`Descriptive Epidemiology, Ethnicity, and
`
`and, Detectionnasi eccrine 1127
`
`GeOptaplic FACT gry een omen Bel canernarnanncanaaie ansnannaas 909
`
`Drug Delivery and Targeting.......0s.s000+aia 1330
`
`Epidemiology of Cancer Survivorship ...sssseseseenersenerees917
`
`Genetic Epidemiology 3: Hematologic, Genitourinary,
`
`Experimental and Molecular Therapeutics (ET)
`
`Gastric/Esophageal, and Head and Neck Cancer......924
`
`DNA Damage and the Cell Cychevsnsssusisercaiutiarensenenaai 150
`
`Dietary Patterns and Cancer Risk ........:csssesesseseseneeesens 991
`
`Drug Resistance 1; Cellular Mechanisms.........0..+0:10004 157
`
`Genetic Epidemiology 4: Other Tumors and
`
`Drug Resistance 2: Platinum Agents and Taxanes............ 164
`
`Functional/Methodologic Studies 0... eee 1113
`
`Histone Deacetylase Inhibitors and Cell Cycle
`
`Genetics and Genomics of Cancer Susceptibility ........... 1380
`
`Inhibltorsicnecsscccnamwmmnvenanenns ceruradteeee 171
`
`Carcinogenesis (CG)
`
`Topoisomerase I and II Targeting Agents ...........csccsesees 178
`
`Hiologteal ‘Therapy CiortibiathOtt resngsqceeeienitvenrersmenne309
`
`Mechanisms of DNA Damage and Carcinogenesis..........136
`
`GSE PETE| ananconemraentrnionenetenepeti se esenmecencmseTicartalecet!316
`
`Signal Transduction Pathways and Tumor Promotion......523
`
`Gene Therapy: 2isisesssesaxtuassccexentiesnsenetincemenenctnmrectenente 323
`
`Molecular Mechanisms of Carcinogenesis........ccccscseeeeee 592
`
`Inhibition of Microtube Function........c sce secsseeeeeeeens 327
`
`Reactive Species and Hormonal Factors in
`
`mTOR/Akt/PI3K Inhibitors and Vascular/
`
`Carcincepnies|S cermansnmenaniemmmnuniocerdeonneamnaree742
`
`Hypoxia ‘Tareeting ApentS ccsrscscsncsccscrsceerseecereeneenss 333
`
`Chemical and Viral Carcinogenesis in Target Organs....1121
`
`Radiation Effects: DNA Repair and Predictive Markers...339
`
`Carcinogenesis Models: in Vitro and in Rodents........... 1170
`
`Signal Transduction... cessesee343
`
`Chemical Mutagenesis and Carcinogenesis ........:0se 1323
`
`Targeting Novel Aspects of Tumor Biology ....scccscssuu 350
`
`Cancer Chemistry (CH)
`Natural Productsssssessisssvecscsvesssssesssucsssudsensuasencusserevesostuver 143
`Drug Discovery: Screening, Rational Design,
`
`aiid: DMPIC. _anrchssrondicenrerennsinareneh iaasincisibe GEE:298
`
`Targets and Screening Approaches sgcsastisianiendenaineD0 7
`
`Small Molecule Inhibitors of Novel Threats... 372
`
`APOPlOSIS vawicerecusseraesancevsvevscneusseverecesncanemnuanaeneesesbeeeeneerens 533
`
`Drug Discovery Lisvsssissnuussiinanonssausansivnienanainanannnrenssananes ao9
`
`New Agents and Therapeutic Approaches ....sscsessssseerseeses 543
`Miltenyi Ex. 1014 Page 7
`
`Miltenyi Ex. 1014 Page 7
`
`

`

`Page
`SessionTitle
`New Targets 1: Mechanisms.........ccccccscsccoeesessscessessssessees 550
`
`Page
`SessionTitle
`Small Molecule Kinase Inhibitors 1 ..cccccccccsscssssseecesees7.1152
`
`New Targets 2: Validation ....c.ccccssssccsesesssssscssesssssvseseesens 556
`
`Small Molecule Kinase Inhibitors 2 ....cccscessesssseseeesed 159
`
`Novel Biological Therapy Agents ....c.ccccccssescesssessssesseess 563
`
`Therapeutic Antibodies and Proteins .......s-ccsssesssserenonsees 1166
`
`Histone Deacetylase and Heat Shock Protein Inhibitors ..577
`
`Novel Kinase Inhibitots.......ee 1185
`
`Molecular Mechanisms of Drug Resistance...sccssesssseeeeee580
`
`Heat Shock Protein Inhibitors, Aurora Kinase, and Other
`
`New Approachesto Biological Therapy......c.cccccccssesesvone604
`
`Mitotic Inhibitors ssisucvosssaruinausadananuecvececeas 1337
`
`Novel Mechanisms of Drug Action....ccsssssssessssecseseeveseene 607
`
`Novel Small Molecule Cancer Therapeutics 1... 1345
`
`Drug Resistance 3: Cell Death.......cccccesescesscessesesesseseene 759
`
`Novel Small Molecule Cancer Therapeutics 2.0... 1352
`
`Drug Resistance 4: Transporters ......c.ccccscscccssesseescseseeeees765
`
`Pharmacology: Nanoparticles and New Drug
`
`Inhibitors of the Proteasome, Ubiquitination,
`
`Delivery Strategies nssuscssscesmmntannencnenawasuanmanunininns 1359
`
`and, NF-KB ........sssecsrsvenserscsersevencenseneevaeutassestenasessesees722
`
`Radiation: Combined Modalities, Cell Death,
`
`Novel Small Molecules and Novel Targets......c.ccccssessseses 778
`
`Bystander Killing, and Vascular Effects .....0.c.cc000. 1367
`
`Novel Targets and Mechanisms1.......ccscesesseesessseseseseseseees785
`
`Individualized Cancer Therapy: Pharmacogenetics
`
`Novel Targets and Mechanisms 2.2.1.....:cesessssesessesasevaveveees791
`
`are iheurnnmnecielprince sis sanueeensitontnmnaninemaaenials 1383
`
`Antibodies csmnnnaaaamaeBaesisdsedsvenetbuedensordcrersesnsnaesedenens944
`
`New Molecular Targets........ccswisscssvnnnimunninccraunrtcvescise 1387
`
`Drug Discovery 2: Combination Strategies Io... 951
`
`Drug Discovery 3: Combination Strategies I].........cc000 957
`
`Endocrinology (EN)
`
`Immunoconjugates, Peptides, and Protein Therapeutics ..963
`
`Molecular Endocrinology ofSolid Malignancies 1...........285
`
`New Targets 3: Compounds, Markers, Signatures............ 970
`
`Molecular Pathways for Sex Hormone Signaling
`
`New Targets 4: Discovery w.eccccssssesessssssssscsesersssensarseanes 976
`
`in Breast and Prostate Cancer ...ccccccccssssseseeseseeees369
`
`Novel Approaches to Drug Discovery ...sssessssessessesesvererees994
`
`Molecular Endocrinology of Solid Malignancies 2...........715
`
`Pharmacology and Pharmacodynamics.u.cssssceseeesereee 1132
`
`Molecular Endocrinology of Breast Cancet...c.c.ccescssese 1291
`
`Pharmacology, Pharmacogenetics, and
`
`Pharmacogenomics....ccscssssssesesesssescscecsestecenscscsesere 1138
`
`Inviterd Abstracts... ssscnssowisnoneninioaninininiiesmontasiicciaiirccs 1397
`
`Radioprotectors, Normal Tissue Injury, and
`
`Author Index. .......cesnusesemawervunanatcctaeaeineasnasiens 1415
`
`Radiation Effects on Immune Reponsse...scsereseeee 1145
`
`Subject, [mden........ssevavansiaeivavedgssiaescbateisivchsceavenennsnvenees 1481
`
`Miltenyi Ex. 1014 Page 8
`
`Miltenyi Ex. 1014 Page 8
`
`

`

`lioblastomas. Finally, recent studies have proposed the existence of CD133-posi-
`tive GBMstem cells. In this study, a panel ofhigh grade humangliomacell cultures
`were analyzedfirst for gene expression profile and further for the expression of stem
`cell markers and differentlineage markers recognizing astrocytes, oligodendrocytes,
`neurons and microglial cells by real-time RT-PCR. Inparallel, the sensitivity to
`imatinib mesylate/STI571/Glivec and AEW541, two small molecular inhibitors
`targeting PDOGF- and IGFl-receptors respectively, were also investigated. 11 out of
`20 cultures displayed CD133 expression measured byreal-time RT-PCR. These
`could be further divided into two subsets both by gene-expression signatures and
`different stem cell and lineage markers. Type I cultures displayed high expression of
`CXCR4, Sox2, EAAT 1 and GFAP,and low Jevel ofCNP, PDGFRB, CXCL12 and
`extracellular matrix proteins as compared to TypeII. Further functional analysis by
`neurosphere assay revealed that Type I cells were better at neurosphere formation
`than TypeIIcells. Interestingly, these two subsets of CD133+ cultures displayed
`differentsensitivities to PDGFR and IGFIRinhibitors. TypeII cells were sensitive
`to either imatinib, AEW541 or both, while Type I cells were insensitive to both.
`However, when a combination treatment with imatinib and AEW541 was tested
`on TypeI cells, a prominent growthinhibition was observed. Clinical significance
`of these subsets was indicated by the coordinated expression of Type I and TypeII
`“markers” in human glioblastoma samples. In summary,
`two novel subsets of
`CD133-positive humanglioma cultures could beidentified and distinct differences
`between the two subsets with regard to sensitivity to AEW541 and imatinib were
`demonstrated. Oneof these subsets, which displayed high level of CKCR4, Sox2,
`EAATI and GFAP expression, was more prone to form neurospheres, wasresistant
`to treatment with PDGERand IGFIRinhibitors individually but showed sensitiv-
`ity to combination treatment. Thefindings suggest continued studies to evaluate
`these novel potential treatment options for GBM based ontargeting of CD133-
`positive cancerstem cells.
`
`#4619 Cord blood and adult endothelial stem/progenitor cells are highly
`X-ray sensitive but their modeof cell death is both dose and age dependent.
`Marc S. Mendonca, Helen Chin-Sinex, Ryan Dhaemers, Laura Mead, Merv C.
`Yoder, David A. Ingram. Jndiana University School ofMedicine, Indianapolis, IN.
`Theability to isolate and characterize endothelial stem/progenitors should lead to
`a better understandingoftheir role in radiation-induced tumor response and nor-
`mal tissue injury. We have characterized the X-ray sensitivity of four high prolifer-
`ative potential endothelial stem/progenitorcell isolates from cord blood (CBM4,
`CBF10) andfrom adult peripheral blood (EPC060805 and LM2). Irradiation with
`160 kVp X-rays revealed these cells to be all equally and highly radiation sensitive
`with 3 Gykilling > 90% ofthecells, without the induction ofapoptosis. However,
`at high radiation doses (10Gyor greater) despite extensive and equal cellkilling, the
`cord blood endothelial progenitors underwent substantial apoptosis but the adult
`endothelial progenitors did not. In addition, after 10 Gy,a stabilization of DNA
`damage response p53 protein and an increase in the proapoptoic Ba