Tumour Microenvironment in Skin Carcinogenesis.
- 作者列表："Georgescu SR","Tampa M","Mitran CI","Mitran MI","Caruntu C","Caruntu A","Lupu M","Matei C","Constantin C","Neagu M
:Tumour microenvironment is a complex system comprising cells and molecules that will provide the necessary conditions for tumour development and progression. Cells residing in the tumour microenvironment gain specific phenotypes and specific functions that are pro-tumorigenic. Tumour progression is in fact a combination between tumour cell characteristics and its interplay with tumour microenvironment. This dynamic network will allow tumour cells to grow, migrate and invade tissues. In the present chapter, we are highlighting some traits that characterise tumour microenvironment in basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma. In skin cancers, there are some common tumour microenvironment characteristics such as the presence of tumour-associated macrophages and regulatory T lymphocytes that are non-tumour cells promoting tumorigenesis. There are also skin cancer type differences in terms of tumour microenvironment characteristics. Thus, markers such as macrophage migration inhibitory factor in melanoma or the extraordinary diverse genetic make-up in the cancer-associated fibroblasts associated to squamous cell carcinoma are just a few of specific traits in skin cancer types. New technological advances for evaluation of tumour environment are presented. Thus, non-invasive skin imaging techniques such as reflectance confocal microscopy can evaluate skin tumour inflammatory infiltrates for density and cellular populations. Analysing tumour micromedium in depth may offer new insights into cancer therapy and identify new therapy targets.
: 肿瘤微环境是一个复杂的系统，由细胞和分子组成，将为肿瘤的发生和发展提供必要的条件。驻留在肿瘤微环境中的细胞获得特定的表型和特定的功能，这些表型和功能是致瘤的。肿瘤进展实际上是肿瘤细胞特征与其与肿瘤微环境相互作用之间的结合。这个动态网络将允许肿瘤细胞生长、迁移和侵入组织。在本章中，我们强调了基底细胞癌、鳞状细胞癌和皮肤黑色素瘤中肿瘤微环境的一些特征。在皮肤癌中，t这里有一些常见的t umour微环境t特征t eris t ics如t he存在t umour-associate t ed巨噬细胞和regula t ory T淋巴t es t ha t非-t umour cells promo t ing t umorigenesis.在肿瘤微环境特征方面也存在皮肤癌类型差异。因此，黑色素瘤中的巨噬细胞迁移抑制因子或与鳞状细胞癌相关的癌症相关成纤维细胞中非凡的多样遗传组成等标志物只是皮肤癌类型中的几个特定特征。介绍了肿瘤环境评价的新技术进展。因此，非侵入性皮肤成像技术，如反射共聚焦显微镜，可以评估密度和细胞群的皮肤肿瘤炎症浸润。深入分析肿瘤微培养基可能为癌症治疗提供新的见解，并确定新的治疗靶点。
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.