2023
Uridine-derived ribose fuels glucose-restricted pancreatic cancer
Nwosu Z, Ward M, Sajjakulnukit P, Poudel P, Ragulan C, Kasperek S, Radyk M, Sutton D, Menjivar R, Andren A, Apiz-Saab J, Tolstyka Z, Brown K, Lee H, Dzierozynski L, He X, PS H, Ugras J, Nyamundanda G, Zhang L, Halbrook C, Carpenter E, Shi J, Shriver L, Patti G, Muir A, Pasca di Magliano M, Sadanandam A, Lyssiotis C. Uridine-derived ribose fuels glucose-restricted pancreatic cancer. Nature 2023, 618: 151-158. PMID: 37198494, PMCID: PMC10232363, DOI: 10.1038/s41586-023-06073-w.Peer-Reviewed Original ResearchConceptsUridine phosphorylase 1Pancreatic ductal adenocarcinomaExpression of uridine phosphorylase 1Central carbon metabolismPDA cellsGlucose-deprived conditionsBlunted tumor growthUridine utilizationImmunocompetent mouse modelPDAC therapyCohort of patientsCarbon metabolismNutrient restrictionPancreatic ductal adenocarcinoma cellsPancreatic cell linesNon-tumor tissuesTumor microenvironmentMetabolic axisMetabolic processesDuctal adenocarcinomaTumor progressionPoor survivalRedox balanceTumor growthSpectrum of metabolites
2020
Cysteine depletion induces pancreatic tumor ferroptosis in mice
Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 2020, 368: 85-89. PMID: 32241947, PMCID: PMC7681911, DOI: 10.1126/science.aaw9872.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesLipid reactive oxygen speciesPancreatic ductal adenocarcinomaLipid ROS productionAmino acid cysteineCell deathPDAC growthCysteine depletionCoenzyme APDAC cellsTumor ferroptosisROS productionFerroptosisCysteineOxygen speciesCatastrophic accumulationTranslatable meansCancer mortalityDuctal adenocarcinomaLeading causeSystem xTumor typesSubunitsSpeciesDeletion
2019
Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer
Halbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S, Lee HJ, Thurston G, Zhang Y, Lazarus J, Sajjakulnukit P, Hong HS, Kremer DM, Nelson BS, Kemp S, Zhang L, Chang D, Biankin A, Shi J, Frankel TL, Crawford HC, Morton JP, Pasca di Magliano M, Lyssiotis CA. Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer. Cell Metabolism 2019, 29: 1390-1399.e6. PMID: 30827862, PMCID: PMC6602533, DOI: 10.1016/j.cmet.2019.02.001.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTumor-associated macrophagesPancreatic cancer therapyRole of macrophagesAbundant infiltrationGemcitabine therapyGemcitabine treatmentFrontline chemotherapyImmune cellsPancreatic cancerDuctal adenocarcinomaMacrophage burdenMurine modelPharmacological depletionFuture treatmentPDA cellsGemcitabineMacrophagesDrug uptakeMacrophage cellsUnknown physiological roleCancer therapyTherapyPhysiological roleTreatment
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