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Retinoids and Interferons as Antiangiogenic Cancer Drugs

  • Chapter
Antiangiogenic Agents in Cancer Therapy

Abstract

Retinoids are a class of chemical compounds that include active metabolites of vitamin A (retinol) as well as a diverse array of synthetic derivatives. Vitamin A is required for normal embryonic development, epithelial homeostasis, maintainance of reproductive capacity, and functioning of the visual cycle (1). Additionally, retinoids have been shown to modulate a wide variety of cellular processes, including proliferation, differentiation, homeostasis, and malignant transformation (for reviews see refs. 2–5). Retinoids also act pharmacologically to restore regulation of differentiation and growth in certain premalignant and malignant cells in vitro and in vivo (6, 7). Consequently, retinoids are under study as therapeutic and chemopreventive agents for a variety of cancers (see refs. 8–10 for reviews). Retinoids are also potent drugs for the treatment of severe cystic acne, psoriasis, and several other dermatologic disorders (11).

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References

  1. Blomhoff, R., Green, M. H., Berg, T., and Norum, K. R. (1990) Transport and storage of vitamin A. Science 250, 399–404.

    CAS  Google Scholar 

  2. Chon, P. (1994) The retinoid signaling pathway: molecular and genetic analyses. Semin. Cell Biol. 5, 115–125.

    Google Scholar 

  3. Chon, P. (1996) A decade of molecular biology of retinoic acid receptors.FASEB J.10, 940–954.

    Google Scholar 

  4. Gudas, L. J., Sporn, M. B., and Roberts, A. B. (1994) Cellular biology and biochemistry of the retinoids, in the Retinoids: Biology, Chemistry, and Medicine (Sporn, M. B. and Roberts, A. B.), Raven, New York, pp. 443–520.

    Google Scholar 

  5. Kastner, P., Mark, M., and Chon, P. (1995) Nonsteroid nuclear receptors: What are genetic studies telling us about their role in real life? Cell 83, 859–869.

    CAS  Google Scholar 

  6. Lotan, R. and Clifford, J. L. (1991) Nuclear receptors for retinoids: mediators of retinoid effects on normal and malignant cells. Biomed. Pharmacother. 45, 145–156.

    Article  CAS  Google Scholar 

  7. Hong, W. K. and Itri, L. M. (1994) Retinoids and human cancer, in The Retinoids: Biology, Chemistry, and Medicine (Sporn, M. B. and Roberts, A. B., eds.), Raven, New York, pp. 597–630.

    Google Scholar 

  8. Lotan, R. (1996) Retinoids in cancer chemoprevention.FASEB J.10, 1031–1039.

    CAS  Google Scholar 

  9. Lippman, S. M., Heyman, R. A., Kurie, J. M., Benner, S. E., and Hong, W. K. (1995) Retinoids and chemoprevention: clinical and basic studies. J. Cell. Biochem. 22(Suppl.), 1–10.

    CAS  Google Scholar 

  10. Smith, M. A., Parkinson, D. R., Cheson, B. D., and Friedman, M. A. (1992) Retinoids in cancer therapy. J. Clin. Oncol. 10, 839–864.

    CAS  Google Scholar 

  11. Orfanos, C. E., Xouboulis, C. C., Almond-Roesler, B., and Geilen, C. C. (1997) Current use and future potential role of retinoids in dermatology. Drugs 53, 358–388.

    Google Scholar 

  12. Newcomer, M. E. (1995) Retinoid-binding proteins: structural determinants important for function.FASEB J.9, 229–239.

    CAS  Google Scholar 

  13. Ross, C. A. (1993) Cellular metabolism and activation of retinoids: roles of cellular retinoid-binding proteins.FASEB J.7, 317–327.

    CAS  Google Scholar 

  14. Dolle, P., Ruberte, E., Kastner, P., Petkovitch, M., Stoner, C. M., Gudas, L. J., and Chon, P. (1989) Differential expression of genes encoding a, ββ and y retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature342, 702–705.

    CAS  Google Scholar 

  15. Dolle, P., Ruberte, E., Leroy, P., Morris-Kay, G., and Chon, P. (1990) Retinoic acid receptors and cellular retinoid binding proteins I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 110, 1133–1151.

    PubMed  CAS  Google Scholar 

  16. Ruberte, E., Dolle, P., Chon, P., and Morriss-Kay, G. (1991) Retinoic acid receptors and cellular retinoid binding proteins II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 111 45–60.

    Google Scholar 

  17. Ruberte, E., Friederich, V., Chon, P., and Morriss-Kay, G. (1993) Retinoic acid receptors and cellular retinoid binding proteins III. Their differential transcript distribution during mouse nervous system development. Development118, 267–282.

    CAS  Google Scholar 

  18. Lampron, C., Rochette-Egly, C., Gorry, P., Dolle, P., Mark, M., Lufkin, T., LeMeur, M., and Chon, P. (1995) Mice deficient in cellular retinoic acid binding protein II (CRABPII) or in both CRABPI and CRABPII are essentially normal. Development 121, 539–548.

    Google Scholar 

  19. Fiorella, P. D. and Napoli, J. L. (1991) Expression of cellular retinoic binding protein (CRABP) in Escherichia coli. J. Biol. Chem. 266, 16,572–16,579.

    Google Scholar 

  20. Boylan, J. F. and Gudas, L. J., (1993) The level of CRABP-I expression influences the amounts and types of all-trans-retinoic acid metabolites in F9 teratocarcinoma stem cells. J. Biol. Chem. 267, 21,486–21,491.

    Google Scholar 

  21. Petkovich, M., Brand, N. J., Krust, A., and Chon, P. (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330, 444–450.

    CAS  Google Scholar 

  22. Giguere, V., Ong, E. S., Segui, P., and Evans, R. M. (1987) Identification of a receptor for the morphogen retinoic acid. Nature 330, 624–629

    CAS  Google Scholar 

  23. Leid, M., Kastner, P., and Chon, P. (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem. Sci. 17, 427–433.

    CAS  Google Scholar 

  24. Mangelsdorf, D. J. and Evans, R. M. (1995) The RXR heterodimers and orphan receptors. Cell 83, 841–850.

    Article  PubMed  CAS  Google Scholar 

  25. Gronemeyer, H. and Laudet, V. (1996) Transcription Factors 3, Nuclear Receptors. Protein Profile vol. 2, Academic Press, New York.

    Google Scholar 

  26. Roy, B., Taneja, R., and Chon, P. (1995) Synergistic activation ofexpression ofretinoic acid (RA)responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor a (RARα)-, RARβ-, or RARγ-selective ligand in combination with a retinoid X receptor-specific ligand. Mol. Cell. Biol. 15, 6481–6487.

    CAS  Google Scholar 

  27. Lotan, R., Dawson, M. I., Zou, C.-C., Jong, L., Lotan, D., and Zou, C.-P. (1995) Enhanced efficacy of combinations of retinoic acid- and retinoid X receptor-selective retinoids and a-interferon inhibition of cervical carcinoma cell proliferation.Cancer Res.55, 232–236.

    CAS  Google Scholar 

  28. Clifford, J. L. and Lippman, S. M. (1997) Mechanism of action of the nuclear retinoid receptors. J. Oncol. Index Rev. 1, 3–5.

    Google Scholar 

  29. Kastner, P., Mark, M., Ghyselinck, N., Krezel, W., Dupe, V., Grondona, J. M., and Chon, P. (1997) Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse development. Development 124, 313–326.

    CAS  Google Scholar 

  30. Nagpal, S., Saunders, M., Kastner, P., Durand, B., Nakshatri, H., and Chon, P. (1992) Promotor context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors. Cell 70, 1007–1019.

    CAS  Google Scholar 

  31. Nagpal, S., Friant, S., and Chon, P. (1993) RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization In vivo. EMBO J. 12, 2349— 2360.

    Google Scholar 

  32. Rochette-Egly, C., Adam, S., Rossignol, M., Egly, J.-M., and Chon, P. (1997) Stimulation of RARα activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell 90, 97–107.

    CAS  Google Scholar 

  33. Durand, B., Saunders, M., Gaudon, C., Roy, B., Losson, R., and Chon, P. (1994) Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activation domain and influence of the nature of the response element on AF-2 activity.EMBO J. 13, 5370–5382.

    CAS  Google Scholar 

  34. Bourget, W., Ruff, M., Chon, P., Gronemeyer, H., and Moras, D. (1995) Crystal structure of the ligand-binding domain of the human nuclear receptor RXRa. Nature 375, 377–382.

    Google Scholar 

  35. Renaud, J.-P., Rochel, N., Ruff, M., Vivat, V., Chon, P., Gronemeyer, H., and Moras, D. (1995) Crystal structure of the RAR-y ligand-binding domain bound to all-trans retinoic acid. Nature 378, 681–689.

    Google Scholar 

  36. Cavailles, V., Dauvois, S., L’Horset, F., Lopez, G., Hoare, S., Kushner, P. J., and Parker, M. (1995) Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J 14, 3741–3751.

    CAS  Google Scholar 

  37. Le Douarin, B., Zechel, C., Garnier, J-M., Lutz, Y., Tora, L., Pierrat, B., Heery, D., Gronemeyer, H., Chon, P., and Losson, R. (1995) The N-terminal part of TIF1, a putative mediator of the liganddependant activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBOJ.14, 2020–2033.

    Google Scholar 

  38. Le Douarin, B., Nielson, A. L., Garnier, J.-M., Ichinose, H., Jeanmougin, F., Losson, R., and Chon, P. (1996) A possible involvement of TIF la and TIF lb in the epigenetic control of transcription by nuclear receptors.EMBO J. 15, 6701–6715.

    Google Scholar 

  39. Onate, S., Tsai, S., Tsai, M.-J., and O’Malley, B. (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270, 1354–1357.

    CAS  Google Scholar 

  40. Voegel, J. J., Heine, M. J.S., Zechel, C., Chon, P., and Gronemeyer, H. (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J.15, 3667–3675.

    CAS  Google Scholar 

  41. vom Baur, E., Zechel, C., Heery, D., Heine, M. J.S., Garnier, J. M., Vivat, V., Le Douarin, B., Gronemeyer, H., Chon, P., and Losson, R. (1996) Differential ligand-dependent interactions between the AF-2 activation domain of nuclear receptors and the putative transcriptional intermediary factors mSUG 1 and TIF I.EMBO J.15, 110–124.

    Google Scholar 

  42. Kurokawa, R., Soderstrom, M., Horlein, A., Halachmi, S., Brown, M., Rosenfeld, M. G., and Glass, C. K. (1995) Polarity-specific activities ofretinoic acid receptors determined by a co-repressor. Nature 377, 451–454.

    CAS  Google Scholar 

  43. Horlein, A. J., Naar, A. M., Heinzel, T., Torchia, J., Gloss, B., Kurokawa, R., Ryan, A., Kamei, Y., Soderstrom, M., Glass, C. K., and Rosenfeld, M. G. (1995) Ligand-independent repression by the thryoid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377, 397–403.

    CAS  Google Scholar 

  44. Chen, J. D. and Evans, R. M. (1995) A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 377, 454–457.

    CAS  Google Scholar 

  45. Giguère, V. (1994) Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling.Endocr. Rev.15, 61–79.

    PubMed  Google Scholar 

  46. Glass, C. K. (1994) Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr. Rev. 15, 391–407.

    CAS  Google Scholar 

  47. Leblanc, B. P. and Stunnenberg, H. G. (1995) 9-cis retinoic acid signaling: changing partners causes some excitement.Genes Dev.9, 1811–1816.

    Google Scholar 

  48. Schulman, I. G., Juguilon, H., and Evans, R. M. (1996) Activation and repression by nuclear hormone receptors: hormone modulates an equilibrium between active and repressive states. Mol. Cell Biol. 16, 3807–3813.

    CAS  Google Scholar 

  49. Mukherjee, R., Davies, P. J.A., Crombie, D. L., Bischoff, E. D., Cesario, R. M., Jow, L., Hamann, L. G., Boehm, M. F., Mondon, C. E., Nadzan, A. M., Paterniti, J. R., and Heyman, R. A. (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 386, 407–410.

    CAS  Google Scholar 

  50. Kalvakolanu, D. V. and Borden, E. C. (1996) An overview of the interferon system: signal transduction and mechanisms of action. Cancer Inv.14, 25–53.

    CAS  Google Scholar 

  51. Diaz, M. O., Bohlander, S., and Allen, G. (1993) Nomenclature of human interferon genes. J. Interferon Res. 13, 234–243.

    Google Scholar 

  52. Ihle, J. N., Witthuhn, B. A., Quelle, F. W., Yamamoto, K., and Silvennoinen, O. (1995) Signaling through the hematopoietic cytokine receptors. Ann. Rev. Immunol. 13, 369–398.

    Article  CAS  Google Scholar 

  53. Heldin, C. H. (1995) Dimerization of cell surface receptors in signal transduction. Cell 80, 213–233.

    CAS  Google Scholar 

  54. Darnell, J. E., Jr. (1997) STATs and gene regulation. Science 277, 1630–1635.

    CAS  Google Scholar 

  55. Muller, M., Briscoe, J., Laxton, C., Guschin, D., Ziemiecki, A., Silvennoinen, O., Harpur, A. G., Barbieri, G., Witthuhn, B. A., Schindler, C., Pellegrini, S., Wilks, A. F., Ihle, J. N., Stark, G. R., and Kerr, I. M. (1993) The protein tyrosine kinase JAK1 complements defects in interferon-a/β and signal transduction. Nature 366, 129–135.

    CAS  Google Scholar 

  56. Silvennoinen, O., Ihle, J. N., Schlessinger, J., and Levy, D. E. (1993) Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature 366, 583–585.

    CAS  Google Scholar 

  57. Velasquez, L., Fellous, M., Stark, G. R., and Pellegrini, S. (1992) A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell 70, 313–322.

    Google Scholar 

  58. Leung, S., Qureshi, S. A., Kerr, I. M., Darnell, J. E., and Stark, G. R. (1995) Role of STAT2 in the alpha interferon signaling pathway. Mol. Cell. Biol. 15, 1312–1317.

    CAS  Google Scholar 

  59. Schindler, C., Fu, X.-Y., Improta, T., Aebersold, R., and Darnell, J. E., Jr. (1992) Proteins of transcription factor ISGF-3: One gene encodes the 91— and 84—kDa ISGF-3 proteins that are activated by interferon a. Proc. Natl. Acad. Sci. USA 89, 7836–7839.

    Article  CAS  Google Scholar 

  60. Qureshi, S. A., Salditt-Georgieff, M., and Darnell, J. E., Jr. (1995) Tyrosine-phosphorylated Statl and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3. Proc.Natl.Acad.Sci. USA 92, 3829–3833.

    Article  PubMed  CAS  Google Scholar 

  61. Haque, J. S. and William, R. G. (1998) Signal transduction in the interferon system. Sem. Oncology 25(Suppl. 1), 14–22.

    CAS  Google Scholar 

  62. Lotan, R., Dawson, M. I., Zou, C.-C., Jong, L., Lotan, D., and Zou, C.-P. (1995) Enhanced efficacy of combinations ofretinoic acid- and retinoid X receptor-selective retinoids and a-interferon in inhibition of cervical carcinoma cell proliferation Cancer Res.55, 232–236.

    CAS  Google Scholar 

  63. Kolla, V., Lindner, D. J., Weihua, X., Borden, E. C., and Kalvakolanu, D. V. (1996) Modulation of interferon (IFN)-inducible gene expression by retinoic acid. J. Biol. Chem. 271, 10,508–10,514.

    Google Scholar 

  64. Lindner, D. J., Borden, E. C., and Kalvakolanu, D. V. (1997) Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo. Clin. Cancer Res.3, 931–937.

    PubMed  CAS  Google Scholar 

  65. Lippman, S., Glisson, B. S., Kavanagh, J. J., Lotan, R., Hong, W. K., Paredes-Espinoza, M., Hittelman, W. N., Holdener, E. E., and Krakoff, I. H. (1993) Retinoic acid and interferon combination studies in human cancer. Eur. J. Cancer. 29A(Suppl. 5), s9—s13.

    Google Scholar 

  66. Lippman, S. M., Lotan, R., and Schleunicer, U. (1997) Retinoid-interferon therapy of solid tumors. Int. J. Cancer. 70, 481–483.

    CAS  Google Scholar 

  67. Gianni, M., Terao, M., Fortino, I., LiCalzi, M., Viggiano, V., Barbui, T., Raldi, A., and Garattini, E. (1997) Stat 1 is induced and activated by all-trans retinoic acid in acute promyelocytic leukemia cells. Blood 89, 1001–1012.

    CAS  Google Scholar 

  68. Cippitelli, M., Ye, J., Viggiano, V., Sica, A., Ghosh, P., Gulino, A., Santoni, A. ,and Young, H. A. (1996) Retinoic acid-induced transcriptional modulation of the human interferon-y promoter. J. Biol. Chem. 271, 26,783–26,793.

    Google Scholar 

  69. Harada, H., Willison, K., Sakakibara, J., Miyamoto, M., Fujita, T., and Taniguchi, T. (1990) Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell 63, 303–312.

    CAS  Google Scholar 

  70. Matikainen, S., Ronni, T., Lehtonen, A., Sareneva, T., Melen., K., Nordling, S., Levy, D. E., and Julkunen, I. (1997) Retinoic acid induces signal transducer and activator of transcription (STAT) 1,STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons.Cell Growth Differ.8, 687–698.

    CAS  Google Scholar 

  71. Weihua, X., Kolla, V., and Kalvakolanu, D. V. (1997) Modulation of interferon action by retinoids. J. Biol. Chem. 272, 9742–9748.

    Article  CAS  Google Scholar 

  72. Pelicano, L., Li, F., Schindler, C., and Chelbi-Alix, M. K. (1997) Retinoic acid enhances the expression of interferon-induced proteins: evidence for multiple mechanisms of action. Oncogene 6, 2349–2359.

    Google Scholar 

  73. Giandomenico, V., Lancillotti, F., Fiorucci, G., Percario, Z. A., Ribavene, R., Malorni, W., Affabris, E., and Romeo, G. (1997) Retinoic acid and IFN inhibition of cell proliferation is associated with apoptosis in squamous carcinoma cell lines: role of IRF-1 and TGase II-dependent pathways.Cell Growth Diff.8, 91–100.

    CAS  Google Scholar 

  74. Yu, M. Tong, J. H., Mao, M., Kan, L. X. Liu, M. M., Sun, Y. W., Fu, G., Jing, Y. K., Yu, L., Lepaslier, D., Lanotte, M., Wang, Z. Y., Chen, Z., Waxman, S., Tan, J. Z., and Chen, S. J. (1997) Cloning of a gene (RIG-G) associated with retinoic acid-induced differentiation of acute promyelocytic leukemia cells and representing a new member of a family of interferon-stimulated genes. Proc. Natl. Acad. Sci. USA 94, 7406–7411.

    Article  CAS  Google Scholar 

  75. Widschwendter, M., Daxenbichler, G., Dapunt, O., and Marth, C. (1995) Effects of retinoic acid and y-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells. Cancer Res.55, 2135–2139.

    CAS  Google Scholar 

  76. Gianni, M., Zanotta, S., Terao, M., Raldi, A., and Garattini, E. (1996) Interferons induce normal and aberrant retinoic-acid receptors type a in acute promyelocytic leukemia cells: potentiation of the induction of retinoid-dependent differentiation markers. Int. J. Cancer 68, 75–83.

    CAS  Google Scholar 

  77. Liu, M., Lee, M.-H., Cohen, M., Bommakanti, M., and Freedman, L. P. (1996) Transcriptional activation ofthe Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937.Genes Dev.10,142–153.

    CAS  Google Scholar 

  78. Chin, Y. E., Kitagawa, M., Su, W.-C. S., You, Z.-H., Iwamoto, Y., and Fu, X.-Y. (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAFI/CIPI mediated by STAT1. Science 272, 719–722.

    CAS  Google Scholar 

  79. Liu, M., Iavarone, A., and Freedman, L. P. (1996) Transcriptional activation of the human p21 WAF I/CIP I gene by retinoic acid receptor. J. Biol. Chem. 271, 31,723–31,728.

    Google Scholar 

  80. Sherr, C. J. and Roberts, J. M. (1995) Inhibitors of mammalian G 1 cyclin-dependent kinases.Genes Dev.9, 1149–1163.

    CAS  Google Scholar 

  81. Missero, C., Calautti, E., Eckner, R., Chin, J., Tsai, L. H., Livingston, D. M., and Dotto, G. P. (1995) Involvement of the cell-cycle inhibitor Cipl/WAFI and the E1A-associated p300 protein in terminal differentiation. Proc. Natl. Acad. Sci. USA 92, 5451–5455.

    Article  CAS  Google Scholar 

  82. Lippman, S. M., Benner, S. E., Hong, W. K., et al. (1994) Cancer chemoprevention. J. Clin. Oncol. 12, 851–873.

    PubMed  CAS  Google Scholar 

  83. Lippman, S. M., Batsakis, J. G., Toth, B. B., et al. (1993) Comparison of low-dose isotretinoin with beta-carotene to prevent oral carcinogenesis. N. Engl. J. Med. 328, 15–20.

    Article  CAS  Google Scholar 

  84. Hong, W. K., Lippman, S. M., Itri, L. M., et al. (1990) Prevention of second primary tumor with isotretinoin in squamous cell carcinoma of the head and neck. N. Engl. J. Med. 323, 795–801.

    Article  CAS  Google Scholar 

  85. Kraemer, K. H., DiGiovanni, J. J., Moshell, A. N., et al. (1988) Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N. Engl. J. Med. 318, 1633–1637.

    Article  CAS  Google Scholar 

  86. Lotan, R., Xu, C., Lippman, S. M., et al. (1995) Suppression of retinoic acid receptor ββ in oral premalignant lesions and its upregulation by isotretinoin. N. Engl. J. Med. 332, 1405–1410.

    Article  CAS  Google Scholar 

  87. Mayne, S. T., Lippman, S. M. (1997) Retinoids and carotenoids, in Cancer: Principles and Practice ofOncology, 5th ed. (DeVita, V. T., Hellman, S., Rosenberg, S. A., eds.), Lippincott-Raven, New York, pp. 585–599.

    Google Scholar 

  88. Bavinck, J. N., Tieben, L. M., van der Woude, F. J., et al. (1995) Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant patients: a double-bind, placebocontrolled study. J. Clin. Oncol. 13, 1933–1938.

    CAS  Google Scholar 

  89. Muto, Y., Moriwaki, H., Ninomiya, M., et al. (1996) Prevention of second primary tumors by an acyclic retinoid, polypretnoic acid, in patients with hepatocellular carcinoma. N. Engl. J. Med. 334,1561–1567.

    Article  CAS  Google Scholar 

  90. Meyskens, F. L. Jr., Surwit, E., Moon, T. E., et al. (1994) Enhancement of regression of cervical intraepithelial neoplasis II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J. Natl. Cancer Inst. 86, 539–543.

    Article  Google Scholar 

  91. Warrell, R. P., Jr, Frankel, S. R., Miller, W. H., Jr., et al. (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N. Engl. J. Med. 324, 1385–1393.

    Article  PubMed  Google Scholar 

  92. Warrell, R. P., de The, H., Wang, Z. Y., et al. (1993) Acute promyelocytic leukemia. N. Engl. J. Med. 329, 177–189.

    Article  CAS  Google Scholar 

  93. Tallman, M. S., Anderson, J. W., Schiffer, C. A., et al. (1997) All-trans-retinoic acid in acute promyelocytic leukemia. N. Engl. J. Med. 337, 1021–1028.

    Article  CAS  Google Scholar 

  94. Castleberry, R. P., Emanuel, P. D., Zuckaman, K. S., et al. (1994) A pilot study of isotretinoin in the treatment of juvenile chronic myelogenous leukemia. N. Engl. J. Med. 331, 1680–1684.

    Article  CAS  Google Scholar 

  95. Cheng, A., Su, I., Chen, C., et al. (1994) Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study. J. Clin. Oncol. 12, 1185–1192.

    CAS  Google Scholar 

  96. Shalinksy, D. R., Bischoff, E. D., Gregory, M. L., et al. (1996) Enhanced antitumor efficacy ofcisplatin in combination with ALRT 1057 (retinoic acid) in human oral squamous carcinoma xenografts in nude mice. Clin. Cancer Res., 2, 511–520.

    Google Scholar 

  97. Aebi, S., Kroning, R., Cenni, B., et al. (1997) All-trans retinoic acid enhances cisplatin-induced apoptosis in human ovarian adenocarcinoma and in squamous head and neck cancercells. Clin. Cancer Res. 3,2033–2038.

    CAS  Google Scholar 

  98. Rutz, H. P., and Little, J. B. (1989) Modification of radiosensitivity and recovery from x-ray damage in vitro by retinoic acid. J. Radiat. Oncol. Biol. Phys. 16, 1285–1288.

    Article  CAS  Google Scholar 

  99. Schiller, U., Hoffmann, W., Mayer, C., et al. (1994) All-trans-retinoic acid modulates the radiosensitivity and differentiation of normal and tumor cells in vitro. Ann. Oncol. 5, 1–3.

    Google Scholar 

  100. Angioli, R., Sevin, B., Perras, J. P., et al. (1993) In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines. Cancer 71, 3717–3725.

    CAS  Google Scholar 

  101. Benbrook, D. M., Shen-Gunther, J., Nunez, E. R., et al. (1997) Differential retinoic acid radiosensitization of cervical carcinoma cell lines. Clin. Cancer Res. 3, 939–945.

    CAS  Google Scholar 

  102. Hoffmann, W., Berg, M., and Rodemann, H. P. (1994) Antiproliferative effects of ionizing radiation, all-trans-retinoic acid and interferon-a on cultured human squamous cell carcinomas. Radiat. Oncol. Invest. 2, 12–19.

    Article  CAS  Google Scholar 

  103. Hoffmann, W., Schiebe, M., Hirnle, P., et al. (1997) 13-cis retinoic acid and interferon-a ± irradiation in the treatment of squamous-cell carcinomas. Int. J. Cancer 70, 475–477.

    Google Scholar 

  104. Hansgen, G., Hansgen, K., and Dunst, J. (1996) Oxygen status of cervical cancers prior and during definitive radiotherapy: possible impact of pretreatment with IFN-α-2a/retinoic acid on oxygenation. Int. J. Rad. Oncol. Biol. Phys. 36, 324 (Abstr 2095).

    Google Scholar 

  105. DeLaney, T. F., Afridi. N., Taghian, A. G., et al. (1996) 13-cis-retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro.Cancer Res.56, 2277–2280.

    Google Scholar 

  106. Widschwendter, M., Daxenbichler, G., Bachmair, F., et al. (1996) Interaction of retinoic acid and interferon-alpha in breast cancer cell lines.Anticancer Res.16, 369–374.

    CAS  Google Scholar 

  107. Fanjul, A. N., Bouterfa, H., Dawson, M., et al. (1996) Potential role for retinoic acid receptorgamma in the inhibition of breast cancer cells by selective retinoids and interferons.Cancer Res.56, 1571–1577.

    CAS  Google Scholar 

  108. Agarwal, C., Hembree, J. R., Rorke, P. A., et al. (1994) Interferon and retinoic acid suppress the growth of human papillomavirus type-16 immortalized cervical epithelial cells, but only interferon suppresses the level of the human papillomavirus transforming oncogenes.Cancer Res.54, 2108–2112.

    CAS  Google Scholar 

  109. Lancillotti, F., Giandomenico, V., Affabris, E., et al. (1995) Interferon alpha-2b and retinoic acid combined treatment affects proliferation and gene expression of human cervical carcinoma cells.Cancer Res.55, 3158–3164.

    CAS  Google Scholar 

  110. Sidky, Y. A. and Borden, E. J. C. (1987) Inhibition of angiogenesis by interferons: effects on tumorand lymphocyte-induced vascular responses. Cancer Res. 47, 5155–5161.

    CAS  Google Scholar 

  111. Majewski, S., Szmurlo, A., Marczak, M., et al. (1994) Synergistic effect of retinoids and interferon alpha on tumor-induced angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines. Int. J. Cancer 57, 81–85.

    CAS  Google Scholar 

  112. Lippman, S. M., Kavanagh, J. J., Paredes-Espinoza, M. M., et al. (1993) 13-cis retinoic acid plus interferon alpha 2a, in locally advanced squamous cell carcinoma of the cervix. J. Natl. Cancer Inst. 85, 499,500.

    Google Scholar 

  113. Lippman, S. M., Kavanagh, J. J., Paredez-Espinoza, M., et al. (1992) 13-cis retinoic acid plus interferon-alpha2a: highly active systemic therapy for squamous cell carcinoma of the cervix. J. Natl. Cancer Inst. 84, 214–245.

    Google Scholar 

  114. Kavanagh, J. J., Lippman, S. M., and Paredes-Espinoza, M. (1996) The combination of 13-cis-retinoic acid and interferon α2a with radiation therapy in squamous cell carcinoma ofthe cervix. Int. J. Gynecol. Cancer 6, 439–444.

    Article  Google Scholar 

  115. Lippman, S. M., Parkinson, D. R., Itri, L. M., et al. (1992) 13-cis-retinoic acid and interferon-2a. Effective combination therapy for advanced squamous cell carcinoma of the skin. J. Natl. Cancer Inst. 84, 235–240.

    Google Scholar 

  116. Toma, S., Palumbo, R., and Vincenti, M. (1994) Efficacy of recombinant interferon-alpha and 13-cisretinoic acid in the treatment of squamous cell carcinomas. Ann. Oncol. 5, 463–465.

    CAS  Google Scholar 

  117. Motzer, R. J., Schwartz, L., Law, T. M., et al. (1995) Interferon alpha-2a and 13-cis retinoic acid in renal cell carcinoma: antitumor activity in a phase II trial and interactions in vitro. J. Clin. Oncol. 13, 1950–1957.

    CAS  Google Scholar 

  118. Antonadou, D., Cardamakis, E., Iliopoulos, P., et al. (1996) Comparative study between exclusive irradiation or combined with IFN-a-2a and isotretinoin in stage IIb and III cervical carcinoma. ASTRO 36, 121 (Abstr. 122).

    Google Scholar 

  119. Hallum, A. V., III, Alberts, D. S., Lippman, S. M., et al. (1995) Phase II study of 13-cis-retinoic acid plus interferon-a2a in heavily pretreated squamous carcinoma of the cervix.Gynecol. Oncol.56, 382–386.

    Article  PubMed  Google Scholar 

  120. Wadler, S., Schwartz, E. L., Haynes, H., et al. (1997) All-trans retinoic acid and interferon-a-2a in patients with metastatic or recurrent carcinoma of the uterine cervix. Cancer 79, 1574–580.

    CAS  Google Scholar 

  121. Weiss, G. R., Liu, P. Y., Alberts, D. S., et al. (1997) A randomized phase II trial of 13-cis-retinoic acid (CRA) or all trans-retinoic acid (ATRA) plus interferon alpha 2a (IFN) for metastatic or recurrent squamous/adenosquamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Proc. Ann. Meet. Am. Soc. Clin. Oncol. 16, 355a (Abstr. 1268).

    Google Scholar 

  122. Atzpodion, J., Buer, J., Probat, M., et al. (1996) Clinical and preclinical role of 13-cis retinoic acid in renal cell carcinoma: Hannover experience. Proc. Ann. Meet. Am. Soc. Clin. Oncol. 15, 247.

    Google Scholar 

  123. Papadimitrakopoulou, V. A., Shin, D. M., Clayman, G., et al. (1997) Efficacy of biochemoprevention in reversal of advanced premalignant lesions (PLs) in the upper aerodigestive tract (UADT). Proc. Ann. Meet. Am. Soc. C/in. Oncol. 16, 383a (abstract 1366).

    Google Scholar 

  124. Arensman, R. M. and Stolar, C. J.H. (1979) Vitamin A effect on tumor angiogenesis. J. Ped. Surg. 14, 809–812.

    Article  CAS  Google Scholar 

  125. Oikawa, T., Hirotani, K., Nakamura, O., Shudo, K., Hiragun, A., and Iwaguchi, T. (1989) A highly potent antiangiogenic activity of retinoids. Cancer Lett.48, 157–162.

    CAS  Google Scholar 

  126. Majewski, S., Szmurlo, A., Marczak, M., Jablonska, S., and Bollag, W. (1993) Inhibition of tumor cellinduced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination.Cancer Lett.75, 35–39.

    CAS  Google Scholar 

  127. Liaudet-Coopman, E. D.E., Berchem, G. J., and Wellstein, A. (1997)In Vivo inhibition ofangiogenesis and induction of apoptosis by retinoic acid in squamous cell carcinoma. Clin. Cancer Res.3,179–184.

    Google Scholar 

  128. Pepper, M. S., Vassalli, J. D., Wilks, J. W. Schweigerer, L., Orci, L., and Montesano, R. (1994) Modulation of bovine microvascular endothelial cell proteolytic properties by inhibitors of angiogenesis. J. Cell. Biochem. 55, 419–334.

    CAS  Google Scholar 

  129. Lingen, M. W., Polverini, P. J., and Bouck, N. P. (1996) Inhibition of squamous cell carcinoma angiogenesis by direct interaction of retinoic acid with endothelial cells.Lab. Invest.74, 476–483.

    PubMed  CAS  Google Scholar 

  130. Ezekowitz, R. A., Mulliken, J. B., and Folkman, J. (1992) Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N. Engl. J. Med. 326, 1456–1463.

    Article  CAS  Google Scholar 

  131. Barlow, C. F., Priebe, C. J., Mulliken, J. B., Barnes, P. D., Mac Donald, D., Folkman, J., and Ezekowitz, R. A. (1998) Spastic diplegia as a complication of interferon alfa-2a treatment of hemangiomas of infancy. J. Pediatr. 132, 527–530.

    Article  CAS  Google Scholar 

  132. Chang, E., Boyd, E., Nelson, C. C., Crowley, D., Law, T., Keough, K. M., Folkman, J., Ezekowitz, R. A., and Castle, V. P. (1997) Successful treatment of infantile hemangiomas with interferon-alpha-2b. J. Pediatr. Hematol. Oncol. 19, 237–244.

    Article  CAS  Google Scholar 

  133. Bollag, W., Majewski, S., and Jablonska, S. (1994) Cancer combination chemotherapy with retinoids: experimental rationale. Leukemia 8(Suppl. 3), S 11-S 15.

    Google Scholar 

  134. Haddad, S. F., Moore, S. A., Schelper, R. L., and Goeken, J. A. (1992) Vascular smooth muscle hyperplasia underlies the formation of glomeruloid vascular structures of glioblastoma multiforme. J. Neuropath. Exp. Neurol. 51, 488–492.

    Article  PubMed  CAS  Google Scholar 

  135. Heyns, A. du P., Eldor, A., Vlodavsky, I., Kaiser, N., Fridman, R., and Panet, A. (1985) The antiproliferative effect of interferon and the mitogenic activity of growth factors are independent cell cycle events. Exp. Cell Res. 161, 297–306.

    Article  CAS  Google Scholar 

  136. Palmer, H. and Libby, P. (1992) Interferon β: A potential autocrine regulator ofhuman vascular smooth muscle cell growth.Lab. Invest.66, 715.

    PubMed  CAS  Google Scholar 

  137. Warner, S. J. C., Friedman, G. B., and Libby, P. (1989) Immune interferon inhibits proliferation and induces 2’-5’-oligoadenylate synthetase gene expression in human vascular smooth muscle cells. J. Clin. Invest. 83, 1174–1182.

    Article  CAS  Google Scholar 

  138. Hansson, G. K. and Holm, J. (1991) Interferon-y inhibits arterial stenosis after injury. Circulation 84, 1266–1272.

    CAS  Google Scholar 

  139. James, T. W., Wagner, R., White, L., Zwolak, R. M., and Brinckerhoff, C. E. (1993) Induction of collagenase and stromelysin gene expression by mechanical injury in a vascular smooth musclederived cell line. J. Cell. Physiol. 157, 426–437.

    Article  CAS  Google Scholar 

  140. Miano, J. M., Topouzis, S., Majesky, M. W., and Olson, E. N. (1995) Retinoid receptor expression and all-trans retinoic acid-mediated growth inhibition in vascular smooth muscle cells. Circulation 93, 1886–1895.

    Google Scholar 

  141. Miano, J. M., Kelly, L. A., Artacho, C. A., Nuckolls, T. A., Piantedosi, R., and Blaner, W. S. (1998) All-trans retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery following balloon withdrawal injury. Circulation, in press.

    Google Scholar 

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Clifford, J.L., Miano, J.M., Lippman, S.M. (1999). Retinoids and Interferons as Antiangiogenic Cancer Drugs. In: Teicher, B.A. (eds) Antiangiogenic Agents in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-453-5_20

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