| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Physiology and Pharmacology and Cancer Research Center, Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
The polyamine-biosynthetic pathway represents an inviting target for the development of agents inhibiting carcinogenesis and tumor growth. Polyamines play an essential role in the proliferation and development of mammalian cells. Deranged polyamine metabolism may be an important factor in carcinogenesis. Depletion of polyamines inhibits growth of neoplastic cells in vitro and in animal models. Several different classes of other anticancer agents may under some conditions exert enhanced effects when polyamine levels are depleted. Some suitable inhibitors of polyamine production are currently available and other promising compounds are presently being tested. It should soon prove possible to block polyamine biosynthesis at every step in the pathway. The use of these inhibitors alone and combined either with each other or with other antitumor agents will enable a full examination of the potential of this approach.
1 Research on polyamines in the author's laboratory was supported by Grants CA-18138, GM-26290, and CA-37606 from the NIH.
Received 10/14/87. Accepted 11/10/87.
This article has been cited by other articles:
![]() |
A. J. Lopez-Contreras, B. Ramos-Molina, A. Cremades, and R. Penafiel Antizyme Inhibitor 2 (AZIN2/ODCp) Stimulates Polyamine Uptake in Mammalian Cells J. Biol. Chem., July 25, 2008; 283(30): 20761 - 20769. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Albeck, O. Dym, T. Unger, Z. Snapir, Z. Bercovich, and C. Kahana Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function Protein Sci., May 1, 2008; 17(5): 793 - 802. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. H. Wei, Y. Yang, G. Wu, and L. J. Ignarro IL-4 and IL-13 upregulate ornithine decarboxylase expression by PI3K and MAP kinase pathways in vascular smooth muscle cells Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1198 - C1205. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Porat, G. Landau, Z. Bercovich, D. Krutauz, M. Glickman, and C. Kahana Yeast Antizyme Mediates Degradation of Yeast Ornithine Decarboxylase by Yeast but Not by Mammalian Proteasome: NEW INSIGHTS ON YEAST ANTIZYME J. Biol. Chem., February 22, 2008; 283(8): 4528 - 4534. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Kramer, P. Diegelman, J. Jell, S. Vujcic, S. Merali, and C. W. Porter Polyamine Acetylation Modulates Polyamine Metabolic Flux, a Prelude to Broader Metabolic Consequences J. Biol. Chem., February 15, 2008; 283(7): 4241 - 4251. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Higashi, H. Ishigure, R. Demizu, T. Uemura, K. Nishino, A. Yamaguchi, K. Kashiwagi, and K. Igarashi Identification of a Spermidine Excretion Protein Complex (MdtJI) in Escherichia coli J. Bacteriol., February 1, 2008; 190(3): 872 - 878. [Abstract] [Full Text] [PDF] |
||||
![]() |
Q. Ma, Y. Wang, X. Gao, Z. Ma, and Z. Song L-Arginine Reduces Cell Proliferation and Ornithine Decarboxylase Activity in Patients with Colorectal Adenoma and Adenocarcinoma Clin. Cancer Res., December 15, 2007; 13(24): 7407 - 7412. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wang, D. J. Feith, P. Welsh, C. S. Coleman, C. Lopez, P. M. Woster, T. G. O'Brien, and A. E. Pegg Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis Carcinogenesis, November 1, 2007; 28(11): 2404 - 2411. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Isome, M. J. Lortie, Y. Murakami, E. Parisi, S. Matsufuji, and J. Satriano The antiproliferative effects of agmatine correlate with the rate of cellular proliferation Am J Physiol Cell Physiol, August 1, 2007; 293(2): C705 - C711. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Bastida, A. Cremades, M. T. Castells, A. J. Lopez-Contreras, C. Lopez-Garcia, J. Sanchez-Mas, and R. Penafiel Sexual dimorphism of ornithine decarboxylase in the mouse adrenal: influence of polyamine deprivation on catecholamine and corticoid levels Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1010 - E1017. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Zahedi, J. J. Bissler, Z. Wang, A. Josyula, L. Lu, P. Diegelman, N. Kisiel, C. W. Porter, and M. Soleimani Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1204 - C1215. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Mani, S. Sandgren, J. Lilja, F. Cheng, K. Svensson, L. Persson, and M. Belting HIV-Tat protein transduction domain specifically attenuates growth of polyamine deprived tumor cells Mol. Cancer Ther., February 1, 2007; 6(2): 782 - 788. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Petros, G. F. Graminski, S. Robinson, M. R. Burns, N. Kisiel, R. F. Gesteland, J. F. Atkins, D. L. Kramer, M. T. Howard, and R. S. Weeks Polyamine Analogs with Xylene Rings Induce Antizyme Frameshifting, Reduce ODC Activity, and Deplete Cellular Polyamines J. Biochem., November 1, 2006; 140(5): 657 - 666. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Soksawatmaekhin, T. Uemura, N. Fukiwake, K. Kashiwagi, and K. Igarashi Identification of the Cadaverine Recognition Site on the Cadaverine-Lysine Antiporter CadB J. Biol. Chem., September 29, 2006; 281(39): 29213 - 29220. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Imai, Y. Hanzawa, M. Komura, K. T. Yamamoto, Y. Komeda, and T. Takahashi The dwarf phenotype of the Arabidopsis acl5 mutant is suppressed by a mutation in an upstream ORF of a bHLH gene Development, September 15, 2006; 133(18): 3575 - 3585. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Rodriguez-Caso, R. Montanez, M. Cascante, F. Sanchez-Jimenez, and M. A. Medina Mathematical Modeling of Polyamine Metabolism in Mammals J. Biol. Chem., August 4, 2006; 281(31): 21799 - 21812. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. E. Pegg Regulation of Ornithine Decarboxylase J. Biol. Chem., May 26, 2006; 281(21): 14529 - 14532. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wang and A. I. Cederbaum S-Adenosyl-L-methionine Attenuates Hepatotoxicity Induced by Agonistic Jo2 Fas Antibody following CYP2E1 Induction in Mice J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 44 - 52. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Young, R. Salomon, W. Au, C. Allan, P. Russell, and Q. Dong Ornithine Decarboxylase (ODC) Expression Pattern in Human Prostate Tissues and ODC Transgenic Mice J. Histochem. Cytochem., February 1, 2006; 54(2): 223 - 229. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Nummela, M. Yin, M. Kielosto, V. Leaner, M. J. Birrer, and E. Holtta Thymosin {beta}4 Is a Determinant of the Transformed Phenotype and Invasiveness of S-Adenosylmethionine Decarboxylase-Transfected Fibroblasts Cancer Res., January 15, 2006; 66(2): 701 - 712. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Igarashi and K. Kashiwagi Polyamine Modulon in Escherichia coli: Genes Involved in the Stimulation of Cell Growth by Polyamines J. Biochem., January 1, 2006; 139(1): 11 - 16. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nishimura, R. Shiina, K. Kashiwagi, and K. Igarashi Decrease in Polyamines with Aging and Their Ingestion from Food and Drink J. Biochem., January 1, 2006; 139(1): 81 - 90. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Hu, S. Washington, M. F. Verderame, and A. Manni Interaction between Polyamines and the Mitogen-Activated Protein Kinase Pathway in the Regulation of Cell Cycle Variables in Breast Cancer Cells Cancer Res., December 1, 2005; 65(23): 11026 - 11033. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Marverti, M. G. Monti, A. E. Pegg, D. E. McCloskey, S. Bettuzzi, A. Ligabue, A. Caporali, D. D'Arca, and M. S. Moruzzi Spermidine/spermine N1-acetyltransferase transient overexpression restores sensitivity of resistant human ovarian cancer cells to N1,N12-bis(ethyl)spermine and to cisplatin Carcinogenesis, October 1, 2005; 26(10): 1677 - 1686. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Barone, T. Okaya, S. Rudich, S. Petrovic, K. Tenrani, Z. Wang, K. Zahedi, R. A. Casero, A. B. Lentsch, and M. Soleimani Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury Am J Physiol Cell Physiol, October 1, 2005; 289(4): C826 - C835. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.-H. Yan, K. Nishimura, K. Yoshida, K. Nakahira, T. Ehara, K. Igarashi, and K. Ishihara Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea-pig heart J. Physiol., March 15, 2005; 563(3): 713 - 724. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Bercovich and C. Kahana Degradation of Antizyme Inhibitor, an Ornithine Decarboxylase Homologous Protein, Is Ubiquitin-dependent and Is Inhibited by Antizyme J. Biol. Chem., December 24, 2004; 279(52): 54097 - 54102. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Soulet, B. Gagnon, S. Rivest, M. Audette, and R. Poulin A Fluorescent Probe of Polyamine Transport Accumulates into Intracellular Acidic Vesicles via a Two-step Mechanism J. Biol. Chem., November 19, 2004; 279(47): 49355 - 49366. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yoshida, K. Kashiwagi, A. Shigemasa, S. Taniguchi, K. Yamamoto, H. Makinoshima, A. Ishihama, and K. Igarashi A Unifying Model for the Role of Polyamines in Bacterial Cell Growth, the Polyamine Modulon J. Biol. Chem., October 29, 2004; 279(44): 46008 - 46013. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. M. Gavin, D. Glesne, Y. Zhao, C. Kubera, and E. Huberman Spermine Acts as a Negative Regulator of Macrophage Differentiation in Human Myeloid Leukemia Cells Cancer Res., October 15, 2004; 64(20): 7432 - 7438. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Ouameur and H.-A. Tajmir-Riahi Structural Analysis of DNA Interactions with Biogenic Polyamines and Cobalt(III)hexamine Studied by Fourier Transform Infrared and Capillary Electrophoresis J. Biol. Chem., October 1, 2004; 279(40): 42041 - 42054. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Fukuchi, R. A. Hiipakka, J. M. Kokontis, K. Nishimura, K. Igarashi, and S. Liao TATA-binding Protein-associated Factor 7 Regulates Polyamine Transport Activity and Polyamine Analog-induced Apoptosis J. Biol. Chem., July 16, 2004; 279(29): 29921 - 29929. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kielosto, P. Nummela, R. Katainen, V. Leaner, M. J. Birrer, and E. Holtta Reversible Regulation of the Transformed Phenotype of Ornithine Decarboxylase- and Ras-Overexpressing Cells by Dominant-Negative Mutants of c-Jun Cancer Res., June 1, 2004; 64(11): 3772 - 3779. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. van Zuylen, J. Bridgewater, A. Sparreboom, F. A. L. M. Eskens, P. de Bruijn, I. Sklenar, A. S. T. Planting, L. Choi, D. Bootle, C. Mueller, et al. Phase I and Pharmacokinetic Study of the Polyamine Synthesis Inhibitor SAM486A in Combination with 5-Fluorouracil/ Leucovorin in Metastatic Colorectal Cancer Clin. Cancer Res., March 15, 2004; 10(6): 1949 - 1955. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Pless, K. Belhadj, H. D. Menssen, W. Kern, B. Coiffier, J. Wolf, R. Herrmann, E. Thiel, D. Bootle, I. Sklenar, et al. Clinical Efficacy, Tolerability, and Safety of SAM486A, a Novel Polyamine Biosynthesis Inhibitor, in Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma: Results from a Phase II Multicenter Study Clin. Cancer Res., February 15, 2004; 10(4): 1299 - 1305. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Qi, J. Ji, N. Wanasen, and L. Soong Enhanced Replication of Leishmania amazonensis Amastigotes in Gamma Interferon-Stimulated Murine Macrophages: Implications for the Pathogenesis of Cutaneous Leishmaniasis Infect. Immun., February 1, 2004; 72(2): 988 - 995. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Huang, J. C. Keen, E. Hager, R. Smith, A. Hacker, B. Frydman, A. L. Valasinas, V. K. Reddy, L. J. Marton, R. A. Casero Jr., et al. Regulation of Polyamine Analogue Cytotoxicity by c-Jun in Human MDA-MB-435 Cancer Cells Mol. Cancer Res., February 1, 2004; 2(2): 81 - 88. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Ruiz-Chica, M. A. Medina, F. Sanchez-Jimenez, and F. J. Ramirez On the interpretation of Raman spectra of 1-aminooxy-spermine/DNA complexes Nucleic Acids Res., January 29, 2004; 32(2): 579 - 589. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Subhi, P. Diegelman, C. W. Porter, B. Tang, Z. J. Lu, G. D. Markham, and W. D. Kruger Methylthioadenosine Phosphorylase Regulates Ornithine Decarboxylase by Production of Downstream Metabolites J. Biol. Chem., December 12, 2003; 278(50): 49868 - 49873. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Randi, S. Hernandez, L. Alvarez, M. Sanchez, M. Schwarcz, and D. L. Kleiman de Pisarev Hexachlorobenzene-Induced Early Changes in Ornithine Decarboxylase and Protein Tyrosine Kinase Activities, Polyamines and c-Myc, c-Fos and c-Jun Proto-Oncogenes in Rat Liver Toxicol. Sci., December 1, 2003; 76(2): 291 - 298. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. C. Wolff, D. K. Armstrong, J. H. Fetting, M. K. Carducci, C. D. Riley, J. F. Bender, R. A. Casero Jr., and N. E. Davidson A Phase II Study of the Polyamine Analog N1,N11-Diethylnorspermine (DENSpm) Daily for Five Days Every 21 Days in Patients with Previously Treated Metastatic Breast Cancer Clin. Cancer Res., December 1, 2003; 9(16): 5922 - 5928. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Babbar, N. A. Ignatenko, R. A. Casero Jr., and E. W. Gerner Cyclooxygenase-independent Induction of Apoptosis by Sulindac Sulfone Is Mediated by Polyamines in Colon Cancer J. Biol. Chem., November 28, 2003; 278(48): 47762 - 47775. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Belting, K. Mani, M. Jonsson, F. Cheng, S. Sandgren, S. Jonsson, K. Ding, J.-G. Delcros, and L.-A. Fransson Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells: A PIVOTAL ROLE FOR NITROSOTHIOL-DERIVED NITRIC OXIDE J. Biol. Chem., November 21, 2003; 278(47): 47181 - 47189. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Guo, R. M. Ray, and L. R. Johnson RhoA stimulates IEC-6 cell proliferation by increasing polyamine-dependent Cdk2 activity Am J Physiol Gastrointest Liver Physiol, October 1, 2003; 285(4): G704 - G713. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kakizoe Chemoprevention of Cancer - Focusing on Clinical Trials Jpn. J. Clin. Oncol., September 1, 2003; 33(9): 421 - 442. [Abstract] [Full Text] [PDF] |
||||
![]() |
R Nicoletti, I Venza, G Ceci, M Visalli, D Teti, and A Reibaldi Vitreous polyamines spermidine, putrescine, and spermine in human proliferative disorders of the retina Br. J. Ophthalmol., August 1, 2003; 87(8): 1038 - 1042. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Y. Y. Fong, D. J. Feith, and A. E. Pegg Antizyme Overexpression in Transgenic Mice Reduces Cell Proliferation, Increases Apoptosis, and Reduces N-Nitrosomethylbenzylamine-induced Forestomach Carcinogenesis Cancer Res., July 15, 2003; 63(14): 3945 - 3954. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Bettuzzi, M. Scaltriti, A. Caporali, M. Brausi, D. D'Arca, S. Astancolle, P. Davalli, and A. Corti Successful Prediction of Prostate Cancer Recurrence by Gene Profiling in Combination with Clinical Data: A 5-year Follow-up Study Cancer Res., July 1, 2003; 63(13): 3469 - 3472. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Chen, K. Alm, S. Vujcic, D. L. Kramer, K. Kee, P. Diegelman, and C. W. Porter The Role of Mitogen-activated Protein Kinase Activation in Determining Cellular Outcomes in Polyamine Analogue-treated Human Melanoma Cells Cancer Res., July 1, 2003; 63(13): 3619 - 3625. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Huang, E. R. Hager, D. L. Phillips, V. R. Dunn, A. Hacker, B. Frydman, J. A. Kink, A. L. Valasinas, V. K. Reddy, L. J. Marton, et al. A Novel Polyamine Analog Inhibits Growth and Induces Apoptosis in Human Breast Cancer Cells Clin. Cancer Res., July 1, 2003; 9(7): 2769 - 2777. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Martinez-Chantar, M. U. Latasa, M. Varela-Rey, S. C. Lu, E. R. Garcia-Trevijano, J. M. Mato, and M. A. Avila L-Methionine Availability Regulates Expression of the Methionine Adenosyltransferase 2A Gene in Human Hepatocarcinoma Cells: ROLE OF S-ADENOSYLMETHIONINE J. Biol. Chem., May 23, 2003; 278(22): 19885 - 19890. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. R. Dash, J. E. Cartwright, and G. St.J. Whitley Nitric oxide inhibits polyamine-induced apoptosis in the human extravillous trophoblast cell line SGHPL-4 Hum. Reprod., May 1, 2003; 18(5): 959 - 968. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Zahedi, Z. Wang, S. Barone, A. E. Prada, C. N. Kelly, R. A. Casero, N. Yokota, C. W. Porter, H. Rabb, and M. Soleimani Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury Am J Physiol Renal Physiol, May 1, 2003; 284(5): F1046 - F1055. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. McCloskey and A. E. Pegg Properties of the Spermidine/Spermine N1-Acetyltransferase Mutant L156F That Decreases Cellular Sensitivity to the Polyamine Analogue N1, N11-Bis(ethyl)norspermine J. Biol. Chem., April 11, 2003; 278(16): 13881 - 13887. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Wolter, L. Turchanowa, and J. Stein Resveratrol-induced modification of polyamine metabolism is accompanied by induction of c-Fos Carcinogenesis, March 1, 2003; 24(3): 469 - 474. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ruchko, M. N. Gillespie, R. S. Weeks, J. W. Olson, and P. Babal Putrescine transport in hypoxic rat main PASMCs is required for p38 MAP kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L179 - L186. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. K. Park, Y. M. Chung, S. Kang, J.-U. Kim, Y.-T. Kim, H. J. Kim, Y. H. Kim, J. S. Kim, and Y. D. Yoo c-Myc Exerts a Protective Function through Ornithine Decarboxylase against Cellular Insults Mol. Pharmacol., December 1, 2002; 62(6): 1400 - 1408. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. L. Siu, E. K. Rowinsky, L. A. Hammond, G. R. Weiss, M. Hidalgo, G. M. Clark, J. Moczygemba, L. Choi, R. Linnartz, N. C. Barbet, et al. A Phase I and Pharmacokinetic Study of SAM486A, a Novel Polyamine Biosynthesis Inhibitor, Administered on a Daily-times-five every-three-week Schedule in Patients with Advanced Solid Malignancies Clin. Cancer Res., July 1, 2002; 8(7): 2157 - 2166. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Hahm, D. S. Ettinger, K. Bowling, B. Hoker, T. L. Chen, Y. Zabelina, and R. A. Casero Jr. Phase I Study of N1,N11-Diethylnorspermine in Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., March 1, 2002; 8(3): 684 - 690. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Nemoto, H. Hori, M. Yoshimoto, Y. Seyama, and S. Kubota Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression Blood, February 15, 2002; 99(4): 1478 - 1481. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-H. Hou, S.-B. Lin, J.-M. P. Yuann, W.-C. Lin, A. H.-J. Wang, and L.-s. Kan Effects of polyamines on the thermal stability and formation kinetics of DNA duplexes with abnormal structure Nucleic Acids Res., December 15, 2001; 29(24): 5121 - 5128. [Abstract] [Full Text] |