Human nucleoside transporters: Biomarkers for response to nucleoside drugs

Nucleosides, Nucleotides and Nucleic Acids

Volumn 28, Issue 5-7, 2009, Pages 450-463

  Damaraju, Vijaya L ^a,b   Sawyer, Michael B ^a,b   MacKey, John R ^a,b   Young, James D ^a   Cass, Carol E ^a,b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b CROSS CANCER INSTITUTE   (Canada)

Author keywords

Anticancer nucleoside drugs; Biomarkers; Clinical response; Immunohistochemistry; Nucleoside transporters

Indexed keywords

ANTINEOPLASTIC AGENT; CAPECITABINE; CLADRIBINE; CLOFARABINE; CYCLOPHOSPHAMIDE; CYTARABINE; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER; FLUDARABINE; FLUOROURACIL; GEMCITABINE; GRANULOCYTE COLONY STIMULATING FACTOR; METHOTREXATE; NUCLEOSIDE DERIVATIVE; NUCLEOSIDE TRANSPORTER;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOCYTIC LEUKEMIA; BLADDER CANCER; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CHEMOSENSITIVITY; CHILDHOOD CANCER; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COLON CANCER; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MONITORING; DRUG PENETRATION; DRUG RESPONSE; DRUG TRANSPORT; GENE EXPRESSION REGULATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HAIRY CELL LEUKEMIA; HEAD AND NECK CANCER; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOHISTOCHEMISTRY; KIDNEY CANCER; LUNG NON SMALL CELL CANCER; MACROGLOBULINEMIA; MYELODYSPLASTIC SYNDROME; NEOPLASM; NONHUMAN; NUCLEOSIDE TRANSPORT; OVARY CANCER; PANCREAS CANCER; PROGNOSIS; PROSTATE CANCER; PROTEIN CONTENT; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; THERAPY; TRANSPORT KINETICS; TREATMENT RESPONSE; WALDENSTROEM MACROGLOBULINEMIA;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL MARKERS; HUMANS; NEOPLASMS; NUCLEOSIDE TRANSPORT PROTEINS; NUCLEOSIDES;

EID: 75749088520     PISSN: 15257770     EISSN: 15322335     Source Type: Journal    
DOI: 10.1080/15257770903044499     Document Type: Review

References (79)

1. Baldwin, S.A.; Mackey, J.R.; Cass, C.E.; Young, J.D. Nucleoside transporters: molecular biology and implications for therapeutic development. Mol. Med. Today 1999, 5, 216-224.
2. Clarke, M.L.; Mackey, J.R.; Baldwin, S.A.; Young, J.D.; Cass, C.E. The role ofmembrane transporters in cellular resistance to anticancer nucleoside drugs. Cancer Treat. Res. 2002, 112, 27-47.
3. Damaraju, V.L.; Damaraju, S.; Young, J.D.; Baldwin, S.A.; Mackey, J.; Sawyer, M.B.; Cass, C.E. Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy. Oncogene 2003, 22, 7524-7536.
4. Kong, W.; Engel, K.; Wang, J. Mammalian nucleoside transporters. Curr. Drug Metab. 2004, 5, 63-84.
5. Mackey, J.R.; Baldwin, S.A.; Young, J.D.; Cass, C.E. Nucleoside transport and its significance for anticancer drug resistance. Drug Resist. Update 1998, 1, 310-324.
6. Baldwin, S.A.; Yao, S.Y.; Hyde, R.J.; Ng, A.M.; Foppolo, S.; Barnes, K.; Ritzel, M.W.; Cass, C.E.; Young, J.D. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J. Biol. Chem. 2005, 280, 15880-15887.
7. Barnes, K.; Dobrzynski, H.; Foppolo, S.; Beal, P.R.; Ismat, F.; Scullion, E.R.; Sun, L.; Tellez, J.; Ritzel, M.W.; Claycomb, W.C.; et al. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ. Res. 2006, 99, 510-519.
8. Smith, K.M.; Slugoski, M.D.; Loewen, S.K.; Ng, A.M.; Yao, S.Y.; Chen, X.Z.; Karpinski, E.; Cass, C.E.; Baldwin, S.A.; Young, J.D. The broadly selective human Na+/nucleoside cotransporter (hCNT3) exhibits novel cation-coupled nucleoside transport characteristics. J. Biol. Chem. 2005, 280, 25436-25449.
9. Baldwin, S.A.; Beal, P.R.; Yao, S.Y.; King, A.E.; Cass, C.E.; Young, J.D. The equilibrative nucleoside transporter family, SLC29. Pflugers. Arch. 2004, 447, 735-743.
10. Griffiths, M.; Beaumont, N.; Yao, S.Y.; Sundaram, M.; Boumah, C.E.; Davies, A.; Kwong, F.Y.; Coe, I.; Cass, C.E.; Young, J.D.; et al. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat. Med. 1997, 3, 89-93.
11. Griffiths, M.; Yao, S.Y.; Abidi, F.; Phillips, S.E.; Cass, C.E.; Young, J.D.; Baldwin, S.A. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem. J. 1997, 328 (Pt 3), 739-743.
12. Ritzel, M.W.; Ng, A.M.; Yao, S.Y.; Graham, K.; Loewen, S.K.; Smith, K.M.; Ritzel, R.G.; Mowles, D.A.; Carpenter, P.; Chen, X.Z.; et al. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J. Biol. Chem. 2001, 276, 2914-2927.
13. Ritzel, M.W.; Yao, S.Y.; Huang, M.Y.; Elliott, J.F.; Cass, C.E.; Young, J.D. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am. J. Physiol. 1997, 272, C707-C714.
14. Ritzel, M.W.; Yao, S.Y.; Ng, A.M.; Mackey, J.R.; Cass, C.E.; Young, J.D. Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol. Membr. Biol. 1998, 15, 203-211.
15. Crawford, C.R.; Patel, D.H.; Naeve, C.; Belt, J.A. Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line. J. Biol. Chem. 1998, 273, 5288-5293.
16. Yao, S.Y.; Ng, A.M.; Vickers, M.F.; Sundaram, M.; Cass, C.E.; Baldwin, S.A.; Young, J.D. Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation. J. Biol. Chem. 2002, 277, 24938-24948.
17. Engel, K.; Zhou, M.;Wang, J. Identification and characterization of a novelmonoamine transporter in the human brain. J. Biol. Chem. 2004, 279, 50042-50049.
18. Govindarajan, R.; Leung, G.P.; Zhou, M.; Tse, C.M.; Wang, J.; Unadkat, J.D. Facilitated Mitochondrial Import of Anti-viral and Anti-cancer Nucleoside Drugs by Human Equilibrative Nucleoside Transporter-3 (hENT3). Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296, 6910-6922
19. Boumah, C.E.; Hogue, D.L.; Cass, C.E. Expression of high levels of nitrobenzylthioinosine-sensitive nucleoside transport in cultured human choriocarcinoma (BeWo) cells. Biochem. J. 1992, 288 (Pt. 3), 987-996.
20. Pressacco, J.; Wiley, J.S.; Jamieson, G.P.; Erlichman, C.; Hedley, D.W.Modulation of the equilibrative nucleoside transporter by inhibitors of DNA synthesis. Br. J. Cancer 1995, 72, 939-942.
21. Smith, C.L.; Pilarski, L.M.; Egerton, M.L.; Wiley, J.S. Nucleoside transport and proliferative rate in human thymocytes and lymphocytes. Blood 1989, 74, 2038-2042.
22. Wiley, J.S.; Cebon, J.S.; Jamieson, G.P.; Szer, J.; Gibson, J.; Woodruff, R.K.; McKendrick, J.J.; Sheridan, W.P.; Biggs, J.C.; Snook, M.B.; et al. Assessment of proliferative responses to granulocytemacrophage colony-stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand for the nucleoside transporter. Leukemia 8, 1994, 181-185.
23. Powell, B.L.; Gregory, B.W.; Evans, J.K.; White, J.C.; Lyerly, E.S.; Chorley, H.M.; Russell, G.B.; Capizzi, R.L. Leukapheresis induced changes in cell cycle distribution and nucleoside transporters in patients with untreated acute myeloid leukemia. Leukemia 1991, 5, 1037-1042.
24. Petersen, A.J.; Brown, R.D.; Pope, B.B.; Jamieson, G.P.; Paterson, A.R.; Gibson, J.; Wiley, J.S.; Joshua, D.E. Multiple myeloma: expression of nucleoside transporters on malignant plasma cells and their relationship to cellular proliferation. Leuk. Lymphoma 1994, 13, 491-499.
25. Robak, T. Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies. Drugs Aging 2005, 22, 983-1012.
26. Beutler, E. Cladribine (2-chlorodeoxyadenosine). Lancet 1992, 340, 952-956.
27. Robak, T.; Korycka, A.; Kasznicki, M.; Wrzesien-Kus, A.; Smolewski, P. Purine nucleoside analogues for the treatment of hematological malignancies: pharmacology and clinical applications. Curr. Cancer Drug Targets 2005, 5, 421-444.
28. Gati, W.P.; Paterson, A.R.; Belch, A.R.; Chlumecky, V.; Larratt, L.M.; Mant, M.J.; Turner, A.R. Es nucleoside transporter content of acute leukemia cells: role in cell sensitivity to cytarabine (araC). Leuk. Lymphoma 1998, 32, 45-54.
29. Molina-Arcas, M.; Marce, S.; Villamor, N.; Huber-Ruano, I.; Casado, F.J.; Bellosillo, B.; Montserrat, E.; Gil, J.; Colomer, D.; Pastor-Anglada, M. Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells. Leukemia 2005, 19, 64-68.
30. Faderl, S.; Gandhi, V.; Keating, M.J.; Jeha, S.; Plunkett, W.; Kantarjian, H.M. The role of clofarabine in hematologic and solid malignancies-development of a next-generation nucleoside analog. Cancer 2005, 103, 1985-1995.
31. King, K.M.; Damaraju, V.L.; Vickers, M.F.; Yao, S.Y.; Lang, T.; Tackaberry, T.E.; Mowles, D.A.; Ng, A.M.; Young, J.D.; Cass, C.E. A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine, and fludarabine by recombinant human nucleoside transporters produced in three model expression systems. Mol. Pharmacol. 2006, 69, 346-353.
32. Zhang, J.; Visser, F.; King, K.M.; Baldwin, S.A.; Young, J.D.; Cass, C.E. The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. Cancer Metastasis Rev. 2007, 26, 85-110.
33. Sundaram, M.; Yao, S.Y.; Ingram, J.C.; Berry, Z.A.; Abidi, F.; Cass, C.E.; Baldwin, S.A.; Young, J.D. Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and anti-cancer drugs. J. Biol. Chem. 2001, 276, 45270-45275.
34. Hubeek, I.; Stam, R.W.; Peters, G.J.; Broekhuizen, R.; Meijerink, J.P.; Van Wering, E.R.; Gibson, B.E.; Creutzig, U.; Zwaan, C.M.; Cloos, J.; et al. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br. J. Cancer 2005, 93, 1388-1394.
35. Galmarini, C.M.; Thomas, X.; Calvo, F.; Rousselot, P.; Rabilloud, M.; El Jaffari, A.; Cros, E.; Dumontet, C. In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia. Br. J. Haematol. 2002, 117, 860-868.
36. Stam, R.W.; den Boer, M.L.; Meijerink, J.P.; Ebus, M.E.; Peters, G.J.; Noordhuis, P.; Janka- Schaub, G.E.; Armstrong, S.A.; Korsmeyer, S.J.; Pieters, R. Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. Blood 2003, 101, 1270-1276.
37. Hu, H.; Endres, C.J.; Chang, C.; Umapathy, N.S.; Lee, E.W.; Fei, Y.J.; Itagaki, S.; Swaan, P.W.; Ganapathy, V.; Unadkat, J.D. Electrophysiological characterization and modeling of the structure activity relationship of the human concentrative nucleoside transporter 3 (hCNT3). Mol. Pharmacol. 2006, 69, 1542-1553.
38. Mackey, J.R.; Yao, S.Y.; Smith, K.M.; Karpinski, E.; Baldwin, S.A.; Cass, C.E.; Young, J.D. Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J. Natl. Cancer Inst. 1999, 91, 1876-1881.
39. Mackey, J.R.; Mani, R.S.; Selner, M.; Mowles, D.; Young, J.D.; Belt, J.A.; Crawford, C.R.; Cass, C.E. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res. 1998, 58, 4349-4357.
40. Achiwa, H.; Oguri, T.; Sato, S.; Maeda, H.; Niimi, T.; Ueda, R. Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer. Cancer Sci. 2004, 95, 753-757.
41. Giovannetti, E.; Del Tacca, M.; Mey, V.; Funel, N.; Nannizzi, S.; Ricci, S.; Orlandini, C.; Boggi, U.; Campani, D.; Del Chiaro, M.; et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res. 2006, 66, 3928-3935.
42. Mey, V.; Giovannetti, E.; De Braud, F.; Nannizzi, S.; Curigliano, G.; Verweij, F.; De Cobelli, O.; Pece, S.; Del Tacca, M.; Danesi, R. In vitro synergistic cytotoxicity of gemcitabine and pemetrexed and pharmacogenetic evaluation of response to gemcitabine in bladder cancer patients. Br. J. Cancer 2006, 95, 289-297.
43. Ishikawa, T.; Utoh, M.; Sawada, N.; Nishida, M.; Fukase, Y.; Sekiguchi, F.; Ishitsuka, H. Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem. Pharmacol. 1998, 55, 1091-1097.
44. Walko, C.M.; Lindley, C. Capecitabine: a review. Clin. Ther. 2005, 27, 23-44.
45. Clarke, M.L.; Damaraju, V.L.; Zhang, J.; Mowles, D.; Tackaberry, T.; Lang, T.; Smith, K.M.; Young, J.D.; Tomkinson, B.; Cass, C.E. The role of human nucleoside transporters in cellular uptake of 4′-thio-beta-D- arabinofuranosylcytosine and beta-D-arabinosylcytosine. Mol. Pharmacol. 2006, 70, 303-310.
46. Lang, T.T.; Selner, M.; Young, J.D.; Cass, C.E. Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Mol. Pharmacol. 2001, 60, 1143-1152.
47. Mackey, J.R.; Jennings, L.L.; Clarke, M.L.; Santos, C.L.; Dabbagh, L.; Vsianska, M.; Koski, S.L.; Coupland, R.W.; Baldwin, S.A.; Young, J.D.; et al. Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. Clin. Cancer Res. 2002, 8, 110-116.
48. Mackey, J.R.; Galmarini, C.M.; Graham, K.A.; Joy, A.A.; Delmer, A.; Dabbagh, L.; Glubrecht, D.; Jewell, L.D.; Lai, R.; Lang, T.; et al. Quantitative analysis of nucleoside transporter and metabolism gene expression in chronic lymphocytic leukemia (CLL): identification of fludarabine-sensitive and -insensitive populations. Blood 2005, 105, 767-774.
49. Garcia-Manteiga, J.; Molina-Arcas, M.; Casado, F.J.; Mazo, A.; Pastor-Anglada, M. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2′,2′-difluorodeoxycytidineinduced cytotoxicity. Clin. Cancer Res. 2003, 9, 5000-5008.
50. Kinsella, A.R.; Smith, D.; Pickard,M. Resistance to chemotherapeutic antimetabolites: a function of salvage pathway involvement and cellular response to DNA damage. Br. J. Cancer 1997, 75, 935-945.
51. Osato, D.H.; Huang, C.C.; Kawamoto, M.; Johns, S.J.; Stryke, D.; Wang, J.; Ferrin, T.E.; Herskowitz, I.; Giacomini, K.M. Functional characterization in yeast of genetic variants in the human equilibrative nucleoside transporter, ENT1. Pharmacogenetics 2003, 13, 297-301.
52. Myers, S.N.; Goyal, R.K.; Roy, J.D.; Fairfull, L.D.; Wilson, J.W.; Ferrell, R.E. Functional single nucleotide polymorphism haplotypes in the human equilibrative nucleoside transporter 1. Pharmacogenet. Genomics 2006, 16, 315-320.
53. Owen, R.P.; Lagpacan, L.L.; Taylor, T.R.; De La Cruz, M.; Huang, C.C.; Kawamoto, M.; Johns, S.J.; Stryke, D.; Ferrin, T.E.; Giacomini, K.M. Functional characterization and haplotype analysis of polymorphisms in the human equilibrative nucleoside transporter, ENT2. Drug Metab. Dispos. 2006, 34, 12-15.
54. Gray, J.H.; Mangravite, L.M.; Owen, R.P.; Urban, T.J.; Chan, W.; Carlson, E.J.; Huang, C.C.; Kawamoto, M.; Johns, S.J.; Stryke, D.; et al. Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol. Pharmacol. 2004, 65, 512-519.
55. Owen, R.P.; Gray, J.H.; Taylor, T.R.; Carlson, E.J.; Huang, C.C.; Kawamoto, M.; Johns, S.J.; Stryke, D.; Ferrin, T.E.; Giacomini, K.M. Genetic analysis and functional characterization of polymorphisms in the human concentrative nucleoside transporter, CNT2. Pharmacogenet. Genomics 2005, 15, 83-90. (Pubitemid 40562985)
56. Li, L.; Tan, C.M.; Koo, S.H.; Chong, K.T.; Lee, E.J. Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians. Pharmacogenet. Genomics 2007, 17, 783-786.
57. Badagnani, I.; Chan, W.; Castro, R.A.; Brett, C.M.; Huang, C.C.; Stryke, D.; Kawamoto, M.; Johns, S.J.; Ferrin, T.E.; Carlson, E.J.; et al. Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 2005, 5, 157-165. (Pubitemid 40852217)
58. Damaraju, S.; Zhang, J.; Visser, F.; Tackaberry, T.; Dufour, J.; Smith, K.M.; Slugoski, M.; Ritzel, M.W.; Baldwin, S.A.; Young, J.D.; et al. Identification and functional characterization of variants in human concentrative nucleoside transporter 3, hCNT3 (SLC28A3), arising from single nucleotide polymorphisms in coding regions of the hCNT3 gene. Pharmacogenet Genomics 2005, 15, 173-182.
59. Cass, C.E.; King, K.M.; Montano, J.T.; Janowska-Wieczorek, A. A comparison of the abilities of nitrobenzylthioinosine, dilazep, and dipyridamole to protect human hematopoietic cells from 7-deazaadenosine (tubercidin). Cancer Res. 1992, 52, 5879-5886.
60. Gati, W.P.; Paterson, A.R.; Larratt, L.M.; Turner, A.R.; Belch, A.R. Sensitivity of acute leukemia cells to cytarabine is a correlate of cellular es nucleoside transporter site content measured by flow cytometry with SAENTA-fluorescein. Blood 1997, 90, 346-353.
61. Wiley, J.S.; Jones, S.P.; Sawyer, W.H. Cytosine arabinoside transport by human leukaemic cells. Eur. J. Cancer Clin. Oncol. 1983, 19, 1067-1074.
62. Wiley, J.S.; Jones, S.P.; Sawyer, W.H.; Paterson, A.R. Cytosine arabinoside influx and nucleoside transport sites in acute leukemia. J. Clin. Invest. 1982, 69, 479-489.
63. Jennings, L.L.; Hao, C.; Cabrita, M.A.; Vickers, M.F.; Baldwin, S.A.; Young, J.D.; Cass, C.E. Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system. Neuropharmacology 2001, 40, 722-731.
64. Reiman, T.; Clarke, M.L.; Dabbagh, L.; Vsianska, M.; Coupland, R.W.; Belch, A.R.; Baldwin, S.A.; Young, J.D.; Cass, C.E.; Mackey, J.R. Differential expression of human equilibrative nucleoside transporter 1 (hENT1) protein in the Reed-Sternberg cells of Hodgkin's disease. Leuk. Lymphoma 2002, 43, 1435-1440.
65. Chow, L.; Lai, R.; Dabbagh, L.; Belch, A.; Young, J.D.; Cass, C.E.; Mackey, J.R. Analysis of human equilibrative nucleoside transporter 1 (hENT1) protein in non-Hodgkin's lymphoma by immunohistochemistry. Mod. Pathol. 2005, 18, 558-564.
66. Marce, S.; Molina-Arcas, M.; Villamor, N.; Casado, F.J.; Campo, E.; Pastor-Anglada, M. Colomer, D. Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica 2006, 91, 895-902.
67. Spratlin, J.; Sangha, R.; Glubrecht, D.; Dabbagh, L.; Young, J.D.; Dumontet, C.; Cass, C.; Lai, R.; Mackey, J.R. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin. Cancer Res. 2004, 10, 6956-6961.
68. Mori, R.; Ishikawa, T.; Ichikawa, Y.; Taniguchi, K.; Matsuyama, R.; Ueda, M.; Fujii, Y.; Endo, I.; Togo, S.; Danenberg, P.V.; et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells. Oncol. Rep. 2007, 17, 1201-1205.
69. Perez-Torras, S.; Garcia-Manteiga, J.;Mercade, E.; Casado, F.J.; Carbo, N.; Pastor-Anglada, M.; Mazo, A. Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer. Biochem. Pharmacol. 2008, 76, 322-329.
70. Seve, P.; Mackey, J.R.; Isaac, S.; Tredan, O.; Souquet, P.J.; Perol, M.; Cass, C.; Dumontet, C. cN-II expression predicts survival in patients receiving gemcitabine for advanced non-small cell lung cancer. Lung Cancer 2005, 49, 363-370.
71. Oguri, T.; Achiwa, H.; Muramatsu, H.; Ozasa, H.; Sato, S.; Shimizu, S.; Yamazaki, H.; Eimoto, T.; Ueda, R. The absence of human equilibrative nucleoside transporter 1 expression predicts nonresponse to gemcitabine-containing chemotherapy in non-small cell lung cancer. Cancer Lett. 2007, 256, 112-119.
72. Farrell, J.J.; Elsaleh, H.; Garcia, M.; Lai, R.; Ammar, A.; Regine, W.F.; Abrams, R.; Benson, A.B.; Macdonald, J.; Cass, C.E.; et al. Human Equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 2008, 136, 187-195.
73. Santini, D.; Perrone, G.; Vincenzi, B.; Lai, R.; Cass, C.; Alloni, R.; Rabitti, C.; Antinori, A.; Vecchio, F.; Morini, S.; et al. Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer. Ann. Oncol. 2008, 19, 724-728.
74. Farre, X.; Guillen-Gomez, E.; Sanchez, L.;Hardisson, D.; Plaza, Y.; Lloberas, J.; Casado, F.J.; Palacios, J.; Pastor-Anglada, M. Expression of the nucleoside-derived drug transporters hCNT1, hENT1 and hENT2 in gynecologic tumors. Int. J. Cancer 2004, 112, 959-966.
75. Gloeckner-Hofmann, K.; Guillen-Gomez, E.; Schmidtgen, C.; Porstmann, R.; Ziegler, R.; Stoss, O.; Casado, F.J.; Ruschoff, J.; Pastor-Anglada, M. Expression of the high-affinity fluoropyrimidinepreferring nucleoside transporter hCNT1 correlates with decreased disease-free survival in breast cancer. Oncology 2006, 70, 238-244.
76. Duflot, S.; Calvo, M.; Casado, F.J.; Enrich, C.; Pastor-Anglada, M. Concentrative nucleoside transporter (rCNT1) is targeted to the apical membrane through the hepatic transcytotic pathway. Exp. Cell Res. 2002, 281, 77-85.
77. Tsang, R.Y.; Santos, C.; Ghosh, S.; Dabbagh, L.; King, K.; Young, J.; Cass, C.E.; Mackey, J.R.; Lai, R. Immunohistochemistry for human concentrative nucleoside transporter 3 protein predicts fludarabine sensitivity in chronic lymphocytic leukemia. Mod. Pathol. 2008, 21, 1387-1393.
78. Marechal, R.; Mackey, J.R.; Lai, R.; Demetter, P.; Peeters, M.; Polus, M.; Cass, C.E.; Young, J.; Salmon, I.; Deviere, J.; et al. Human equilibrative nucleoside transporter-1 (hENT-1) and human concentrative nucleoside transporter-3 (hCNT-3) predict survival after adjuvant therapy in resected pancreatic adenocarcinoma. Clinical Cancer Research 2009, 15, 2913-2919.
79. Lai, R.; Bartlett, N.L.;Mackey, J.R.; Jung, S.H.; Johnson, J.L.; Cook, J.R.; Jones, D.; Cass, C.E.; Young, J.D.; Said, J.; et al. High expression of nucleoside transporter protein hENT1 in Reed-Sternberg cells is associated with treatment failure in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine and liposomal doxorubicin-a CALGB 59804 correlative study. Leuk. Lymphoma 2008, 49, 1202-1205.