Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in non-melanoma skin cancer mouse models.
Proc SPIE Int Soc Opt Eng. 2015 Mar 2;9308:93080Q.
Rollakanti K 1, Anand S 2, Maytin EV 3.
1Department of Chemical and Biomedical Engineering, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, USA 44115 ; Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA 44195.
2Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA 44195 ; Department of Dermatology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA 44195.
3Department of Chemical and Biomedical Engineering, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH, USA 44115 ; Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA 44195 ; Department of Dermatology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA 44195.
Non-melanoma skin cancers (NMSCs) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common form of human cancer worldwide, and their incidence is increasing. Photodynamic therapy (PDT), mediated by topically applied aminolevulinic acid (ALA) and subsequent exposure to light (either a laser or a noncoherent source), is being increasingly used for the treatment of dermatological disorders, including BCC and SCC. However, therapeutic responses of NMSCs to ALA-PDT are currently not superior to standard therapies, although the latter have undesirable side effects including scarring. In this study, we report that preconditioning of skin tumors with calcitriol (active form of Vitamin D; Vit D) prior to ALA-PDT, significantly improves the treatment outcome. In BCC and UVB-induced SCC mouse models, we identified an increase in tumor-specific accumulation of ALA induced photosensitizer (protoporphyrin IX, PpIX) due to Vit D preconditioning, of up to 6-fold in vivo.
- increased expression of differentiation (145 fold, p < 0.02) and
- proliferation (42 fold, p < 0.005) markers were identified in BCC tumors, all leading to
- increased tumor destruction (18.3 fold, p < 0.03)
with the combination approach, as compared to ALA-PDT alone.
Histomorphological changes identified using hematoxylin and eosin staining, and results of TUNEL staining, together documented a beneficial effect of Vit D pretreatment upon tumor cell death. We conclude that this new combination approach with Vit D and ALA-PDT has great potential to achieve complete remission of NMSC tumors, with excellent cosmetic results and an overall beneficial impact upon patient care.
I had not noticed a hint of this wonderful benefit in previous studies
I have separately used topical vitamin D and Low Level Laser Therapy for other uses.
Questions as a result of this study include:
Is the ALA needed?
What frequencies of light does PDT use?
Would normal vitamin D provide some fraction of the 18X benefit of active vitamin D?
Note: ALA-based PDT is routinely used in Europe, but not the US
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