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alfunctiontoprovidethebioenergetic/synthetic/growthrequirementsforthep- gression of the neoplastic cell to malignancy. In the absence of the metabolic transformation, theneoplasticmalignantcellwillnotachieveitsmalignantpot- tial. Thus, itiscriticaltoestablishtheroleofthemitochondriainthemalignant process. Moreover, speci?calterationsindifferentcancertypesmustbeidenti?ed. Such information will provide new approaches to the treatment and perhaps preventionofdifferingcancers. TheadventofMetabolomicsforthedetectionof v vi Preface cancer and progression of malignancy is dependent upon the elucidation and identi?cationofalteredmetabolismandmitochondrialfunction. Thus, thisexciting journeyincancerresearchhasbarelybegunandhasalongwaytogo. Thisbook, Mitochondria and Cancer, and its subject matter provide a roadmap and the preparationtoproceedonthisjourney. Wearegreatlyindebtedtothecontributingauthorsfortheirenthusiasticsupport andwritingachapterintheirareaofexpertise. WearegratefultoMs. DonnaOvak for secretarial help and our families for their patience and support in putting togetherthisbook. Thisbookisdedicatedtopast, present, andfuture mitoch- driacs aroundtheworld. Buffalo, NY KeshavK. Singh Baltimore, MD LeslieC. Costello Contents MitochondriaandCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 KjerstinM. Owens, J. S. Modica-Napolitano, andKeshavK. Singh WarburgandhisLegacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 MichaelRistowandTimJ. Schulz TheLipogenicSwitchinCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 KoenBrusselmansandJohannesV. Swinnen CitrateMetabolisminProstateandOtherCancers . . . . . . . . . . . . . . . . . . . . . . . . . 61 RentyB. FranklinandLeslieC. Costello IntegrationofGenetic, Proteomic, andMetabolicApproachesin TumorCellMetabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 LeslieC. CostelloandRentyB. Franklin MitochondrialRespirationandDifferentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 RobertoScatena, PatriziaBottoni, andBrunoGiardina IntegrationofEnergyMetabolismandControlofApoptosis inTumorCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 JohnG. PastorinoandJanB. Hoek EnergyGeneratingPathwaysandtheTumorSuppressorp53 . . . . . . . . . . . 131 ChadA. Corcoran, YingHuang, andM. SaeedSheikh MitochondrialTumorSuppressors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 BoraE. Baysal MitochondriainHematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 StefanieZanssen vii viii Contents MitochondriaandOncocytomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 J. Lima, V. Maximo, P. Soares, R. Portugal, S. Guimara es, andM. Sobrinho-Simo es MitochondriaasTargetsforCancerTherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 StephenJ. RalphandJiriNeuzil ReversingtheWarburgEffect: MetabolicModulationasa NovelCancerTherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 GopinathSutendraandEvangelosD. Michelakis MitochondrialNanotechnologyforCancerTherapy . . . . . . . . . . . . . . . . . . . . . . 265 VolkmarWeissig, GerardG. M. D Souza, Shing-MingCheng, andSarathiBoddapati Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 Contributors BoraE. Baysal DepartmentofPathology, YaleUniversitySchoolofMedicine,310CedarStreet, NewHaven, CT06520-8023, USA, bora. baysal@yale. edu SarathiBoddapati Department of Pharmaceutical Sciences, Midwestern University College of PharmacyGlendale, Glendale, AZ, USA PatriziaBottoni DipartimentodiMedicinadiLaboratorio, Universita CattolicadelSacroCuore, LargoA. Gemelli8,00168Rome, Italy KoenBrusselmans LaboratoryforExperimentalMedicineandEndocrinology, KatholiekeUniversiteit Leuven, Leuven, Belgium Shing-MingCheng Department of Pharmaceutical Sciences, Midwestern University College of PharmacyGlendale.