Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurofibromas are benign tumors that comprise primarily of Schwann cells and fibroblasts. Mast cells have been found scattered in the tumor tissue, and their role in promoting the proliferation of neurofibroma has been suggested. Tranilast (N-[3,4-dimethoxycinnamolyl]anthranilic acid) is an anti-allergic drug that inhibits release of the chemical mediators from mast cells and it used for the treatment of keloids and hypertrophic scars by its inhibition of growth-promoting transforming growth factor (TGF)-beta(1) from fibroblasts. We assumed that tranilast would suppress neurofibroma cell growth. In order to prove this hypothesis, we investigated the effectiveness of tranilast in inhibiting the tumor growth using a new cell culture system obtained from patients with neurofibromas. We called this culture system with the mixture of Schwann cells and fibroblasts "NF1 cells culture". Mast cells were differentiated from CD34(+) peripheral blood mononuclear cells of normal healthy subjects, and were co-cultured with NF1 cells. Three days after tranilast (10 approximately 100 microM) added to the culture dishes, we counted viable cell numbers and measured the concentrations of TGF-beta(1), stem cell factor (SCF) and tryptase, which exists in the histamine granule, in the culture medium. Tranilast significantly suppressed proliferation of the NF1 cells and lowered the levels of TGF-beta(1), SCF and tryptase. These results suggest that tranilast retards tumor proliferation through not only suppression of cell growth factor, but also the inhibition of a chemical mediator released from mast cells. Thus, tranilast can be a potent therapeutic agent to inhibit the growth of neurofibromas.
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PMID:Tranilast, an anti-allergic drug, down-regulates the growth of cultured neurofibroma cells derived from neurofibromatosis type 1. 1928 54

Although classical neurofibromas are commonly encountered skin lesions, histologic variants are infrequent. We report a greater than 15-year retrospective review of a single institution's experience with the histopathologic diagnosis of neurofibroma of the female breast with a focus on the hyalinized variant. An electronic histopathology record review (CoPathPlus; Cerner Corp, North Kansas City, MO) was conducted from January 1, 2000, to October 16, 2015, for all "neurofibroma" diagnoses rendered in "females" at the anatomical site "breast". All cases were microscopically revisited and subclassified into 1 of 10 histopathologic categories. Immunohistochemistry (IHC) for S100, tryptase, and CD117 were performed on 19 hyalinized and 19 age-matched classical neurofibromas. During the study period, 62,021 breast specimens were reviewed at our institution. Of these, 86 (0.14%) were diagnosed as neurofibromas. Subclassification was as follows: 50 classical (58%), 19 hyalinized (22%), 6 diffuse (7%), 5 cellular (6%), 3 myxoid (4%), 2 epithelioid (2%), and 1 plexiform (1%). All hyalinized and age-matched classical neurofibromas were S100 positive. The mean number of IHC-positive mast cells per high-power field (hpf) was 34.5 by tryptase and 26.8 by CD117 for the hyalinized subset and 22.5 by tryptase and 19.3 by CD117 for the classical cohort. Published literature reports a 2.6% incidence of hyalinized neurofibromas at nonspecial cutaneous sites. Our series details a 22% incidence in the breast. Regarding pathophysiology, there is a statistically significant increase in the average number of IHC-positive mast cells per hpf in hyalinized variants when compared with classical neurofibromas of the breast both by tryptase (P = 0.00157) and CD117 (P = 0.00901).
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PMID:Hyalinized Neurofibromas: Not Just Rare Variants in Skin of the Female Breast. 3087 Jan 67