Biological functions and therapeutic use of erythropoiesis-stimulating agents: Perplexities and perspectives

British Journal of Haematology

Volumn 146, Issue 2, 2009, Pages 127-141

  Merchionne, Francesca ^a   Dammacco, Franco ^a  

^a POLICLINICO   (Italy)

Author keywords

Anaemia; Cancer; Erythropoietin; Erythropoietin receptor; Survival

Indexed keywords

CONTINUOUS ERYTHROPOIESIS RECEPTOR ACTIVATOR; ERYTHROPOIETIN RECEPTOR; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; RECOMBINANT ERYTHROPOIETIN;

ANEMIA; CANCER SURVIVAL; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; ERYTHROPOIESIS; HUMAN; PRIORITY JOURNAL; REVIEW; TUMOR GROWTH;

ANEMIA; ANTINEOPLASTIC AGENTS; BLOOD PHYSIOLOGICAL PROCESSES; ERYTHROPOIETIN, RECOMBINANT; HEMATINICS; HUMANS; NEOPLASMS; RECEPTORS, ERYTHROPOIETIN;

EID: 67649970420     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2009.07702.x     Document Type: Review

References (124)

1. Aapro, M., Scherhag, A. Burger, H.U. (2008) Effect of treatment with epoetin-β on survival, tumour progression and thromboembolic events in patients with cancer: an updated meta-analysis of 12 randomised controlled studies including 2301 patients. British Journal of Cancer, 99, 14 22. (Pubitemid 351920217)
2. Acs, G., Acs, P., Beckwith, S.M., Pitts, R.L., Clements, E., Wong, K. Verma, A. (2001) Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Research, 61, 3561 3565. (Pubitemid 32694960)
3. Acs, G., Zhang, P.J., McGrath, C.M., Acs, P., McBroom, J., Mohyeldin, A., Liu, S., Lu, H. Verma, A. (2003) Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression. American Journal of Pathology, 162, 1789 1806. (Pubitemid 36613038)
4. Andratschke, N., Schnaiter, A., Weber, W.A., Cai, L., Schill, S., Wiedenmann, N., Schwaiger, M., Molls, M. Nieder, C. (2006) Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction. International Journal of Radiation Oncology, Biology, Physics, 64, 1513 1518.
5. Arcasoy, M.O. (2008) The non-haematopoietic biological effects of erythropoietin. British Journal of Haematology, 141, 14 31. (Pubitemid 351347536)
6. Bagnis, C., Beaufils, H., Jacquiaud, C., Adabra, Y., Jouanneau, C., Le, N.G., Jaudon, M.C., Bourbouze, R., Jacobs, C. Deray, G. (2001) Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat. Nephrology, Dialysis, Transplantation, 16, 932 938. (Pubitemid 32440364)
7. Baz, R., Walker, E., Choueiri, T.K., Abou, J.R., Brand, C., McGowan, B., Yiannaki, E., Andresen, S. Hussein, M.A. (2007) Recombinant human erythropoietin is associated with increased overall survival in patients with multiple myeloma. Acta Haematologica, 117, 162 167. (Pubitemid 46496800)
8. Belenkov, A.I., Shenouda, G., Rizhevskaya, E., Cournoyer, D., Belzile, J.P., Souhami, L., Devic, S. Chow, T.Y. (2004) Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin. Molecular Cancer Therapy, 3, 1525 1532. (Pubitemid 40136707)
9. Bennett, C.L., Angelotta, C., Yarnold, P.R., Evens, A.M., Zonder, J.A., Raisch, D.W. Richardson, P. (2006) Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer. Journal of the American Medical Association, 296, 2558 2560. (Pubitemid 44903859)
10. Bennett, C.L., Silver, S.M., Djulbegovic, B., Samaras, A.T., Blau, C.A., Gleason, K.J., Barnato, S.E., Elverman, K.M., Courtney, D.M., McKoy, J.M., Edwards, B.J., Tigue, C.C., Raisch, D.W., Yarnold, P.R., Dorr, D.A., Kuzel, T.M., Tallman, M.S., Trifilio, S.M., West, D.P., Lai, S.Y. Henke, M. (2008) Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. Journal of the American Medical Association, 299, 914 924.
11. Besarab, A., Bolton, W.K., Browne, J.K., Egrie, J.C., Nissenson, A.R., Okamoto, D.M., Schwab, S.J. Goodkin, D.A. (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. New England Journal of Medicine, 339, 584 590. (Pubitemid 28385655)
12. Bianchi, R., Buyukakilli, B., Brines, M., Savino, C., Cavaletti, G., Oggioni, N., Lauria, G., Borgna, M., Lombardi, R., Cimen, B., Comelekoglu, U., Kanik, A., Tataroglu, C., Cerami, A. Ghezzi, P. (2004) Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proceedings of the National Academy of Sciences of the United States of America, 101, 823 828. (Pubitemid 38121042)
13. Bianchi, R., Brines, M., Lauria, G., Savino, C., Gilardini, A., Nicolini, G., Rodriguez-Menendez, V., Oggioni, N., Canta, A., Penza, P., Lombardi, R., Minoia, C., Ronchi, A., Cerami, A., Ghezzi, P. Cavaletti, G. (2006) Protective effect of erythropoietin and its carbamylated derivative in experimental Cisplatin peripheral neurotoxicity. Clinical Cancer Research, 12, 2607 2612.
14. Bittorf, T., Buchse, T., Sasse, T., Jaster, R. Brock, J. (2001) Activation of the transcription factor NF-kappaB by the erythropoietin receptor: structural requirements and biological significance. Cellular Signalling, 13, 673 681. (Pubitemid 32728428)
15. Bohlius, J., Langensiepen, S., Schwarzer, G., Seidenfeld, J., Piper, M., Bennett, C. Engert, A. (2005) Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. Journal of the National Cancer Institute, 97, 489 498. (Pubitemid 40590430)
16. Bohlius, J., Wilson, J., Seidenfeld, J., Piper, M., Schwarzer, G., Sandercock, J., Trelle, S., Weingart, O., Bayliss, S., Brunskill, S., Djulbegovic, B., Benett, C.L., Langensiepen, S., Hyde, C. Engert, E. (2006) Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. Journal of the National Cancer Institute, 98, 708 714. (Pubitemid 43821788)
17. Boogaerts, M., Coiffier, B. Kainz, C. & the Epoetin β QOL Working Group 2003) Impact of epoetin β on quality of life in patients with malignant disease. British Journal of Cancer, 88, 988 995. (Pubitemid 36560764)
18. Bouscary, D., Pene, F., Claessens, Y.E., Muller, O., Chrétien, S., Fontenay-Roupie, M., Gisselbrecht, S., Mayeux, P. Lacombe, C. (2003) Critical role for PI3-kinase in the control of erythropoietin-induced erythroid progenitor proliferation. Blood, 101, 3436 3442.
19. Brines, M. Cerami, A. (2005) Emerging biological roles for erythropoietin in the nervous system. Nature Reviews Neuroscience, 6, 484 494. (Pubitemid 40769173)
20. Brines, M., Grasso, G., Fiordaliso, F., Sfacteria, A., Ghezzi, P., Fratelli, M., Latini, R., Xie, Q.W., Smart, J., Su-Rick, C.J., Pobre, E., Diaz, D., Gomez, D., Hand, C., Coleman, T. Cerami, A. (2004) Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proceedings of the National Academy of Sciences of the United States of America, 101, 14907 14912. (Pubitemid 39410773)
21. Brown, W.M., Maxwell, P., Graham, A.N.J., Yakkundi, A., Dunlop, E.A., Shi, Z., Johnston, P.G. Lappin, T.R.J. (2007) Erythropoietin receptor expression in non-small cell lung carcinoma: a question of antibody specificity. Stem Cells, 25, 718 722. (Pubitemid 46354231)
22. Calvillo, L., Latini, R., Kajstura, J., Leri, A., Anversa, P., Ghezzi, P., Salio, M., Cerami, A. Brines, M. (2003) Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proceedings of the National Academy of Sciences of the United States of America, 100, 4802 4806. (Pubitemid 36457809)
23. Carlini, R.G., Reyes, A.A. Rothstein, M. (1995) Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney International, 47, 740 745.
24. Caro, J.J., Salas, M., Ward, A. Goss, G. (2001) Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer, 91, 2214 2221. (Pubitemid 32552805)
25. Chang, J., Couture, F., Young, S., McWatters, K.L. Lau, C.Y. (2005) Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. Journal of Clinical Oncology, 23, 2597 2605. (Pubitemid 46179448)
26. Dammacco, F., Silvestris, F., Castoldi, G.L., Grassi, B., Bernasconi, C., Nadali, G., Perona, G., De Laurenzi, A., Torelli, U., Ascari, E., Rossi Ferrini, P.L., Caligaris-Cappio, F., Pileri, A. Resegotti, L. (1998) The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy. International Journal of Clinical and Laboratory Research, 28, 127 134.
27. Dammacco, F., Castoldi, G. Rodjer, S. (2001) Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. British Journal of Haematology, 113, 172 179. (Pubitemid 32423318)
28. Digicaylioglu, M. Lipton, S.A. (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature, 412, 641 647. (Pubitemid 32772276)
29. Dunlop, E.A., Percy, M.J., Boland, M.P., Maxwell, A.P. Lappin, T.R. (2006) Induction of signalling in non-erythroid cells by pharmacological levels of erythropoietin. Neurodegenerative Diseases, 3, 94 100. (Pubitemid 43760374)
30. Dunlop, E.A., Maxwell, A.P. Lappin, T.R. (2007) Impaired downregulation following erythropoietin receptor activation in non-small cell lung carcinoma. Stem Cells, 25, 380 384. (Pubitemid 46232792)
31. Dunst, J. (2001) The use of epoetin alfa to increase and maintain hemoglobin levels during radiotherapy. Seminars in Oncology, 28 (2 suppl. 8 42 48. (Pubitemid 32522237)
32. Ebert, B.L. Bunn, H.F. (1999) Regulation of the erythropoietin gene. Blood, 94, 1864 1877. (Pubitemid 29430402)
33. Ehrenreich, H., Hasselblatt, M., Dembowski, C., Cepek, L., Lewczuk, P., Stiefel, M., Rustenbeck, H.H., Breiter, N., Jacob, S., Knerlich, F., Bohn, M., Poser, W., Ruther, E., Kochen, M., Gefeller, O., Gleiter, C., Wessel, T.C., De, R.M., Itri, L., Prange, H., Cerami, A., Brines, M. Siren, A.L. (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Molecular Medicine, 8, 495 505. (Pubitemid 36337492)
34. Elliott, S., Busse, L., Bass, M.B., Lu, H., Sarosi, I., Sinclair, A.M., Spahr, C., Um, M., Van, G. Begley, G. (2006) Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood, 107, 1892 1895. (Pubitemid 43289368)
35. Fandrey, J. (2004) Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression. The American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 286, R977 R988.
36. Feldman, L., Wang, Y., Rhim, J.S., Bhattacharya, N., Loda, M. Sytkowski, A.J. (2006) Erythopoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells. Prostate, 66, 135 145. (Pubitemid 43191235)
37. Fu, P. Arcasoy, M.O. (2007) Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochemical and Biophysical Research Communications, 354, 372 378. (Pubitemid 46161367)
38. Fu, P., Jiang, X. Arcasoy, M.O. (2009) Constitutively active erythropoietin receptor expression in breast cancer cells promotes cellular proliferation and migration through a MAP-kinase dependent pathway. Biochemical and Biophysical Research Communications, 379, 696 701.
39. Grote, T., Yeilding, A.L., Castillo, R., Butler, D., Fishkin, E., Henry, D.H., DeLeo, M., Fink, K. Sullivan, D.J. (2005) Efficacy and safety analysis of epoetin alfa in patients with small-cell lung cancer: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 23, 9377 9386. (Pubitemid 46260197)
40. Haller, H., Christel, C., Dannenberg, L., Thiele, P., Lindschau, C. Luft, F.C. (1996) Signal transduction of erythropoietin in endothelial cells. Kidney International, 50, 481 488. (Pubitemid 26274375)
41. Hamadmad, S.N. Hohl, R.J. (2008) Erythropoietin stimulates cancer cell migration and activates RhoA protein through a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent mechanism. Journal of Pharmacological Experimental Therapy, 324, 1227 1233.
42. Hamed, S., Barshack, I., Luboshits, G., Wexler, D., Deutsch, V., Keren, G. George, J. (2006) Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy. European Heart Journal, 27, 1876 1883. (Pubitemid 44297396)
43. Hardee, M.E., Kirkpatrick, J.P., Shan, S., Snyder, S.A., Vujaskovic, Z., Rabbani, Z.N., Dewhirst, M.W. Blackwell, K.L. (2005) Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis. British Journal of Cancer, 93, 1350 1355. (Pubitemid 41752861)
44. Hardee, M.E., Arcasoy, M.O., Blackwell, K.L., Kirkpatrick, J.P. Dewhirst, M.W. (2006) Erythropoietin biology in cancer. Clinical Cancer Research, 12, 332 339. (Pubitemid 43166118)
45. Hardee, M.E., Cao, Y., Fu, P., Jiang, X., Zhao, Y., Rabbani, Z.N., Vujaskovic, Z., Dewhirst, M.W. Arcasoy, M.O. (2007) Erythropoietin blockade inhibits the induction of tumor angiogenesis and progression. PLoS ONE, 2, e549.
46. Haroon, Z.A., Amin, K., Jiang, X. Arcasoy, M.O. (2003) A novel role for erythropoietin during fibrin-induced wound-healing response. American Journal of Pathology, 163, 993 1000. (Pubitemid 37040135)
47. Harrison, L.B., Chadha, M., Hill, R.J., Hu, K. Shasha, D. (2002) Impact of tumor hypoxia and anemia on radiation therapy outcomes. The Oncologist, 7, 492 508. (Pubitemid 36008998)
48. Hedenus, M., Adriansson, M., San Miguel, J., Kramer, M.H., Schipperus, M.R., Juvonen, E., Taylor, K., Belch, A., Altés, A., Martinelli, G., Watson, D., Matcham, J., Rossi, G. Littlewood, T.J. (2003) Darbepoetin alfa 20000161 Study Group. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. British Journal of Haematology, 122, 394 403.
49. Hedenus, M., Vansteenkiste, J., Kotasek, D., Austin, M. Amado, R.G. (2005) Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials. Journal of Clinical Oncology, 23, 6941 6948. (Pubitemid 46260280)
50. Heeschen, C., Aicher, A., Lehmann, R., Fichtlscherer, S., Vasa, M., Urbich, C., Mildner-Rihm, C., Martin, H., Zeiher, A.M. Dimmeler, S. (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood, 102, 1340 1346. (Pubitemid 36988041)
51. Henke, M., Laszig, R., Rube, C., Schafer, U., Haase, K.D., Schilcher, B., Mose, S., Beer, K.T., Burger, U., Dougherty, C. Frommhold, H. (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet, 362, 1255 1260. (Pubitemid 37324251)
52. Henke, M., Mattern, D., Pepe, M., Bezay, C., Weissenberger, C., Werner, M. Pajonk, F. (2006) Do erythropoietin receptors on cancer cells explain unexpected clinical findings? Journal of Clinical Oncology, 24, 4708 4713. (Pubitemid 46630934)
53. Hortner, M., Nielsch, U., Mayr, L.M., Heinrich, P.C. Haan, S. (2002) A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. European Journal of Biochemistry, 269, 2516 2526. (Pubitemid 34539280)
54. Jeong, J.Y., Feldman, L., Solar, P., Szenajch, J. Sytkowski, A.J. (2008) Characterization of erythropoietin receptor and erythropoietin expression and function in human ovarian cancer cells. International Journal of Cancer, 122, 274 280. (Pubitemid 350234712)
55. Joiner, B., Hirst, V.K., McKeown, S.R., McAleer, J.J. Hirst, D.G. (1993) The effect of recombinant human erythropoietin treatment on tumour radiosensitivity and cancer-associated anaemia in the mouse. British Journal of Cancer, 68, 720 726. (Pubitemid 23301276)
56. Katodritou, E., Verrou, E., Hadjiaggelidou, C., Gastari, V., Laschos, K., Kontovinis, L., Kapetanos, D., Constantinou, N., Terpos, E. Zervas, K. (2008) Erythropoiesis-stimulating agents are associated with reduced survival in patients with multiple myeloma. American Journal of Hematology, 83, 697 701.
57. Kilic, E., Kilic, U., Soliz, J., Bassetti, C.L., Gassmann, M. Hermann, D.M. (2005) Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB Journal, 19, 2026 2028. (Pubitemid 41759753)
58. Klingmuller, U. (1997) The role of tyrosine phosphorylation in proliferation and maturation of erythroid progenitor cells - signals emanating from the erythropoietin receptor. European Journal of Biochemistry, 249, 637 647. (Pubitemid 27479032)
59. Klingmuller, U., Lorenz, U., Cantley, L.C., Neel, B.G. Lodish, H.F. (1995) Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell, 80, 729 738.
60. Kokhaei, P., Abdalla, A.O., Hansson, L., Mikaelsson, E., Kubbies, M., Haselbeck, A., Jernberg-Wiklund, H., Mellstedt, H. Osterborg, A. (2007) Expression of erythropoietin receptor and in vitro functional effects of epoetins in B-cell malignancies. Clinical Cancer Research, 13, 3536 3544. (Pubitemid 46955113)
61. Kumar, S.M., Yu, H., Fong, D., Acs, G. Xu, X. (2006) Erythropoietin activates the phosphoinositide 3-kinase/Akt pathway in human melanoma cells. Melanoma Research, 16, 275 283. (Pubitemid 44090171)
62. Lai, S.Y., Childs, E.E., Xi, S., Coppelli, F.M., Gooding, W.E., Wells, A., Ferris, R.L. Grandis, J.R. (2005) Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma. Oncogene, 24, 4442 4449. (Pubitemid 40961767)
63. LaMontagne, K.R., Butler, J., Marshall, D.J., Tullai, J., Gechtman, Z., Hall, C., Meshaw, A. Farrell, F.X. (2006) Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models. Molecular Cancer Therapy, 5, 347 355.
64. Lee, S.H., Li, C., Lim, S.W., Ahn, K.O., Choi, B.S., Kim, Y.S., Moon, I.S., Kim, J., Bang, B.K. Yang, C.W. (2005) Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy. American Journal of Nephrology, 25, 64 76. (Pubitemid 40529278)
65. Lester, R.D., Jo, M., Campana, W.M. Gonias, S.L. (2005) Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia. Journal of Biological Chemistry, 280, 39273 39277. (Pubitemid 41713881)
66. Leyland-Jones, B. BEST investigators and Study Group 2003) Breast cancer trial with erythropoietin terminated unexpectedly. Lancet Oncology, 4, 459 460 Comment in: Lancet Oncology 2004; 5, 206-207) (Pubitemid 37009952)
67. Leyland-Jones, B., Semiglazov, V., Pawlicki, M., Pienkowski, T., Tjulandin, S., Manikhas, G., Makhson, A., Roth, A., Dodwell, D., Baselga, J., Biakhov, M., Valuckas, K., Voznyi, E., Liu, X. Vercammen, E. (2005) Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. Journal of Clinical Oncology, 23, 5960 5972. (Pubitemid 46300213)
68. Li, J., Vesey, D.A., Johnson, D.W. Gobe, G. (2007) Erythropoietin reduces cisplatin-induced apoptosis in renal carcinoma cells via a PKC dependent pathway. Cancer Biological Therapy, 6, 1944 1950. (Pubitemid 351590408)
69. Lipsic, E., van der Meer, P., Voors, A.A., Westenbrink, B.D., van den Heuvel, A.F., de Boer, H.C., van Zonneveld, A.J., Schoemaker, R.G., van Gilst, W.H., Zijlstra, F. van Veldhuisen, D.J. (2006) A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovascular Drugs and Therapy, 20, 135 141. (Pubitemid 43876097)
70. Littlewood, T.J., Bajetta, E., Nortier, J.W., Vercammen, E. Rapoport, B. (2001) Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 19, 2865 2874. (Pubitemid 32538196)
71. Liu, W.M., Powles, T., Shamash, J., Propper, D., Oliver, T. Joel, S. (2004) Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity. Oncogene, 23, 981 990. (Pubitemid 38250944)
72. Liu, R., Suzuki, A., Guo, Z., Mizuno, Y. Urabe, T. (2006) Intrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro. Journal of Neurochemistry, 96, 1101 1110.
73. Longmore, G.D. (2007) Do cancer cells express functional erythropoietin receptors? New England Journal of Medicine, 356, 2447. (Pubitemid 46919768)
74. Ludwig, H., Van Belle, S., Barrett-Lee, P., Birgegård, G., Bokemeyer, C., Gascón, P., Kosmidis, P., Krzakowski, M., Nortier, J., Olmi, P., Schneider, M. Schrijvers, D. (2004) The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. European Journal of Cancer, 40, 2293 2306. (Pubitemid 39348881)
75. Ludwig, H., Anderson, K., Dammacco, F., Hedenus, M., Osterborg, A. Durie, B. (2008) ESAs not the culprit: more studies required. American Journal of Hematology, 83, 880.
76. Macdougall, I.C. (2005) CERA (Continuous Erythropoietin Receptor Activator): a new erythropoiesis-stimulating agent for the treatment of anemia. Current Hematology Reports, 4, 436 440.
77. van der Meer, P., Lipsic, E., Henning, R.H., Boddeus, K., van der Velden, J., Voors, A.A., van Veldhuisen, D.J., van Gilst, W.H. Schoemaker, R.G. (2005) Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. Journal of the American College of Cardiology, 46, 125 133. (Pubitemid 40905140)
78. Melli, G., Jack, C., Lambrinos, G.L., Ringkamp, M. Hoke, A. (2006) Erythropoietin protects sensory axons against paclitaxel-induced distal degeneration. Neurobiology of Disease, 24, 525 530. (Pubitemid 44716681)
79. Menon, M.P., Karur, V., Bogacheva, O., Bogachev, O., Cuetara, B. Wojchowski, D.M. (2006) Signals for stress erythropoiesis are integrated via an erythropoietin receptor-phosphotyrosine-343-Stat5 axis. Journal of Clinical Investigation, 116, 683 694. (Pubitemid 43326877)
80. Mittelman, M., Neumann, D., Peled, A., Kanter, P. Haran-Ghera, N. (2001) Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proceedings of the National Academy of Sciences of the United States of America, 98, 5181 5186. (Pubitemid 32397103)
81. Mittelman, M., Zeidman, A., Kanter, P., Katz, O., Oster, H., Rund, D. Neumann, D. (2004) Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies. European Journal of Haematology, 72, 155 165. (Pubitemid 38250792)
82. Mohyeldin, A., Lu, H., Dalgard, C., Lai, S.Y., Cohen, N., Acs, G. Verma, A. (2005) Erythropoietin signaling promotes invasiveness of human head and neck squamous cell carcinoma. Neoplasia, 7, 537 543. (Pubitemid 40791872)
83. Moon, C., Krawczyk, M., Paik, D., Lakatta, E.G. Talan, M.I. (2005) Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovascular Drugs and Therapy, 19, 243 250. (Pubitemid 41778804)
84. Osterborg, A., Brandberg, Y. Hedenus, M. (2005) Impact of epoetin-β on survival of patients with lymphoproliferative malignancies: long-term follow up of a large randomized study. British Journal of Haematology, 129, 206 209. (Pubitemid 40562441)
85. Osterborg, A., Aapro, M., Cornes, P., Haselbeck, A., Hayward, C.R. Jelkmann, W. (2007) Preclinical studies of erythropoietin receptor expression in tumour cells: impact on clinical use of erythropoietic proteins to correct cancer-related anaemia. European Journal of Cancer, 43, 510 519. (Pubitemid 46177584)
86. Overgaard, J., Hoff, C. Sand, H.H. (2007) Randomized study of the importance of novel erythropoiesis stimulating protein (Aranesp) for the effect of radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC): the Danish Head and Neck Cancer Group DAHANCA 10 rand. European Journal of Cancer, Suppl, 5, 7.
87. Pirker, R., Ramlau, R.A., Schuette, W., Zatloukal, P., Ferreira, I., Lillie, T. Vansteenkiste, J.F. (2008) Safety and efficacy of darbepoetin alpha in previously untreated extensive-stage small-cell lung cancer treated with platinum plus etoposide. Journal of Clinical Oncology, 26, 2342 2349.
88. Prutchi-Sagiv, S., Golishevsky, N., Oster, H.S., Katz, O., Cohen, A., Naparstek, E., Neumann, D. Mittelman, M. (2006) Erythropoietin treatment in advanced multiple myeloma is associated with improved immunological functions: could it be beneficial in early disease? British Journal of Haematology, 135, 660 672. (Pubitemid 44674077)
89. Razzouk, B.I., Hord, J.D., Hockenberry, M., Hinds, P.S., Feusner, J., Williams, D. Rackoff, W.R. (2006) Double-blind, placebo-controlled study of quality of life, hematologic end points, and safety of weekly epoetin alfa in children with cancer receiving myelosuppressive chemotherapy. Journal of Clinical Oncology, 24, 3583 3589. (Pubitemid 46630530)
90. Ribatti, D., Presta, M., Vacca, A., Ria, R., Giuliani, R., Dell'Era, P., Nico, B., Roncali, L. Dammacco, F. (1999) Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood, 93, 2627 2636. (Pubitemid 29181195)
91. Rizzo, J.D., Somerfield, M.R., Hagerty, K.L., Seidenfeld, J., Bohlius, J., Bennett, C.L., Cella, D.F., Djulbegovic, B., Goode, M.J., Jakubowski, A.A., Rarick, M.U., Regan, D.H. Lichtin, A.E. (2008) Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood, 111, 25 41.
92. Sakanaka, M., Wen, T.C., Matsuda, S., Masuda, S., Morishita, E., Nagao, M. Sasaki, R. (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proceedings of the National Academy of Sciences of the United States of America, 95, 4635 4640. (Pubitemid 28207965)
93. Sasaki, A., Yasukawa, H., Shouda, T., Kitamura, T., Dikic, I. Yoshimura, A. (2000) CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. Journal of Biological Chemistry, 275, 29338 29347. (Pubitemid 32043805)
94. Savonije, J.H., van Groeningen, C.J., van Bochove, A., Honkoop, A.H., van Felius, C.L., Wormhoudt, L.W. Giaccone, G. (2005) Effects of early intervention with epoetin alfa on transfusion requirement, hemoglobin level and survival during platinum-based chemotherapy: results of a multicenter randomised controlled trial. European Journal of Cancer, 41, 1560 1569. (Pubitemid 40981838)
95. Sharples, E.J. Yaqoob, M.M. (2006) Erythropoietin in experimental acute renal failure. Nephron. Experimental Nephrology, 104, e83 e88.
96. Shasha, D. (2001) The negative impact of anemia on radiotherapy and chemoradiation outcomes. Seminars in Hematology, 38 (Suppl. 7 8 15. (Pubitemid 32850964)
97. Shikama, Y., Barber, D.L., D'Andrea, A.D. Sieff, C.A. (1996) A constitutively activated chimeric cytokine receptor confers factor-independent growth in hematopoietic cell lines. Blood, 88, 455 464. (Pubitemid 26240376)
98. Silver, D.F. Piver, M.S. (1999) Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in SCID mice bearing human ovarian cancer: a possible oxygen effect. Gynecologic Oncology, 73, 280 284. (Pubitemid 29215744)
99. Silverberg, D.S., Wexler, D., Blum, M., Iaina, A., Sheps, D., Keren, G. Schwartz, D. (2005) Erythropoietin in heart failure. Seminars in Nephrology, 25, 397 403. (Pubitemid 41653433)
100. Sinclair, A.M., Todd, M.D., Forsythe, K., Knox, S.J., Elliott, S. Begley, C.G. (2007) Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. Cancer, 110, 477 488.
101. Sinclair, A.M., Rogers, N., Busse, L., Archibeque, I., Brown, W., Kassner, P.D., Watson, J.E., Arnold, G.E., Nguyen, K.C., Powers, S. Elliott, S. (2008) Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells. British Journal of Cancer, 98, 1059 1067.
102. Singh, A.K., Szczech, L., Tang, K.L., Barnhart, H., Sapp, S., Wolfson, M. Reddan, D. (2006) Correction of anemia with epoetin alfa in chronic kidney disease. New England Journal of Medicine, 355, 2085 2098. (Pubitemid 44749317)
103. Smith, Jr., R.E., Aapro, M.S., Ludwig, H., Pinter, T., Smakal, M., Ciuleanu, T.E., Chen, L., Lillie, T. Glaspy, J.A. (2008) Darbepoetin alpha for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Journal of Clinical Oncology, 26, 1040 1050.
104. Spivak, J.L. (1994) Recombinant human erythropoietin and the anemia of cancer. Blood, 84, 997 1004. (Pubitemid 24245861)
105. Strauss, H.G., Haensgen, G., Dunst, J., Hayward, C.R.W., Burgers, H.U., Scherhag, A. Koelbl, H. (2008) Effects of anemia correction with epoetin beta in patients receiving radiochemotherapy for advanced cervical cancer. International Journal of Gynecological Cancer, 18, 515 524. (Pubitemid 351668300)
106. Stuben, G., Thews, O., Pottgen, C., Knuhmann, K., Vaupel, P. Stuschke, M. (2001) Recombinant human erythropoietin increases the radiosensitivity of xenografted human tumours in anaemic nude mice. Journal of Cancer Research and Clinical Oncology, 127, 346 350. (Pubitemid 32453676)
107. Thews, O., Koenig, R., Kelleher, D.K., Kutzner, J. Vaupel, P. (1998) Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia. British Journal of Cancer, 78, 752 756. (Pubitemid 28418307)
108. Thews, O., Kelleher, D.K. Vaupel, P. (2001) Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors. Cancer Research, 61, 1358 1361. (Pubitemid 34292556)
109. Tilbrook, P.A. Klinken, S.P. (1999) The erythropoietin receptor. International Journal of Biochemistry and Cell Biology, 31, 1001 1005. (Pubitemid 29454540)
110. Toth, C., Martinez, J.A., Liu, W.Q., Diggle, J., Guo, G.F., Ramji, N., Mi, R., Hoke, A. Zochodne, D.W. (2008) Local erythropoietin signaling enhances regeneration in peripheral axons. Neuroscience, 154, 767 783.
111. Tramontano, A.F., Muniyappa, R., Black, A.D., Blendea, M.C., Cohen, I., Deng, L., Sowers, J.R., Cutaia, M.V. El-Sherif, N. (2003) Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochemical and Biophysical Research Communications, 308, 990 994. (Pubitemid 36976556)
112. Um, M. Lodish, H.F. (2006) Antiapoptotic effects of erythropoietin in differentiated neuroblastoma SH-SY5Y cells require activation of both the STAT-5 and AKT signaling pathways. Journal of Biological Chemistry, 281, 5648 5656. (Pubitemid 43847662)
113. Um, M., Gross, A.W. Lodish, H.F. (2007) A "classical" homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells. Cellular Signalling, 19, 634 645. (Pubitemid 46107815)
114. Vansteenkiste, J., Pirker, R., Massuti, B., Barata, F., Font, A., Fiegl, M., Siena, S., Gateley, J., Tomita, D., Colowick, A.B. Musil, J. (2002) Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. Journal of the National Cancer Institute, 94, 1211 1220. (Pubitemid 34993871)
115. Watanabe, D., Suzuma, K., Matsui, S., Kurimoto, M., Kiryu, J., Kita, M., Suzuma, I., Ohashi, H., Ojima, T., Murakami, T., Kobayashi, T., Masuda, S., Nagao, M., Yoshimura, N. Takagi, H. (2005) Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. New England Journal of Medicine, 353, 782 792. (Pubitemid 41215487)
116. Westenfelder, C. Baranowski, R.L. (2000) Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney International, 58, 647 657. (Pubitemid 30620014)
117. Wilkinson, P.M., Antonopoulos, M., Lahousen, M., Lind, M. Kosmidis, P. for the EPO-INT-45 Study Group 2006) Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial. British Journal of Cancer, 94, 947 954.
118. Witzig, T.E., Silberstein, P.T., Loprinzi, C.L., Sloan, J.A., Novotny, P.J., Mailliard, J.A., Rowland, K.M., Alberts, S.R., Krook, J.E., Levitt, R. Morton, R.F. (2005) Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. Journal of Clinical Oncology, 23, 2606 2617. (Pubitemid 46179449)
119. Won, Y.J., Yoo, J.Y., Lee, J.H., Hwang, S.J., Kim, D. Hong, H.N. (2007) Erythropoietin is neuroprotective on GABAergic neurons against kainic acid-excitotoxicity in the rat spinal cell cultures. Brain Research, 1154, 31 39. (Pubitemid 46856347)
120. Wright, J.R., Ung, Y.C., Julian, J.A., Pritchard, K.I., Whelan, T.J., Smith, C., Szechtman, B., Roa, W., Mulroy, L., Rudinskas, L., Gagnon, B., Okawara, G.S. Levine, M.N. (2007) Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. Journal of Clinical Oncology, 25, 1027 1032. (Pubitemid 46596751)
121. Yasuda, Y., Masuda, S., Chikuma, M., Inoue, K., Nagao, M. Sasaki, R. (1998) Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. Journal of Biological Chemistry, 273, 25381 25387. (Pubitemid 28443305)
122. Yasuda, Y., Musha, T., Tanaka, H., Fujita, Y., Fujita, H., Utsumi, H., Matsuo, T., Masuda, S., Nagao, M., Sasaki, R. Nakamura, Y. (2001) Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice. British Journal of Cancer, 84, 836 843. (Pubitemid 32275660)
123. Yasuda, Y., Fujita, Y., Matsuo, T., Koinuma, S., Hara, S., Tazaki, A., Onozaki, M., Hashimoto, M., Musha, T., Ogawa, K., Fujita, H., Nakamura, Y., Shiozaki, H. Utsumi, H. (2003) Erythropoietin regulates tumour growth of human malignancies. Carcinogenesis, 24, 1021 1029. (Pubitemid 36833185)
124. Yu, X., Shacka, J.J., Eells, J.B., Suarez-Quian, C., Przygodzki, R.M., Beleslin-Cokic, B., Lin, C.S., Nikodem, V.M., Hempstead, B., Flanders, K.C., Costantini, F. Noguchi, C.T. (2002) Erythropoietin receptor signalling is required for normal brain development. Development, 129, 505 516. (Pubitemid 34863815)