皮肤肿瘤

20 0 3 3 3 4 7　结缔组织生长因子在瘢痕疙瘩中表达的研究 /陈晓栋 (中国医科院协和医大皮研所 )…∥中华皮肤科杂志 .-2 0 0 3 ,3 6(7) . -3 81～ 3 83应用半定量逆转录聚合酶链反应技术检测。结果显示 ,结缔组织生长因子 (CT G F ) m RN A在瘢痕疙瘩及其边缘正常皮肤中的表达均明显高于正常人对照 (P <0 .0 1 ) ,瘢痕疙瘩 CT G F的表达高低与病程无相关性 ;免疫组化证实 C T G F 在瘢痕疙瘩呈强表达 ,在正常人皮肤无表达 ;在瘢痕疙瘩组织边缘 ,CT G F 表达呈现由强至弱的过渡现象。提示 C T G F与瘢痕疙瘩的慢性纤维化有关 ,其…     

皮肤肿瘤

20060992CTGF在病理性瘢痕中的表达及意义/杨贤金(安庆市宜城医院整形科),张一鸣∥中国美容医学.-2005,14(6).-668~669对11例增长性瘢痕、10例瘢痕疙瘩及10例正常皮肤组织进行免疫组化(SP法)染色,观察细胞生长因子(CTGF)在正常皮肤、增生性瘢痕、瘢痕疙瘩中的表达。结果:正常皮     

血小板衍化生长因子受体蛋白在瘢痕疙瘩中的表达

目的 探讨血小板衍化生长因子受体(PDGFR)-α和-β在瘢痕疙瘩组织和瘢痕疙瘩来源成纤维细胞中的表达及其在瘢痕疙瘩发病中的作用.方法 应用免疫组化法检测15份瘢痕疙瘩和10份正常人皮肤标本PDGFR-α和-β蛋白的分布.体外原代培养成纤维细胞和蛋白质印迹法检测PDGFR蛋白的表达.结果 在瘢痕疙瘩组织中PDGFR-β表达明显增高,而PDGFR-α在瘢痕疙瘩中的表达似与瘢痕疙瘩的临床生长状态有关.在边缘充血、浸润生长明显的皮损,PDGFR-α呈强烈表达;而在边缘稳定、无明显浸润态势之皮损,PDGFR-α呈低表达.体外培养的成纤维细胞中,PDGFR-α比PDGFR-β表达更为丰富.结论 两种PDGFR的表达增高导致瘢痕疙瘩成纤维细胞对PDGF敏感性提高,决定了PDGF在瘢痕疙瘩发病机制中的作用.     

存活素在瘢痕疙瘩皮损中的表达及其与Bcl-2表达的关系

目的:检测存活素(survivin)在瘢痕疙瘩皮损中的表达及其与Bcl-2的相关性.方法:采用免疫组化方法(SABC),检测survivin和Bcl-2在45例瘢痕疙瘩皮损中的表达,并与10例正常皮肤组织中的表达进行对照.结果:survivin在正常皮肤组织中不表达,在瘢痕疙瘩皮损中survivin表达阳性率62.2%(28/45),Bcl-2阳性表达率33.3%(15/45);survivin的表达与Bcl-2表达密切相关.结论:survivin在瘢痕疙瘩中表达上调,可能抑制细胞凋亡;Bcl-2的上调与survivin的表达可能在瘢痕疙瘩的形成中起协同作用.     

皮肤肿瘤

20 0 4 36 87　瘢痕疙瘩组织中转醛醇酶活性的研究 /张一鸣 (南京医大生化与分子生物学系 )… / /中华皮肤科杂志 .- 2 0 0 4 ,37(6 ) .- 35 7以正常人皮肤为对照 ,用蛋白印迹法和 RT- PCR法进行检测。结果发现 ,瘢痕疙瘩组中转醛醇酶活性显著低于正常组织 ,而转醛醇酶蛋白和 m RNA表达与正常组织无显著差异。提示转醛醇酶活性低下对瘢痕疙瘩生成有意义。图 2参 4　 (马勇 )2 0 0 4 36 88　血小板衍化生长因子受体蛋白在瘢痕疙瘩中的表达 /陈晓栋 (中国医科院中国协和医大皮研所 )… / /中华皮肤科杂志 .- 2 0 0 3,36 (12 ) .- 6 87～ 6 89用免疫组化法检测瘢痕疙瘩中血小板衍化生长因子 (PDGFR) - α和 - β蛋白的分布 ,并体外培养原代成纤维细胞 ,用蛋白印迹法检测 PDGFR蛋白的表达。结果瘢痕疙瘩组织中 PDGFR- β表达明显增高 ,而 PDGFR- α的表达似与瘢痕疙瘩的临床生长状态有关 ,PDGFR- α在边缘充血、浸润生长明显的皮损呈强烈表达 ,而边缘稳定、无明显浸润态势皮损呈低表达 ;体外培养的成纤维细...     

皮肤肿瘤

20 0 4 2 4 44　端粒酶在瘢痕疙瘩及其周围外观正常皮肤中的表达 /王强 (中国医科院协和医大皮研所 )… //中华皮肤科杂志 .- 2 0 0 ,36 (10 ) .- 589～ 590采用链霉亲和素 -过氧化物酶免疫组化法 ,对 17例瘢痕疙瘩标本、10例瘢痕疙瘩周围外观正常皮肤标本及 9例正常人皮肤标本的成纤维细胞端粒酶的活性进行检测。结果显示在瘢痕疙瘩标本中 ,50 .5%的成纤维细胞中端粒酶活性检出阳性 ,且阳性细胞平均染色较深 ;在瘢痕疙瘩周围外观正常皮肤标本中 ,2 1.1%阳性 ;在正常人皮肤标本中 ,7.9%阳性 ,且阳性细胞平均染色深度明显浅于前两组。各组间…     

正常皮肤、增生性瘢痕与瘢痕疙瘩成纤维细胞培养及生物学特征的研究

目的:分析正常皮肤、增生性瘢痕和瘢痕疙瘩成纤维细胞在形态学、生长动力学及生物学的特性.方法:采用组织块培养法培养细胞;MTT法检测细胞在血清饥饿状态下的活性;免疫组织化学法检测3种成纤维细胞中结缔组织生长因子(CTGF)和胸苷磷酸化酶(TP)的表达.结果:正常皮肤、增生性瘢痕和瘢痕疙瘩成纤维细胞在形态与生长动力学上基本相似,血清饥饿对不同来源的成纤维细胞生长的影响并没有显著的差别.CTGF、TP在增生性瘢痕和瘢痕疙瘩成纤维细胞中均呈强阳性表达,而在正常皮肤成纤维细胞中的表达却很微弱,且有显著差别.结论:正常皮肤、增生性瘢痕与瘢痕疙瘩3类成纤维细胞在体外培养状态下,其形态、生长特性以及对血清饥饿的影响无显著差异.3类成纤维细胞对细胞因子具有不同的反应特性.     

瘢痕疙瘩组织中ICAM-1、VEGF、c-fos表达的免疫组化检测

采取免疫组化SP方法检测了细胞间粘附分子 1(ICAM 1)、血管内皮细胞生长因子 (VEGF)、以及原癌基因 (c fos)在瘢痕疙瘩、普通瘢痕、正常皮肤组织中的表达。结果表明ICAM 1、VEGF、c fos在瘢痕疙瘩中表达皆增强。ICAM 1主要表达在真皮浅层血管、浸润的炎细胞、成纤维细胞 ;VEGF、c fos主要表达在表皮、真皮血管、皮肤附属器 ;部分瘢痕疙瘩标本成纤维细胞c fos染色阳性 ,提示瘢痕疙瘩组织中血管内皮细胞处于一种激活状态 ,瘢痕疙瘩组织血管内皮细胞和成纤维细胞增殖异常。     

皮肤肿瘤

20 0 0 4 0 31　瘢痕疙瘩组织中 ICAM- 1、VEGF、c- fos表达的免疫组化检测 /阎国富 (三军大新桥医院皮肤科 )…∥临床皮肤科杂志 .- 2 0 0 0 ,2 9( 3) .- 139～ 141采用免疫组化 SP方法检测了细胞间粘附分子 - 1( ICAM- 1)、血管内皮细胞生长因子 ( VEGF)及原癌基因 ( c- fos)在瘢痕疙瘩、普通瘢痕、正常皮肤组织中的表达。结果表明 ICAM- 1、VEGF、c- fos在瘢痕疙瘩中表达皆增强。ICAM- 1主要表达在真皮浅层血管、浸润的炎细胞、成纤维细胞 ;VEGF、c- fos主要表达在表皮、真皮血管、皮肤附属器 ;部分瘢痕疙瘩标本成纤维细胞…     

晚期糖基化终末产物及其受体在瘢痕疙瘩中的表达

目的 研究晚期糖基化终末产物（AGE）及其受体（AGER）在瘢痕疙瘩中的表达。方法 瘢痕疙瘩、增生性瘢痕和正常人群血清、皮肤组织标本各20份,以荧光分光光度计检测三组人群血清中AGE含量,分别采用免疫组化法、Western印迹分析检测三组人群皮肤组织标本中AGE和AGER表达情况。结果 瘢痕疙瘩组血清中AGE含量为（0.713 ± 0.098） AU/ml,增生性瘢痕组为（0.699 ± 0.077） AU/ml,明显高于正常人群组（0.179 ± 0.056） AU/ml,三组差异有统计学意义（F = 283.82,P < 0.01）。免疫组化显示,AGE、AGER在瘢痕疙瘩、增生性瘢痕皮肤组织标本中表达阳性,正常人群组织表达则为阴性。Western印迹检测显示,瘢痕疙瘩、增生性瘢痕组织中AGE和AGER蛋白表达均明显高于正常人群,差异有统计学意义（F值分别为18.04、42.80,P < 0.05）,而瘢痕疙瘩和增生性瘢痕组之间差异无统计学意义（P > 0.05）。结论 AGE和AGER在瘢痕疙瘩中表达升高,在其发病过程中可能发挥一定的促进作用。     

Upregulation of the NNP-1 (novel nuclear protein-1, D21S2056E) gene in keloid tissue determined by cDNA microarray and in situ hybridization

BACKGROUND: A keloid results from excessive collagen deposition, the cause of which remains elusive. A thorough understanding of the pathophysiology of keloid tissue can help determine the most appropriate treatment strategy. OBJECTIVES: To assess the differences in gene expression between keloids and adjacent normal skin in order to define the genes involved in keloid formation. METHODS: Three Korean patients with keloids underwent excision of the keloid and adjacent normal skin, which was used as the control. We investigated expression patterns of genes in the keloids and the normal skin using cDNA microarray and in situ hybridization techniques. RESULTS: Nine genes in the keloid tissue were consistently upregulated over the 2.0 ratio compared with the normal control from the cDNA microarray composed of 3063 clones: collagen type I alpha1 (NM_000088), DNA segment on chromosome 21 (unique) 2056 expressed sequence (D21S2056E, NNP-1, NM_003683), suppressor of Ty 5 homologue (NM_003169), phosphoglycerate dehydrogenase (NM_032692), adenosine triphosphate synthase beta (NM_001686), serine (or cysteine) proteinase inhibitor, clade H (heat shock protein 47, NM_001235), LIV-1 protein, oestrogen regulated (LIV-1, NM_012319), interleukin-11 receptor alpha (IL11RA, NM_004512) and carbonyl reductase 3 (CBR3, NM_001236). From the in situ hybridization study, the staining signals in the keloid tissue hybridized with anti sense probes of NNP-1 mRNA were stronger than signals in normal controls. Further, endothelial epithelium, but not the epidermis, expressed the signal equally in both keloid and normal control tissue. CONCLUSIONS: We identified nine upregulated genes in keloid tissue using cDNA microarray. Of the nine, the NNP-1 gene was confirmed by topological information using the in situ hybridization technique. We conclude that these nine genes, especially NNP-1, probably contribute either directly or indirectly to keloid formation.     

端粒酶在瘢痕疙瘩及其周围外观正常皮肤中的表达

目的 探讨端粒酶的活性与瘢痕疙瘩发病的关系。方法 采用链霉亲和素-过氧化物酶(SP)免疫组化法,对17例瘢痕疙瘩标本、10例瘢痕疙瘩周围外观正常皮肤标本及9例正常人对照组标本的成纤维细胞中端粒酶的活性进行检测,用SPSS统计软件进行相应统计学分析。结果 在瘢痕疙瘩标本中,50.5%的成纤维细胞中端粒酶活性检出阳性,且阳性细胞平均染色较深;在瘢痕疙瘩周围外观正常皮肤标本中,21.1%的成纤维细胞中端粒酶活性检出阳性;在正常人皮肤标本中,7.9%的成纤维细胞中端粒酶活性检出阳性,且阳性细胞平均染色深度明显浅于前两组。各组间两两比较,差异均有显著性(P<0.05)。结论 端粒酶的活性增高在瘢痕疙瘩的发病机制中有重要作用。     

成纤维细胞活化蛋白在瘢痕疙瘩组织中的表达及意义

 目的:了解成纤维细胞活化蛋白（FAP）在瘢痕疙瘩组织中的表达情况，探讨FAP在瘢痕疙瘩发病机制中的作用。方法:采用免疫组化染色技术检测30例瘢痕疙瘩组织（病例组）和20例正常皮肤组织（对照组）中FAP的表达强度，并比较两组间及瘢痕疙瘩不同临床分级之间FAP表达阳性率的差异。结果:病例组瘢痕疙瘩组织中FAP在成纤维细胞和血管内皮细胞内表达，阳性率为73.33％；对照组正常皮肤组织中未见FAP表达，两组间FAP表达阳性率比较,差异有统计学意义（  X²=26.19,P=0.001）；瘢痕疙瘩临床分级中,轻度与重度之间及中度与重度之间比较，FAP表达阳性率差异均有统计学意义（P值分别为0.002、0.006）。结论:瘢痕疙瘩组织中FAP表达阳性率明显高于正常皮肤组织；瘢痕疙瘩临床分级越严重，FAP表达阳性率越高；FAP可能参与瘢痕疙瘩的发病机制，针对FAP的干预可能有助于瘢痕疙瘩的治疗。     

Co-ordinate induction of collagen type I and biglycan expression in keloids

Proteoglycans are macromolecules displaying structural roles as well as regulatory functions in the maintenance of the extracellular matrix. Biglycan/PG-I and decorin/PG-II are two small proteoglycans that are structurally related but differ considerably in their localization in vivo and behaviour in vitro. Decorin and, to a minor extent, biglycan, can be located at the surface of type I collagen fibrils and have been shown to influence collagen fibrillogenesis. However, the physiological role of biglycan in the dermis is not known. Biopsies obtained from keloids were bisected and processed for total RNA extraction and immunohistochemistry. Northern blot analysis of total RNA obtained from keloids with high growth tendency in vivo showed a marked induction of biglycan and collagen α1(I) mRNA expression in comparison with total RNA obtained from normal skin or keloids with little growth tendency. In contrast, decorin mRNA expression remained largely unaltered. Studying these biopsies by immunohistochemistry, decorin expression in the dermis was unaltered comparing normal and keloid tissue, whereas a markedly increased staining for biglycan was observed in the keloid tissue, which was most pronounced in the nodular formations, and was a characteristie feature of keloids. The altered expression of biglycan in keloid tissue might be involved in the abnormal regulation of extracellular matrix deposition either through the binding of growth factors or by influencing the three-dimensional organization of collagen fibres or associated molecules.     

Studies of transforming growth factors beta 1-3 and their receptors I and II in fibroblast of keloids and hypertrophic scars

Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterized by an abnormal deposition of extracellular matrix components, particularly collagen. There is uncertain evidence that transforming growth factor-beta (TGFss) is involved in keloid formation. Therefore we investigated the expression of TGFss1, 2 and 3 and their receptors in keloids, hypertrophic scars and normal skin. Dermal fibroblasts were obtained from punch biopsies of patients with keloids and hypertrophic scars and from normal skin of healthy individuals. Total RNA was isolated and the expression of TGFss1, 2 and 3 and of TGFss receptors I and II (TGFssRI and II) was analysed by real-time PCR using the Lightcycler technique. Our data demonstrate significantly lower TGFss2 mRNA expression in hypertrophic scar fibroblasts as compared with fibroblasts derived from keloids and normal skin (p<0.05). In contrast, TGFss3 mRNA expression was significantly lower in keloid fibroblasts in comparison with fibroblasts derived from hypertrophic scar and normal skin (p<0.01). TGFssRI mRNA expression was significantly decreased in hypertrophic scar fibroblasts (p<0.01) and TGFssRII mRNA expression was decreased in keloids compared with hypertrophic scar fibroblasts (p<0.001). The ratio of TGFssRI/TGFssRII expression was increased in keloids compared with hypertrophic scar and normal skin fibroblasts. As recently supposed, an increased TGFssRI/TGFssRII ratio could promote fibrosis. Therefore our data support a possible role of TGFssRI and TGFssRII in combination with a certain TGFss expression pattern as fibrosis-inducing factors in keloids.     

Decorin‐expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids

Decorin is a natural transforming growth factor‐β1 (TGF‐β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid‐derived fibroblasts (KFs) were transduced with decorin‐expressing adenovirus (dE1‐RGD/GFP/DCN), and we examined the therapeutic potential of decorin‐expressing Ad for treating pathologic skin fibrosis. Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1‐RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR) and secreted TGF‐β1 were assessed by Western blotting and ELISA. And type I and III collagen, and matrix metalloproteinase‐1 (MMP‐1) and matrix metalloproteinase‐3 (MMP‐3) mRNA levels were measured by real‐time RT‐PCR. Additionally, we immunohistochemically investigated the expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1‐RGD/GFP/DCN. Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1‐RGD/GFP/DCN, secreted TGF‐β1 and EGFR protein expressions were decreased in TGF‐β1‐treated HDFs and KFs. Also, type I and III collagen mRNA levels were decreased, and the expression of MMP‐1 and MMP‐3 mRNA was strongly upregulated. In addition, the expression of type I and III collagen, fibronectin and elastin was significantly reduced in dE1‐RGD/GFP/DCN‐transduced keloid spheroids. These results support the utility of decorin‐expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids.     

瘢痕旁和瘢痕下扩张器埋植治疗17例胸部瘢痕疙瘩

目的 探讨瘢痕旁和瘢痕下扩张器埋植治疗前胸部大面积瘢痕疙瘩的疗效。方法 从2006年3月至2009年6月,17例前胸部大面积瘢痕疙瘩患者共接受21个扩张器埋植。瘢痕面积最大15.7 cm × 5.5 cm,最小4.5 cm × 3.0 cm。其中瘢痕旁埋植12个,瘢痕下埋植9个。瘢痕旁埋植扩张器容量70 ~ 400 ml,瘢痕下埋植80 ~ 500 ml。经6 ~ 8周注水扩张后,行瘢痕疙瘩切除、扩张器取出和扩张皮瓣转移术,同时给予术中即时皮内注射复方倍他米松注射液、术后浅表电子束照射联合治疗,随访12 ~ 50个月。结果 除1个扩张器瘢痕下埋植后感染导致提前取出手术失败外,余20个扩张器均顺利完成整个治疗过程。主要并发症为扩张器外露4个,其中瘢痕旁1个,瘢痕下埋植3个,但未影响二期手术。扩张不满意2个,其中瘢痕旁和瘢痕下各1个。除2例复发外,余15例自觉症状均明显缓解,效果满意。2例复发患者均为扩张不满意,缝合时切口张力较大、且术后延期拆线者。结论 瘢痕旁和瘢痕下扩张器埋植为治疗前胸部大面积瘢痕疙瘩的较为理想的选择方法。切口缝合的张力是决定瘢痕疙瘩术后是否复发的关键。