Effects of photodynamic therapy evaluated in a novel three-dimensional squamous cell carcinoma organ construct of the skin.

Squamous cell carcinoma (SCC) of the skin is a malignant neoplasm that occurs in all ethnic groups primarily due to chronic sun exposure and constitutes a major health problem worldwide. Novel therapies for SCC are in development but as yet no in vitro models capable of screening these therapies and their mechanism of action before proceeding to clinical trials in human subjects have emerged. For this reason we have developed and characterized a novel three-dimensional human SCC construct and validated it using photodynamic therapy (PDT), a well-established modality for treating in situ SCCs.

Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro.

Retinoic acid exerts a variety of effects on gene transcription that regulate growth, differentiation, and inflammation in normal and neoplastic skin cells. Because there is a lack of information regarding the influence of metabolic transformation of retinoids on their pharmacologic effects in skin, we have analyzed the functional activity of all-trans-, 9-cis-, and 13-cis-retinoic acid and their 4-oxo-metabolites in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts using gene and protein expression profiling techniques, including cDNA microarrays, two-dimensional gel electrophoresis, and MALDI-MS. It was previously thought that the 4-oxo-metabolites of RA are inert catabolic end-products but our results indicate instead that they display strong and isomer-specific transcriptional regulatory activity in both NHEKs and dermal fibroblasts.

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept.

Hailey-Hailey disease (HHD) is an autosomal dominant trait characterized by erythematous and oozing skin lesions preponderantly involving the body folds. In the present unusual case, however, unilateral segmental areas along the lines of Blaschko showing a rather severe involvement were superimposed on the ordinary symmetrical phenotype. Based on this observation and similar forms of mosaicism as reported in other autosomal dominant skin disorders, we postulated that in such cases, 2 different types of segmental involvement can be distinguished.

Phenotype diversity in familial cylindromatosis: a frameshift mutation in the tumor suppressor gene CYLD underlies different tumors of skin appendages.

Familial cylindromatosis (turban tumor syndrome; Brooke-Spiegler syndrome) (OMIM numbers 123850, 132700, 313100, and 605041) is a rare autosomal dominantly inherited tumor syndrome. The disorder can present with cutaneous adnexal tumors such as cylindromas, trichoepitheliomas, and spiradenomas, and tumors preferably develop in hairy areas of the body such as head and neck. In affected families, mutations have been demonstrated in the CYLD gene located on chromosome 16q12-13 and reveal the characteristic attributes of a tumor suppressor.