Sirolimus Reduces the Incidence and Progression of UVB-Induced Skin Cancer in SKH Mice even with Co-administration of Cyclosporine A
| Autor: | Donna F. Kusewitt, Anne M. VanBuskirk, Duncan F. Jason, Brian C. Wulff, Tatiana M. Oberyszyn, Jennifer M. Thomas-Ahner |
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| Rok vydání: | 2008 |
| Předmět: |
Neoplasms
Radiation-Induced Skin Neoplasms Neutrophils Ultraviolet Rays Antineoplastic Agents Cell Count Dermatology Pharmacology Biochemistry Transforming Growth Factor beta1 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Mast Cells Molecular Biology 030304 developmental biology Antibacterial agent Skin Sirolimus 0303 health sciences Mice Hairless Protein synthesis inhibitor integumentary system business.industry Incidence Cancer Neoplasms Second Primary Cell Biology Ciclosporin medicine.disease 3. Good health Tumor Burden Calcineurin Transplantation 030220 oncology & carcinogenesis Immunology Cyclosporine Disease Progression Female Lymph Nodes Skin cancer business Immunosuppressive Agents medicine.drug |
| Zdroj: | Journal of Investigative Dermatology. 128(10):2467-2473 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2008.121 |
| Popis: | Transplant immunosuppressants have been implicated in the increased incidence of non-melanoma skin cancer in transplant recipients, most of whom harbor considerable UVB-induced DNA damage in their skin prior to transplantation. This study was designed to evaluate the effects of two commonly used immunosuppressive drugs, cyclosporine A (CsA) and sirolimus (SRL), on the development and progression of UVB-induced non-melanoma skin cancer. SKH-1 hairless mice were exposed to UVB alone for 15 weeks, and then were treated with CsA, SRL, or CsA+SRL for 9 weeks following cessation of UVB treatment. Compared with vehicle, CsA treatment resulted in enhanced tumor size and progression. In contrast, mice treated with SRL or CsA+SRL had decreased tumor multiplicity, size, and progression compared with vehicle-treated mice. CsA, but not SRL or combined treatment, increased dermal mast cell numbers and TGF-beta1 levels in the skin. These findings demonstrate that specific immunosuppressive agents differentially alter the cutaneous tumor microenvironment, which in turn may contribute to enhanced development of UVB-induced skin cancer in transplant recipients. Furthermore, these results suggest that CsA alone causes enhanced growth and progression of skin cancer, whereas co-administration of SRL with CsA causes the opposite effect. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub |
| Databáze: | OpenAIRE |
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