Susceptibility of T cell receptor-alpha chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus.

The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-alpha(-/-) mice and B6 TCR-delta(-/-) mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-alpha(-/-) mice with low FU (0.2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2.0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-delta(-/-) mice at a very low incidence. Specifically, the skin lesions of TCR-alpha(-/-) mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.

Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma.

The long-term effects of Lipiodol-transcatheter arterial embolization (Lp-TAE) combined with cisplatin (CDDP) or doxorubicin (ADM) on unresectable hepatocellular carcinoma (HCC) were analyzed. Eighty-four consecutive patients with unresectable HCC were treated with TAE. Of the 84, 38 patients were treated with CDDP-Lp-TAE (CDDP group), whereas the remaining 46 patients were treated with ADM-Lp-TAE (ADM group). No significant difference in characteristics of patients and tumors was noted between the groups. CDDP (50 mg) or ADM (20-50 mg) was administered with Lp followed by embolization of the feeding arteries using gelatin sponge particles. The mean number of TAE treatments was 3.3 in the CDDP group and 1.9 in the ADM group (p < 0.01). The 5-year overall survival rates of the CDDP group and the ADM group were 19% and 6%, respectively. The overall survival rate of the CDDP group was significantly higher than that of the ADM group (p < 0.05). No serious side effects were observed in either group. CDDP-Lp-TAE improved the prognosis of unresectable HCC compared with ADM-Lp-TAE, which may be attributable to the fact that CDDP-Lp-TAE treatment could be repeated more times than ADM-Lp-TAE.