Kenichi Hiramoto

Experimental therapy using interferon-gamma and anti-Fas antibody against oral malignant melanoma cells.

The Fas/FasL signalling system plays an important role in chemotherapy-induced apoptosis in several different cell types. After interferon-gamma (IFN-&ggr;) treatment, we have previously reported a significant increase in Fas expression in oral malignant melanoma cell lines (MMN9, PMP, MAA, HMG) in vitro, and combination therapy using IFN-&ggr; and anti-Fas antibody (CH-11) has shown a synergistic anti-proliferative effect in MMN9 cells. There have been several in-vitro studies using CH-11, but there are few reports of its anti-tumour effect in vivo. In this study, we investigated experimental therapy using anti-Fas antibody against MMN9 in vivo in a mouse model, and histologically examined tumour tissue removed from BALB/c nude mice. Animals that received both IFN-&ggr; and CH-11 showed a 53.8% increase in anti-tumour effect (P=0.0018) 20 days after the first administration. In the histological study, the combined administration group tested positive in terminal deoxynucleotidyl transferase-mediated nick end labelling staining, and showed significantly increased levels of Fas expression on immunostaining compared with the vehicle group. These results show the efficacy of anticancer therapy using IFN-&ggr; and anti-Fas antibody via the modulation of Fas-mediated apoptosis. Moreover, inhibition of IFN-&ggr;/CH-11-induced apoptosis with a general caspase inhibitor (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) reduced cell death significantly in vitro. Bcl-2 cleavage did not occur under these conditions, suggesting a relationship between caspase activation and Bc1-2 cleavage in MMN9 cells.

Squamous Cell Carcinoma of the Lower Lip in an Elderly Patient with Xeroderma Pigmentosum

Abstract Xeroderma pigmentosum is a rare, autosomal recessive genetic disease accompanied by abnormal DNA function due to damage by ultraviolet radiation. Xeroderma pigmentosum typically has general features of high light sensitivity and a high incidence of skin cancer in regions exposed to sunlight. We report the case of squamous cell carcinoma of the lower lip in an 82-year-old patient with xeroderma pigmentosum who was successfully treated with peplomycin after first receiving treatment for diabetes.