Human malignant melanoma represents a difficult therapeutic challenge to both medical scientists and practicing physicians. However, the biologic uniqueness of the tumor may provide opportunities for exploitation in therapeutics. This study proposed to undertake a systemic approach to the chemotherapy of malignant melanoma based upon the uniqueness of pigment-cell metabolic pathway pertaining to conversion of tyrosine and dopa with subsequent formation of melanin by tyrosinase and its related enzymes. The sulphur homologue of tyrosine, cysteinylphenol (CP), its amine derivative, cysteaminylphenol (CAP), and their N-acetyl and alpha-methyl derivatives have been synthesized and tested in in vivo and in vitro melanocytotoxicity and antimelanoma effects. These phenolic thioethers (PTEs) and phenolic thioether amine (amides) (PTEAs), which are substrates of tyrosinase, showed significant cytotoxicity that is selective to melanocytes and melanoma cells. Most previous attempts to impair the melanin pathway as a therapeutic strategy have been of limited success because they have been directed to catecholic compounds that are unstable and insufficient in lethality at physiologically tolerable doses. By contrast, our approach relies on phenolic compounds, PTEs and PTEAs, which are more stable than catechols and become toxic only after oxidation by tyrosinase. We found PTEA as the most promising agent for the future development of chemotherapeutic agents. The possible biologic, chemical, and pharmacologic reactions of these synthetic compounds within the melanoma cells are studied and discussed.

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A 41-year-old woman with desmoplastic trichoepithelioma associated with pigmented nevus presented. Pigmented nevus had been present on her face at birth. She had received cryotherapy and dermabrasion at a small part of the pigmented nevus. As a result of the therapy, the discoloration disappeared. The lesion lately increased and became hard. Histologically, the lesion was composed of two distinctive but intimately mixed cellular components; nevus cells and basaloid cells. In the pigmented lesion, basaloid cells were not present. To our knowledge, this is the first reported case of desmoplastic trichoepithelioma associated with nevocellular nevus in Japan.

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