To enhance the selective delivery of antitumor drugs into regional lymph nodes and cancerous tissues via a hyaluronate (HA) receptor (CD44), we synthesized HA-mitomycin C complex and HA-epirubicin complex. To investigate the specific distribution of HA into regional lymph nodes and to evaluate the HA receptor on lewis lung carcinoma cells, we also synthesized 14C-labelled HA and fluorescent HA (FR-HA). The metabolic studies of 14C-HA and HA-epirubicin complex were performed in rats. The specific distribution of both compounds to the lymph nodes were observed after sc treatment. Internalization mechanisms of HA into carcinoma cells (lewis lung carcinoma) via HA receptor was investigated using fluorescent HA (FR-HA) in vitro. Internalization of FR-HA following binding to the cell surfaces was observed. HA-Mitomycin C (MMC) exhibited potent anti-metastatic effects against lewis lung carcinoma implanted in mice at an extremely low dose (0.01 mg/kg) whereas free MMC had no effects.
A wide variety of cutaneous manifestations have been described in association with Crohn’s disease (CD). We describe a patient with a 2-year history of CD who developed both lichen planus (LP) and lichen nitidus (LN) in addition to erythema nodosum (EN) lesions. The clinical course of EN reflected the activity of the bowel disease, whereas LP and LN appeared to persist independently of the ongoing disease activity. Immunohistochemical studies of the infiltrates in these cutaneous and intestinal lesions showed that the majority of the infiltrates were T cells expressing T cell receptor (TCR)-αβ. Analyses of TCR V gene expression in these infiltrating T cells demonstrated a different pattern of Vβ expression that provides an explanation for the difference in the clinical courses of these lesions. LP and LN lesions are likely to be mediated by T cells with antigen specificity distinct from those that cause EN and intestinal lesions.
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