{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:10:04Z","timestamp":1778814604803,"version":"3.51.4"},"reference-count":58,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry and Physics of Lipids"],"published-print":{"date-parts":[[2012,5]]},"DOI":"10.1016\/j.chemphyslip.2012.02.006","type":"journal-article","created":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T19:47:18Z","timestamp":1330026438000},"page":"462-474","source":"Crossref","is-referenced-by-count":17,"title":["Cancer and sphingolipid storage disease therapy using novel synthetic analogs of sphingolipids"],"prefix":"10.1016","volume":"165","author":[{"given":"Shimon","family":"Gatt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arie","family":"Dagan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0005","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0891-5849(01)00655-4","article-title":"Ceramide in apoptosis signaling: relationship with oxidative stress","volume":"31","author":"Andrieu-Abadie","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0010","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1517\/14728221003752768","article-title":"Targeting sphingolipid metabolism in head and neck cancer: rational therapeutic potentials","volume":"14","author":"Beckham","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0015","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/sj.onc.1208019","article-title":"Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression","volume":"24","author":"Bektas","year":"2005","journal-title":"Oncogene"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0020","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0025","doi-asserted-by":"crossref","first-page":"257","DOI":"10.7326\/0003-4819-82-2-257","article-title":"The lipid storage diseases: new concepts and control","volume":"82","author":"Brady","year":"1975","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0030","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1242\/jcs.02637","article-title":"Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling","volume":"118","author":"Chalfant","year":"2005","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0035","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0076-6879(00)12916-7","article-title":"Synthesis of fluorescent substrates and their application to study of sphingolipid metabolism in vitro and in intact cells","volume":"312","author":"Dagan","year":"2000","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0040","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1388-1981(03)00122-7","article-title":"Synthetic, non-natural sphingolipid analogs inhibit the biosynthesis of cellular sphingolipids, elevate ceramide and induce apoptotic cell death","volume":"1633","author":"Dagan","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0045","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1194\/jlr.M500136-JLR200","article-title":"A lipid analogue that inhibits sphingomyelin hydrolysis and synthesis, increases ceramide, and leads to cell death","volume":"46","author":"Darroch","year":"2005","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0050","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/nrg963","article-title":"Enzyme replacement and enhancement therapies: lessons from lysosomal disorders","volume":"3","author":"Desnick","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0055","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1089\/hum.1992.3.6-633","article-title":"Toward gene therapy for Niemann\u2013Pick disease (NPD): separation of retrovirally corrected and noncorrected NPD fibroblasts using a novel fluorescent sphingomyelin","volume":"3","author":"Dinur","year":"1992","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0060","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1038\/sj.mt.6300167","article-title":"Role of acid ceramidase in resistance to FasL: therapeutic approaches based on acid ceramidase inhibitors and FasL gene therapy","volume":"15","author":"Elojeimy","year":"2007","journal-title":"Mol. Ther."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0065","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.embor.7400208","article-title":"The complex life of simple sphingolipids","volume":"5","author":"Futerman","year":"2004","journal-title":"EMBO Rep."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0070","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1016\/S0021-9258(18)51879-2","article-title":"Enzymic hydrolysis and synthesis of ceramides","volume":"238","author":"Gatt","year":"1963","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0075","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/sj.leu.2404084","article-title":"Caspase-dependent and -independent cell death of Jurkat human leukemia cells induced by novel synthetic ceramide analogs","volume":"20","author":"Granot","year":"2006","journal-title":"Leukemia"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0080","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/oxfordjournals.bmb.a011629","article-title":"Ceramide signaling in apoptosis","volume":"53","author":"Haimovitz-Friedman","year":"1997","journal-title":"Br. Med. Bull."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0085","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bbalip.2009.01.006","article-title":"CERT-mediated trafficking of ceramide","volume":"1791","author":"Hanada","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0090","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1126\/science.274.5294.1855","article-title":"Functions of ceramide in coordinating cellular responses to stress","volume":"274","author":"Hannun","year":"1996","journal-title":"Science"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0095","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0962-8924(99)01694-3","article-title":"Ceramide in the eukaryotic stress response","volume":"10","author":"Hannun","year":"2000","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0100","doi-asserted-by":"crossref","first-page":"25847","DOI":"10.1074\/jbc.R200008200","article-title":"The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind","volume":"277","author":"Hannun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0105","first-page":"43","article-title":"The novel second messenger ceramide: identification, mechanism of action, and cellular activity","volume":"25","author":"Hannun","year":"1993","journal-title":"Adv. Lipid Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0110","doi-asserted-by":"crossref","first-page":"32978","DOI":"10.1074\/jbc.M301936200","article-title":"Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase","volume":"278","author":"He","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0115","first-page":"415","article-title":"Possible role of ceramide as an indicator of chemoresistance: decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia","volume":"9","author":"Itoh","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0120","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1046\/j.1523-1747.1998.00137.x","article-title":"A potential role for ceramide in the regulation of mouse epidermal keratinocyte proliferation and differentiation","volume":"110","author":"Jung","year":"1998","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0125","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.cellsig.2007.12.006","article-title":"The sphingolipid salvage pathway in ceramide metabolism and signaling","volume":"20","author":"Kitatani","year":"2008","journal-title":"Cell. Signal."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0130","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1146\/annurev.physiol.60.1.643","article-title":"Regulation of ceramide production and apoptosis","volume":"60","author":"Kolesnick","year":"1998","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0135","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1517\/13543784.10.3.455","article-title":"Substrate reduction therapy for glycosphingolipid storage disorders","volume":"10","author":"Lachmann","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0140","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0092-8674(00)81661-X","article-title":"Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate","volume":"99","author":"Lee","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0145","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0083-6729(04)67013-0","article-title":"TRAIL and ceramide","volume":"67","author":"Lee","year":"2004","journal-title":"Vitam. Horm."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0150","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.2741\/2843","article-title":"Acid ceramidase inhibition: a novel target for cancer therapy","volume":"13","author":"Liu","year":"2008","journal-title":"Front. Biosci."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0155","doi-asserted-by":"crossref","first-page":"14550","DOI":"10.1074\/jbc.273.23.14550","article-title":"Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C?","volume":"273","author":"Luberto","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0160","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1388-1981(02)00341-4","article-title":"Sphingosine kinase, sphingosine-1-phosphate, and apoptosis","volume":"1585","author":"Maceyka","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0165","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/mt.2008.281","article-title":"Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer","volume":"17","author":"Mahdy","year":"2009","journal-title":"Mol. Ther."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0170","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/sj.clpt.6100296","article-title":"Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies","volume":"83","author":"Mimeault","year":"2008","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0290","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0175","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/376037a0","article-title":"Identification and inhibition of the ICE\/CED-3 protease necessary for mammalian apoptosis","volume":"376","author":"Nicholson","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0180","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/PL00000836","article-title":"Sphingolipids in mammalian cell signalling","volume":"58","author":"Ohanian","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0185","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/365557a0","article-title":"Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens","volume":"365","author":"Olivera","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0190","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-4419-6741-1_13","article-title":"Cancer treatment strategies targeting sphingolipid metabolism","volume":"688","author":"Oskouian","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0195","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/j.bbamem.2006.08.019","article-title":"Acid ceramidase and human disease","volume":"1758","author":"Park","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0200","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2165\/00126839-200607060-00003","article-title":"A chaperone-mediated approach to enzyme enhancement as a therapeutic option for the lysosomal storage disorders","volume":"7","author":"Pastores","year":"2006","journal-title":"Drugs RD"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0205","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.plipres.2010.10.003","article-title":"Sphingolipids and expression regulation of genes in cancer","volume":"50","author":"Patwardhan","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0210","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3109\/07357900903478915","article-title":"Synthetic, non-natural analogs of ceramide elevate cellular ceramide, inducing apoptotic death to prostate cancer cells and eradicating tumors in mice","volume":"28","author":"Qin","year":"2010","journal-title":"Cancer Invest."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0215","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1046\/j.1432-1033.2001.01845.x","article-title":"Killing cancer cells by poly-drug elevation of ceramide levels: a hypothesis whose time has come?","volume":"268","author":"Radin","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0220","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1042\/bj20021878","article-title":"Killing tumours by ceramide-induced apoptosis: a critique of available drugs","volume":"371","author":"Radin","year":"2003","journal-title":"Biochem. J."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0225","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.canlet.2003.08.034","article-title":"Ceramide synthesis and metabolism as a target for cancer therapy","volume":"206","author":"Reynolds","year":"2004","journal-title":"Cancer Lett."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0230","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10549-007-9836-9","article-title":"Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer","volume":"112","author":"Ruckhaberle","year":"2008","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0235","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1043-6618(03)00050-1","article-title":"Intracellular signal transduction pathways activated by ceramide and its metabolites","volume":"47","author":"Ruvolo","year":"2003","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0240","doi-asserted-by":"crossref","first-page":"11754","DOI":"10.1074\/jbc.M011400200","article-title":"Ceramide regulates protein synthesis by a novel mechanism involving the cellular PKR activator RAX","volume":"276","author":"Ruvolo","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0245","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4161\/cbt.11.2.14624","article-title":"Dysregulation of sphingolipid metabolism in cancer","volume":"11","author":"Ryland","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0250","first-page":"1233","article-title":"Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer","volume":"61","author":"Selzner","year":"2001","journal-title":"Cancer Res."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0255","doi-asserted-by":"crossref","first-page":"662","DOI":"10.2174\/138945008785132402","article-title":"Targeting SphK1 as a new strategy against cancer","volume":"9","author":"Shida","year":"2008","journal-title":"Curr. Drug Targets"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0260","doi-asserted-by":"crossref","first-page":"10642","DOI":"10.1523\/JNEUROSCI.3584-04.2004","article-title":"Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann\u2013Pick-A mouse leads to a marked decrease in lysosomal storage pathology","volume":"24","author":"Shihabuddin","year":"2004","journal-title":"J. Neurosci."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0265","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/jlb.65.3.341","article-title":"Sphingosine 1-phosphate: a prototype of a new class of second messengers","volume":"65","author":"Spiegel","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0270","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ccr.2007.04.011","article-title":"Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs","volume":"11","author":"Swanton","year":"2007","journal-title":"Cancer Cell"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0275","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2165\/00003495-199244010-00007","article-title":"Alglucerase. A review of its therapeutic use in Gaucher's disease","volume":"44","author":"Whittington","year":"1992","journal-title":"Drugs"},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0280","doi-asserted-by":"crossref","first-page":"E211","DOI":"10.1152\/ajpendo.91014.2008","article-title":"Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome","volume":"297","author":"Yang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.chemphyslip.2012.02.006_bib0285","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1098\/rstb.2003.1272","article-title":"Gaucher disease and the clinical experience with substrate reduction therapy","volume":"358","author":"Zimran","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B: Biol. Sci."}],"container-title":["Chemistry and Physics of Lipids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009308412000230?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009308412000230?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T17:32:53Z","timestamp":1640885573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009308412000230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5]]},"references-count":58,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["S0009308412000230"],"URL":"https:\/\/doi.org\/10.1016\/j.chemphyslip.2012.02.006","relation":{},"ISSN":["0009-3084"],"issn-type":[{"value":"0009-3084","type":"print"}],"subject":[],"published":{"date-parts":[[2012,5]]}}}