Table of Contents
ISRN Developmental Biology
Volume 2013 (2013), Article ID 241016, 18 pages
http://dx.doi.org/10.1155/2013/241016
Review Article

Thalidomide Embryopathy: An Enigmatic Challenge

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

Received 9 July 2013; Accepted 18 August 2013

Academic Editors: J. M. Hurle and G. Tettamanti

Copyright © 2013 Neil Vargesson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Vargesson, “Thalidomide-induced limb defects: resolving a 50-year-old puzzle,” BioEssays, vol. 31, no. 12, pp. 1327–1336, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. N. Vargesson, “Thalidomide,” in Reproductive and Developmental Toxicology, R. Gupta, Ed., pp. 395–403, Academic Press, Elsevier, Amsterdam, The Netherlands, 2011. View at Google Scholar
  3. W. Lenz, “A short history of thalidomide embryopathy,” Teratology, vol. 38, no. 3, pp. 203–215, 1988. View at Google Scholar · View at Scopus
  4. S. V. Rajkumar, “Thalidomide: tragic past and promising future,” Mayo Clinic Proceedings, vol. 79, no. 7, pp. 899–903, 2004. View at Google Scholar · View at Scopus
  5. F. O. Kelsey, “Events after thalidomide,” Journal of Dental Research, vol. 46, no. 6, pp. 1201–1205, 1967. View at Google Scholar · View at Scopus
  6. F. O. Kelsey, “Thalidomide update: regulatory aspects,” Teratology, vol. 38, no. 3, pp. 221–226, 1988. View at Google Scholar · View at Scopus
  7. R. W. Smithells and C. G. H. Newman, “Recognition of thalidomide defects,” Journal of Medical Genetics, vol. 29, no. 10, pp. 716–723, 1992. View at Google Scholar · View at Scopus
  8. T. D. Stephens, C. J. W. Bunde, and B. J. Fillmore, “Mechanism of action in thalidomide teratogenesis,” Biochemical Pharmacology, vol. 59, no. 12, pp. 1489–1499, 2000. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Kajii, M. Kida, and K. Takahashi, “The effect of thalidomide intake during 113 human pregnancies,” Teratology, vol. 8, no. 2, pp. 163–166, 1973. View at Google Scholar · View at Scopus
  10. T. Kajii and M. Shinohara, “Thalidomide in Japan,” The Lancet, vol. 1, no. 7279, pp. 501–502, 1963. View at Google Scholar · View at Scopus
  11. W. Lenz and K. Knapp, “Thalidomide embryopathy,” Archives of Environmental Health, vol. 5, pp. 100–105, 1962. View at Google Scholar · View at Scopus
  12. W. G. McBride, “Studies of the etiology of thalidomide dysmorphogenesis,” Teratology, vol. 14, no. 1, pp. 71–87, 1976. View at Google Scholar · View at Scopus
  13. C. G. H. Newman, “Clinical observations on the thalidomide syndrome,” Proceedings of the Royal Society of Medicine, vol. 70, no. 4, pp. 225–227, 1977. View at Google Scholar · View at Scopus
  14. C. G. H. Newman, “Teratogen update: clinical aspects of thalidomide embryopathy—a continuing preoccupation,” Teratology, vol. 32, no. 1, pp. 133–144, 1985. View at Google Scholar · View at Scopus
  15. C. G. H. Newman, “The thalidomide syndrome: risks of exposure and spectrum of malformations,” Clinics in Perinatology, vol. 13, no. 3, pp. 555–573, 1986. View at Google Scholar · View at Scopus
  16. R. W. Smithells, “Thalidomide and malformations in liverpool,” The Lancet, vol. 279, no. 7242, pp. 1270–1273, 1962. View at Google Scholar · View at Scopus
  17. R. W. Smithells, “Defects and disabilities of thalidomide children,” British medical journal, vol. 1, no. 5848, pp. 269–272, 1973. View at Google Scholar · View at Scopus
  18. I. M. Leck and E. L. Millar, “Incidence of malformations since the introduction of thalidomide,” British Medical Journal, vol. 2, no. 5296, pp. 16–20, 1962. View at Google Scholar · View at Scopus
  19. H. B. Taussig, “A study of the German outbreak of phocomelia. The thalidomide syndrome,” The journal of the American Medical Association, vol. 180, pp. 1106–1114, 1962. View at Google Scholar · View at Scopus
  20. U. K. Government Report, “Deformities caused by Thalidomide,” Reports on Public Health and Medical Subjects. : 112, Ministry of Health, HMSO, London, UK, 1964. View at Google Scholar
  21. G. F. Somers, “Thalidomide and congenital abnormalities,” The Lancet, vol. 1, no. 7235, pp. 912–913, 1962. View at Google Scholar · View at Scopus
  22. R. W. Smithells and I. Leck, “The incidence of limb and ear defects since the withdrawal of thalidomide,” The Lancet, vol. 1, no. 7290, pp. 1095–1097, 1963. View at Google Scholar · View at Scopus
  23. B. M. Ances, “New concerns about thalidomide,” Obstetrics and Gynecology, vol. 99, no. 1, pp. 125–128, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. F. O. Kelsey, “Drug embryopathy: the thalidomide story,” Maryland State Medical Journal, vol. 12, pp. 594–597, 1963. View at Google Scholar
  25. M. T. Miller and K. Stromland, “Teratogen update: thalidomide: a review, with a focus on ocular findings and new potential uses,” Teratology, vol. 60, pp. 306–321, 1999. View at Google Scholar
  26. H. B. TAUSSIG, “The thalidomide syndrome,” Scientific American, vol. 207, pp. 29–35, 1962. View at Google Scholar · View at Scopus
  27. J. Sheskin, “Thalidomide in the Treatment of Lepra Reactions,” Clinical Pharmacology and Therapeutics, vol. 6, pp. 303–306, 1965. View at Google Scholar
  28. R. J. D'Amato, M. S. Loughnan, E. Flynn, and J. Folkman, “Thalidomide is an inhibitor of angiogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 4082–4085, 1994. View at Google Scholar · View at Scopus
  29. M. E. Franks, G. R. Macpherson, and W. D. Figg, “Thalidomide,” The Lancet, vol. 363, no. 9423, pp. 1802–1811, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. T. Facon, J. Y. Mary, C. Hulin et al., “Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial,” The Lancet, vol. 370, no. 9594, pp. 1209–1218, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Palumbo and M. Boccadoro, “A new standard of care for elderly patients with myeloma,” The Lancet, vol. 370, no. 9594, pp. 1191–1192, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. B. Ladizinski, E. J. Shannon, M. R. Sanchez, and W. R. Levis, “Thalidomide and analogues: potential for immunomodulation of inflammatory and neoplastic dermatologic disorders,” Journal of Drugs in Dermatology, vol. 9, no. 7, pp. 814–826, 2010. View at Google Scholar · View at Scopus
  33. J. J. Wu, D. B. Huang, K. R. Pang, S. Hsu, and S. K. Tyring, “Thalidomide: dermatological indications, mechanisms of action and side-effects,” British Journal of Dermatology, vol. 153, no. 2, pp. 254–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Lebrin, S. Srun, K. Raymond et al., “Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia,” Nature Medicine, vol. 16, no. 4, pp. 420–428, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. M. R. Horton and R. W. Hallowell, “Revisiting thalidomide: fighting with caution against idiopathic pulmonary fibrosis,” Drugs Today, vol. 48, pp. 661–671, 2012. View at Google Scholar
  36. J. Knobloch, D. Jungck, and A. Koch, “Apoptosis induction by thalidomide: critical for limb teratogenicity but therapeutic potential in idiopathic pulmonary fibrosis?” Current Molecular Pharmacology, vol. 4, no. 1, pp. 26–61, 2011. View at Google Scholar · View at Scopus
  37. E. E. Castilla, P. Ashton-Prolla, E. Barreda-Mejia et al., “Thalidomide, a current teratogen in South America,” Teratology, vol. 54, pp. 273–277, 1996. View at Google Scholar
  38. L. Schuler-Faccini, R. C. F. Soares, A. C. M. de Sousa et al., “New cases of thalidomide embryopathy in Brazil,” Birth Defects Research A, vol. 79, no. 9, pp. 671–672, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. F. S. L. Vianna, J. S. Lopez-Camelo, J. C. L. Leite et al., “Epidemiological surveillance of birth defects compatible with thalidomide embryopathy in Brazil,” PLoS ONE, vol. 6, no. 7, Article ID e21735, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. F. S. Vianna, L. Schuler-Faccini, J. C. Leite et al., “Recognition of the phenotype of thalidomide embryopathy in countries endemic for leprosy: new cases and review of the main dysmorphological findings,” Clinical Dysmorphology, vol. 22, pp. 59–63, 2013. View at Google Scholar
  41. W. G. McBride, “Thalidomide embryopathy,” Teratology, vol. 16, no. 1, pp. 79–82, 1977. View at Google Scholar · View at Scopus
  42. M. T. Miller, K. Strömland, L. Ventura, M. Johansson, J. M. Bandim, and C. Gillberg, “Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review,” International Journal of Developmental Neuroscience, vol. 23, no. 2-3, pp. 201–219, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. W. H. James, “Teratogenetic properties of thalidomide,” British Medical Journal, vol. 2, no. 5469, p. 1064, 1965. View at Google Scholar · View at Scopus
  44. K. L. Hallene, E. Oby, B. J. Lee et al., “Prenatal exposure to thalidomide, altered vasculogenesis, and CNS malformations,” Neuroscience, vol. 142, no. 1, pp. 267–283, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. M. T. Miller and K. K. Strömland, “What can we learn from the thalidomide experience: an ophthalmologic perspective,” Current Opinion in Ophthalmology, vol. 22, no. 5, pp. 356–364, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. L. Henkel and H. G. Willert, “Dysmelia classification and a pattern of malformation in a group of congenital defects of the limbs,” Journal of Bone and Joint Surgery B, vol. 51, no. 3, pp. 399–414, 1969. View at Google Scholar · View at Scopus
  47. A. L. Speirs, “Thalidomide and congenital abnormalities,” The Lancet, vol. 1, no. 7224, pp. 303–305, 1962. View at Google Scholar · View at Scopus
  48. I. Leck and R. W. Smithells, “The ascertainment of malformations,” Lancet, vol. 1, pp. 101–103, 1963. View at Google Scholar
  49. J. McCredie and H.-G. Willert, “Longitudinal limb deficiencies and the sclerotomes. An analysis of 378 dysmelic malformations induced by thalidomide,” Journal of Bone and Joint Surgery B, vol. 81, no. 1, pp. 9–23, 1999. View at Publisher · View at Google Scholar · View at Scopus
  50. K. C. Oberg, J. M. Feenstra, P. R. Manske, and M. A. Tonkin, “Developmental biology and classification of congenital anomalies of the hand and upper extremity,” Journal of Hand Surgery, vol. 35, no. 12, pp. 2066–2076, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Towers and C. Tickle, “Generation of pattern and form in the developing limb,” International Journal of Developmental Biology, vol. 53, no. 5-6, pp. 805–812, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Zuniga, R. Zeller, and S. Probst, “The molecular basis of human congenital limb malformations,” Wiley Interdisciplinary Reviews: Developmental Biology, vol. 1, pp. 803–822, 2012. View at Google Scholar
  53. K. C. Oberg, T. E. Harris, M. D. Wongworawat, and V. E. Wood, “Combined congenital radial and ulnar longitudinal deficiencies: report of 2 cases,” Journal of Hand Surgery, vol. 34, no. 7, pp. 1298–1302, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Therapontos, L. Erskine, E. R. Gardner, W. D. Figg, and N. Vargesson, “Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 21, pp. 8573–8578, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Schmidt and F. M. Salzano, “Dissimilar effects of thalidomide in dizygotic twins,” Acta Geneticae Medicae et Gemellologiae, vol. 29, no. 4, pp. 295–297, 1980. View at Google Scholar · View at Scopus
  56. R. J. Newman, “Shoulder joint replacement for osteoarthrosis in association with thalidomide-induced phocomelia,” Clinical Rehabilitation, vol. 13, no. 3, pp. 250–252, 1999. View at Publisher · View at Google Scholar · View at Scopus
  57. L. Ruffing, “Evaluation of thalidomide children,” Birth Defects, vol. 13, no. 1, pp. 287–300, 1977. View at Google Scholar · View at Scopus
  58. J. F. Cullen, “Ocular defects in thalidomide babies,” British Journal of Ophthalmology, vol. 48, pp. 151–153, 1964. View at Google Scholar
  59. R. Cuthbert and A. L. Speirs, “Thalidomide induced malformations—a radiological survey,” Clinical Radiology, vol. 14, no. 2, pp. 163–169, 1963. View at Google Scholar · View at Scopus
  60. G. Livingstone, “Congenital ear abnormalities due to thalidomide,” Proceedings of the Royal Society of Medicine, vol. 58, pp. 493–497, 1965. View at Google Scholar
  61. C. G. D. Brook, S. N. Jarvis, and C. G. H. Newman, “Linear growth of children with limb deformities following exposure to thalidomide in utero,” Acta Paediatrica Scandinavica, vol. 66, no. 6, pp. 673–675, 1977. View at Google Scholar · View at Scopus
  62. G. Chamberlain, “The obstetric problems of the thalidomide children,” British Medical Journal, vol. 298, no. 6665, p. 6, 1989. View at Google Scholar · View at Scopus
  63. I. Fletcher, “Review of the treatment of thalidomide children with limb deficiency in great Britain,” Clinical Orthopaedics and Related Research, vol. 148, pp. 18–25, 1980. View at Google Scholar · View at Scopus
  64. B. J. Soules, “Thalidomide victims in a rehabilitation center,” Ha-Ahot be-Yisrael, vol. 12, no. 60, pp. 43–45, 1966. View at Google Scholar · View at Scopus
  65. J. M. Hansen and C. Harris, “Redox control of teratogenesis,” Reproductive Toxicology, vol. 35, pp. 165–179, 2013. View at Publisher · View at Google Scholar
  66. J. Ashby and H. Tinwell, “Thalidomide is not a human mutagen,” British Medical Journal, vol. 325, no. 7374, p. 1245, 2002. View at Google Scholar · View at Scopus
  67. J. Kohlhase and L. B. Holmes, “Mutations in SALL4 in malformed father and daughter postulated previously due to reflect mutagenesis by thalidomide,” Birth Defects Research A, vol. 70, no. 8, pp. 550–551, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Kohlhase, L. Schubert, M. Liebers et al., “Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy,” Journal of Medical Genetics, vol. 40, no. 7, pp. 473–478, 2003. View at Google Scholar · View at Scopus
  69. A. W. Bates, “A case of Roberts syndrome described in 1737,” Journal of Medical Genetics, vol. 38, no. 8, pp. 565–567, 2001. View at Google Scholar · View at Scopus
  70. E. S.-Y. Goh, C. Li, S. Horsburgh, Y. Kasai, E. Kolomietz, and C. F. Morel, “The Roberts syndrome/SC phocomelia spectrum—a case report of an adult with review of the literature,” American Journal of Medical Genetics A, vol. 152, no. 2, pp. 472–478, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. B. Schüle, A. Oviedo, K. Johnston, S. Pai, and U. Francke, “Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation,” American Journal of Human Genetics, vol. 77, no. 6, pp. 1117–1128, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Vega, Q. Waisfisz, M. Gordillo et al., “Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion,” Nature Genetics, vol. 37, no. 5, pp. 468–470, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Mönnich, Z. Kuriger, C. G. Print, and J. A. Horsfield, “A zebrafish model of roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle,” PLoS ONE, vol. 6, no. 5, Article ID e20051, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. G. Whelan, E. Kreidl, J. M. Peters, and G. Eichele, “The non-redundant function of cohesin acetyltransferase Esco2: some answers and new questions,” Nucleus, vol. 3, pp. 330–334, 2012. View at Google Scholar
  75. S. Cundari and G. Cavaletti, “Thalidomide chemotherapy-induced peripheral neuropathy: actual status and new perspectives with thalidomide analogues derivatives,” Mini-Reviews in Medicinal Chemistry, vol. 9, no. 7, pp. 760–768, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Delforge, J. Bladé, M. A. Dimopoulos et al., “Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues,” The Lancet Oncology, vol. 11, no. 11, pp. 1086–1095, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. F. O. Kelsey, “Problems raised for the FDA by the occurrence of thalidomide embryopathy in Germany, 1960-1961,” American Journal of Public Health and the Nation'S Health, vol. 55, pp. 703–707, 1965. View at Google Scholar
  78. A. C. Peltier and J. W. Russell, “Advances in understanding drug-induced neuropathies,” Drug Safety, vol. 29, no. 1, pp. 23–30, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. P. G. Richardson, M. Delforge, M. Beksac et al., “Management of treatment-emergent peripheral neuropathy in multiple myeloma,” Leukemia, vol. 26, no. 4, pp. 595–608, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. M. S. Raab, K. Podar, I. Breitkreutz, P. G. Richardson, and K. C. Anderson, “Multiple myeloma,” The Lancet, vol. 374, no. 9686, pp. 324–339, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Q. Lacy, S. R. Hayman, M. A. Gertz et al., “Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma,” Journal of Clinical Oncology, vol. 27, no. 30, pp. 5008–5014, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. P. G. Richardson, D. Siegel, R. Baz et al., “Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib,” Blood, vol. 121, pp. 1961–1967, 2013. View at Google Scholar
  83. A. Palumbo, J. Freeman, L. Weiss, and P. Fenaux, “The clinical safety of lenalidomide in multiple myeloma and myelodysplastic syndromes,” Expert Opinion on Drug Safety, vol. 11, no. 1, pp. 107–120, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. P. M. Voorhees, J. Laubach, K. C. Anderson, and P. G. Richardson, “Peripheral neuropathy in multiple myeloma patients receiving lenalidomide, bortezomib, and dexamethasone (RVD) therapy,” Blood, vol. 121, article 858, 2013. View at Google Scholar
  85. C. Mahony, L. Erskine, J. Niven et al., “Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic invitro,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, pp. 12703–12708, 2013. View at Google Scholar
  86. R. L. Smith, S. Fabro, H. Schumacher, and R. T. Williams, “Studies on the relationship between the chemical structure and embryotoxic activity of thalidomide and related compounds,” in Embryopathic Activity of Drugs, J. M. Robson, F. Sullivan, and R. L. Smith, Eds., pp. 194–209, Churchill, London, UK, 1965. View at Google Scholar
  87. C. P. Castaneda, J. B. Zeldis, J. Freeman, C. Quigley, N. A. Brandenburg, and R. Bwire, “RevAssist: a comprehensive risk minimization programme for preventing fetal exposure to lenalidomide,” Drug Safety, vol. 31, no. 9, pp. 743–752, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. K. Uhl, E. Cox, R. Rogan et al., “Thalidomide use in the US: experience with pregnancy testing in the S.T.E.P.S. programme,” Drug Safety, vol. 29, no. 4, pp. 321–329, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. J. B. Zeldis, B. A. Williams, S. D. Thomas, and M. E. Elsayed, “S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide,” Clinical Therapeutics, vol. 21, no. 2, pp. 319–330, 1999. View at Publisher · View at Google Scholar · View at Scopus
  90. J. B. Bartlett, K. Dredge, and A. G. Dalgleish, “The evolution of thalidomide and its IMiD derivatives as anticancer agents,” Nature Reviews Cancer, vol. 4, no. 4, pp. 314–322, 2004. View at Google Scholar · View at Scopus
  91. C. Galustian, M.-C. Labarthe, J. B. Bartlett, and A. G. Dalgleish, “Thalidomide-derived immunomodulatory drugs as therapeutic agents,” Expert Opinion on Biological Therapy, vol. 4, no. 12, pp. 1963–1970, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. K. S. Bauer, S. C. Dixon, and W. D. Figg, “Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent,” Biochemical Pharmacology, vol. 55, no. 11, pp. 1827–1834, 1998. View at Publisher · View at Google Scholar · View at Scopus
  93. M. G. Marks, J. Shi, M. O. Fry et al., “Effects of putative hydroxylated thalidomide metabolites on blood vessel density in the chorioallantoic membrane (CAM) assay and on tumor and endothelial cell proliferation,” Biological and Pharmaceutical Bulletin, vol. 25, no. 5, pp. 597–604, 2002. View at Publisher · View at Google Scholar · View at Scopus
  94. A. L. Moreira, E. P. Sampaio, A. Zmuidzinas, P. Frindt, K. A. Smith, and G. Kaplan, “Thalidomide exerts its inhibitory action on tumor necrosis factor α by enhancing mRNA degradation,” Journal of Experimental Medicine, vol. 177, no. 6, pp. 1675–1680, 1993. View at Google Scholar · View at Scopus
  95. F. Payvandi, L. Wu, M. Haley et al., “Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-α, IL-1β, and LPS-stimulated human PBMC in a partially IL-10-dependent manner,” Cellular Immunology, vol. 230, no. 2, pp. 81–88, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. T. Hideshima, D. Chauhan, Y. Shima et al., “Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy,” Blood, vol. 96, no. 9, pp. 2943–2950, 2000. View at Google Scholar · View at Scopus
  97. W. Luo, Q.-S. Yu, I. Salcedo et al., “Design, synthesis and biological assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-α inhibitory activity,” Bioorganic and Medicinal Chemistry, vol. 19, no. 13, pp. 3965–3972, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. D. Ribatti, G. Mangialardi, and A. Vacca, “Antiangiogenic therapeutic approaches in multiple myeloma,” Current Cancer Drug Targets, vol. 12, pp. 768–775, 2012. View at Google Scholar
  99. P. Carmeliet, N. Mackman, L. Moons et al., “Role of tissue factor in embryonic blood vessel development,” Nature, vol. 383, no. 6595, pp. 73–75, 1996. View at Publisher · View at Google Scholar · View at Scopus
  100. N. Vargesson, “Vascularization of the developing chick limb bud: role of The TGFβ signalling pathway,” Journal of Anatomy, vol. 202, no. 1, pp. 93–103, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. E. Crivellato, “The role of angiogenic growth factors in organogenesis,” International Journal of Developmental Biology, vol. 55, no. 4-5, pp. 365–375, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. T. B. Knudsen and N. C. Kleinstreuer, “Disruption of embryonic vascular development in predictive toxicology,” Birth Defects Research C, vol. 93, no. 4, pp. 312–323, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. H. Chang, D. Huylebroeck, K. Verschueren, Q. Guo, M. M. Matzuk, and A. Zwijsen, “Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects,” Development, vol. 126, no. 8, pp. 1631–1642, 1999. View at Google Scholar · View at Scopus
  104. N. Ferrara, K. Carver-Moore, H. Chen et al., “Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene,” Nature, vol. 380, no. 6573, pp. 439–442, 1996. View at Publisher · View at Google Scholar · View at Scopus
  105. F. Shalaby, J. Rossant, T. P. Yamaguchi et al., “Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice,” Nature, vol. 376, no. 6535, pp. 62–66, 1995. View at Google Scholar · View at Scopus
  106. J. D. Leslie, L. Ariza-McNaughton, A. L. Bermange, R. McAdow, S. L. Johnson, and J. Lewis, “Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis,” Development, vol. 134, no. 5, pp. 839–844, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Therapontos and N. Vargesson, “Zebrafish notch signalling pathway mutants exhibit trunk vessel patterning anomalies that are secondary to somite misregulation,” Developmental Dynamics, vol. 239, no. 10, pp. 2761–2768, 2010. View at Google Scholar · View at Scopus
  108. B. M. Kenyon, F. Browne, and R. J. D'Amato, “Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization,” Experimental Eye Research, vol. 64, no. 6, pp. 971–978, 1997. View at Publisher · View at Google Scholar · View at Scopus
  109. E. R. Lepper, N. F. Smith, M. C. Cox, C. D. Scripture, and W. D. Figg, “Thalidomide metabolism and hydrolysis: mechanisms and implications,” Current Drug Metabolism, vol. 7, no. 6, pp. 677–685, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. N. A. Warfel, E. R. Lepper, C. Zhang, W. D. Figg, and P. A. Dennis, “Importance of the stress kinase p38α in mediating the direct cytotoxic effects of the Thalidomide analogue, CPS49, in cancer cells and endothelial cells,” Clinical Cancer Research, vol. 12, pp. 3502–3509, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. S. S. W. Ng, M. Gütschow, M. Weiss et al., “Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide analogues,” Cancer Research, vol. 63, no. 12, pp. 3189–3194, 2003. View at Google Scholar · View at Scopus
  112. J. M. Hansen, S.-G. Gong, M. Philbert, and C. Harris, “Misregulation of gene expression in the redox-sensitive NF-κB-dependent limb outgrowth pathway by thalidomide,” Developmental Dynamics, vol. 225, no. 2, pp. 186–194, 2002. View at Publisher · View at Google Scholar · View at Scopus
  113. T. Ito, H. Ando, T. Suzuki et al., “Identification of a primary target of thalidomide teratogenicity,” Science, vol. 327, no. 5971, pp. 1345–1350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. J. Knobloch, J. D. Shaughnessy Jr., and U. Rüther, “Thalidomide induces limb deformities by perturbing the Bmp/Dkk1/Wnt signaling pathway,” The FASEB Journal, vol. 21, no. 7, pp. 1410–1421, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. N. Vargesson and E. Laufer, “Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function,” Developmental Biology, vol. 240, no. 2, pp. 499–516, 2001. View at Publisher · View at Google Scholar · View at Scopus
  116. C. J. J. Lee, N. Shibata, M. J. Wiley, and P. G. Wells, “Fluorothalidomide: a characterization of maternal and developmental toxicity in rabbits and mice,” Toxicological Sciences, vol. 122, no. 1, pp. 157–169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. J. Boylen, H. Horne, and W. Johnson, “Teratogenic effects of thalidomide and related substances,” The Lancet, vol. 1, p. 552, 1963. View at Google Scholar · View at Scopus
  118. J. Knobloch, I. Schmitz, K. Götz, K. Schulze-Osthoff, and U. Rüther, “Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression, and stimulation of caspase-dependent cell death,” Molecular and Cellular Biology, vol. 28, no. 2, pp. 529–538, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. J. H. Siamwala, V. Veeriah, M. K. Priya et al., “Nitric oxide rescues thalidomide mediated teratogenicity,” Scientific Reports, vol. 2, article 679, 2012. View at Google Scholar
  120. J. M. Hansen, K. K. Harris, M. A. Philbert, and C. Harris, “Thalidomide modulates nuclear redox status and preferentially depletes glutathione in rabbit limb versus rat limb,” Journal of Pharmacology and Experimental Therapeutics, vol. 300, no. 3, pp. 768–776, 2002. View at Publisher · View at Google Scholar · View at Scopus
  121. K. P. Tamilarasan, G. K. Kolluru, M. Rajaram, M. Indhumathy, R. Saranya, and S. Chatterjee, “Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration of endothelial cells,” BMC Cell Biology, vol. 7, article 17, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. S. Majumder, M. Rajaram, A. Muley et al., “Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase,” British Journal of Pharmacology, vol. 158, no. 7, pp. 1720–1734, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. T. Yabu, H. Tomimoto, Y. Taguchi, S. Yamaoka, Y. Igarashi, and T. Okazaki, “Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate,” Blood, vol. 106, no. 1, pp. 125–134, 2005. View at Publisher · View at Google Scholar · View at Scopus
  124. A. I. Whitsel, C. B. Johnson, and C. J. Forehand, “An in ovo chicken model to study the systemic and localized teratogenic effects of valproic acid,” Teratology, vol. 66, no. 4, pp. 153–163, 2002. View at Publisher · View at Google Scholar · View at Scopus
  125. J. M. Hansen and C. Harris, “A novel hypothesis for thalidomide-induced limb teratogenesis: redox misregulation of the NF-κB pathway,” Antioxidants and Redox Signaling, vol. 6, no. 1, pp. 1–14, 2004. View at Google Scholar · View at Scopus
  126. R. Neubert, N. Hinz, R. Thiel, and D. Neubert, “Down-regulation of adhesion receptors on cells of primate embryos as a probable mechanism of the teratogenic action of thalidomide,” Life Sciences, vol. 58, no. 4, pp. 295–316, 1995. View at Publisher · View at Google Scholar · View at Scopus
  127. A. Vacca, C. Scavelli, V. Montefusco et al., “Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma,” Journal of Clinical Oncology, vol. 23, no. 23, pp. 5334–5346, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. T. D. Stephens, “Proposed mechanisms of action in thalidomide embryopathy,” Teratology, vol. 38, no. 3, pp. 229–239, 1988. View at Google Scholar · View at Scopus
  129. T. D. Stephens and B. J. Fillmore, “Hypothesis: thalidomide embryopathy-proposed mechanism of action,” Teratology, vol. 61, pp. 189–195, 2000. View at Google Scholar
  130. J. McCredie, “History, heresy and radiology in scientific discovery,” Journal of Medical Imaging and Radiation Oncology, vol. 53, no. 5, pp. 433–441, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. J. McCredie and W. G. McBride, “Some congenital abnormalities: possibly due to embryonic peripheral neuropathy,” Clinical Radiology, vol. 24, no. 2, pp. 204–211, 1973. View at Google Scholar · View at Scopus
  132. F. Edom-Vovard, B. Schuler, M.-A. Bonnin, M.-A. Teillet, and D. Duprez, “Fgf4 positively regulates scleraxis and tenascin expression in chick limb tendons,” Developmental Biology, vol. 247, no. 2, pp. 351–366, 2002. View at Publisher · View at Google Scholar · View at Scopus
  133. T. Fukuda, S. Takeda, R. Xu et al., “Sema3A regulates bone-mass accrual through sensory innervations,” Nature, vol. 497, pp. 490–493, 2013. View at Google Scholar
  134. S. Harsum, J. D. W. Clarke, and P. Martin, “A reciprocal relationship between cutaneous nerves and repairing skin wounds in the developing chick embryo,” Developmental Biology, vol. 238, no. 1, pp. 27–39, 2001. View at Publisher · View at Google Scholar · View at Scopus
  135. T. R. Strecker and T. D. Stephens, “Peripheral nerves do not play a trophic role in limb skeletal morphogenesis,” Teratology, vol. 27, no. 2, pp. 159–167, 1983. View at Google Scholar · View at Scopus
  136. G. J. Swanson, “Paths taken by sensory nerve fibres in aneural chick wing buds,” Journal of Embryology and Experimental Morphology, vol. 86, pp. 109–124, 1985. View at Google Scholar · View at Scopus
  137. P. Martin and J. Lewis, “Origins of the neurovascular bundle: interactions between developing nerves and blood vessels in embryonic chick skin,” International Journal of Developmental Biology, vol. 33, no. 3, pp. 379–387, 1989. View at Google Scholar · View at Scopus
  138. T. Parman, M. J. Wiley, and P. G. Wells, “Free radical-mediated oxidative dna damage in the mechanism of thalidomide teratogenicity,” Nature Medicine, vol. 5, no. 5, pp. 582–585, 1999. View at Publisher · View at Google Scholar · View at Scopus
  139. P. G. Wells, G. P. Mccallum, C. S. Chen et al., “Oxidative stress in developmental origins of disease: teratogenesis, neurodevelopmental deficits, and cancer,” Toxicological Sciences, vol. 108, no. 1, pp. 4–18, 2009. View at Publisher · View at Google Scholar · View at Scopus
  140. P. G. Wells, Y. Bhuller, C. S. Chen et al., “Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species,” Toxicology and Applied Pharmacology, vol. 207, no. 2, pp. S354–S366, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. J. L. Galloway, I. Delgado, M. A. Ros, and C. J. Tabin, “A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning,” Nature, vol. 460, no. 7253, pp. 400–404, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. L. Wolpert, C. Tickle, and M. Sampford, “The effect of cell killing by X-irradiation on pattern formation in the chick limb,” Journal of Embryology and Experimental Morphology, vol. 50, pp. 175–198, 1979. View at Google Scholar · View at Scopus
  143. A. Barasa, “On the regulative capacity of the chick embryo limb bud,” Experientia, vol. 20, no. 8, p. 443, 1964. View at Publisher · View at Google Scholar · View at Scopus
  144. A. Hornbruch, Abnormalities Along the Proximo-Distal Axis of the Chick Wing Bud:the Effect of Surgical Intervention, Walter de Gruyter, Berlin, Germany, 1980.
  145. C. Mahony, “Vargesson N. Molecular analysis of regulative events in the developing chick limb,” Journal of Anatomy, vol. 223, pp. 1–13, 2013. View at Google Scholar
  146. F. V. Mariani, C. P. Ahn, and G. R. Martin, “Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning,” Nature, vol. 453, no. 7193, pp. 401–405, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. D. E. Hague, J. R. Idle, S. C. Mitchell, and R. L. Smith, “Racemates revisited: heterochiral assemblies and the example of DL-thalidomide,” Xenobiotica, vol. 41, no. 10, pp. 837–843, 2011. View at Publisher · View at Google Scholar · View at Scopus
  148. N. A. Jönsson, “Chemical structure and teratogenic properties. IV. An outline of a chemical hypothesis for the teratogenic action of thalidomide,” Acta Pharmaceutica Suecica, vol. 9, no. 6, pp. 543–562, 1972. View at Google Scholar · View at Scopus
  149. J. Ashby, H. Tinwell, R. D. Callander et al., “Thalidomide: lack of mutagenic activity across phyla and genetic endpoints,” Mutation Research, vol. 396, no. 1-2, pp. 45–64, 1997. View at Publisher · View at Google Scholar · View at Scopus
  150. K. Strömland, E. Philipson, and M. A. Grönlund, “Offspring of male and female parents with thalidomide embryopathy: birth defects and functional anomalies,” Teratology, vol. 66, no. 3, pp. 115–121, 2002. View at Publisher · View at Google Scholar · View at Scopus
  151. W. G. McBride and A. P. Read, “Thalidomide may be a mutagen,” British Medical Journal, vol. 308, no. 6944, pp. 1635–1636, 1994. View at Google Scholar · View at Scopus
  152. A. Broyl, R. Kuiper, M. van Duin et al., “High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance,” Blood, vol. 121, pp. 624–627, 2012. View at Google Scholar
  153. A. Lopez-Girona, D. Mendy, T. Ito et al., “Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide,” Leukemia, vol. 26, pp. 2326–2335, 2012. View at Google Scholar
  154. Y. X. Zhu, E. Braggio, C.-X. Shi et al., “Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide,” Blood, vol. 118, no. 18, pp. 4771–4779, 2011. View at Publisher · View at Google Scholar · View at Scopus
  155. K. M. Lee, S. J. Yang, Y. D. Kim et al., “Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high-fat diet-Induced obesity and insulin resistance in mice,” Diabetes, vol. 62, pp. 1855–1864, 2013. View at Google Scholar
  156. T. Ito, H. Ando, and H. Handa, “Teratogenic effects of thalidomide: molecular mechanisms,” Cellular and Molecular Life Sciences, vol. 68, no. 9, pp. 1569–1579, 2011. View at Publisher · View at Google Scholar · View at Scopus
  157. K. Dredge, R. Horsfall, S. P. Robinson et al., “Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro,” Microvascular Research, vol. 69, no. 1-2, pp. 56–63, 2005. View at Publisher · View at Google Scholar · View at Scopus
  158. L. Lu, F. Payvandi, L. Wu et al., “The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions,” Microvascular Research, vol. 77, no. 2, pp. 78–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  159. M. Ema, R. Ise, H. Kato et al., “Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide,” Reproductive Toxicology, vol. 29, no. 1, pp. 49–56, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. F. S. Vianna, L. Fraga, L. Tovo-Rodrigues et al., “Polymorphisms in the nitric oxide synthase gene in thalidomide embryopathy,” Nitric Oxide, vol. 30, pp. 89–92, 2013. View at Publisher · View at Google Scholar
  161. K. Meganathan, S. Jagtap, V. Wagh et al., “Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells,” PLoS One, vol. 7, no. 8, Article ID e44228, 2012. View at Google Scholar
  162. M. Brooun, A. Manoukian, H. Shimizu, H. R. Bode, and H. McNeill, “Organizer formation in Hydra is disrupted by thalidomide treatment,” Developmental Biology, vol. 378, pp. 51–63, 2013. View at Google Scholar
  163. B. E. Hagstrom and S. Lonning, “The teratogenic action of thalidomide on marine fish larvae,” Experientia, vol. 33, no. 9, pp. 1227–1228, 1977. View at Google Scholar · View at Scopus
  164. M. Marin-Padilla, “Thalidomide injury to an implanted armadillo blastocyst,” The Anatomical Record, vol. 149, pp. 359–361, 1964. View at Google Scholar
  165. H.-J. Merker, W. Heger, K. Sames, H. Sturje, and D. Neubert, “Embryotoxic effects of thalidomide-derivatives in the non-human primate callithrix jacchus. I. Effects of 3-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-dioxopiperidine (EM 12) on skeletal development,” Archives of Toxicology, vol. 61, no. 3, pp. 165–179, 1988. View at Google Scholar · View at Scopus
  166. C. J. J. Lee, L. L. Goncxalves, and P. G. Wells, “Resistance of CD-1 and ogg1 DNA repair-deficient mice to thalidomide and hydrolysis product embryopathies in embryo culture,” Toxicological Sciences, vol. 122, no. 1, pp. 146–156, 2011. View at Publisher · View at Google Scholar · View at Scopus
  167. J. A. Dipaolo, H. Gatzek, and J. Pickren, “Malformations induced in the mouse by thalidomide,” The Anatomical Record, vol. 149, pp. 149–155, 1964. View at Google Scholar
  168. S. Fabro and R. L. Smith, “The teratogenic activity of thalidomide in the rabbit,” The Journal of Pathology and Bacteriology, vol. 91, no. 2, pp. 511–519, 1966. View at Google Scholar · View at Scopus
  169. S. Fabro, R. L. Smith, and R. T. Williams, “Toxicity and teratogenicity of optical isomers of thalidomide,” Nature, vol. 215, no. 98, p. 296, 1967. View at Google Scholar · View at Scopus
  170. I. D. Fratta, E. B. Sigg, and K. Maiorana, “Teratogenic effects of thalidomide in rabbits, rats, hamsters, and mice,” Toxicology and Applied Pharmacology, vol. 7, no. 2, pp. 268–286, 1965. View at Google Scholar · View at Scopus
  171. L. M. Newman, E. M. Johnson, and R. E. Staples, “Assessment of the effectiveness of animal developmental toxicity testing for human safety,” Reproductive Toxicology, vol. 7, no. 4, pp. 359–390, 1993. View at Google Scholar · View at Scopus
  172. M. Parkhie and M. Webb, “Embryotoxicity and teratogenicity of thalidomide in rats,” Teratology, vol. 27, no. 3, pp. 327–332, 1983. View at Google Scholar · View at Scopus
  173. K. T. Szabo and R. L. Steelman, “Effects of thalidomide treatment of inbred female mice on pregnancy, fetal development, and mortality of offspring,” American Journal of Veterinary Research, vol. 28, no. 127, pp. 1829–1835, 1967. View at Google Scholar · View at Scopus
  174. K. T. Szabo and R. L. Steelman, “Effects of maternal thalidomide treatment on pregnancy, fetal development, and mortality of the offspring in random-bred mice,” American Journal of Veterinary Research, vol. 28, no. 127, pp. 1823–1828, 1967. View at Google Scholar · View at Scopus
  175. C. J. J. Lee, L. L. Gonçalves, and P. G. Wells, “Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)-dependent, reactive oxygen species (ROS)-mediated mechanism,” The FASEB Journal, vol. 25, no. 7, pp. 2468–2483, 2011. View at Publisher · View at Google Scholar · View at Scopus
  176. K. T. Al-Jamal, W. T. Al-Jamal, S. Akerman et al., “Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 9, pp. 3966–3971, 2010. View at Publisher · View at Google Scholar · View at Scopus
  177. A. Jurand, “Early changes in limb buds of chick embryos after thalidomide treatment,” Journal of Embryology and Experimental Morphology, vol. 16, no. 2, pp. 289–300, 1966. View at Google Scholar · View at Scopus
  178. M. S. Christian, O. L. Laskin, V. Sharper, A. Hoberman, D. I. Stirling, and L. Latriano, “Evaluation of the developmental toxicity of lenalidomide in rabbits,” Birth Defects Research B, vol. 80, no. 3, pp. 188–207, 2007. View at Publisher · View at Google Scholar · View at Scopus
  179. F. Chung, J. Lu, B. D. Palmer et al., “Thalidomide pharmacokinetics and metabolite formation in mice, rabbits, and multiple myeloma patients,” Clinical Cancer Research, vol. 10, no. 17, pp. 5949–5956, 2004. View at Publisher · View at Google Scholar · View at Scopus
  180. J. Lu, N. Helsby, B. D. Palmer et al., “Metabolism of thalidomide in liver microsomes of mice, rabbits, and humans,” Journal of Pharmacology and Experimental Therapeutics, vol. 310, no. 2, pp. 571–577, 2004. View at Publisher · View at Google Scholar · View at Scopus
  181. D. Veselá, D. Veselý, and R. Jelínek, “Embryotoxicity in chick embryo of thalidomide hydrolysis products following metabolic activation by rat liver homogenate,” Functional and Developmental Morphology, vol. 4, no. 4, pp. 313–316, 1994. View at Google Scholar · View at Scopus
  182. J. Knobloch, K. Reimann, L.-O. Klotz, and U. Rüther, “Thalidomide resistance is based on the capacity of the glutathione- dependent antioxidant defense,” Molecular Pharmaceutics, vol. 5, no. 6, pp. 1138–1144, 2008. View at Publisher · View at Google Scholar · View at Scopus
  183. R. J. D'Amato, S. Lentzsch, K. C. Anderson, and M. S. Rogers, “Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma,” Seminars in Oncology, vol. 28, no. 6, pp. 597–601, 2001. View at Google Scholar · View at Scopus
  184. S. Lentzsch, M. S. Rogers, R. LeBlanc et al., “S-3-amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice,” Cancer Research, vol. 62, no. 8, pp. 2300–2305, 2002. View at Google Scholar · View at Scopus