STAT3 、STAT5A、STAT5B和STAT6 蛋白在人基底细胞癌中过表达。
- 作者列表："Sławińska M","Lakomy J","Biernat W","Sokołowska-Wojdyło M","Karczewska J","Zabłotna M","Jankau J","Nowicki RJ","Sobjanek M
BACKGROUND:The molecular pathogenesis of basal cell carcinoma (BCC) is still not precisely described and is the subject of ongoing studies. The role of signal transducers and activators of transcription (STATs) in human epithelial carcinogenesis has been poorly investigated, but in the era of studies on inhibitors targeting STAT proteins this topic seems worth exploring. Increased expression of STAT3 in human nonmelanoma skin cancer (NMSC) has been confirmed in a few studies, but to our knowledge, expression of STAT5A, STAT5B and STAT6 in BCC has not been previously evaluated. AIM:To measure expression of STAT3, STAT5A, STAT5B and STAT6 expression in different histopathological subtypes of human BCC and its correlation with selected clinical variables. METHODS:Immunohistochemistry was used to assess 60 BCC tumour specimens [20 superficial (s)BCCs, 20 nodular (n)BCCs and 20 infiltrative (i)BCCs] and to compare with specimens of healthy skin. There was no significant difference in age or sex between the three groups of patients with BCC. As many tumours showed heterogeneity of staining, the H-score system was applied to calculate the intensity of immunoexpression. RESULTS:Expression of STAT3, STAT5A, STAT5B and STAT6 was observed in all histopathological subtypes of BCC, and was stronger than the expression within the adjacent epidermis and also stronger than the expression within the epidermis in the healthy control group. Statistical analysis revealed no significant differences in mean H-scores calculated for sBCCs, nBCCs and iBCCs. There were no statistically significant associations between STAT3, STAT5A, STAT5B and STAT6 expression and patient sex/age, and tumour size/site. CONCLUSION:Our results confirm a possible role of STATs in the pathogenesis of BCC and should encourage future investigations on the possible therapeutic implications of this finding.
背景: 基底细胞癌 (BCC) 的分子发病机制仍没有精确描述，是正在进行的研究的主题。信号转导子和转录激活子 (STATs) 在人类上皮癌变中的作用研究甚少，但在针对STAT蛋白的抑制剂研究时代，这一课题似乎值得探索。STAT3 在人非黑色素瘤皮肤癌 (NMSC) 中的表达增加已在一些研究中得到证实，但据我们所知，STAT5A、STAT5B和STAT6 在BCC中的表达尚未被评估。 目的: 检测STAT3 、STAT5A、STAT5B和STAT6 在不同组织病理学亚型BCC中的表达及其与临床变量的相关性。 方法S: immunhi s tochemi s try wa s u s ed to a s s e s 60 BCC tumor s pecimen s [20 s uperficial (s)BCC s，20 个结节性 (n)BCC s和 20 个浸润性 (i)BCC s]，并与健康s亲属的s pecimen s进行比较。3 组BCC患者的年纪或性别差别无统计学意义。由于许多肿瘤显示染色异质性，应用H评分系统计算免疫表达强度。 结果: STAT3 、STAT5A、STAT5B和STAT6 在BCC各组织病理学亚型中均有表达，并且在健康对照组中强于相邻表皮内的表达，也强于表皮内的表达。统计分析显示，计算的sBCCs、nBCCs和iBCCs的平均H评分无显著差异。STAT3 、STAT5A、STAT5B和STAT6 表达与患者性别/年龄、肿瘤大小/部位之间无统计学显著相关性。 结论: 我们的结果证实了STATs在BCC发病机制中的可能作用，并应鼓励今后研究这一发现可能的治疗意义。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.