2022
Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells.
McBrearty N, Cho C, Chen J, Zahedi F, Peck A, Radaelli E, Assenmacher C, Pavlak C, Devine A, Yu P, Lu Z, Zhang H, Li J, Pitarresi J, Astsaturov I, Cukierman E, Rustgi A, Stanger B, Rui H, Fuchs S. Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells. Molecular Cancer Research 2022, 21: 228-239. PMID: 36378658, PMCID: PMC9992122, DOI: 10.1158/1541-7786.mcr-22-0602.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancer cellsPDAC cellsCH25H expressionTumor growthT cell tumor infiltrationMouse PDAC cellsImmune checkpoint inhibitorsCancer cellsDownregulation of MHCPancreatic intraepithelial neoplasiaImmune-competent hostsHuman pancreatic cancerPotential translational importanceAccumulation of cholesterolCheckpoint inhibitorsIntraepithelial neoplasiaPoor prognosisTumor infiltrationPancreatic cancerDuctal adenocarcinomaTherapeutic approachesCH25HTumor progressionCholesterol deficit
2020
Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
Gui J, Zahedi F, Ortiz A, Cho C, Katlinski K, Alicea-Torres K, Li J, Todd L, Zhang H, Beiting D, Sander C, Kirkwood J, Snow B, Wakeham A, Mak T, Diehl J, Koumenis C, Ryeom S, Stanger B, Puré E, Gabrilovich D, Fuchs S. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nature Cancer 2020, 1: 603-619. PMID: 34124690, PMCID: PMC8194112, DOI: 10.1038/s43018-020-0064-0.Peer-Reviewed Original ResearchConceptsPre-metastatic nicheFibroblast activation proteinStress-activated protein kinasePrimary tumor-derived factorsActivation proteinDisseminated malignant cellsNormal cellsActivity of p38Tumor-derived factorsExpression of chemokinesActivation of p38αInactivation of p38Subsequent pulmonary metastasesStimulation of expressionType I interferonProtein kinaseLung infiltrationP38 inhibitorAdjuvant therapyMetastatic diseaseP38α kinasePulmonary metastasesLung metastasesPoor prognosisMetastatic cancer
2019
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, Carbone CJ, Yu Q, Katlinski KV, Katlinskaya YV, Handa S, Haas V, Volk SW, Brice AK, Wals K, Matheson NJ, Antrobus R, Ludwig S, Whiteside TL, Sander C, Tarhini AA, Kirkwood JM, Lehner PJ, Guo W, Rui H, Minn AJ, Koumenis C, Diehl JA, Fuchs SY. An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles. Cancer Cell 2019, 35: 33-45.e6. PMID: 30645975, PMCID: PMC6336114, DOI: 10.1016/j.ccell.2018.12.001.Peer-Reviewed Original ResearchConceptsTumor-derived extracellular vesiclesMelanoma lung metastasisPre-metastatic nicheLung metastasesAdjuvant melanoma therapyAnti-hypertensive drugsUse of reserpineExtracellular vesiclesType I interferon receptorMelanoma patientsPoor prognosisCH25HMelanoma therapyIFN receptorInterferon receptorMetastasisNormal cellsHealthy cellsReceptorsUptakeCellsPatientsPrognosisReserpineTherapy