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ABSTRACT: Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions; however, their involvement in the pathogenesis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is currently unknown. In this study, we first confirmed the histological diagnosis by detecting fusion COL1A1-PDGFB transcripts in DFSP, and examined the expression of all FGFRs (FGFR1-4), some of their ligands (FGF1, 2, 9), and forkhead box N1 (FOXN1) as a downstream target of FGFR3 in DF and DFSP by immunohistochemical analysis. Although we failed to detect the expression of FGF1 and FGF9 as specific ligands for FGFR3 in DF, overexpression of FGFR3 and FOXN1 was observed in the epidermal regions of DF, suggesting that the epidermal regions of DF were similar to seborrhoeic keratosis both in terms of histological features and the activation of FGFR3/FOXN1. In addition, strong expression of FGF2 and FGFR4 was observed in the tumor lesions of DF. Expression patterns of FGFR3/FOXN1 and FGF2/FGFR4 in DF were in contrast with those of DFSP. The activation of FGFR signaling pathways may be not only relevant to the pathogenesis of DF, but also very useful in the differential diagnosis of DF and DFSP. J. Med. Invest. 60: 106-113, February, 2013.
The Journal of Medical Investigation 01/2013; 60(1-2):106-13.
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European journal of dermatology: EJD 06/2011; 21(5):779-80. · 2.53 Impact Factor
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The Journal of Dermatology 01/2011; 38(1):94-6. · 1.49 Impact Factor
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ABSTRACT: Scherschum et al. proposed diltiazem-associated photodistributed hyperpigmentation as a novel type of drug-induced photosensitive lichenoid eruption. The characteristic clinical features were slate-gray reticulated hyperpigmentation on sun-exposed areas, while lichenoid dermatitis with prominent pigmentary incontinence was noted histologically. Although the clinical and histological features were similar to those of lichen planus pigmentosus, the histological features did not show either compact hyperkeratosis or wedge-shaped hypergranulosis, which are typical histological features of lichen planus. We describe two Japanese cases of diltiazem-associated photodistributed hyperpigmentation, who were successfully treated with topical tacrolimus, and review the published work.
The Journal of Dermatology 09/2010; 37(9):807-11. · 1.49 Impact Factor
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ABSTRACT: Swetter et al. proposed primary dermal melanoma (PDM) as a distinct entity based on an excellent prognosis. The histopathological features of PDM are extremely similar to those of metastatic melanoma or clear cell sarcoma (CCS). We describe a 38-year-old woman with a subcutaneous tumor in her left thigh. Physical and imaging examinations showed no evidence of metastatic melanoma. The lesion showed obvious strong expression of KIT by immunohistochemistry, but no EWS-ATF1 fusion transcript specific for CCS was detected by reverse transcription polymerase chain reaction. In further analyses of KIT expression in other tumors, three of four primary melanomas (75%) and six of 12 metastatic melanomas (50%) were moderately or strongly positive, however, both the primary and metastatic lesions of CCS tested negative. We believe this to be a case of PDM, and emphasize the distinctiveness of PDM.
The Journal of Dermatology 07/2009; 36(6):346-52. · 1.49 Impact Factor
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Acta Dermato-Venereologica 02/2009; 89(4):435-7.
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ABSTRACT: The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.
Archives for Dermatological Research 06/2007; 299(2):103-6. · 2.28 Impact Factor
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ABSTRACT: The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead
transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds
of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases
each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen’s disease (BD), and actinic keratosis (AK) by immunohistochemical
analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study.
In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was
observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of
skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting
cell proliferation and promoting apoptosis in non-melanoma skin cancers.
Archives for Dermatological Research 01/2007; 299(2):103-106. · 2.28 Impact Factor
