PPARγ ΚΑΙ AΘΗΡΟΓΕΝΕΣΗ 6732. Silverstein RL, Baird M, Lo SK. Sense and antisense cDNA transfectionof CD36 (glycoprotein IV) in melanoma cells. Role of CD36 as athrombospondin receptor. J Biol Chem 1992, 267:16607–1661233. Tandon NN, Kralisz U, Jamieson GA. Identification of glyco pro teinIV (CD36) as a primary receptor for platelet-collagen adhesion. J BiolChem 1989, 264:7576–758334. Oquendo P, Hundt E, Lawler J. CD36 directly mediates cytoadherenceof Plasmodium falciparum parasitized erythrocytes. Cell 1989,58:95–10135. Nicholson AC, Febbraio M, Han J. CD36 in atherosclerosis. The roleof a class B macrophage scavenger receptor. Ann N Y Acad Sci 2000,902:128–131, discussion 131–13336. Michalik L, Auwerx J, Berger JP et al. International Union of Pharmacology.LXI. Peroxisome proliferator-activated receptors. PharmacolRev 2006, 58:726–74137. Qi C, Zhu Y, Reddy JK. Peroxisome proliferator-activated receptors,coactivators, and downstream targets. Cell Biochem Biophys 2000,32(Spring):187–20438. Umesono K, Murakami KK, Thompson CC. Direct repeats as selectiveresponse elements for the thyroid hormone, retinoic acid, and vitaminD3 receptors. Cell 1991, 65:1255–126639. Green S, Wahli W. Peroxisome proliferator-activated receptors: findingthe orphan a home. Mol Cell Endocrinol 1994, 100:149–15340. Tham DM, Wang YX, Rutledge JC. Modulation of vascular inflammationby PPARs. Drug News Perspect 2003, 16:109–11641. Braissant O, Foufelle F, Scotto C et al. Differential expression of peroxisomeproliferator-activated receptors (PPARs): tissue distribution ofPPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996,137:354–36642. Blanquart C, Barbier O, Fruchart JC. Peroxisome proliferator-activatedreceptors: regulation of transcriptional activities and roles ininflammation. J Steroid Biochem Mol Biol 2003, 85:267–27343. Peters JM, Gonzalez FJ. Sorting out the functional role(s) of peroxisomeproliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferationand cancer. Biochim Biophys Acta 2009, 1796:230–24144. Zieleniak A, Wojcik M, Wozniak LA. Structure and physiological functionsof the human peroxisome proliferator-activated receptor gamma.Arch Immunol Ther Exp (Warsz) 2008, 56:331–34545. Bar-Tana J. Peroxisome proliferator-activated receptor gamma (PPARgamma)activation and its consequences in humans. Toxicol Lett 2001,120:9–1946. Debril MB, Renaud JP, Fajas L. The pleiotropic functions of peroxisomeproliferator-activated receptor gamma. J Mol Med 2001, 79:30–4747. Houseknecht KL, Cole BM, Steele PJ. Peroxisome proliferator-activatedreceptor gamma (PPAR-gamma) and its ligands: a review. DomestAnim Endocrinol 2002, 22:1–2348. Lehmann JM, Moore LB, Smith-Oliver TA et al. An antidiabetic thiazolidinedioneis a high affinity ligand for peroxisome proliferator-activatedreceptor gamma (PPAR-gamma). J Biol Chem 1995, 270:12953–1295649. Hihi AK, Michalik L, Wahli W. PPARs: transcriptional effectors of fattyacids and their derivatives. Cell Mol Life Sci 2002, 59:790–79850. Lehmann JM, Lenhard JM, Oliver BB et al. Peroxisome proliferatoractivatedreceptors alpha and gamma are activated by indomethacinand other non-steroidal anti-inflammatory drugs. J Biol Chem 1997,272:3406–341051. Rosen ED, Spiegelman BM. PPAR-gamma: a nuclear regulator ofmetabolism, differentiation and cell growth. J Biol Chem 2001, 276:37731–3773452. Subbaramaiah K, Lin DT, Hart JC et al. Peroxisome proliferator-activatedreceptor gamma ligands suppress the transcriptional activationof cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300. J Biol Chem 2001, 276:12440–1244853. Su CG, Wen X, Bailey ST et al. A novel therapy for colitis utilizingPPAR-gamma ligands to inhibit the epithelial inflammatory response.J Clin Invest 1999, 104:383–38954. Camp HS, Tafuri SR. Regulation of peroxisome proliferator-activatedreceptor gamma activity by mitogen-activated protein kinase. J BiolChem 1997, 272:10811–1081655. Han J, Hajjar DP, Tauras JM et al. Transforming growth factor-beta1(TGF-beta1) and TGF-beta2 decrease expression of CD36, the type Bscavenger receptor, through mitogen-activated protein kinase phosphorylationof peroxisome proliferator-activated receptor-gamma. JBiol Chem 2000, 275:1241–124656. Shao D, Rangwala SM, Bailey ST et al. Interdomain communi cationregulating ligand binding by PPAR-gamma. Nature 1998, 396:377–38057. Tontonoz P, Nagy L, Alvarez JG et al. PPAR-gamma promotes monocyte/macrophagedifferentiation and uptake of oxidized LDL. Cell1998, 93:241–25258. Reiss AB, Vagell ME. PPAR-gamma activity in the vessel wall: antiatherogenicproperties. Curr Med Chem 2006, 13:3227–323859. Goetze S, Xi XP, Kawano H et al. PPAR-gamma-ligands inhibit migrationmediated by multiple chemoattractants in vascular smooth musclecells. J Cardiovasc Pharmacol 1999, 33:798–80660. Law RE, Meehan WP, Xi XP et al. Troglitazone inhibits vascularsmooth muscle cell growth and intimal hyperplasia. J Clin Invest 1996,98:1897–190561. Ricote M, Li AC, Willson TM et al. The peroxisome proliferator-activatedreceptor-gamma is a negative regulator of macrophage activation.Nature 1998, 391:79–8262. Ross R. Cellular and molecular studies of atherogenesis. Atherosclerosis1997, 131(Suppl):S3–S463. Brewer HBJr. The lipid-laden foam cell: an elusive target for therapeuticintervention. J Clin Invest 2000, 105:703–70564. Prescott SM, McIntyre TM, Zimmerman GA. Sol Sherry lecture inthrombosis: molecular events in acute inflammation. ArteriosclerThromb Vasc Biol 2002, 22:727–73365. Hansson GK. Immune mechanisms in atherosclerosis. ArteriosclerThromb Vasc Biol 2001, 21:1876–1879066. Nagy L, Tontonoz P, Alvarez JG. Oxidized LDL regulates macrophagegene expression through ligand activation of PPAR-gamma. Cell 1998,93:229–24067. Barlic J, Zhang Y, Foley JF. Oxidized lipid-driven chemokine receptorswitch, CCR2 to CX3CR1, mediates adhesion of human macrophagesto coronary artery smooth muscle cells through a peroxisome proliferator-activatedreceptor gamma-dependent pathway. Circulation2006, 114:807–81968. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production ofmonocyte inflammatory cytokines. Nature 1998, 391:82–8669. Pasceri V, Wu HD, Willerson JT. Modulation of vascular inflammationin vitro and in vivo by peroxisome proliferator-activated receptorgammaactivators. Circulation 2000, 101:235–23870. de Dios ST, O’Brien RC, Little PJ. Clinical thiazolidinediones as PPARgammaligands with the potential for the prevention of cardiovasculardisease in diabetes. Curr Diabetes Rev 2006, 2:227–23971. Jung Y, Song S, Choi C. Peroxisome proliferator activated receptorgamma agonists suppress TNFalpha-induced ICAM-1 expression byendothelial cells in a manner potentially dependent on inhibition ofreactive oxygen species. Immunol Lett 2008, 117:63–6972. Majai G, Sarang Z, Csomos K. PPAR-gamma-dependent regulation ofhuman macrophages in phagocytosis of apoptotic cells. Eur J Immunol2007, 37:1343–135473. Berry A, Balard P, Coste A et al. IL-13 induces expression of CD36 inhuman monocytes through PPAR-gamma activation. Eur J Immunol2007, 37:1642–1652Ημερομηνία Υποβολής 19/10/2010Ημερομηνία Έγκρισης 01/12/2010© 2011 Ελληνική Εταιρεία Αθηροσκλήρωσης
CASEREPORTENΔΙΑΦΕΡΟΝΠΕΡΙΣΤΑΤΙΚΟHellenic Journal of Atherosclerosis 2(1):68–70A patientwith capecitabineassociated severehypertriglyceridemiaA. Kei, E. Liberopoulos, C. Tolis,N. Pavlidis, M. ElisafDepartment of Internal Medicine, Medical School,University of Ioannina, Ioannina, GreeceΕλληνική Επιθεώρηση Αθηροσκλήρωσης 2(1):68–70Σοβαρήυπερτριγλυκεριδαιμίασε ασθενή που λάμβανεκαπεσιταμπίνηA. Κεή, Ε. Λυμπερόπουλος, Κ. Τόλης,Ν. Παυλίδης, M. ΕλισάφΠαθολογική Κλινική, Ιατρική Σχολή, ΠανεπιστήμιοΙωαννίνων, ΙωάννιναABSTRACT: Capecitabine, an orally administered adjuvanttherapy for colorectal and breast cancer, has beenrarely associated with severe hypertriglyceridemia andhypercholesterolemia. We present a case of a 72-yearoldCaucasian woman with metastatic breast cancertreated with capecitabine. She was presented with severehypertriglyceridemia (fasting triglycerides 1213mg/dL) at the end of 4th circle of capecitabine therapy.Hypertriglyceridemia was treated with fenofibrate administration.Capecitabine-treated patients should beregularly screened for lipid abnormalities.Key words: Breast cancer, capecitabine, dyslipidemia,hypertriglyceridemia, lipids.ΠΕΡΙΛΗΨΗ: H καπεσιταμπίνη είναι συμπληρωματικήαγωγή για τον καρκίνο του παχέος εντέρου καιτου μαστού, και έχει σπάνια συσχετισθεί με σοβαρήυπερτριγλυκεριδαιμία και υπερχοληστερολαιμία.Παρουσιάζεται η περίπτωση μιας γυναίκας 72 ετών μεμεταστατικό καρκίνο του μαστού που λάμβανε καπεσιταμπίνη.Η ασθενής παρουσίασε σοβαρή υπερτιγλυκεριδαιμία(τριγλυκερίδα νηστείας 1,213 mg/dL) μετάτον 4ο κύκλο θεραπείας με καπεσιταμπίνη. Η υπερτριγλυκεριδαιμίαανταποκρίθηκε πλήρως στη χορήγησηφενοφιμπράτης. Συμπερασματικά, το λιπιδαιμικό προφίλθα πρέπει να ελέγχεται τακτικά σε ασθενείς πουλαμβάνουν καπεσιταμπίνη.Λέξεις ευρετηρίου: Kαρκίνος του μαστού, καπεσιταμπίνη,δυσλιπιδαιμία, υπερτριγλυκεριδαιμία, λιπίδια.1. IntroductionCapecitabine (Xeloda®, Roche) is an orally administeredprodrug of 5-fluorouracil licensed in USA andEurope for adjuvant therapy in colorectal, breast andgastric cancer. 1,2 According to prescription information,capecitabine is rarely (0.2%) associated withsevere hypertriglyceridemia (>5–10 times increaseabove normal levels). 2 To our best of knowledge, 7capecitabine-associated cases of hypertriglyceridemiahave been fully described in literature. 3–7 In one study42 patients (24 with breast cancer, 17 with colorectalcancer and 1 with a pancreatic islet tumor) wereadministered capecitabine at a dose of 1200 mg/m2twice daily for 2 weeks every 21 days. Capecitabineassociatedhypertriglyceridemia was observed in 5/12patients who were tested for serum cholesterol andtriglycerides. 8 Moreover, according to another report,Ε. LiberopoulosDepartment of Internal Medicine, Medical School,University of Ioannina, GR-451 00 Ioannina, Greecee-mail: vaglimp@yahoo.comΕ. ΛυμπερόπουλοςΠαθολογική Κλινική, Ιατρική Σχολή, ΠανεπιστήμιοΙωαννίνων, 451 00 Ιωάννιναe-mail: vaglimp@yahoo.com© 2011 Ελληνική Εταιρεία Αθηροσκλήρωσης
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