Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas.
ABSTRACT Immunosuppression favors the development of skin cancer. Experimental data suggest that sirolimus (SRL) has antitumoral and antiangiogenic properties. An investigation was undertaken into the effects of SRL on squamous cell carcinoma (SCC) developing in organ transplant recipients (OTR) receiving immunosuppressive treatments, with special emphasis on vascularization.
SCC that developed in eight OTR before and after conversion from calcineurin inhibitors (CNI) to SRL were compared for thickness, differentiation, ulceration, perineural invasion, density of peritumoral infiltrate, peritumoral vascularization, density of T-regulatory cells and of intratumoral Langerhans cells and growth fraction.
SCC developing under SRL showed lower peritumoral vascularization and thickness, and higher growth fraction and density of peritumoral T-regulatory cells.
Conversion from CNI to SRL at clinically relevant doses is associated in vivo with a reduced vascularization and thickness of post-transplant human cutaneous SCC. This effect could account for the beneficial effect of SRL on immunosuppression-induced skin carcinogenesis in humans.
- SourceAvailable from: Faisal R Ali[Show abstract] [Hide abstract]
ABSTRACT: Solid organ transplant recipients are predisposed to actinic keratoses (AK) and nonmelanoma skin cancers, owing to the lifelong immunosuppression required. Today, increasing numbers of organ transplants are being performed and organ transplant recipients (OTRs) are surviving much longer. Photodynamic therapy (PDT) is proving a highly effective treatment modality for AK amongst this susceptible group of patients. Following an overview of the pathogenesis of AK amongst OTRs, the authors review current safety and efficacy data and how this relates to the role of PDT for the treatment of AK in OTRs.BioMed research international. 01/2013; 2013:349526.
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ABSTRACT: Skin cancers are the commonest cancers after organ transplantation, affecting in the long term 60–75% of the patients. They include mostly carcinomas, especially squamous and basal cell carcinomas, but also melanoma, Kaposi’s sarcoma and other rare skin tumours such as Merkel cell carcinoma. The management of these tumours necessitates a multidisciplinary approach comprising dermatological treatments and revision of immunosuppression. Prevention consists of strict sun protection and early treatment of premalignant lesions.Oncologie 15(2). · 0.08 Impact Factor
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ABSTRACT: Non-melanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid-organ transplant recipients, NMSCs represent a significant disease burden and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, Ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.Photodermatology Photoimmunology and Photomedicine 02/2014; · 1.52 Impact Factor