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001-es BibID:	BIBFORM001012
Első szerző:	Bodó Enikő
Cím:	Dissecting the impact of chemotherapy on the human hair follicle : a pragmatic in vitro assay for studying the pathogenesis and potential management of hair follicle dystrophy / Bodó E., Tobin D. J., Kamenisch Y., Bíró T., Berneburg M., Funk W., Paus R.
Dátum:	2007
ISSN:	0002-9440 (Print)
Megjegyzések:	Chemotherapy-induced alopecia represents one of the major unresolved problems of clinical oncology. The underlying molecular pathogenesis in humans is virtually unknown because of the lack of adequate research models. Therefore, we have explored whether microdissected, organ-cultured, human scalp hair follicles (HFs) in anagen VI can be exploited for dissecting and manipulating the impact of chemotherapy on human HFs. Here, we show that these organ-cultured HFs respond to a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC), in a manner that resembles chemotherapy-induced HF dystrophy as it occurs in vivo: namely, 4-HC induced melanin clumping and melanin incontinence, down-regulated keratinocyte proliferation, massively up-regulated apoptosis of hair matrix keratinocytes, prematurely induced catagen, and up-regulated p53. In addition, 4-HC induced DNA oxidation and the mitochondrial DNA common deletion. The organ culture system facilitated the identification of new molecular targets for chemotherapy-induced HF damage by microarray technology (eg, interleukin-8, fibroblast growth factor-18, and glypican 6). It was also used to explore candidate chemotherapy protectants, for which we used the cytoprotective cytokine keratinocyte growth factor as exemplary pilot agent. Thus, this novel system serves as a powerful yet pragmatic tool for dissecting and manipulating the impact of chemotherapy on the human HF.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	The American Journal of Pathology. - 171 : 4 (2007), p. 1153-1167. -
További szerzők:	Tobin, Desmund J. Kamenisch, York Berneburg, Mark Funk, Wolfgang Paus, Ralf Bíró Tamás (1968-) (élettanász)
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001-es BibID:	BIBFORM041514
Első szerző:	Samuelov, Liat
Cím:	Topobiology of Human Pigmentation : P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis / Samuelov Liat, Sprecher Eli, Sugawara Koji, Singh Suman K., Tobin Desmond J., Tsuruta Daisuke, Bíró Tamás, Kloepper Jennifer E., Paus Ralf
Dátum:	2013
ISSN:	0022-202X
Megjegyzések:	P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. Since patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane ?-catenin, while glycogen synthase kinase 3 beta (GSK3?) and phospho-?-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3?/Wnt signaling is required for maintaining expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3?-mediated canonical Wnt signaling
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal Of Investigative Dermatology. - 133 : 6 (2013), p. 1591-1600. -
További szerzők:	Sprecher, Eli Sugawara, Koji Singh, Suman K. Tobin, Desmund J. Tsuruta, Daisuke Bíró Tamás (1968-) (élettanász) Kloepper, Jennifer E. Paus, Ralf
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