Cell surface nucleolin as a target for anti-cancer therapies

Recent Patents on Anti-Cancer Drug Discovery

Volumn 9, Issue 2, 2014, Pages 137-152

  Koutsioump, Marina ^a   Papadimitriou, Evangelia ^a  

^a UNIVERSITY OF PATRAS   (Greece)

Author keywords

Angiogenesis; Cancer; Cell surface nucleolin; Growth factors; Ligand specific internalization; Targeted delivery approaches

Indexed keywords

HEPARIN; LACTOFERRIN; MITOGEN ACTIVATED PROTEIN KINASE 11; NUCLEOLIN; OLIGONUCLEOTIDE; QUARFLOXIN; AGRO 100; ANTINEOPLASTIC AGENT; HB-19 PEPTIDE; N6L PEPTIDE; OLIGODEOXYRIBONUCLEOTIDE; PEPTIDE; PHOSPHOPROTEIN; RNA BINDING PROTEIN;

ANGIOGENESIS; APOPTOSIS; CARCINOGENESIS; CELL CYCLE REGULATION; CELL SURFACE; CYTOTOXICITY; DOWN REGULATION; GENE MUTATION; GENETIC TRANSCRIPTION; HUMAN; INTERNALIZATION; NEUROENDOCRINE TUMOR; NONHUMAN; PATENT; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; CELL ADHESION; CELL DIFFERENTIATION; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; NEOVASCULARIZATION (PATHOLOGY); PROCEDURES;

ANTINEOPLASTIC AGENTS; CELL ADHESION; CELL DIFFERENTIATION; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; OLIGODEOXYRIBONUCLEOTIDES; PATENTS AS TOPIC; PEPTIDES; PHOSPHOPROTEINS; RNA-BINDING PROTEINS;

EID: 84901245809     PISSN: 15748928     EISSN: 22123970     Source Type: Journal    
DOI: 10.2174/1574892808666131119095953     Document Type: Review

References (216)

1. Lischwe MA, Richards RL, Busch RK, Busch H. Localization of phosphoprotein C23 to nucleolar structures and to the nucleolus organizer regions. Exp Cell Res 1981; 136(1): 101-9.
2. Bugler B, Caizergues-Ferrer M, Bouche G, Bourbon H, Amalric F. Detection and localization of a class of proteins immunologically related to a 100-kDa nucleolar protein. Eur J Biochem 1982; 128(2- 3): 475-80.
3. Biggiogera M, Burki K, Kaufmann SH, Shaper JH, Gas N, Amalric F, et al. Nucleolar distribution of proteins B23 and nucleolin in mouse preimplantation embryos as visualized by immunoelectron microscopy. Development 1990; 110(4): 1263-70.
4. Shaw PJ, Jordan EG. The nucleolus. Annu Rev Cell Dev Biol 1995; 11: 93-121.
5. Ochs R, Lischwe M, O'Leary P, Busch H. Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Exp Cell Res 1983; 146(1): 139-49.
6. Orrick LR, Olson MO, Busch H. Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by twodimensional polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 1973; 70(5): 1316-20.
7. Warrener P, Petryshyn R. Phosphorylation and proteolytic degradation of nucleolin from 3T3-F442A cells. Biochem Biophys Res Commun 1991; 180(2): 716-23.
8. Tawfic S, Goueli SA, Olson MO, Ahmed K. Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate. Prostate 1994; 24(2): 101-6.
9. Wang SA, Li HY, Hsu TI, Chen SH, Wu CJ, Chang WC, et al. Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis. J Biol Chem 2011; 286(51): 43816-29.
10. Chen CM, Chiang SY, Yeh NH. Increased stability of nucleolin in proliferating cells by inhibition of its self-cleaving activity. J Biol Chem 1991; 266(12): 7754-8.
11. Schneider HR, Reichert GH, Issinger OG. Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110- kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells. Eur J Biochem 1986; 161(3): 733-8.
12. Caizergues-Ferrer M, Belenguer P, Lapeyre B, Amalric F, Wallace MO, Olson MO. Phosphorylation of nucleolin by a nucleolar type NII protein kinase. Biochemistry 1987; 26(24): 7876-83.
13. Belenguer P, Caizergues-Ferrer M, Labbe JC, Doree M, Amalric F. Mitosis-specific phosphorylation of nucleolin by p34Cdc2 protein kinase. Mol Cell Biol 1990; 10(7): 3607-18.
14. Peter M, Nakagawa J, Doree M, Labbe JC, Nigg EA. Identification of major nucleolar proteins as candidate mitotic substrates of Cdc2 kinase. Cell 1990; 60(5): 791-801.
15. Csermely P, Schnaider T, Cheatham B, Olson MO, Kahn CR. Insulin induces the phosphorylation of nucleolin. A possible mechanism of insulin-induced RNA efflux from nuclei. J Biol Chem 1993; 268(13): 9747-52.
16. Zhou G, Seibenhener ML, Wooten MW. Nucleolin is a protein kinase C-zeta substrate. Connection between cell surface signaling and nucleus in PC12 cells. J Biol Chem 1997; 272(49): 31130-7.
17. Barel M, Le Romancer M, Frade R. Activation of the EBV/C3d receptor (CR2, CD21) on human B lymphocyte surface triggers tyrosine phosphorylation of the 95-kDa nucleolin and its interaction with phosphatidylinositol 3 kinase. J Immunol 2001; 166(5): 3167-73.
18. Reyes-Reyes EM, Akiyama SK. Cell-surface nucleolin is a signal transducing P-selectin binding protein for human colon carcinoma cells. Exp Cell Res 2008; 314(11-12): 2212-23.
19. Fang SH, Yeh NH. The self-cleaving activity of nucleolin determines its molecular dynamics in relation to cell proliferation. Exp Cell Res 1993; 208(1): 48-53.
20. Losfeld ME, Khoury DE, Mariot P, Carpentier M, Krust B, Briand JP, et al. The cell surface expressed nucleolin is a glycoprotein that triggers calcium entry into mammalian cells. Exp Cell Res 2009; 315(2): 357-69.
21. Lapeyre B, Bourbon H, Amalric F. Nucleolin, the major nucleolar protein of growing eukaryotic cells: An unusual protein structure revealed by the nucleotide sequence. Proc Natl Acad Sci USA 1987; 84(6): 1472-6.
22. Srivastava M, Fleming PJ, Pollard HB, Burns AL. Cloning and sequencing of the human nucleolin cDNA. FEBS Lett 1989; 250(1): 99-105.
23. Mamrack MD, Olson MO, Busch H. Amino acid sequence and sites of phosphorylation in a highly acidic region of nucleolar nonhistone protein C23. Biochemistry 1979; 18(15): 3381-6.
24. Rao SV, Mamrack MD, Olson MO. Localization of phosphorylated highly acidic regions in the NH2-terminal half of nucleolar protein C23. J Biol Chem 1982; 257(24): 15035-41.
25. Bourbon HM, Bugler B, Caizergues-Ferrer M, Amalric F, Zalta JP. Maturation of a 100 kDa protein associated with preribosomes in Chinese hamster ovary cells. Mol Biol Rep 1983; 9(1-2): 39-47.
26. Lischwe MA, Roberts KD, Yeoman LC, Busch H. Nucleolar specific acidic phosphoprotein C23 is highly methylated. J Biol Chem 1982; 257(24): 14600-2.
27. Olson MO, Thompson BA. Distribution of proteins among chromatin components of nucleoli. Biochemistry 1983; 22(13): 3187-93.
28. Erard MS, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F. A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem 1988; 175(3): 525-30.
29. Ghisolfi-Nieto L, Joseph G, Puvion-Dutilleul F, Amalric F, Bouvet P. Nucleolin is a sequence-specific RNA-binding protein: Characterization of targets on pre-ribosomal RNA. J Mol Biol 1996; 260(1): 34-53.
30. Cong R, Das S, Ugrinova I, Kumar S, Mongelard F, Wong J, et al. Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase I transcription. Nucleic Acids Res 2012; 40(19): 9441-54.
31. Bouche G, Caizergues-Ferrer M, Bugler B, Amalric F. Interrelations between the maturation of a 100 kDa nucleolar protein and pre rRNA synthesis in CHO cells. Nucleic Acids Res 1984; 12(7): 3025-35.
32. Egyhazi E, Pigon A, Chang JH, Ghaffari SH, Dreesen TD, Wellman SE, et al. Effects of anti-C23 (nucleolin) antibody on transcription of ribosomal DNA in Chironomus salivary gland cells. Exp Cell Res 1988; 178(2): 264-72.
33. Angelov D, Bondarenko VA, Almagro S, Menoni H, Mongelard F, Hans F, et al. Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. EMBO J 2006; 25(8): 1669-79.
34. Bugler B, Bourbon H, Lapeyre B, Wallace MO, Chang JH, Amalric F, et al. RNA binding fragments from nucleolin contain the ribonucleoprotein consensus sequence. J Biol Chem 1987; 262(23): 10922-5.
35. Creancier L, Prats H, Zanibellato C, Amalric F, Bugler B. Determination of the functional domains involved in nucleolar targeting of nucleolin. Mol Biol Cell 1993; 4(12): 1239-50.
36. Lischwe MA, Cook RG, Ahn YS, Yeoman LC, Busch H. Clustering of glycine and NG,NG-dimethylarginine in nucleolar protein C23. Biochemistry 1985; 24(22): 6025-8.
37. Lapeyre B, Amalric F, Ghaffari SH, Rao SV, Dumbar TS, Olson MO. Protein and cDNA sequence of a glycine-rich, dimethylarginine-containing region located near the carboxylterminal end of nucleolin (C23 and 100 kDa). J Biol Chem 1986; 261(20): 9167-73.
38. Bandziulis RJ, Swanson MS, Dreyfuss G. RNA-binding proteins as developmental regulators. Genes Dev 1989; 3(4): 431-7.
39. Bouvet P, Diaz JJ, Kindbeiter K, Madjar JJ, Amalric F. Nucleolin interacts with several ribosomal proteins through its RGG domain. J Biol Chem 1998; 273(30): 19025-9.
40. Stepanova V, Lebedeva T, Kuo A, Yarovoi S, Tkachuk S, Zaitsev S, et al. Nuclear translocation of urokinase-type plasminogen activator. Blood 2008; 112(1): 100-10.
41. Dumler I, Stepanova V, Jerke U, Mayboroda OA, Vogel F, Bouvet P, et al. Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin. Curr Biol 1999; 9(24): 1468-76.
42. Said EA, Krust B, Nisole S, Svab J, Briand JP, Hovanessian AG. The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. J Biol Chem 2002; 277(40): 37492-502.
43. Hovanessian AG. Midkine, a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin. Cell Res 2006; 16(2): 174-81.
44. Legrand D, Vigie K, Said EA, Elass E, Masson M, Slomianny MC, et al. Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. Eur J Biochem 2004; 271(2): 303-17.
45. Allain FH, Gilbert DE, Bouvet P, Feigon J. Solution structure of the two N-terminal RNA-binding domains of nucleolin and NMR study of the interaction with its RNA target. J Mol Biol 2000; 303(2): 227-41.
46. Roger B, Moisand A, Amalric F, Bouvet P. Nucleolin provides a link between RNA polymerase I transcription and pre-ribosome assembly. Chromosoma 2003; 111(6): 399-407.
47. Storck S, Thiry M, Bouvet P. Conditional knockout of nucleolin in DT40 cells reveals the functional redundancy of its RNA-binding domains. Biol Cell 2009; 101(3): 153-67.
48. Borer RA, Lehner CF, Eppenberger HM, Nigg EA. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 1989; 56(3): 379-90.
49. Schmidt-Zachmann MS, Nigg EA. Protein localization to the nucleolus: A search for targeting domains in nucleolin. J Cell Sci 1993; 105 (Pt 3): 799-806.
50. Xue Z, Melese T. Nucleolar proteins that bind NLSs: A role in nuclear import or ribosome biogenesis? Trends Cell Biol 1994; 4(12): 414-7.
51. Gillet G, Michel D, Crisanti P, Guerin M, Herault Y, Pessac B, et al. Serum factors and v-Src control two complementary mitogenic pathways in quail neuroretinal cells in culture. Oncogene 1993; 8(3): 565-74.
52. Ugrinova I, Monier K, Ivaldi C, Thiry M, Storck S, Mongelard F, et al. Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol Biol 2007; 8: 66.
53. Ma N, Matsunaga S, Takata H, Ono-Maniwa R, Uchiyama S, Fukui K. Nucleolin functions in nucleolus formation and chromosome congression. J Cell Sci 2007; 120(Pt 12): 2091-105.
54. Yang A, Shi G, Zhou C, Lu R, Li H, Sun L, et al. Nucleolin maintains embryonic stem cell self-renewal by suppression of p53 protein-dependent pathway. J Biol Chem 2011; 286(50): 43370-82.
55. Xu Z, Joshi N, Agarwal A, Dahiya S, Bittner P, Smith E, et al. Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest. J Neurooncol 2012; 108(1): 59-67.
56. Ying GG, Proost P, van Damme J, Bruschi M, Introna M, Golay J. Nucleolin, a novel partner for the Myb transcription factor family that regulates their activity. J Biol Chem 2000; 275(6): 4152-8.
57. Gonzalez V, Hurley LH. The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity. Biochemistry 2010; 49(45): 9706-14.
58. Chen J, Guo K, Kastan MB. Interactions of nucleolin and ribosomal protein L26 (RPL26) in translational control of human p53 mRNA. J Biol Chem 2012; 287(20): 16467-76.
59. Yang TH, Tsai WH, Lee YM, Lei HY, Lai MY, Chen DS, et al. Purification and characterization of nucleolin and its identification as a transcription repressor. Mol Cell Biol 1994; 14(9): 6068-74.
60. Samuel S, Twizere JC, Beifuss KK, Bernstein LR. Nucleolin binds specifically to an AP-1 DNA sequence and represses AP1- dependent transactivation of the matrix metalloproteinase-13 gene. Mol Carcinog 2008; 47(1): 34-46.
61. Fahling M, Steege A, Perlewitz A, Nafz B, Mrowka R, Persson PB, et al. Role of nucleolin in posttranscriptional control of MMP-9 expression. Biochim Biophys Acta 2005; 1731(1): 32-40.
62. Shang Y, Kakinuma S, Nishimura M, Kobayashi Y, Nagata K, Shimada Y. Interleukin-9 receptor gene is transcriptionally regulated by nucleolin in T-cell lymphoma cells. Mol Carcinog 2012; 51(8): 619-27.
63. Uribe DJ, Guo K, Shin YJ, Sun D. Heterogeneous nuclear ribonucleoprotein K and nucleolin as transcriptional activators of the vascular endothelial growth factor promoter through interaction with secondary DNA structures. Biochemistry 2011; 50(18): 3796-806.
64. Liang P, Jiang B, Lv C, Huang X, Sun L, Zhang P, et al. The expression and proangiogenic effect of nucleolin during the recovery of heat-denatured HUVECs. Biochim Biophys Acta 2013; 1830(10): 4500-12.
65. Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, et al. Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor beta transcription in breast cancer cells. PLoS One 2012; 7(5): e38278.
66. Masumi A, Fukazawa H, Shimazu T, Yoshida M, Ozato K, Komuro K, et al. Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional activation. Oncogene 2006; 25(37): 5113-24.
67. Huddleson JP, Ahmad N, Lingrel JB. Up-regulation of the KLF2 transcription factor by fluid shear stress requires nucleolin. J Biol Chem 2006; 281(22): 15121-8.
68. Jerke U, Tkachuk S, Kiyan J, Stepanova V, Kusch A, Hinz M, et al. Stat1 nuclear translocation by nucleolin upon monocyte differentiation. PLoS One 2009; 4(12): e8302.
69. Bates P, Mergny JL, Yang D. Quartets in G-major. The First International Meeting on Quadruplex DNA. EMBO Rep 2007; 8(11): 1003-10.
70. Drygin D, Siddiqui-Jain A, O'Brien S, Schwaebe M, Lin A, Bliesath J, et al. Anticancer activity of CX-3543: A direct inhibitor of rRNA biogenesis. Cancer Res 2009; 69(19): 7653-61.
71. Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Pineda-Roman M, et al. Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA. Blood 2007; 109(7): 3069-75.
72. Fogal V, Sugahara KN, Ruoslahti E, Christian S. Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature. Angiogenesis 2009; 12(1): 91-100.
73. Zhang B, Wang H, Jiang B, Liang P, Liu M, Deng G, et al. Nucleolin/C23 is a negative regulator of hydrogen peroxideinduced apoptosis in HUVECs. Cell Stress Chaperones 2010; 15(3): 249-57.
74. Jiang B, Zhang B, Liang P, Song J, Deng H, Tu Z, et al. Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress. FEBS J 2010; 277(3): 642-52.
75. Wise JF, Berkova Z, Mathur R, Zhu H, Braun FK, Tao RH, et al. Nucleolin inhibits Fas ligand binding and suppresses Fas-mediated apoptosis in vivo via a surface nucleolin-Fas complex. Blood 2013; 121(23): 4729-39.
76. Lee CH, Chang SC, Chen CJ, Chang MF. The nucleolin binding activity of hepatitis delta antigen is associated with nucleolus targeting. J Biol Chem 1998; 273(13): 7650-6.
77. Kusakawa T, Shimakami T, Kaneko S, Yoshioka K, Murakami S. Functional interaction of hepatitis C Virus NS5B with nucleolin GAR domain. J Biochem 2007; 141(6): 917-27.
78. Calle A, Ugrinova I, Epstein AL, Bouvet P, Diaz JJ, Greco A. Nucleolin is required for an efficient herpes simplex virus type 1 infection. J Virol 2008; 82(10): 4762-73.
79. Strang BL, Boulant S, Coen DM. Nucleolin associates with the human cytomegalovirus DNA polymerase accessory subunit UL44 and is necessary for efficient viral replication. J Virol 2010; 84(4): 1771-84.
80. Cancio-Lonches C, Yocupicio-Monroy M, Sandoval-Jaime C, Galvan-Mendoza I, Urena L, Vashist S, et al. Nucleolin interacts with the feline calicivirus 3' untranslated region and the proteasepolymerase NS6 and NS7 proteins, playing a role in virus replication. J Virol 2011; 85(16): 8056-68.
81. Carson SD, Chapman NN, Tracy SM. Purification of the putative coxsackievirus B receptor from HeLa cells. Biochem Biophys Res Commun 1997; 233(2): 325-8.
82. Nisole S, Krust B, Hovanessian AG. Anchorage of HIV on permissive cells leads to coaggregation of viral particles with surface nucleolin at membrane raft microdomains. Exp Cell Res 2002; 276(2): 155-73.
83. Bose S, Basu M, Banerjee AK. Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells. J Virol 2004; 78(15): 8146-58.
84. Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG. Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat Med 2011; 17(9): 1132-5.
85. Xiao X, Feng Y, Zhu Z, Dimitrov DS. Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor. Biochem Biophys Res Commun 2011; 411(2): 253-8.
86. Thongtan T, Wikan N, Wintachai P, Rattanarungsan C, Srisomsap C, Cheepsunthorn P, et al. Characterization of putative Japanese encephalitis virus receptor molecules on microglial cells. J Med Virol 2012; 84(4): 615-23.
87. Qin Z, Lavingia B, Zou Y, Stastny P. Antibodies against nucleolin in recipients of organ transplants. Transplantation 2011; 92(7): 829-35.
88. Minota S, Jarjour WN, Suzuki N, Nojima Y, Roubey RA, Mimura T, et al. Autoantibodies to nucleolin in systemic lupus erythematosus and other diseases. J Immunol 1991; 146(7): 2249-52.
89. Valdez BC, Henning D, Busch RK, Srivastava M, Busch H. Immunodominant RNA recognition motifs of human nucleolin/C23. Mol Immunol 1995; 32(16): 1207-13.
90. Hirata D, Iwamoto M, Yoshio T, Okazaki H, Masuyama J, Mimori A, et al. Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice. Clin Immunol 2000; 97(1): 50-8.
91. Caudle WM, Kitsou E, Li J, Bradner J, Zhang J. A role for a novel protein, nucleolin, in Parkinson's disease. Neurosci Lett 2009; 459(1): 11-5.
92. Jin J, Li GJ, Davis J, Zhu D, Wang Y, Pan C, et al. Identification of novel proteins associated with both alpha-synuclein and DJ-1. Mol Cell Proteomics 2007; 6(5): 845-59.
93. Dranovsky A, Vincent I, Gregori L, Schwarzman A, Colflesh D, Enghild J, et al. Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology. Neurobiol Aging 2001; 22(4): 517-28.
94. Jiang B, Zhang B, Liang P, Chen G, Zhou B, Lv C, et al. Nucleolin protects the heart from ischaemia-reperfusion injury by upregulating heat shock protein 32. Cardiovasc Res 2013; 99(1): 92-101.
95. Krust B, Vienet R, Cardona A, Rougeot C, Jacotot E, Callebaut C, et al. The anti-HIV pentameric pseudopeptide HB-19 is preferentially taken up in vivo by lymphoid organs where it forms a complex with nucleolin. Proc Natl Acad Sci USA 2001; 98(24): 14090-5.
96. Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol 2003; 163(4): 871-8.
97. Huang Y, Shi H, Zhou H, Song X, Yuan S, Luo Y. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood 2006; 107(9): 3564-71.
98. Shi H, Huang Y, Zhou H, Song X, Yuan S, Fu Y, et al. Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin. Blood 2007; 110(8): 2899-906.
99. Mi Y, Thomas SD, Xu X, Casson LK, Miller DM, Bates PJ. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 2003; 278(10): 8572-9.
100. Krust B, El Khoury D, Nondier I, Soundaramourty C, Hovanessian AG. Targeting surface nucleolin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignant tumor cell type. BMC Cancer 2011; 11: 333.
101. Joo EJ, ten Dam GB, van Kuppevelt TH, Toida T, Linhardt RJ, Kim YS. Nucleolin: Acharan sulfate-binding protein on the surface of cancer cells. Glycobiology 2005; 15(1): 1-9.
102. Tate A, Isotani S, Bradley MJ, Sikes RA, Davis R, Chung LW, et al. Met-independent hepatocyte growth factor-mediated regulation of cell adhesion in human prostate cancer cells. BMC Cancer 2006; 6: 197.
103. Hamma-Kourbali Y, Bermek O, Bernard-Pierrot I, Karaky R, Martel-Renoir D, Frechault S, et al. The synthetic peptide P111- 136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells. BMC Cancer 2011; 11: 212.
104. Turck N, Lefebvre O, Gross I, Gendry P, Kedinger M, Simon- Assmann P, et al. Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin. J Cell Physiol 2006; 206(2): 545-55.
105. Qiu W, Zhou F, Zhang Q, Sun X, Shi X, Liang Y, et al. Overexpression of nucleolin and different expression sites both related to the prognosis of gastric cancer. APMIS 2013; 121(10): 919-25.
106. Destouches D, El Khoury D, Hamma-Kourbali Y, Krust B, Albanese P, Katsoris P, et al. Suppression of tumor growth and angiogenesis by a specific antagonist of the cell-surface expressed nucleolin. PLoS One 2008; 3(6): e2518.
107. Semenkovich CF, Ostlund RE, Jr., Olson MO, Yang JW. A protein partially expressed on the surface of HepG2 cells that binds lipoproteins specifically is nucleolin. Biochemistry 1990; 29(41): 9708-13.
108. Deng JS, Ballou B, Hofmeister JK. Internalization of anti-nucleolin antibody into viable HEp-2 cells. Mol Biol Rep 1996; 23(3-4): 191-5.
109. Meng GZ, Xiao SJ, Zeng SE, Li YQ. Downregulation of cellsurface- expressed nucleolin inhibits the growth of hepatocellular carcinoma cells in vitro. Zhonghua Zhong Liu Za Zhi 2011; 33(1): 23-7.
110. Krust B, El Khoury D, Soundaramourty C, Nondier I, Hovanessian AG. Suppression of tumorigenicity of rhabdoid tumor derived G401 cells by the multivalent HB-19 pseudopeptide that targets surface nucleolin. Biochimie 2011; 93(3): 426-33.
111. Jordan P, Heid H, Kinzel V, Kubler D. Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins. Biochemistry 1994; 33(49): 14696-706.
112. Hoja-Lukowicz D, Przybylo M, Pochec E, Drabik A, Silberring J, Kremser M, et al. The new face of nucleolin in human melanoma. Cancer Immunol Immunother 2009; 58(9): 1471-80.
113. El Khoury D, Destouches D, Lengagne R, Krust B, Hamma- Kourbali Y, Garcette M, et al. Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice. BMC Cancer 2010; 10: 325.
114. Destouches D, Huet E, Sader M, Frechault S, Carpentier G, Ayoul F, et al. Multivalent pseudopeptides targeting cell surface nucleoproteins inhibit cancer cell invasion through tissue inhibitor of metalloproteinases 3 (TIMP-3) release. J Biol Chem 2012; 287(52): 43685-93.
115. Galzio R, Rosati F, Benedetti E, Cristiano L, Aldi S, Mei S, et al. Glycosilated nucleolin as marker for human gliomas. J Cell Biochem 2012; 113(2): 571-9.
116. Koutsioumpa M, Polytarchou C, Courty J, Zhang Y, Kieffer N, Mikelis C, et al. Interplay between alphavbeta3 integrin and nucleolin regulates human endothelial and glioma cell migration. J Biol Chem 2013; 288(1): 343-54.
117. Hovanessian AG, Soundaramourty C, El Khoury D, Nondier I, Svab J, Krust B. Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization. PLoS One 2010; 5(12): e15787.
118. Hovanessian AG, Puvion-Dutilleul F, Nisole S, Svab J, Perret E, Deng JS, et al. The cell-surface-expressed nucleolin is associated with the actin cytoskeleton. Exp Cell Res 2000; 261(2): 312-28.
119. Carpentier M, Morelle W, Coddeville B, Pons A, Masson M, Mazurier J, et al. Nucleolin undergoes partial N- and Oglycosylations in the extranuclear cell compartment. Biochemistry 2005; 44(15): 5804-15.
120. Burks DJ, Wang J, Towery H, Ishibashi O, Lowe D, Riedel H, et al. IRS pleckstrin homology domains bind to acidic motifs in proteins. J Biol Chem 1998; 273(47): 31061-7.
121. Lemmon MA, Ferguson KM. Signal-dependent membrane targeting by Pleckstrin Homology (PH) domains. Biochem J 2000; 350 (Pt 1): 1-18.
122. Koutsioumpa M, Poimenidi E, Theodoropoulou C, Papadimitriou E. Receptor protein tyrosine phosphatase beta/zeta is a regulator of vascular endothelial growth factor-induced endothelial cell migration. 4th FEBS Advanced Lecture Course, Matrix Pathobiology, Signaling and Molecular Targets, Kos, Greece, September 26- October 1, 2013.
123. Lindmo K, Stenmark H. Regulation of membrane traffic by phosphoinositide 3-kinases. J Cell Sci 2006; 119(Pt 4): 605-14.
124. Grant BD, Donaldson JG. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 2009; 10(9): 597-608.
125. Schwab MS, Dreyer C. Protein phosphorylation sites regulate the function of the bipartite NLS of nucleolin. Eur J Cell Biol 1997; 73(4): 287-97.
126. Ding Y, Song N, Liu C, He T, Zhuo W, He X, et al. Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin. Arterioscler Thromb Vasc Biol 2012; 32(9): e126-34.
127. Watanabe T, Tsuge H, Imagawa T, Kise D, Hirano K, Beppu M, et al. Nucleolin as cell surface receptor for tumor necrosis factoralpha inducing protein: A carcinogenic factor of Helicobacter pylori. J Cancer Res Clin Oncol 2010; 136(6): 911-21.
128. Losfeld ME, Leroy A, Coddeville B, Carpentier M, Mazurier J, Legrand D. N-Glycosylation influences the structure and selfassociation abilities of recombinant nucleolin. FEBS J 2011; 278(14): 2552-64.
129. Matthews DA. Adenovirus protein V induces redistribution of nucleolin and B23 from nucleolus to cytoplasm. J Virol 2001; 75(2): 1031-8.
130. Lee YH, Marquez AP, Mungunsukh O, Day RM. Hepatocyte growth factor inhibits apoptosis by the profibrotic factor angiotensin II via extracellular signal-regulated kinase 1/2 in endothelial cells and tissue explants. Mol Biol Cell 2010; 21(23): 4240-50.
131. Garcia MC, Williams J, Johnson K, Olden K, Roberts JD. Arachidonic acid stimulates formation of a novel complex containing nucleolin and RhoA. FEBS Lett 2011; 585(4): 618-22.
132. Koutsioumpa M, Drosou G, Mikelis C, Theochari K, Vourtsis D, Katsoris P, et al. Pleiotrophin expression and role in physiological angiogenesis in vivo: Potential involvement of nucleolin. Vasc Cell 2012; 4: 4.
133. Nisole S, Said EA, Mische C, Prevost MC, Krust B, Bouvet P, et al. The anti-HIV pentameric pseudopeptide HB-19 binds the Cterminal end of nucleolin and prevents anchorage of virus particles in the plasma membrane of target cells. J Biol Chem 2002; 277(23): 20877-86.
134. Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp Mol Pathol 2009; 86(3): 151-64.
135. Kleinman HK, Weeks BS, Cannon FB, Sweeney TM, Sephel GC, Clement B, et al. Identification of a 110-kDa nonintegrin cell surface laminin-binding protein which recognizes an A chain neurite-promoting peptide. Arch Biochem Biophys 1991; 290(2): 320-5.
136. Larrucea S, Gonzalez-Rubio C, Cambronero R, Ballou B, Bonay P, Lopez-Granados E, et al. Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement. J Biol Chem 1998; 273(48): 31718-25.
137. Harms G, Kraft R, Grelle G, Volz B, Dernedde J, Tauber R. Identification of nucleolin as a new L-selectin ligand. Biochem J 2001; 360(Pt 3): 531-8.
138. Wang Y, Mao M, Xu JC. Cell-surface nucleolin is involved in lipopolysaccharide internalization and signalling in alveolar macrophages. Cell Biol Int 2011; 35(7): 677-85.
139. Hirano K, Miki Y, Hirai Y, Sato R, Itoh T, Hayashi A, et al. A multifunctional shuttling protein nucleolin is a macrophage receptor for apoptotic cells. J Biol Chem 2005; 280(47): 39284-93.
140. Miki Y, Oguri E, Hirano K, Beppu M. Macrophage recognition of cells with elevated calcium is mediated by carbohydrate chains of CD43. Cell Struct Funct 2013; 38(1): 43-54.
141. Nisole S, Krust B, Callebaut C, Guichard G, Muller S, Briand JP, et al. The anti-HIV pseudopeptide HB-19 forms a complex with the cell-surface-expressed nucleolin independent of heparan sulfate proteoglycans. J Biol Chem 1999; 274(39): 27875-84.
142. Callebaut C, Nisole S, Briand JP, Krust B, Hovanessian AG. Inhibition of HIV infection by the cytokine midkine. Virology 2001; 281(2): 248-64.
143. Said EA, Courty J, Svab J, Delbe J, Krust B, Hovanessian AG. Pleiotrophin inhibits HIV infection by binding the cell surfaceexpressed nucleolin. FEBS J 2005; 272(18): 4646-59.
144. Take M, Tsutsui J, Obama H, Ozawa M, Nakayama T, Maruyama I, et al. Identification of nucleolin as a binding protein for midkine (MK) and heparin-binding growth associated molecule (HBGAM). J Biochem 1994; 116(5): 1063-8.
145. Kilpelainen I, Kaksonen M, Kinnunen T, Avikainen H, Fath M, Linhardt RJ, et al. Heparin-binding growth-associated molecule contains two heparin-binding beta-sheet domains that are homologous to the thrombospondin type I repeat. J Biol Chem 2000; 275(18): 13564-70.
146. Raulo E, Tumova S, Pavlov I, Pekkanen M, Hienola A, Klankki E, et al. The two thrombospondin type I repeat domains of the heparin-binding growth-associated molecule bind to heparin/ heparan sulfate and regulate neurite extension and plasticity in hippocampal neurons. J Biol Chem 2005; 280(50): 41576-83.
147. Dubail J, Kesteloot F, Deroanne C, Motte P, Lambert V, Rakic JM, et al. ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity. Cell Mol Life Sci 2010; 67(24): 4213-32.
148. Zhuo W, Luo C, Wang X, Song X, Fu Y, Luo Y. Endostatin inhibits tumour lymphangiogenesis and lymphatic metastasis via cell surface nucleolin on lymphangiogenic endothelial cells. J Pathol 2010; 222(3): 249-60.
149. Re RN, Cook JL. An intracrine view of angiogenesis. Bioessays 2006; 28(9): 943-53.
150. Santos SC, Miguel C, Domingues I, Calado A, Zhu Z, Wu Y, et al. VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing. Exp Cell Res 2007; 313(8): 1561-74.
151. De Donatis A, Comito G, Buricchi F, Vinci MC, Parenti A, Caselli A, et al. Proliferation versus migration in platelet-derived growth factor signaling: The key role of endocytosis. J Biol Chem 2008; 283(29): 19948-56.
152. Caswell P, Norman J. Endocytic transport of integrins during cell migration and invasion. Trends Cell Biol 2008; 18(6): 257-63.
153. Sadowski L, Pilecka I, Miaczynska M. Signaling from endosomes: Location makes a difference. Exp Cell Res 2009; 315(9): 1601-9.
154. Di Segni A, Farin K, Pinkas-Kramarski R. Identification of nucleolin as new ErbB receptors- interacting protein. PLoS One 2008; 3(6): e2310.
155. Farin K, Schokoroy S, Haklai R, Cohen-Or I, Elad-Sfadia G, Reyes-Reyes ME, et al. Oncogenic synergism between ErbB1, nucleolin, and mutant Ras. Cancer Res 2011; 71(6): 2140-51.
156. Inder KL, Hill MM, Hancock JF. Nucleophosmin and nucleolin regulate K-Ras signaling. Commun Integr Biol 2010; 3(2): 188-90.
157. Inder KL, Lau C, Loo D, Chaudhary N, Goodall A, Martin S, et al. Nucleophosmin and nucleolin regulate K-Ras plasma membrane interactions and MAPK signal transduction. J Biol Chem 2009; 284(41): 28410-9.
158. Destouches D, Page N, Hamma-Kourbali Y, Machi V, Chaloin O, Frechault S, et al. A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins. Cancer Res 2011; 71: 3296-305.
159. Birmpas C, Briand JP, Courty J, Katsoris P. The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis. Vasc Cell 2012; 4(1): 21.
160. Soundararajan S, Wang L, Sridharan V, Chen W, Courtenay-Luck N, Jones D, et al. Plasma membrane nucleolin is a receptor for the anticancer aptamer AS1411 in MV4-11 leukemia cells. Mol Pharmacol 2009; 76(5): 984-91.
161. Girvan AC, Teng Y, Casson LK, Thomas SD, Juliger S, Ball MW, et al. AGRO100 inhibits activation of nuclear factor-kappaB (NFkappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin. Mol Cancer Ther 2006; 5(7): 1790-9.
162. Teng Y, Girvan AC, Casson LK, Pierce WM, Jr., Qian M, Thomas SD, et al. AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res 2007; 67(21): 10491-500.
163. Soundararajan S, Chen W, Spicer EK, Courtenay-Luck N, Fernandes DJ. The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res 2008; 68(7): 2358-65.
164. Pichiorri F, Palmieri D, De Luca L, Consiglio J, You J, Rocci A, et al. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation. J Exp Med 2013; 210(5): 951-68.
165. Laber DA, Sharma VR, Bhupalam L, Taft B, Hendler FJ, Barnhart KM. Update on the first Phase I study of AGRO100 in advanced cancer. J Clin Oncol ASCO Annual Meeting Proceedings 2005; 23(16S): 3064.
166. Chen X, Kube DM, Cooper MJ, Davis PB. Cell surface nucleolin serves as receptor for DNA nanoparticles composed of pegylated polylysine and DNA. Mol Ther 2008; 16(2): 333-42.
167. Moura V, Lacerda M, Figueiredo P, Corvo ML, Cruz ME, Soares R, et al. Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: Impact on the treatment of breast cancer. Breast Cancer Res Treat 2012; 133(1): 61-73.
168. Orringer DA, Koo YE, Chen T, Kim G, Hah HJ, Xu H, et al. In vitro characterization of a targeted, dye-loaded nanodevice for intraoperative tumor delineation. Neurosurgery 2009; 64(5): 965-71discussion 71-2.
169. Drecoll E, Gaertner FC, Miederer M, Blechert B, Vallon M, Muller JM, et al. Treatment of peritoneal carcinomatosis by targeted delivery of the radio-labeled tumor homing peptide bi-DTPA-[F3]2 into the nucleus of tumor cells. PLoS One 2009; 4(5): e5715.
170. Hu Q, Gu G, Liu Z, Jiang M, Kang T, Miao D, et al. F3 peptidefunctionalized PEG-PLA nanoparticles co-administrated with tLyP-1 peptide for anti-glioma drug delivery. Biomaterials 2013; 34(4): 1135-45.
171. Ireson CR, Kelland LR. Discovery and development of anticancer aptamers. Mol Cancer Ther 2006; 5(12): 2957-62.
172. Ko MH, Kim S, Kang WJ, Lee JH, Kang H, Moon SH, et al. In vitro derby imaging of cancer biomarkers using quantum dots. Small 2009; 5(10): 1207-12.
173. Lee KY, Kang H, Ryu SH, Lee DS, Lee JH, Kim S. Bioimaging of nucleolin aptamer-containing 5-(N-benzylcarboxyamide)-2'-deoxyuridine more capable of specific binding to targets in cancer cells. J Biomed Biotechnol 2010; 2010: 168306.
174. Shieh YA, Yang SJ, Wei MF, Shieh MJ. Aptamer-based tumortargeted drug delivery for photodynamic therapy. ACS Nano 2010; 4(3): 1433-42.
175. Watanabe T, Hirano K, Takahashi A, Yamaguchi K, Beppu M, Fujiki H, et al. Nucleolin on the cell surface as a new molecular target for gastric cancer treatment. Biol Pharm Bull 2010; 33(5): 796-803.
176. Mongelard F, Bouvet P. AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr Opin Mol Ther 2010; 12(1): 107-14.
177. Hwang do W, Ko HY, Lee JH, Kang H, Ryu SH, Song IC, et al. A nucleolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer. J Nucl Med 2010; 51(1): 98-105.
178. Reyes-Reyes EM, Teng Y, Bates PJ. A new paradigm for aptamer therapeutic AS1411 action: Uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. Cancer Res 2010; 70(21): 8617-29.
179. Guo J, Gao X, Su L, Xia H, Gu G, Pang Z, et al. Aptamerfunctionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials 2011; 32(31): 8010-20.
180. Li LL, Yin Q, Cheng J, Lu Y. Polyvalent mesoporous silica nanoparticle-aptamer bioconjugates target breast cancer cells. Adv Healthc Mater 2012; 1(5): 567-72.
181. Lian S, Zhang P, Gong P, Hu D, Shi B, Zeng C, et al. A universal quantum dots-aptamer probe for efficient cancer detection and targeted imaging. J Nanosci Nanotechnol 2012; 12(10): 7703-8.
182. Ai J, Guo W, Li B, Li T, Li D, Wang E. DNA G-quadruplextemplated formation of the fluorescent silver nanocluster and its application to bioimaging. Talanta 2012; 88: 450-5.
183. Dam DH, Lee JH, Sisco PN, Co DT, Zhang M, Wasielewski MR, et al. Direct observation of nanoparticle-cancer cell nucleus interactions. ACS Nano 2012; 6(4): 3318-26.
184. Kotula JW, Pratico ED, Ming X, Nakagawa O, Juliano RL, Sullenger BA. Aptamer-mediated delivery of splice-switching oligonucleotides to the nuclei of cancer cells. Nucleic Acid Ther 2012; 22(3): 187-95.
185. Aravind A, Jeyamohan P, Nair R, Veeranarayanan S, Nagaoka Y, Yoshida Y, et al. AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery. Biotechnol Bioeng 2012; 109(11): 2920-31.
186. Kim JK, Choi KJ, Lee M, Jo MH, Kim S. Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle. Biomaterials 2012; 33(1): 207-17.
187. Song C, Wu J, Jiang C, Shen X, Qiao Q, Hu Y. Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery. Mol Pharm 2013; 10: 3555-63.
188. Yu D, Zhang Y, Mao Z, Gao C. Study of the selective uptake progress of aptamer-modified PLGA particles by liver cells. Macromol Biosci 2013; 13(10): 1413-21.
189. Hua X, Zhou Z, Yuan L, Liu S. Selective collection and detection of MCF-7 breast cancer cells using aptamer-functionalized magnetic beads and quantum dots based nano-bio-probes. Anal Chim Acta 2013; 788: 135-40.
190. Luo, Y., Shi, H. Nucleolin-mediated cancer diagnostics and therapy. US20060258605 (2006) & US20090191224 (2009).
191. Luo, Y., Shi, H., Zhang, Z. Auxiliary method for diagnosis and therapy of cancer with nucleolin. EP1912066 (2008), CA2607832 (2006), WO2006119706 (2006), EP2375251 (2011) & CN1862258 (2012).
192. Bennett, C.F., Cowsert, L.M. Antisense inhibition of nucleolin expression. WO2001032832 (2001).
193. Lin, C.T., Wu, H.C. Nucleolin antisense sequence for inhibition of cancer cell proliferation. US20050026860 (2005).
194. Lee, J.H., Kim, S.H., Kwon, M.J., Kang, H.G., Ryu, S.H., Kim, J.I., Kim, Y.D., Chae, Y.C., Jang, S.K., Im, J.H., Lee, S.H., Lee, H.J., Jang, E.J., Ki, K.S. Nucleolin specific aptamer and use thereof. US20100317723 (2011) & WO2011129494 (2011).
195. Bates, P.J., Miller, D.M., Trent, J.O. Antiproliferative activity of Grich oligonucleotides and method of using same to bind to nucleolin. US20080318888 (2008), US20080318889 (2008), US7314926 (2008), EP1930340 (2008), US20090326047 (2009), US20110178161 (2011), US7960540 (2011) & US8114850 (2012).
196. Bates, P.J., Reyes-Reyes, E.M. Methods of increasing macropinocytosis in cancer cells. WO2011109677 (2012) & US20130065227 (2013).
197. Barve, S.S., Bates, P.J., Girvan, A.C. Method for inhibiting NFkappa B signaling and use to treat or prevent human diseases. US20050187176 (2005) & WO2005037323 (2005).
198. Barve, S.S., Bates, P.J., Girvan, A.C. Use of gro to treat or prevent inflammation. WO2005037323 (2005).
199. Bates, P.J., Miller, D.M., Trent, J.O., Xu, X. A method for the treatment of maligant diseases by inhibiting nucleolin. WO2005035579 (2005), CA2546730 (2005), EP1687337 (2006), US7357928 (2008), US8029784 (2011) & US20120014942 (2012).
200. Sutkowski, N., Fernandes, D., Hoel, B., Rubinchik, S. Human monoclonal antibodies to human nucleolin. WO2011062997 (2011), CN102770529 (2012), EP2501800 (2013) & US20130115674 (2013).
201. Alila, H., Leuschner, C. Nucleolin-binding peptides, nucleolinbinding lytic peptides, fusion constructs and methods of making and using same. US20110124564 (2011) & WO2011031477 (2011).
202. Courty, J., Hovanessian, A., Briand, J.P., Guichard, G., Hamma, Y. Use of multivalent synthetic ligands of surface nucleolin for treating cancer or inflammation. CA2650485 (2007), WO2007125210 (2008), CN101454341 (2009), EP2013232 (2009), US20110065649 (2011) & EP2540737 (2013).
203. Courty, J., Zimmer, R. Multivalent synthetic compounds as antibiotic treatment. WO2012045751 (2012).
204. Courty, J., Zimmer, R. Compositions comprising multivalent synthetic ligands of surface nucleolin and glycosaminoglycans. WO2012045750 (2012), CA2813646 (2012) & CA2813665 (2012).
205. Miller, D.M., Bates, P.J., Trent, J.O., Xu, X. Method for the diagnosis and prognosis of malignant diseases. US20030194754 (2003), WO2003086174 (2004), EP1492440 (2008), US7541150 (2009) & CA2490724 (2010).
206. Bates, P.J., Choi, E. Methods and products to target, capture and characterize stem cells, US20090226914 (2009), WO2009088837 (2009) & WO2009088837 (2009).
207. Oh, P., Schnitzer, J.E. Tissue-specific imaging and therapeutic agents targeting proteins expressed on lung endothelial cell surface. CA2572348 (2005), WO2005117977 (2006), US20060024231 (2006) & EP1756165 (2007).
208. Oh, P., Schnitzer, J.E. Imaging and therapeutic agents targeting proteins expressed on endothelial cell surface. CA2572453 (2005), US20060024232 (2006), EP1755686 (2007) & WO2005117999 (2008).
209. Christian, S., Porkka, K., Ruoslahti, E. HMGN2 peptides and related molecules that selectively home to tumor blood vessels and tumor cells. US20040186056 (2004), US20090098633 (2009), US7544767 (2009), US8048983 (2011) & US20120121501 (2012).
210. Luo, Y., Zhuo, W., Fu, Y., Chang, G. Use of nucleolin as a biomarker for lymphangiogenesis in cancer prognosis and therapy. US20130023479 (2013).
211. Bates, P.J., Malik, M.T., Kang, K.A. Anti-Nucleolin agentconjugated nanoparticles. WO2012167173 (2012).
212. Odom, T.W., Dam D.-H.M., Lee, J.H. Aptamer-loaded, biocompatible nanoconstructs for nuclear-targeted cancer therapy. WO2013070763 (2013) & US20130115254 (2013).
213. Nuno Sereno de Almeida Moreira, J., Ligia Gomes da Silva, C., Bimbo, L., Oliveira dos Santos, A., da Conceicao Monteiro Pedroso de Lima, M., Paulo de Magalhaes Simoes, S. F3-peptide targeted lipid-based nanoparticles useful for the treatment of angiogenesis- dependent diseases. WO2011119058 (2013).
214. Nuno Sereno de Almeida Moreira, J., Lucia Dantas Nunes Caldeira de Moura, V., Paulo de Magalhaes Simoes, S., da Conceicao Monteiro Pedroso de Lima, M. Targeted delivery to human diseases and disorders. US20090291049 (2007), WO2009142525 (2010) & US20120282172 (2012).
215. Lucia Dantas Nunes Caldeira de Moura, V., Paulo de Magalhaes Simoes, S., da Conceicao Monteiro Pedroso de Lima, M., Nuno Sereno de Almeida Moreira, J. Capsulating system binding to nucleolin. WO2009142525 (2010), EP2291199 (2011) & US8231895 (2012).
216. Bates, P.J., Mi, Y. A method for the detection of apoptosis. CA2489520 (2004), WO2004003554 (2004) & EP1516186 (2010).