1. Riccardi VM. The genetic predisposition to and histogenesis of neurofibromas and neurofibrosarcoma in neurofibromatosis type 1. Neurosurg Focus. 2007; 22(6): E3. doi: 10.3171/foc.2007.22.6.4
2. Sehgal VN, Srivastava G, Aggarwal AK, Oberai R. Plexiform neurofibromas in neurofibromatosis type 1. Int J Dermatol. 2009; 48: 971-974. doi: 10.1111/j.1365-4632.2008.04041.x
3. Pasmant E, Sabbagh A, Spurlock G, et al. NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat. 2010; 31: E1506-E1518. doi: 10.1002/humu.21271
4. Brown RM, Klesse LJ, Le LQ. Cutaneous features predict paraspinal neurofibromas in neurofibromatosis type 1. J Invest Dermatol. 2010; 130: 2167-2169. doi: 10.1038/jid.2010.206
5. De Raedt T, Brems H, Wolkenstein P, et al. Elevated risk for MPNST in NF1 microdeletion patients. Am J Hum Genet. 2003; 72: 1288-1292. doi: 10.1086/374821
6. Khosrotehrani K, Bastuj-Garin S, Riccardi VM, Birch P, Friedman JM, Wolkenstein P. Subcutaneous neurofibromas are associated with mortality in neurofibromatoss 1: a cohort study of 703 patients. Am J Med Genet A. 2005; 132: 49-53. doi: 10.1002/ajmg.a.30394
7. Riccardi VM, Eichner JE. Neurofibromatosis: phenotype, natural history, and pathogenesis. 1st ed. Baltimore: Johns Hopkins University Press; 1986.
8. Chen Z, Liu C, Patel AJ, Liao CP, Wang Y, Le LQ. Cells of origin in the embryonic nerve roots for NF1-associate plexiform neurofibromas. Cancer Cell. 2014; 26: 695-706. doi: 10.1016/j.ccell.2014.09.009
9. Carod-Artal FJ, Melo M, da Silva RT, Rizzo I, Vazquez C, Brenner C. Type I neurofibromatosis presenting as a progressive cervical myelopathy. The first case reported in Kaxinawa Indians. Rev Neurol. 2000; 31: 307-310.
10. Riccardi VM, Powell PP. Neurofibrosarcoma as a complication of von Recklinghausen neurofibromatosis. Neurofibromatosis. 1989; 2: 152-165.
11. Mautner VF, Friedrich RE, Von Deimling A, et al. Malignant peripheral nerve sheath tumors in Neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma. Neuroradiology. 2003; 45: 618-625. doi: 10.1007/s00234-003-0964-6
12. Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2 ed. Baltimore: Johns Hopkins University Press; 1992.
13. Lascano EF. Mast cells in human tumors. Cancer. 1958; 6: 1110-1113. doi: 10.1002/1097-0142(195811/12)11:6<1110::aid-cncr2820110604>3.0.co;2-g
14. Cawley EP, Hoch-Ligitti C. Association of tissue mast cells and skin tumors. Arch Dermatol. 1961; 83: 92-96. doi: 10.1001/archderm.1961.01580070098010
15. Pineda A. Mast cells-their presence and ultrastructural characteristics in peripheral nerve tumors. Arch Neurol. 1965; 13: 372-382. doi: 10.1001/archneur.1965.00470040038006
16. Issacson P. Mast cells in benign nerve sheath tumors. J Pathol. 1976; 119: 193-196. doi: 10.1002/path.1711190402
17. Reed ML, Jacoby RA. Cutaneous neuroanatomy and neuropathology. Normal nerves, neural-crest derivatives, and benign neural neoplasms in the skin. Am J Dermatopathol. 1983; 5: 335-362.
18. Kirkpatrick CJ, Curry A. Interaction between mast cells and perineurial fibroblasts in neurofibromas. Pathol Res Pract. 1988; 183: 453-458. doi: 10.1016/S0344-0338(88)80092-X
19. Johnson MD, Kamso-Pratt J, Federspiel CF, Whetsell WO, Jr. Mast cell and lymphoreticular infiltrates in neurofibromas. Comparison with nerve sheath tumors. Arch Pathol Lab Med. 1989; 113: 1263-1270.
20. Donhuijsen K, Sastry M, Volker B, Leder LD. Mast cell frequency in soft tissue tumors. Relation to type and grade of malignancy. Pathol Res Pract. 1992; 188: 61-66. doi: 10.1016/S0344-0338(11)81157-X
21. Sanguinetti C, Greco F, De Palma L, Specchia N, Toesca A, Nori S. The ultrastructure of peripheral neurofibroma: the role of mast cells and their interaction with perineurial cells. Ital J Orthop Traumatol. 1992; 18: 207-216.
22. Carr NJ, Warren AY. Mast cell numbers in melanocytic naevi and cutaneous neurofibromas. J Clin Pathol. 1993; 46: 86-87. doi: 10.1136/jcp.46.1.86
23. Nurnberger M, Moll I. Semiquantitative aspects of mast cells in normal skin and in neurofibromas of neurofibromatosis types 1 and 5. Dermatology. 1994; 188: 296-299. doi: 10.1159/000247170
24. Hermes B, Feldmann-Boddeker I, Welker P, et al. Altered expression of mast cell chymase and tryptase and of c-Kit in human cutaneous scar tissue. J Invest Dermatol. 2000; 114: 51-55. doi: 10.1046/j.1523-1747.2000.00837.x
25. Kurosawa M, Amano H, Kanbe N, et al. Heterogeneity of mast cells in mastocytosis and inhibitory effect of ketotifen and ranitidine on indolent systemic mastocytosis. J Allergy Clin Immunol. 1997; 100: S25-S32. doi: 10.1016/s0091-6749(97)70001-0
26. Dudeck A, Leist M, Rubant S, et al. Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E- and P-selectin, VCAM-1 and PECAM-1. Exp Dermatol. 2010; 19: 424-434. doi: 10.1111/j.1600-0625.2010.01073.x
27. Garg K, Ryan JJ, Bowlin GL. Modulation of mast cell adhesion, proliferation, and cytokine secretion on electrospun bioresorbable vascular grafts. J Biomed Mater Res A. 2011; 97: 405-413. doi: 10.1002/jbm.a.33073
28. Riccardi VM. Ketotifen suppression of NF1 neurofibroma growth over 30 years. Am J Med Genet A. 2015; 167(7): 1570-1577. doi: 10.1002/ajmg.a.37045
29. Riccardi VM. The pathophysiology of neurofibromatosis. IV. Dermatologic insights into heterogeneity and pathogenesis. J Am Acad Dermatol. 1980; 3: 157-166.
30. Riccardi VM. Cutaneous manifestations of neurofibromatosis cellular interaction, pigmentation, and mast cells. Birth Defects. 1981; 17(2): 129-145.
31. North CA, North RB, Epstein JA, Piantadosi S, Wharam MD. Low-grade cerebral astrocytomas: survival and quality of life after radiation therapy. Cancer. 1990; 66: 6-14. doi: 10.1002/1097-0142(19900701)66:1<6::AID-CNCR2820660103>3.0.CO;2-F
32. Riccardi VM. Cell-cell interaction as an epigenetic determinant in the expression of mutant neural crest cells. Birth Defects. 1979; 15(B): 89-98.
33. Riccardi VM. The potential role of trauma and mast cells in the pathogenesis of neurofibromas. In: Ishibashi Y, Hori Y, eds. Tuberous sclerosis and neurofibromatosis: epidemiology, pathophysiology, biology and management. 1st ed. Amsterdam: Elsevier; 1990: 167-190.
34. Riccardi VM. Histogenesis control genes: embryology, wound healing and NF1 (Letter to the Editor). Teratology. 2000; 62: 4. doi: 10.1002/1096-9926(200007)62:1<4::AID-TERA2>3.0.CO;2-Q
35. De Raedt T, Maertens O, Chmara M, et al. Somatic loss of wild type NF1 allele in neurofibromas: Comparison of NF1 microdeletion and non-microdeletion patients. Genes Chromosomes Cancer. 2006; 45: 893-904. doi: 10.1002/gcc.20353
36. Spurlock G, Griffiths S, Uff J, Upadhyaya M. Somatic alterations of the NF1 gene in an NF1 individual with multiple benign tumours (internal and external) and malignant tumour types. Fam Cancer. 2007; 6: 463-471. doi: 10.1007/s10689-007-9149-5
37. Spyk SL, Thomas N, Cooper DN, Upadhyaya M. Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis. Hum Genomics. 2011; 5: 623-690. doi: 10.1186/1479-7364-5-6-623
38. Thomas L, Kluwe L, Chuzhanova N, Mautner V, Upadhyaya M. Analysis of NF1 somatic mutations in cutaneous neurofibromas from patients with high tumor burden. Neurogenetics. 2010; 11(4): 391-400. doi: 10.1007/s10048-010-0240-y
39. Levi-Schaffer F, Kupietzky A. Mast cells enhance migration and proliferation of fibroblasts into an in vitro wound. Exp Cell Res. 1990; 188: 42-49. doi: 10.1016/0014-4827(90)90275-F
40. Koivunen J, Karvonen SL, Yla-Outinen H, Aaltonen V, Oikarinen A, Peltonen J. NF1 tumor suppressor in epidermal wound healing with special focus on wound healing in patients with type 1 neurofibromatosis. Arch Dermatol Res. 2005; 296: 547-554. doi: 10.1007/s00403-005-0564-x
41. Hebda PA, Collins MA, Tharp MD. Mast cell and myofibroblast in wound healing. Dermatol Clin. 1993; 11: 685-696.
42. Grieb G, Steffens G, Pallua N, Bernhagen J, Bucala R. Circulating fibrocytes-biology and mechanisms in wound healing and scar formation. Int Rev Cell Mol Biol. 2011; 291: 1-19. doi: 10.1016/B978-0-12-386035-4.00001-X
43. Artuc M, Hermes B, Steckelings UM, Grutzkau A, Henz BM. Mast cells and their mediators in cutaneous wound healing-active participants or innocent bystanders? Exp Dermatol. 1999; 8: 1-16. doi: 10.1111/j.1600-0625.1999.tb00342.x
44. Gallant-Behm CL, Hildebrand KA, Hart DA. The mast cell stabilizer ketotifen prevents development of excessive skin wound contraction and fibrosis in red Duroc pigs. Wound Repair Regen. 2008; 16: 226-233. doi: 10.1111/j.1524-475X.2008.00363.x
45. Atit RP, Crowe MJ, Greenbalgh DG, Wenstrup RJ, Ratner N. The Nf1 tumor suppressor regulates mouse skin wound healing, fibroblast proliferation and collagen deposited by fibroblasts. J Invest Dermatol.1999; 112: 835-842. doi: 10.1046/j.1523-1747.1999.00609.x
46. Dvorak AM, Kissell S. Granule changes of human skin mast cells characteristic of piecemeal degranulation and associated with recovery during wound healing in situ. J Leukocyte Biol. 1991; 49: 197-210. doi: 10.1002/jlb.49.2.197
47. Giorno R, Lieber J, Claman HN. Ultrastructural evidence for mast cell activation in a case of neurofibromatosis. Neurofibromatosis. 1988; 2: 35-41.
48. Jones CJ, Kirkpatrick CJ, Stoddart RW. An ultrastructure study of the morphology and lectin-binding properties of human mast cell granules. Histochem J. 1988; 183: 453-461. doi: 10.1007/bf01002429
49. Ingram DA, Yang F-C, Travers JB, et al. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. J Exp Med. 2000; 191: 181-188. doi: 10.1084/jem.191.1.181
50. Yang F-C, Ingram DA, Chen S, et al. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. J Clin Invest. 2003; 112: 1851-1861. doi: 10.1172/JCI200319195
51. Viskochil D. It takes two to tango: mast cell and Schwann cell interactions in neurofibromas. J Clin Invest. 2003; 112: 1791-1793. doi: 10.1172/JCI200320503
52. Yang FC, Ingram DA, Chen S, et al. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. J Clin Invest. 2003; 112: 1851-1861. doi: 10.1172/jci19195
53. McDaniel AS, Allen JD, Park SJ, et al. Pak1 regulates multiple c-Kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/- mast cells. Blood. 2008; 112: 4646-4654. doi: 10.1182/blood-2008-04-155085
54. Yang FC, Ingram DA, Chen S, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/– and c-kit-dependent bone marrow. Cell. 2008; 135: 437-448. doi: 10.1016/j.cell.2008.08.041
55. Reilly KM, Van Dyke T. It takes a (dysfunctional) village to raise a tumor. Cell. 2008; 135: 408-410. doi: 10.1016/j.cell.2008.10.009
56. Yang FC, Chen S, Clegg T, et al. Nf1+/- mast cells induce neurofibroma-like phenotypes through secreted TGF-beta signaling. Hum Mol Genet. 2006; 15: 2421-2437. doi: 10.1093/hmg/ddl165
57. Staser K, Yang FC, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood. 2010; 116: 157-164. doi: 10.1182/blood-2009-09-242875
58. Staser K, Yang FC, Clapp DW. Plexiform neurofibroma genesis: questions of Nf1 gene dose and hyperactive mast cells. Curr Opin Hematol. 2010; 17: 287-293. doi: 10.1097/MOH.0b013e328339511b
59. Chen S, Burgin S, McDaniel A, et al. Nf1-/- Schwann cell-conditioned medium modulates mast cell degranulation by c-Kit-mediated hyperactivation of phosphatidylinositol 3-kinase. Am J Pathol. 2010; 177: 3125-3132. doi: 10.2353/ajpath.2010.100369
60. Yang FC, Staser K, Clapp DW. The plexiform neurofibroma microenvironment. Cancer Microenviron. 2012; 5: 307-310. doi: 10.1007/s12307-012-0115-x
61. Yamamoto M, Yamauchi T, Okano K, Takahashi M, Watabe S, Yamamoto Y. Tranilast, an anti-allergic drug, down-regulates the growth of cultured neurofibroma cells derived from neurofibromatosis type 1. Tohoku J Exp Med. 2009; 217: 193-201. doi: 10.1620/tjem.217.193
62. Ribeiro S, Napoli I, White IJ, et al. Injury signals cooperate with nf1 loss to relieve the tumor-suppressive environment of adult peripheral nerve. Cell Rep. 2013; 5. doi: 10.1016/j.celrep.2013.08.033
63. Grenz A, Eltzschig HK. Mast cells and intestinal injury: a novel link between hypoxia and inflammation. Crit Care Med. 2013; 41: 2246-2248. doi: 10.1097/CCM.0b013e318283cc70
64. Oskeritzian CA. Mast cells and wound healing. Adv Wound Care (New Rochelle). 2012; 1: 23-28. doi: 10.1089/wound.2011.0357
65. Enoksson M, Lyberg K, Moller-Westerberg C, Fallon PG, Nilsson G, Lunderius-Andersson C. Mast cells as sensors of cell injury through IL-33 recognition. J Immunol. 2011; 186: 2523-2528. doi: 10.4049/jimmunol.1003383
66. Riccardi VM. Mast cell stabilization to decrease neurofibroma growth: preliminary experience with ketotifen. Arch Dermatol. 1987; 123: 1011-1016. doi: 10.1001/archderm.1987.01660320053011
67. Riccardi VM. A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching. Arch Dermatol. 1993; 129: 577-581. doi: 10.1001/archderm.1993.01680260047004
68. Krause L. Ketotifen and neurofibromatosis. Arch Dermatol. 1988; 124: 651-652.
69. Riccardi VM, Huston DP. Ketotifen and neurofibromatosis. Arch Dermatol. 1988; 124: 652. doi: 10.1001/archderm.1988.01670050010004
70. Hellal F, Hurtado A, Ruschel J, et al. Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury. Science. 2011; 331: 928-931. doi: 10.1126/science.1201148
71. Haustein UF. Ketotifen inhibits urticaria and tumor progression in neurofibromatosis. Dermatol Monatsschr. 1989; 175: 581-584.
72. Anastasiadou E, Slack FJ. Cancer: malicious exosomes. Science. 2014; 346: 1459-1460. doi: 10.1126/science.aaa4024
73. Walker M, Harley R, LeRoy EC. Ketotifen prevents skin fibrosis in the tight skin mouse. J Rheumatol. 1990; 17: 57-59.
74. Qu Z, Adelson DL. Bovine ncRNAs are abundant, primarily intergenic, conserved and associated with regulatory genes. PLoS ONE. 2012; 7: e42638. doi: 10.1371/journal.pone.0042638
75. Overed-Sayer C, Rapley L, Mustelin T, Clarke DL. Are mast cells instrumental for fibrotic diseases? Front Pharmacol. 2013; 4: 174. doi: 10.3389/fphar.2013.00174
76. Monument MJ, Hart DA, Befus AD, Salo PT, Zhang M, Hildebrand KA. The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures. Inflamm Res. 2012; 61: 285-292. doi: 10.1007/s00011-011-0409-3
77. Ehrlich HP. A snapshot of direct cell-cell communications in wound healing and scarring. Adv Wound Care (New Rochelle). 2013; 2: 113-121. doi: 10.1089/wound.2012.0414
78. Hei ZQ, Gan XL, Huang PJ, Wei J, Shen N, Gao WL. Influence of ketotifen, cromolyn sodium, and compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats. BMC Gastroenterol. 2008; 8: 42. doi: 10.1186/1471-230X-8-42
79. Kalia N, Brown NJ, Wood RF, Pockley AG. Ketotifen abrogates local and systemic consequences of rat intestinal ischemia-reperfusion injury. J Gastroenterol Hepatol. 2005; 20: 1032-1038. doi: 10.1111/j.1440-1746.2005.03767.x
80. Sanchez-Patan F, Aller MA, Cuellar C, et al. Mast cell inhibition by ketotifen reduces splanchnic inflammatory response in a portal hypertension model in rats. Exp Toxicol Pathol. 2008; 60: 347-355. doi: 10.1016/j.etp.2008.03.008
81. Karmeli F, Eliakim R, Okon E, Rachmilewitz D. Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabilizer. Gastroenterology. 1991; 100: 1206-1216.
82. Eliakim R, Karmeli F, Rachmilewitz D. Ketotifen-Old drug, new indication: reduction of gastric mucosal injury. Scand J Gastroenterol. 1993; 28: 202-204. doi: 10.3109/00365529309096072
83. Ting S. Ketotifen and systemic mastocytosis. J Allergy Clin Immunol. 1990; 85: 818. doi: 10.1016/0091-6749(90)90205-i
84. Póvoa P, Ducla-Soares J, Fernandes A, Palma-Carlos AG. A case of systemic mastocytosis: therapeutic efficacy of ketotifen. J Intern Med. 1991; 229: 475-477. doi: 10.1111/j.1365-2796.1991.tb00379.x
85. Graves L, III, Stechschulte DJ, Morris DC, Lukert BP. Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes. J Bone Miner Res. 1990; 5: 1113-1119. doi: 10.1002/jbmr.5650051104
86. Riccardi VM. Hiding in Plain Sight: A consideration of NF1-Associated Hypovitaminosis D and its treatment. J Genet Syndromes Gene Therapy. 2014. doi: 10.4172/2157-7412.1000223
87. Mena E, Brookstein JJ, Holt JF, Fry WJ. Neurofibromatosis and renovascular hypertension in children. AJR. 1973; 118: 39-45. doi: 10.2214/ajr.118.1.39
88. Geller M, Ribeiro MG, Araujo AP, de Oliveira LJ, Nunes FP. Serum IgE levels in neurofibromatosis 1. Int J Immunogenet. 2006; 33: 111-115. doi: 10.1111/j.1744-313X.2006.00579.x
89. Nakayama J, Sato C, Imafuku S. In vitro responses of neurofibroma fibroblasts, mast cells and Schwann cells obtained from patients with neurofibromatosis 1 to 308-nm excimer light and/or vitamin D. J Dermatol. 2013; 40. doi: 10.1111/1346-8138.12242