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Mediators of Inflammation
Volume 2012, Article ID 563709, 16 pages
http://dx.doi.org/10.1155/2012/563709
Review Article

Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

1Dermatology Department, CHUVI and University of Vigo, Vigo, Spain
2University of Vigo, Vigo, Spain
3Analytical Chemistry Department, University of Vigo, Vigo, Spain

Received 18 February 2012; Revised 20 July 2012; Accepted 22 July 2012

Academic Editor: Kazuhito Asano

Copyright © 2012 Carmen Rodriguez-Cerdeira et al. 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. G. Martín Ezquerra, M. Sánchez Regaña, E. Herrera Acosta, and P. Umbert Millet, “Topical tacrolimus for the treatment of psoriasis on the face, genitalia, intertriginous areas and corporal plaques.,” Journal of Drugs in Dermatology, vol. 5, no. 4, pp. 334–336, 2006. View at Google Scholar · View at Scopus
  2. A. K. Gupta and M. Chow, “Pimecrolimus: a review,” Journal of the European Academy of Dermatology and Venereology, vol. 17, no. 5, pp. 493–503, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. A. A. Alzolibani and K. Zedan, “Macrolides in chronic inflammatory skin disorders,” Mediators of Inflammation, vol. 2012, Article ID 159354, 7 pages, 2012. View at Publisher · View at Google Scholar
  4. M. Czarnecka-Operacz and D. Jenerowicz, “Topical calcineurin inhibitors in the treatment of atopic dermatitis-an update on safety issues,” Journal of the German Society of Dermatology, vol. 10, no. 3, pp. 167–173, 2012. View at Publisher · View at Google Scholar
  5. L. Berk, M. M. Mita, J. Kreisberg et al., “Analysis of the pharmacodynamic activity of the mTOR inhibitor ridaforolimus (AP23573, MK-8669) in a phase 1 clinical trial,” Cancer Chemotherapy and Pharmacology, vol. 69, no. 5, pp. 1369–1377, 2012. View at Publisher · View at Google Scholar
  6. S. Krengel, I. Satzger, M. Alter, A. Kapp, and R. Gutzmer, “Remission of an iatrogenic Kaposi sarcoma in a patient with myasthenia gravis after switching immunosuppressive therapy to the mTOR inhibitor everolimus,” Der Hautarzt, vol. 63, no. 7, pp. 573–576, 2012. View at Google Scholar
  7. A. Sugawara, A. Sueki, T. Hirose et al., “Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents,” Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 11, pp. 3373–3376, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Kanehisa and S. Goto, “KEGG: Kyoto encyclopedia of genes and genomes,” Nucleic Acids Research, vol. 28, no. 1, pp. 27–30, 2000. View at Google Scholar · View at Scopus
  9. BioCarta-Charting Pathways of Life, http://www.biocarta.com/.
  10. M. Czarnecka-Operacz and D. Jenerowicz, “Topical calcineurin inhibitors in the treatment of atopic dermatitis-an update on safety issues,” Journal der Deutschen Dermatologischen Gesellschaft, vol. 10, no. 3, pp. 167–162, 2012. View at Google Scholar
  11. K. Wolff, C. Fleming, J. Hanifin et al., “Efficacy and tolerability of three different doses of oral pimecrolimus in the treatment of moderate to severe atopic dermatitis: a randomized controlled trial,” British Journal of Dermatology, vol. 152, no. 6, pp. 1296–1303, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Naldi and B. Rzany, “Chronic plaque psoriasis,” Clinical Evidence, no. 13, pp. 2070–2098, 2005. View at Google Scholar · View at Scopus
  13. R. E. Kalb, J. Bagel, N. J. Korman et al., “Treatment of intertriginous psoriasis: from the Medical Board of the National Psoriasis Foundation,” Journal of the American Academy of Dermatology, vol. 60, no. 1, pp. 120–124, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. C. Fabroni and T. Lotti, “Pimecrolimus in dermatology,” Giornale Italiano di Dermatologia e Venereologia, vol. 144, no. 3, pp. 321–325, 2009. View at Google Scholar · View at Scopus
  15. A. B. Gottlieb, C. E. M. Griffiths, V. C. Ho et al., “Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial,” British Journal of Dermatology, vol. 152, no. 6, pp. 1219–1227, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. M. R. Roopashree, R. V. Gondhalekar, M. C. Shashikanth, J. George, S. H. Thippeswamy, and A. Shukla, “Pathogenesis of oral lichen planus-a review,” Journal of Oral Pathology and Medicine, vol. 39, no. 10, pp. 729–734, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. P. López-Jornet, F. Camacho-Alonso, and N. Salazar-Sanchez, “Topical tacrolimus and pimecrolimus in the treatment of oral lichen planus: an update,” Journal of Oral Pathology and Medicine, vol. 39, no. 3, pp. 201–205, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Elad, J. B. Epstein, N. Yarom, S. Drucker, R. Tzach, and I. Von Bltzingslöwen, “Topical immunomodulators for management of oral mucosal conditions, a systematic review; part I: calcineurin inhibitors,” Expert Opinion on Emerging Drugs, vol. 15, no. 4, pp. 713–726, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. N. van Geel, R. Speeckaert, I. Mollet et al., “In vivo vitiligo induction and therapy model: double-blind, randomized clinical trial,” Pigment Cell and Melanoma Research, vol. 25, no. 1, pp. 57–65, 2012. View at Publisher · View at Google Scholar
  20. O. Köse, E. Arca, and Z. Kurumlu, “Mometasone cream versus pimecrolimus cream for the treatment of childhood localized vitiligo,” Journal of Dermatological Treatment, vol. 21, no. 3, pp. 133–139, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. Wardhana and E. A. Datau, “Chronic autoimmune urticaria,” Acta Medica Indonesiana, vol. 44, no. 2, pp. 165–174, 2012. View at Google Scholar
  22. A. M. Marsland, S. Soundararajan, K. Joseph, and A. P. Kaplan, “Effects of calcineurin inhibitors on an in vitro assay for chronic urticaria,” Clinical and Experimental Allergy, vol. 35, no. 5, pp. 554–559, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. M. B. Kim, G. W. Kim, H. J. Park et al., “Pimecrolimus 1% cream for the treatment of rosacea,” The Journal of Dermatology, vol. 38, no. 12, pp. 1135–1139, 2011. View at Publisher · View at Google Scholar
  24. H. Ucak, B. Kandi, D. Cicek, N. Halisdemir, and S. B. Dertlıoğlu, “The comparison of treatment with clobetasol propionate 0.05% and topical pimecrolimus 1% treatment in the treatment of alopecia areata,” The Journal of Dermatological Treatment, vol. 25, no. 7, pp. 345–249, 2011. View at Google Scholar
  25. A. Katoulis, S. Georgala, E. Bozi, E. Papadavid, D. Kalogeromitros, and N. Stavrianeas, “Frontal fibrosing alopecia: treatment with oral dutasteride and topical pimecrolimus,” Journal of the European Academy of Dermatology and Venereology, vol. 23, no. 5, pp. 580–582, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. S. L. Moschella, “Neutrophilic dermatoses,” in Dermatology, J. L. Bolognia, J. L. Jorizzo, and R. P. Rapini, Eds., vol. 1, pp. 415–418, 2003. View at Google Scholar
  27. V. Bellini, S. Simonetti, and P. Lisi, “Successful treatment of severe pyoderma gangrenosum with pimecrolimus cream 1% [10],” Journal of the European Academy of Dermatology and Venereology, vol. 22, no. 1, pp. 113–115, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. J. R. M. Carneiro, H. T. Fuzii, C. Kayser et al., “IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions,” Clinics, vol. 66, no. 1, pp. 77–82, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Barikbin, S. Givrad, M. Yousefi, and F. Eskandari, “Pimecrolimus 1% cream versus betamethasone 17-valerate 0.1% cream in the treatment of facial discoid lupus erythematosus: a double-blind, randomized pilot study,” Clinical and Experimental Dermatology, vol. 34, no. 7, pp. 776–780, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Hamzaoui, R. Klii, O. Harzallah, C. Attig, and S. Mahjoub, “Behçet's disease in women,” La Revue de Medecine Interne, vol. 33, no. 10, pp. 552–555, 2012. View at Publisher · View at Google Scholar
  31. C. Chams-Davatchi, B. Barikbin, F. Shahram et al., “Pimecrolimus versus placebo in genital aphthous ulcers of Behcet's disease: a randomized double-blind controlled trial,” International Journal of Rheumatic Diseases, vol. 13, no. 3, pp. 253–258, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Schmook, J. Kraft, B. Benninghoff et al., “Treatment of cutaneous chronic graft-versus-host disease with topical pimecrolimus [4],” Bone Marrow Transplantation, vol. 36, no. 1, pp. 87–88, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Sakuma, Y. Higashi, N. Sato et al., “Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids),” International Immunopharmacology, vol. 1, no. 6, pp. 1219–1226, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Sakuma, Y. Kato, F. Nishigaki et al., “FK506 potently inhibits T cell activation induced TNF-α and IL-1β production in vitro by human peripheral blood mononuclear cells,” British Journal of Pharmacology, vol. 130, no. 7, pp. 1655–1663, 2000. View at Google Scholar · View at Scopus
  35. K. H. Kim and T. Kono, “Overview of efficacy and safety of tacrolimus ointment in patients with atopic dermatitis in Asia and other areas,” International Journal of Dermatology, vol. 50, no. 9, pp. 1153–1161, 2011. View at Publisher · View at Google Scholar
  36. T. C. Keaney, T. Bhutani, P. Sivanesan et al., “Open-label, pilot study examining sequential therapy with oral tacrolimus and topical tacrolimus for severe atopic dermatitis,” Journal of the America Academy of Dermatology, vol. 67, no. 4, pp. 636–641, 2012. View at Google Scholar
  37. L. Laino and A. DiCarlo, “Palmoplantar pustular psoriasis: clinical and video thermographic evaluation before and after topical tacrolimus treatment,” Archives of Dermatology, vol. 147, no. 6, p. 760, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. A. N. Lin, “Innovative use of topical calcineurin inhibitors,” Dermatologic Clinics, vol. 28, no. 3, pp. 535–545, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. S. A. Vogel, B. Yentzer, S. A. Davis, S. R. Feldman, and K. M. Cordoro, “Trends in pediatric psoriasis outpatient health care delivery in the United States,” Archives of Dermatology, vol. 148, no. 1, pp. 66–71, 2012. View at Publisher · View at Google Scholar
  40. V. Madan and C. E. M. Griffiths, “Systemic ciclosporin and tacrolimus in dermatology,” Dermatologic Therapy, vol. 20, no. 4, pp. 239–250, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. A. T. Goldstein, D. Thaçi, and T. Luger, “Topical calcineurin inhibitors for the treatment of vulvar dermatoses,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 146, no. 1, pp. 22–29, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. E. Suys, “Randomized study of topical tacrolimus ointment as possible treatment for resistant idiopathic pruritus ani,” Journal of the American Academy of Dermatology, vol. 66, no. 2, pp. 327–328, 2012. View at Publisher · View at Google Scholar
  43. E. Baubion, M. S. Doutre, and M. Beylot-Barry, “Oral lichen planus and treatment with topical tacrolimus rinse,” Annales de Dermatologie et de Venereologie, vol. 136, no. 3, pp. 276–278, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. E. Baubion, M. S. Doutre, and M. Beylot-Barry, “Oral lichen planus and treatment with topical tacrolimus rinse,” Annales de Dermatologie et de Venereologie, vol. 136, no. 3, pp. 276–278, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Katsarou, M. Makris, K. Papagiannaki, E. Lagogianni, A. Tagka, and D. Kalogeromitros, “Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand eczema: a prospective randomized clinical study,” European Journal of Dermatology, vol. 22, no. 2, pp. 192–196, 2012. View at Publisher · View at Google Scholar
  46. S. Kathuria, B. K. Khaitan, M. Ramam, and V. K. Sharma, “Segmental vitiligo: a randomized controlled trial to evaluate efficacy and safety of 0.1% tacrolimus ointment vs 0.05% fluticasone propionate cream,” Indian Journal of Dermatology, Venereology and Leprology, vol. 78, no. 1, pp. 68–73, 2012. View at Publisher · View at Google Scholar
  47. D. Goldman, “Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report,” Journal of the American Academy of Dermatology, vol. 44, no. 6, pp. 995–998, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Garg and G. P. Thami, “Clinical efficacy of tacrolimus in rosacea,” Journal of the European Academy of Dermatology and Venereology, vol. 23, no. 2, pp. 239–240, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. B. H. Thiers, “Topical tacrolimus: treatment failure in a patient with alopecia areata,” Archives of Dermatology, vol. 136, no. 1, p. 124, 2000. View at Google Scholar · View at Scopus
  50. C. Kuldeep, H. Singhal, A. K. Khare, A. Mittal, L. K. Gupta, and A. Garg, “Randomized comparison of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized alopecia areata,” International Journal of Trichology, vol. 3, no. 1, pp. 20–24, 2011. View at Publisher · View at Google Scholar
  51. C. G. Larsen and J. P. Thyssen, “Pustular penile pyoderma gangrenosum successfully treated with topical tacrolimus ointment,” Acta Dermato-Venereologica, vol. 92, no. 1, pp. 104–105, 2012. View at Publisher · View at Google Scholar
  52. A. V. Marzano, V. Trevisan, R. Lazzari, and C. Crosti, “Topical tacrolimus for the treatment of localized, idiopathic, newly diagnosed pyoderma gangrenosum,” Journal of Dermatological Treatment, vol. 21, no. 3, pp. 140–143, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Altieri, K. Vaziri, and B. A. Orkin, “Topical tacrolimus for parastomal pyoderma gangrenosum: a report of two cases,” Ostomy Wound Management, vol. 56, no. 9, pp. 56–59, 2010. View at Google Scholar · View at Scopus
  54. M. Sugano, Y. Shintani, K. Kobayashi, N. Sakakibara, I. Isomura, and A. Morita, “Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus,” Journal of Dermatology, vol. 33, no. 12, pp. 887–891, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. C. E. Lampropoulos and D. P. D'Cruz, “Topical calcineurin inhibitors in systemic lupus erythematosus,” Therapeutics and Clinical Risk Management, vol. 15, no. 6, pp. 95–101, 2010. View at Google Scholar
  56. K. Suzuki, H. Kameda, K. Amano et al., “Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus,” Rheumatology International, vol. 31, no. 6, pp. 757–763, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. D. J. B. Marks and A. W. Segal, “Innate immunity in inflammatory bowel disease: a disease hypothesis,” Journal of Pathology, vol. 214, no. 2, pp. 260–266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. K. McSharry, A. M. Dalzell, K. Leiper, and W. El-Matary, “Systematic review: the role of tacrolimus in the management of Crohn's disease,” Alimentary Pharmacology and Therapeutics, vol. 34, no. 11-12, pp. 1282–1294, 2011. View at Publisher · View at Google Scholar
  59. J. Woo, T. M. Wright, B. Lemster, D. Borochovitz, M. A. Nalesnik, and A. W. Thomson, “Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lpr mice,” Clinical and Experimental Immunology, vol. 100, no. 1, pp. 118–125, 1995. View at Google Scholar · View at Scopus
  60. E. Rallis, A. Economidi, C. Verros, and P. Papadakis, “Successful treatment of patch type mycosis fungoides with tacrolimus ointment 0.1%.,” Journal of Drugs in Dermatology, vol. 5, no. 9, pp. 906–907, 2006. View at Google Scholar · View at Scopus
  61. Q. H. Dé Tran, E. Guay, S. Chartier, and J. Tousignant, “Tacrolimus in dermatology,” Journal of Cutaneous Medicine and Surgery, vol. 5, no. 4, pp. 329–335, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. F. N. Yalçindağ, F. Batioğlu, and O. Ozdemir, “Penetration of topically applied tacrolimus into the aqueous humor in Behçet's disease,” Annals of Ophthalmology, vol. 39, no. 1, pp. 15–17, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Evereklioglu, “Managing the symptoms of Behçet's disease,” Expert Opinion on Pharmacotherapy, vol. 5, no. 2, pp. 317–328, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. K. Matsumura, H. Nakase, and T. Chiba, “Efficacy of oral tacrolimus on intestinal Behcet's disease,” Inflammatory Bowel Diseases, vol. 16, no. 2, pp. 188–189, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. R. F. Jubran and P. A. Dinndorf, “Successful therapy of refractory graft versus host disease with tacrolimus and psoralen plus ultraviolet light,” Therapeutic Drug Monitoring, vol. 20, no. 2, pp. 236–239, 1998. View at Publisher · View at Google Scholar · View at Scopus
  66. K. Fortune and D. Couriel, “Tacrolimus in hematopoietic stem cell transplantation,” Expert Opinion on Drug Metabolism and Toxicology, vol. 5, no. 7, pp. 835–841, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. W. Sabry, R. Le Blanc, A. C. Labbé et al., “Graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil in HLA-matched nonmyeloablative transplant recipients is associated with very low incidence of GVHD and nonrelapse mortality,” Biology of Blood and Marrow Transplantation, vol. 15, no. 8, pp. 919–929, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Kettritz, U. Goebel, A. Fiebeler, W. Schneider, and F. Luft, “The protean face of sarcoidosis revisited,” Nephrology Dialysis Transplantation, vol. 21, no. 10, pp. 2690–2694, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Katoh, H. Mihara, and H. Yasuno, “Cutaneous sarcoidosis successfully treated with topical tacrolimus,” British Journal of Dermatology, vol. 147, no. 1, pp. 154–156, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Alijotas-Reig, V. Garcia-Gimenez, and M. Vilardell-Tarre's, “Tacrolimus in the treatment of chronic and refractory late-onset immune-mediated adverse effects related to silicone injections,” Dermatologic Surgery, vol. 38, no. 1, pp. 38–47, 2012. View at Publisher · View at Google Scholar
  71. T. Rosen, “The Propionibacterium acnes genome: from the laboratory to the clinic.,” Journal of Drugs in Dermatology, vol. 6, no. 6, pp. 582–586, 2007. View at Google Scholar · View at Scopus
  72. J. Raloff, “Triggering autoimmune assaults,” Science News, vol. 173, p. 10, 2008. View at Google Scholar
  73. A. M. Marsland and C. E. M. Griffiths, “The macrolide immunosuppressants in dermatology: mechanisms of action,” European Journal of Dermatology, vol. 12, no. 6, pp. 618–621, 2002. View at Google Scholar · View at Scopus
  74. L. Beretta, A. C. Gingras, Y. V. Svitkin, M. N. Hall, and N. Sonenberg, “Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation,” EMBO Journal, vol. 15, no. 3, pp. 658–664, 1996. View at Google Scholar · View at Scopus
  75. P. Petruzzo, S. Testelin, J. Kanitakis et al., “First human face transplantation: 5 years outcomes,” Transplantation, vol. 93, no. 2, pp. 236–240, 2012. View at Publisher · View at Google Scholar
  76. B. D. Kahan, “Fifteen years of clinical studies and clinical practice in renal transplantation: reviewing outcomes with De Novo use of sirolimus in combination with cyclosporine,” Transplantation Proceedings, vol. 40, no. 10, pp. S17–S20, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. T. H. Mathew, C. Van Buren, B. D. Kahan, K. Butt, S. Hariharan, and J. J. Zimmerman, “A comparative study of sirolimus tablet versus oral solution for prophylaxis of acute renal allograft rejection,” Journal of Clinical Pharmacology, vol. 46, no. 1, pp. 76–87, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. W. Jia, V. Sun, N. Tran et al., “Long-term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: implications for effective port wine stain treatment,” Lasers in Surgery and Medicine, vol. 42, no. 2, pp. 105–112, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Kourembanas, R. L. Hannan, and D. V. Faller, “Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells,” Journal of Clinical Investigation, vol. 86, no. 2, pp. 670–674, 1990. View at Google Scholar · View at Scopus
  80. D. Shweiki, A. Itin, D. Soffer, and E. Keshet, “Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis,” Nature, vol. 359, no. 6398, pp. 843–845, 1992. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Guba, P. Von Breitenbuch, M. Steinbauer et al., “Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor,” Nature Medicine, vol. 8, no. 2, pp. 128–135, 2002. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Seufferlein and E. Rozengurt, “Rapamycin inhibits constitutive p70(s6k) phosphorylation, cell proliferation, and colony formation in small cell lung cancer cells,” Cancer Research, vol. 56, no. 17, pp. 3895–3897, 1996. View at Google Scholar · View at Scopus
  83. R. J. Knight, M. Villa, R. Laskey et al., “Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients,” Clinical Transplantation, vol. 21, no. 4, pp. 460–465, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. C. H. Squarize, R. M. Castilho, T. H. Bugge, and J. S. Gutkind, “Accelerated wound healing by mTOR activation in genetically defined mouse models,” PLoS ONE, vol. 5, no. 5, Article ID e10643, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. A. D. Ormerod, S. A. A. Shah, P. Copeland, G. Omar, and A. Winfield, “Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial,” British Journal of Dermatology, vol. 152, no. 4, pp. 758–764, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. A. Fasolo and C. Sessa, “Current and future directions in mammalian target of rapamycin inhibitors development,” Expert Opinion on Investigational Drugs, vol. 20, no. 3, pp. 381–394, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. E. Frigerio, M. D. Colombo, C. Franchi, A. Altomare, C. Garutti, and G. F. Altomare, “Severe psoriasis treated with a new macrolide: everolimus,” British Journal of Dermatology, vol. 156, no. 2, pp. 372–374, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. S. G. A. Van Velsen, I. M. Haeck, and C. A. F. M. Bruijnzeel-Koomen, “Severe atopic dermatitis treated with everolimus,” Journal of Dermatological Treatment, vol. 20, no. 6, pp. 365–367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Mayerhofer, K. J. Aichberger, S. Florian et al., “Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells,” FASEB Journal, vol. 19, no. 8, pp. 960–962, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. X. Wan, N. Shen, A. Mendoza, C. Khanna, and L. J. Helman, “CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1α/VEGF signaling,” Neoplasia, vol. 8, no. 5, pp. 394–401, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. K. A. Furge, J. P. MacKeigan, and B. T. Teh, “Kinase targets in renal-cell carcinomas: reassessing the old and discovering the new,” The Lancet Oncology, vol. 11, no. 6, pp. 571–578, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Mencarelli, E. Distrutti, B. Renga et al., “Development of non-antibiotic macrolide that corrects inflammation-driven immune dysfunction in models of inflammatory bowel diseases and arthritis,” European Journal of Pharmacology, vol. 665, no. 1–3, pp. 29–39, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. R. J. Xavier and D. K. Podolsky, “Unravelling the pathogenesis of inflammatory bowel disease,” Nature, vol. 448, no. 7152, pp. 427–434, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Seral, S. Carryn, P. M. Tulkens, and F. Van Bambeke, “Influence of P-glycoprotein and MRP effux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus,” Journal of Antimicrobial Chemotherapy, vol. 51, no. 5, pp. 1167–1173, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. A. Sugawara, A. Sueki, T. Hirose et al., “Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents,” Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 11, pp. 3373–3376, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. V. M. Rivera, R. M. Squillace, D. Miller et al., “Ridaforolimus (AP23573; MK-8669), a potent mtor inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens,” Molecular Cancer Therapeutics, vol. 10, no. 6, pp. 1059–1071, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Hashemolhosseini, Y. Nagamine, S. J. Morley, S. Desrivières, L. Mercep, and S. Ferrari, “Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability,” Journal of Biological Chemistry, vol. 273, no. 23, pp. 14424–14429, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. I. B. Rosenwald, R. Kaspar, D. Rousseau et al., “Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post-transcriptional levels,” Journal of Biological Chemistry, vol. 270, no. 36, pp. 21176–21180, 1995. View at Publisher · View at Google Scholar · View at Scopus