Katsuhiko Tsukamoto

Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF-M.

Little is known about the mechanisms involved in the dysfunction of melanocytes in vitiligo epidermis. It is hypothesized that some cytokine/receptor interactions may be affected, resulting in dysfunction and/or loss of melanocytes. This study has compared the expression of endothelin (ET)‐1, the ET‐1 receptor (ETBR), granulocyte macrophage colony stimulating factor (GM‐CSF), stem cell factor (SCF), the SCF receptor (KIT protein), tyrosinase, and S100α between lesional and non‐lesional vitiligo epidermis. Analysis by reverse transcription‐polymerase chain reaction (RT‐PCR) and by western blotting for ET‐1 and SCF unexpectedly demonstrated up‐regulated expression of these cytokines in lesional vitiligo epidermis. Immunohistochemistry with antibodies to melanocyte markers revealed that at the edge of the lesional epidermis, melanocytes remain and express tyrosinase, S100α and ETBR, but not KIT protein or melanocyte‐specific microphthalmia‐associated transcription factor (MITF‐M). Quantitation of the staining revealed a slight or moderate decrease in the number of S100α, tyrosinase, and ETBR‐positive cells at the edge of the lesional epidermis. In contrast, the number of cells expressing KIT protein was markedly decreased at the edge of the lesional epidermis compared with the non‐lesional epidermis. At the centre of the lesional epidermis, there was complete loss of melanocytes expressing KIT protein, S100α, ETBR, and/or tyrosinase. Western blotting revealed down‐regulated expression of c‐kit and MITF‐M proteins at the edge of the lesional epidermis in vitiligo. These findings suggest that reduction in the expression of KIT protein by melanocytes and its downstream effectors, including MITF‐M, may be associated with the dysfunction and/or loss of melanocytes in vitiligo epidermis. Copyright

Serum soluble IL-2 receptor (sIL-2R) and eosinophil cationic protein (ECP) levels in atopic dermatitis.

We examined the serum soluble IL-2 receptor and eosinophil cationic protein levels in patients with atopic dermatitis (n = 21), patients with urticaria (n = 12), and normal healthy individuals (n = 14). We found that both soluble IL-2 receptor levels and eosinophil cationic protein levels were significantly higher in atopic dermatitis than in urticaria or normal controls. Although both soluble IL-2 receptor levels and eosinophil cationic protein levels were significantly correlated with clinical severity scores in atopic dermatitis, the correlation between eosinophil cationic protein levels and clinical severity scores was higher than that between soluble IL-2 receptor levels and clinical severity scores. However, soluble IL-2 receptor levels, eosinophil cationic protein levels and clinical severity scores were not significantly correlated with IgE levels. The chronological changes of soluble IL-2 receptor and eosinophil cationic protein levels differ from patient to patient. However, levels of soluble IL-2 receptor and eosinophil cationic protein seem to parallel to each other in 65% of patients with AD. Measurement of serum eosinophil cationic protein or soluble IL-2 receptor levels may be a useful tool to monitor the short-term or long-term disease activity of atopic dermatitis in conjunction with clinical severity scores.

A case of lymphoepithelioma-like carcinoma of the skin associated with Epstein-Barr virus infection.

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm with histopathologic similarities to nasopharyngeal carcinoma. The association of nasopharyngeal carcinoma with Epstein-Barr virus (EBV) is well documented. EBV has also been reported to be associated with LELC in only four sites (the stomach, salivary glands, lung, and thymus), but not in the skin. We report herein a case of EBV-positive LELCS. An 82-year-old female presented with a red nodule on the right cheek. Histologically, the entire dermis was occupied by atypical tumor cell nests with dense lymphocytic infiltration. Neoplastic cells were strongly positive for cytokeratin 14 but were negative for cytokeratins 19 and 20. EBV genomes in neoplastic cells were detected by polymerase chain reaction analysis and in situ hybridization for EBV-encoded RNA, suggesting an association with EBV.

Improving chemotherapeutic drug penetration in melanoma by imatinib mesylate

BACKGROUND Imatinib mesylate has specific activity in inhibiting select tyrosine kinase receptors, including platelet-derived growth factor receptors (PDGFRs) and c-kit. In general, melanomas widely express PDGFR and c-kit, and their in vivo resistance to chemotherapy is attributable to high tumor interstitial fluid pressure (IFP). Recent studies have suggested that PDGFR-beta inhibition reduces tumor IFP, and thus increases the uptake of concomitantly administered drugs. OBJECTIVE The present study was designed to investigate the potential of imatinib mesylate as a therapy for melanoma or as an adjuvant to chemotherapeutics. METHODS Using in vivo mouse models, the effect of imatinib mesylate on the growth of melanoma with or without dacarbazine was studied. RESULTS Imatinib mesylate enhanced the antitumor effect of dacarbazine on in vivo growth and lung metastases of melanoma cells, although treatment with only imatinib mesylate had no effect. We could detect perivascular expression of PDGF beta-receptor in melanoma tumors. Interestingly, dacarbazine uptake in melanoma was more than three-times increased by treatment with imatinib mesylate, while its uptake in serum or bone marrow was not affected by imatinib mesylate. CONCLUSIONS These data suggest interference with PDGF receptors, or their ligands, as a novel strategy to increase drug uptake and therapeutic effectiveness of chemotherapy for melanoma.