Mitochondria and Cancer

ISBN-13: 9781441927385 / Angielski / Miękka / 2010 / 289 str.

Keshav Singh; Leslie Costello

Opis

Weareenteringintoaneraofre-awakeningoftheimportanceandinterestinthe role ofaltered intermediary metabolisminthedevelopmentandprogressionof malignancy. Therefore, thisbookMitochondriaandCanceristimelyandrelevant tocontemporaryandfutureresearch, training, andeducation. Thehallmarkstudies ofOttoWarburgetal. (1926)sparkedtheeraoftumorcellmetabolism. Fromthen untilaround1980, studiesofintermediarymetabolismofnormalandmalignant cellsweremajorareasofresearchandofgraduateandpostgraduatetrainingin biomedicalsciences. Thisperiodwasdominatedbymitochondrialstudiesandby thoseextraordinaryoutstandingscientistswhowereaffectionatelyreferredtoasthe "mitochondriacs." However, theadvent, development, andsubsequentdominance ofmoleculargenetics/molecularbiologyandmoleculartechnologyinbiomedical researchwereaccompaniedbythenearlycompletesubmersionofinterestinareas ofintermediarymetabolismandtumorcellmetabolism. Forthepast30orsoyears, graduateandpostgraduatetraining, experienceandfocusinbiochemistry, meta- lism, enzymology, cellphysiologyhavedeclined, beingdisplacedbythedo- nanceofmoleculartechnologies. Therecentrevelationsandadvancesinmolecular genetics/molecularbiologyandthedevelopmentofmolecularandnanotechnology providenewdimensionstoapplytotheunderstandingandelucidationoftheroleof intermediarymetabolismandmitochondrialfunctioninthedevelopmentandp- gressionofcancers. Toaddresstheissuesoftumormetabolism, thepresentand futuregenerationsofresearchersmustintegratetheknowledgeandmethods of biochemistrywiththeknowledgeandtechnologyofmolecularbiology. Thefocusonmitochondriaiscentraltodiscussionsandissuesofintermediary metabolism. Thegenetictransformationofnormalfunctionalcellstoneoplastic cellsimposestheneedforalterationsinintermediarymetabolismandmitochond- 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 . . . .

Spis treści

Mitochondria and Cancer.- Warburg and his Legacy.- The Lipogenic Switch in Cancer.- Citrate Metabolism in Prostate and Other Cancers.- Integration of Genetic, Proteomic, and Metabolic Approaches in Tumor Cell Metabolism.- Mitochondrial Respiration and Differentiation.- Integration of Energy Metabolism and Control of Apoptosis in Tumor Cells.- Energy Generating Pathways and the Tumor Suppressor p53.- Mitochondrial Tumor Suppressors.- Mitochondria in Hematology.- Mitochondria and Oncocytomas.- Mitochondria as Targets for Cancer Therapy.- Reversing the Warburg Effect: Metabolic Modulation as a Novel Cancer Therapy.- Mitochondrial Nanotechnology for Cancer Therapy.

Blurb

Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.