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Volumn 88, Issue 8, 2003, Pages 3902-3912

Identification of steroid sulfate transport processes in the human mammary gland

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPENTENONE; CYSTEINE; ESTROGEN; ESTRONE SULFATE; N ETHYLMALEIMIDE; ORGANIC ANION TRANSPORTER; PRASTERONE SULFATE; PROSTAGLANDIN A1; PROSTAGLANDIN A2; RNA; STEROID; STILBENE DERIVATIVE; THIOL REAGENT;

EID: 0041381393     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.2003-030174     Document Type: Article
Times cited : (134)

References (55)
  • 1
    • 20644453757 scopus 로고    scopus 로고
    • Cancer risk related to mammary gland structure and development
    • Russo J, Hu YF, Silva ID, Russo IH 2001 Cancer risk related to mammary gland structure and development. Microsc Res Tech 2001 52:204-223
    • (2001) Microsc Res Tech 2001 , vol.52 , pp. 204-223
    • Russo, J.1    Hu, Y.F.2    Silva, I.D.3    Russo, I.H.4
  • 2
    • 0034466972 scopus 로고    scopus 로고
    • Estrogen receptor transcription and transactivation: Estrogen receptor α and estrogen receptor β: Regulation by selective estrogen receptor modulators and importance in breast cancer
    • Katzenellenbogen BS, Katzenellenbogen JA 2000 Estrogen receptor transcription and transactivation: estrogen receptor α and estrogen receptor β: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Res 2:335-344
    • (2000) Breast Cancer Res , vol.2 , pp. 335-344
    • Katzenellenbogen, B.S.1    Katzenellenbogen, J.A.2
  • 3
    • 0032076761 scopus 로고    scopus 로고
    • DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: Its role during aging
    • Labrie F, Belanger A, Luu-The V, Labrie C, Simard J, Cusan L, Gomez JL, Candas B 1998 DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging. Steroids 63:322-328
    • (1998) Steroids , vol.63 , pp. 322-328
    • Labrie, F.1    Belanger, A.2    Luu-The, V.3    Labrie, C.4    Simard, J.5    Cusan, L.6    Gomez, J.L.7    Candas, B.8
  • 4
    • 0035666689 scopus 로고    scopus 로고
    • High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: A renewed role for adrenalectomy
    • Morris KT, Toth-Fejel S, Schmidt J, Fletcher WS, Pommier RF 2001 High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Surgery 130:947-953
    • (2001) Surgery , vol.130 , pp. 947-953
    • Morris, K.T.1    Toth-Fejel, S.2    Schmidt, J.3    Fletcher, W.S.4    Pommier, R.F.5
  • 5
    • 0035932023 scopus 로고    scopus 로고
    • Dehydroepiandrosterone stimulates proliferation and gene expression in MCF-7 cells after conversion to estradiol
    • Schmitt M, Klinga K, Schnarr B, Morfin R, Mayer D 2001 Dehydroepiandrosterone stimulates proliferation and gene expression in MCF-7 cells after conversion to estradiol. Mol Cell Endocrinol 173:1-13
    • (2001) Mol Cell Endocrinol , vol.173 , pp. 1-13
    • Schmitt, M.1    Klinga, K.2    Schnarr, B.3    Morfin, R.4    Mayer, D.5
  • 7
    • 0034016224 scopus 로고    scopus 로고
    • Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues
    • Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR 2000 Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72:23-27
    • (2000) J Steroid Biochem Mol Biol , vol.72 , pp. 23-27
    • Chetrite, G.S.1    Cortes-Prieto, J.2    Philippe, J.C.3    Wright, F.4    Pasqualini, J.R.5
  • 8
    • 0020680641 scopus 로고
    • Estrone sulfate concentrations in plasma of normal individuals, postmenopausal women with breast cancer, and men with cirrhosis
    • Remy-Martin A, Prost O, Nicollier M, Burnod J, Adessi GL 1983 Estrone sulfate concentrations in plasma of normal individuals, postmenopausal women with breast cancer, and men with cirrhosis. Clin Chem 29:86-89
    • (1983) Clin Chem , vol.29 , pp. 86-89
    • Remy-Martin, A.1    Prost, O.2    Nicollier, M.3    Burnod, J.4    Adessi, G.L.5
  • 9
    • 0021680756 scopus 로고
    • Estrone sulfatase activity in the human brain and estrone sulfate levels in the normal menstrual cycle
    • Platia MP, Fencl MD, Elkind-Hirsch KE, Canick JA, Tulchinsky D 1984 Estrone sulfatase activity in the human brain and estrone sulfate levels in the normal menstrual cycle. J Steroid Biochem 21:237-241
    • (1984) J Steroid Biochem , vol.21 , pp. 237-241
    • Platia, M.P.1    Fencl, M.D.2    Elkind-Hirsch, K.E.3    Canick, J.A.4    Tulchinsky, D.5
  • 10
    • 0028206648 scopus 로고
    • Metabolism of es trone sulfate by normal breast tissue: Influence of menopausal status and oral contraceptives
    • Soderqvist G, Olsson H, Wilking N, von Schoultz B, Carlstrom K 1994 Metabolism of es trone sulfate by normal breast tissue: influence of menopausal status and oral contraceptives. J Steroid Biochem Mol Biol 48:221-224
    • (1994) J Steroid Biochem Mol Biol , vol.48 , pp. 221-224
    • Soderqvist, G.1    Olsson, H.2    Wilking, N.3    Von Schoultz, B.4    Carlstrom, K.5
  • 11
    • 0030871364 scopus 로고    scopus 로고
    • Age and sex related differences in serum levels of unconjugated dehydroepiandrosterone and its sulphate in normal subjects
    • Sulcova J, Hill M, Hampl R, Starka L 1997 Age and sex related differences in serum levels of unconjugated dehydroepiandrosterone and its sulphate in normal subjects. J Endocrinol 154:57-62
    • (1997) J Endocrinol , vol.154 , pp. 57-62
    • Sulcova, J.1    Hill, M.2    Hampl, R.3    Starka, L.4
  • 12
    • 0034053341 scopus 로고    scopus 로고
    • 17β-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinoma in situ and intraductal proliferative lesions of the human breast
    • Ariga N, Moriya T, Suzuki T, Kimura M, Ohuchi N, Satomi S, Sasano H 2000 17β-Hydroxysteroid dehydrogenase type 1 and type 2 in ductal carcinoma in situ and intraductal proliferative lesions of the human breast. Anticancer Res 20:1101-1108
    • (2000) Anticancer Res , vol.20 , pp. 1101-1108
    • Ariga, N.1    Moriya, T.2    Suzuki, T.3    Kimura, M.4    Ohuchi, N.5    Satomi, S.6    Sasano, H.7
  • 13
    • 0034132569 scopus 로고    scopus 로고
    • 17β-Hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: A correlation to chnicopathological parameters
    • Suzuki T, Moriya T, Ariga N, Kaneko C, Kanazawa M, Sasano H 2000 17β-Hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: a correlation to chnicopathological parameters. Br J Cancer 82:518-523
    • (2000) Br J Cancer , vol.82 , pp. 518-523
    • Suzuki, T.1    Moriya, T.2    Ariga, N.3    Kaneko, C.4    Kanazawa, M.5    Sasano, H.6
  • 15
    • 0037123341 scopus 로고    scopus 로고
    • Endogenous sex hormones and breast cancer in postmenopausal women: Reanalysis of nine prospective studies
    • Endogenous Hormones and Breast Cancer Collaborative Group 2002 Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606-616.
    • (2002) J Natl Cancer Inst , vol.94 , pp. 606-616
  • 16
    • 0037427972 scopus 로고    scopus 로고
    • The superfamily of organic anion transporting polypeptides
    • Hagenbuch B, Meier PJ 2003 The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609:1-18
    • (2003) Biochim Biophys Acta , vol.1609 , pp. 1-18
    • Hagenbuch, B.1    Meier, P.J.2
  • 17
    • 0034880349 scopus 로고    scopus 로고
    • The organic anion transporter family: From physiology to ontogeny and the clinic
    • Sweet DH, Bush KT, Nigam SK 2001 The organic anion transporter family: from physiology to ontogeny and the clinic. Am J Physiol Renal Physiol 281:F197-F205
    • (2001) Am J Physiol Renal Physiol , vol.281
    • Sweet, D.H.1    Bush, K.T.2    Nigam, S.K.3
  • 20
    • 0037733365 scopus 로고    scopus 로고
    • A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane
    • Konig J, Cui Y, Nies AT, Keppler D 2000 A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol 278:G156-G164
    • (2000) Am J Physiol Gastrointest Liver Physiol , vol.278
    • Konig, J.1    Cui, Y.2    Nies, A.T.3    Keppler, D.4
  • 22
    • 0034709561 scopus 로고    scopus 로고
    • Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family
    • Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A 2000 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 273:251-260
    • (2000) Biochem Biophys Res Commun , vol.273 , pp. 251-260
    • Tamai, I.1    Nezu, J.2    Uchino, H.3    Sai, Y.4    Oku, A.5    Shimane, M.6    Tsuji, A.7
  • 23
    • 0036793106 scopus 로고    scopus 로고
    • Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter
    • Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ 2002 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol 16:2283-2296
    • (2002) Mol Endocrinol , vol.16 , pp. 2283-2296
    • Pizzagalli, F.1    Hagenbuch, B.2    Stieger, B.3    Klenk, U.4    Folkers, G.5    Meier, P.J.6
  • 24
    • 0035039326 scopus 로고    scopus 로고
    • Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney
    • Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H 2001 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol 59:1277-1286
    • (2001) Mol Pharmacol , vol.59 , pp. 1277-1286
    • Cha, S.H.1    Sekine, T.2    Fukushima, J.I.3    Kanai, Y.4    Kobayashi, Y.5    Goya, T.6    Endou, H.7
  • 25
    • 0000518648 scopus 로고    scopus 로고
    • Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta
    • Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H 2000 Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem 275:4507-4512
    • (2000) J Biol Chem , vol.275 , pp. 4507-4512
    • Cha, S.H.1    Sekine, T.2    Kusuhara, H.3    Yu, E.4    Kim, J.Y.5    Kim, D.K.6    Sugiyama, Y.7    Kanai, Y.8    Endou, H.9
  • 27
    • 0014514028 scopus 로고
    • Dehydration of prostaglandins: Study by spectroscopic method
    • Andersen NH 1969 Dehydration of prostaglandins: study by spectroscopic method. J Lipid Res 10:320-325
    • (1969) J Lipid Res , vol.10 , pp. 320-325
    • Andersen, N.H.1
  • 29
    • 0025860171 scopus 로고
    • Production of analytical quantities of recombinant proteins in Chinese hamster ovary cells using sodium butyrate to elevate gene expression
    • Palermo DP, DeGraaf ME, Marotti KR, Rehberg E, Post LE 1991 Production of analytical quantities of recombinant proteins in Chinese hamster ovary cells using sodium butyrate to elevate gene expression. J Biotechnol 19:35-47
    • (1991) J Biotechnol , vol.19 , pp. 35-47
    • Palermo, D.P.1    DeGraaf, M.E.2    Marotti, K.R.3    Rehberg, E.4    Post, L.E.5
  • 30
    • 0027402499 scopus 로고
    • Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue
    • Lazard D, Sastre X, Frid MG, Glukhova MA, Thiery JP, Koteliansky VE 1993 Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue. Proc Natl Acad Sci USA 90:999-1003
    • (1993) Proc Natl Acad Sci USA , vol.90 , pp. 999-1003
    • Lazard, D.1    Sastre, X.2    Frid, M.G.3    Glukhova, M.A.4    Thiery, J.P.5    Koteliansky, V.E.6
  • 31
    • 0034857677 scopus 로고    scopus 로고
    • Functional characterization of human organic anion transporting polypeptide B (OA TP-B) in comparison with liver-specific OATP-C
    • Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A 2001 Functional characterization of human organic anion transporting polypeptide B (OA TP-B) in comparison with liver-specific OATP-C. Pharm Res 18:1262-1269
    • (2001) Pharm Res , vol.18 , pp. 1262-1269
    • Tamai, I.1    Nozawa, T.2    Koshida, M.3    Nezu, J.4    Sai, Y.5    Tsuji, A.6
  • 32
    • 0030444771 scopus 로고    scopus 로고
    • Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene
    • Zhao Y, Agarwal VR, Mendelson CR, Simpson ER 1996 Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137:5739-5742
    • (1996) Endocrinology , vol.137 , pp. 5739-5742
    • Zhao, Y.1    Agarwal, V.R.2    Mendelson, C.R.3    Simpson, E.R.4
  • 33
    • 0035053973 scopus 로고    scopus 로고
    • Cyclopentenone prostaglandins: New insights on biological activities and cellular targets
    • Straus DS, Glass CK 2001 Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med Res Rev 21:185-210
    • (2001) Med Res Rev , vol.21 , pp. 185-210
    • Straus, D.S.1    Glass, C.K.2
  • 34
    • 0036827601 scopus 로고    scopus 로고
    • Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction
    • Alcorn J, Lu X, Moscow JA, McNamara PJ 2002 Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction. J Pharmacol Exp Ther 303:487-496
    • (2002) J Pharmacol Exp Ther , vol.303 , pp. 487-496
    • Alcorn, J.1    Lu, X.2    Moscow, J.A.3    McNamara, P.J.4
  • 35
    • 0033602028 scopus 로고    scopus 로고
    • The human mammary gland basement membrane is integral to the polarity of luminal epithelial cells
    • Slade MJ, Coope RC, Gomm JJ, Coombes RC 1999 The human mammary gland basement membrane is integral to the polarity of luminal epithelial cells. Exp Cell Res 247:267-278
    • (1999) Exp Cell Res , vol.247 , pp. 267-278
    • Slade, M.J.1    Coope, R.C.2    Gomm, J.J.3    Coombes, R.C.4
  • 37
    • 0035546023 scopus 로고    scopus 로고
    • Involvement of up-regulation of 17 β-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers
    • Miyoshi Y, Ando A, Shiba E, Taguchi T, Tamaki Y, Noguchi S 2001 Involvement of up-regulation of 17 β-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers. Int J Cancer 2001 94:685-689
    • (2001) Int J Cancer 2001 , vol.94 , pp. 685-689
    • Miyoshi, Y.1    Ando, A.2    Shiba, E.3    Taguchi, T.4    Tamaki, Y.5    Noguchi, S.6
  • 40
    • 0035794228 scopus 로고    scopus 로고
    • Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1
    • Qian YM, Song WC, Cui H, Cole SP, Deeley RG 2001 Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1. J Biol Chem 276:6404-6411
    • (2001) J Biol Chem , vol.276 , pp. 6404-6411
    • Qian, Y.M.1    Song, W.C.2    Cui, H.3    Cole, S.P.4    Deeley, R.G.5
  • 41
    • 0031465938 scopus 로고    scopus 로고
    • Dehydroepiandrosterone stimulates the estrogen response element
    • Bruder JM, Sobek L, Oettel M 1997 Dehydroepiandrosterone stimulates the estrogen response element. J Steroid Biochem Mol Biol 62:461-466
    • (1997) J Steroid Biochem Mol Biol , vol.62 , pp. 461-466
    • Bruder, J.M.1    Sobek, L.2    Oettel, M.3
  • 42
    • 0033214658 scopus 로고    scopus 로고
    • Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α
    • Maggiolini M, Donze O, Jeannin E, Ando S, Picard D 1999 Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α. Cancer Res 59:4864-4869
    • (1999) Cancer Res , vol.59 , pp. 4864-4869
    • Maggiolini, M.1    Donze, O.2    Jeannin, E.3    Ando, S.4    Picard, D.5
  • 44
    • 0020571243 scopus 로고
    • Pattern of plasma pregnenolone sulfate levels in humans from birth to adulthood
    • de Peretti E, Mappus E 1983 Pattern of plasma pregnenolone sulfate levels in humans from birth to adulthood. J Clin Endocrinol Metab 57:550-556
    • (1983) J Clin Endocrinol Metab , vol.57 , pp. 550-556
    • De Peretti, E.1    Mappus, E.2
  • 45
    • 0018579911 scopus 로고
    • Metabolism of pregnenolone by human breast cancer. Evidence for 17α-hydroxylase and 17,20-lyase
    • Abul-Hajj YJ, Iverson R, Kiang DT 1979 Metabolism of pregnenolone by human breast cancer. Evidence for 17α-hydroxylase and 17,20-lyase. Steroids 34:817-827
    • (1979) Steroids , vol.34 , pp. 817-827
    • Abul-Hajj, Y.J.1    Iverson, R.2    Kiang, D.T.3
  • 48
    • 0036829273 scopus 로고    scopus 로고
    • Aromatase and prostaglandin inter-relationships in breast adipose tissue: Significance for breast cancer development
    • Karuppu D, Kalus A, Simpson ER, Clyne C 2002 Aromatase and prostaglandin inter-relationships in breast adipose tissue: significance for breast cancer development. Breast Cancer Res Treat 76:103-109
    • (2002) Breast Cancer Res Treat , vol.76 , pp. 103-109
    • Karuppu, D.1    Kalus, A.2    Simpson, E.R.3    Clyne, C.4
  • 49
    • 0036126252 scopus 로고    scopus 로고
    • Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells
    • Richards JA, Petrel TA, Brueggemeier RW 2002 Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells. J Steroid Biochem Mol Biol 80:203-212
    • (2002) J Steroid Biochem Mol Biol , vol.80 , pp. 203-212
    • Richards, J.A.1    Petrel, T.A.2    Brueggemeier, R.W.3
  • 50
    • 0034610759 scopus 로고    scopus 로고
    • Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase
    • Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG 2000 Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403:103-108
    • (2000) Nature , vol.403 , pp. 103-108
    • Rossi, A.1    Kapahi, P.2    Natoli, G.3    Takahashi, T.4    Chen, Y.5    Karin, M.6    Santoro, M.G.7
  • 52
    • 0031560438 scopus 로고    scopus 로고
    • The rat serotonin transporter: Identification of cysteine residues important for substrate transport
    • Sur C, Schloss P, Betz H 1997 The rat serotonin transporter: identification of cysteine residues important for substrate transport. Biochem Biophys Res Commun 241:68-72
    • (1997) Biochem Biophys Res Commun , vol.241 , pp. 68-72
    • Sur, C.1    Schloss, P.2    Betz, H.3
  • 53
    • 0029131908 scopus 로고
    • Glucose transporter function is controlled by transporter oligomeric structure. A single, intramolecular disulfide promotes GLUT1 tetramerization
    • Zottola RJ, Cloherty EK, Coderre PE, Hansen A, Hebert DN, Carruthers A 1995 Glucose transporter function is controlled by transporter oligomeric structure. A single, intramolecular disulfide promotes GLUT1 tetramerization. Biochemistry 34:9734-9747
    • (1995) Biochemistry , vol.34 , pp. 9734-9747
    • Zottola, R.J.1    Cloherty, E.K.2    Coderre, P.E.3    Hansen, A.4    Hebert, D.N.5    Carruthers, A.6
  • 54
    • 0023766839 scopus 로고
    • The hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate by MCF-7 human breast cancer cells
    • MacIndoe JH 1988 The hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate by MCF-7 human breast cancer cells. Endocrinology 123:1281-1287
    • (1988) Endocrinology , vol.123 , pp. 1281-1287
    • MacIndoe, J.H.1
  • 55
    • 0033734846 scopus 로고    scopus 로고
    • Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: Inhibition by novel non-steroidal steroid sulfatase inhibitors
    • Billich A, Nussbaumer P, Lehr P 2000 Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors. J Steroid Biochem Mol Biol 73:225-235
    • (2000) J Steroid Biochem Mol Biol , vol.73 , pp. 225-235
    • Billich, A.1    Nussbaumer, P.2    Lehr, P.3


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