<strong>Purpose:</strong> To establish whether Curaderm, a topical pharmacotherapy for skin cancer, irritates or sensitizes normal skin. <strong>Methods:</strong> The dermal irritation and skin...<strong>Purpose:</strong> To establish whether Curaderm, a topical pharmacotherapy for skin cancer, irritates or sensitizes normal skin. <strong>Methods:</strong> The dermal irritation and skin sensitization toxicity of Curaderm were investigated in rabbits and guinea pigs in compliance with the Organization for Economic Cooperation and Development guideline. To assess dermal irritation, rabbits were dermally exposed to Curaderm for varying periods of time. To assess hypersensitivity, the guinea-pig maximisation test was applied. <strong>Results:</strong> Curaderm was only negligibly irritating using the criteria of erythema and oedema. Curaderm did not produce any sensitization toxicity of the skin. <strong>Conclusion:</strong> These studies confirm the non-toxic observations on normal skin experienced in the clinical setting when treating skin cancer and reinforce the specificity of Curaderm towards cancer cells.展开更多
Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human ...Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real- time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in nor- mal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermalkeratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Con- versely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by inter- fering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.展开更多
乳房重建是乳腺癌外科治疗中不可或缺的组成部分,目前以假体为基础的乳房重建(implan-based breast recon-struction,IBBR)已成为主要的重建方式。19世纪80年代,IBBR开始应用于乳房切除的病人,由于术中将假体直接植入皮下,术后...乳房重建是乳腺癌外科治疗中不可或缺的组成部分,目前以假体为基础的乳房重建(implan-based breast recon-struction,IBBR)已成为主要的重建方式。19世纪80年代,IBBR开始应用于乳房切除的病人,由于术中将假体直接植入皮下,术后假体移位、皮瓣坏死、感染以及明显的包膜挛缩等并发症发生较多,一度影响了IBBR的开展。1982年,Radovan开拓了胸肌下假体植入的方式,利用胸大肌作为假体的覆盖和支撑,明显减少了上述并发症的发生,并在过去的25年中成为经典的IBBR术式。但由于胸大肌的覆盖面积受限,不足以覆盖假体外侧和下缘部分,近年来将人工材料作为胸大肌延伸覆盖,甚至替代胸肌完成IBBR,得到了越来越多的应用,而人工材料的发展和应用也成为了临床关注的热点之一。展开更多
文摘<strong>Purpose:</strong> To establish whether Curaderm, a topical pharmacotherapy for skin cancer, irritates or sensitizes normal skin. <strong>Methods:</strong> The dermal irritation and skin sensitization toxicity of Curaderm were investigated in rabbits and guinea pigs in compliance with the Organization for Economic Cooperation and Development guideline. To assess dermal irritation, rabbits were dermally exposed to Curaderm for varying periods of time. To assess hypersensitivity, the guinea-pig maximisation test was applied. <strong>Results:</strong> Curaderm was only negligibly irritating using the criteria of erythema and oedema. Curaderm did not produce any sensitization toxicity of the skin. <strong>Conclusion:</strong> These studies confirm the non-toxic observations on normal skin experienced in the clinical setting when treating skin cancer and reinforce the specificity of Curaderm towards cancer cells.
文摘Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real- time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in nor- mal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermalkeratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Con- versely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by inter- fering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.
文摘乳房重建是乳腺癌外科治疗中不可或缺的组成部分,目前以假体为基础的乳房重建(implan-based breast recon-struction,IBBR)已成为主要的重建方式。19世纪80年代,IBBR开始应用于乳房切除的病人,由于术中将假体直接植入皮下,术后假体移位、皮瓣坏死、感染以及明显的包膜挛缩等并发症发生较多,一度影响了IBBR的开展。1982年,Radovan开拓了胸肌下假体植入的方式,利用胸大肌作为假体的覆盖和支撑,明显减少了上述并发症的发生,并在过去的25年中成为经典的IBBR术式。但由于胸大肌的覆盖面积受限,不足以覆盖假体外侧和下缘部分,近年来将人工材料作为胸大肌延伸覆盖,甚至替代胸肌完成IBBR,得到了越来越多的应用,而人工材料的发展和应用也成为了临床关注的热点之一。