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.     

手术联合局部放疗治疗耳部瘢痕疙瘩的临床观察

目的 观察采用“月牙形”切口手术联合局部放疗治疗耳部瘢痕疙瘩患者中的临床疗效。方法选取2015年6月—2017年6月北京中医药大学东方医院耳鼻咽喉科收治的60例耳部瘢痕患者为研究对象，应用“月牙形”切口手术切除瘢痕内核，术后辅助局部放疗。结果60例患者中2例放疗后发生皮瓣血运障碍致使局部紫暗肿胀，经换药后好转，所有患者随访12～20个月，治愈42例（70.00%），显效16例（26.67%），总有效率96.67%；复发2例，复发率 3.33%。结论采用“月牙形”切口手术联合局部放疗治疗耳部瘢痕疙瘩效果理想，复发率低，值得推广应用。     

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。     

电离辐射对瘢痕疙瘩成纤维细胞增殖的影响

目的:明确电离辐射对瘢痕疙瘩成纤维细胞(KFb)增殖的影响。方法:MTT比色法、流式细胞仪检测不同剂量电离辐射照射前后KFb形态、增殖和存活力变化;通过测定培养基上清液中羟脯氨酸含量,明确处理前后胶原总体水平变化。结果:4Gy X-Rays作用72 h后,KFb增殖抑制率为(47.88±1.82)%高于正常皮肤成纤维细胞(39.86±0.07)%(P0.05);KFb细胞的形态发生了明显的变化,KFb细胞培养上清液中羟脯氨酸含量照射72 h后为(11.749±0.9428)μg/mL高于照射前的(18.689±0.8484)μg/mL(P0.05)。结论:电离辐射能够抑制KFb细胞的增殖及胶原的产生。     

人参皂苷Rg3对培养人瘢痕疙瘩成纤维细胞增殖活性的影响

目的：研究人参皂苷Rg3(GS-Rg3)对体外培养人瘢痕疙瘩的直接抑制作用及可能机制。方法：通过活细胞计数法与MTT比色法分别检测不同浓度GS-Rg3(25、50、100和200 mg·L^-1)在不同作用时间(24、48和72 h)对成纤维细胞增殖活性的影响。 结果：与对照组相比GS-Rg3对瘢痕疙瘩成纤维细胞有抑制作用,随着时间延长及浓度增加,抑制作用有增加趋势。最大抑制浓度为100 mg·L^-1。 结论：GS-Rg3对体外培养人瘢痕疙瘩成纤维细胞有抑制作用,且随着时间延长及浓度增加,其抑制作用增强。     

A Retrospective Registry Study Evaluating the Long-Term Efficacy and Safety of Superficial Radiation Therapy Following Excision of Keloid Scars

BACKGROUND: Surgical treatment of keloid scars is associated with an approximately 70% recurrence rate at the excision site. OBJECTIVE: We sought to assess keloid recurrence rates when superficial radiation therapy (SRT) was applied following surgical excision. METHODS: Medical records were reviewed of subjects treated for keloid scars followed by SRT (SRT-100™; Sensus Healthcare, Boca Raton, Florida) using a biologically effective dose (BED) of 30Gy and for whom the required retrospective data was available. Eligible subjects (N=61) were treated for 96 keloid scars with SRT. Subjects were male (48%) and female (52%) with a mean age of 38.87 years. Subjects were treated for ≥1 keloid scars following removal by sutured excision (93%) or tangential excision with secondary intention technique (7%). Almost all subjects (98%) received BED 30Gy with irradiation scheme of three 6Gy SRT treatments on Days 1, 2 and 3 following surgery. Mean energy of 100KV (73%) or 70KV (27%) were applied. RESULTS: Ten treated keloidectomy sites (10.4%) had recurrences (i.e., presence of any new tissue growth on the surgical scar) within 12 months increasing to 11 (12.7%) at 18 months. Kaplan-Meier survival probability cure rate was 85.6% from 24 months post-SRT treatment onwards. Transient hyperpigmentation was the most frequent adverse event and there were no malignancies in the treatment area during follow-up evaluations. CONCLUSIONS: SRT with a BED value of 30 Gy delivered to keloidectomy excision sites immediately following excision was well-tolerated and resulted in markedly fewer long-term recurrences than reported following keloidectomy alone. Most keloid scar recurrences occurred within one year. There were no malignancies during follow-up evaluations.