Green tea (-)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met.

Hepatocyte growth factor (HGF) and c-Met have recently attracted a great deal of attention as prognostic indicators of patient outcome, and they are important in the control of tumor growth and invasion. Epigallocatechin-3-gallate (EGCG) has been shown to modulate multiple signal pathways in a manner that controls the unwanted proliferation and invasion of cells, thereby imparting cancer chemopreventive and therapeutic effects. In this study, we investigated the effects of EGCG in inhibiting HGF-induced tumor growth and invasion of oral cancer in vitro and in vivo. We examined the effects of EGCG on HGF-induced cell proliferation, migration, invasion, induction of apoptosis and modulation of HGF/c-Met signaling pathway in the KB oral cancer cell line. We investigated the antitumor effect and inhibition of c-Met expression by EGCG in a syngeneic mouse model (C3H/HeJ mice, SCC VII/SF cell line). HGF promoted cell proliferation, migration, invasion and induction of MMP (matrix metalloproteinase)-2 and MMP-9 in KB cells. EGCG significantly inhibited HGF-induced phosphorylation of Met and cell growth, invasion and expression of MMP-2 and MMP-9. EGCG blocked HGF-induced phosphorylation of c-Met and that of the downstream kinases AKT and ERK, and inhibition of p-AKT and p-ERK by EGCG was associated with marked increases in the phosphorylation of p38, JNK, cleaved caspase-3 and poly-ADP-ribose polymerase. In C3H/HeJ syngeneic mice, as an in vivo model, tumor growth was suppressed and apoptosis was increased by EGCG. Our results suggest that EGCG may be a potential therapeutic agent to inhibit HGF-induced tumor growth and invasion in oral cancer.

Tissue-engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation.

OBJECTIVES/HYPOTHESIS: Treatment and management of tracheal defects remain challenging in head and neck surgery. Various reconstruction techniques have been used, with no consensus on the best approach. The purpose of this study was to explore a novel strategy to fabricate tissue-engineered trachea by using fibrin/hyaluronic acid (HA) composite gel and evaluate the feasibility of creating tracheal cartilage. STUDY DESIGN: A preliminary animal experiment. METHODS: Chondrocytes from rabbit cartilage were expanded and seeded into a culture dish at high density to form mechanically stable allograft tracheal cartilage using fibrin/HA composite gel. After a longitudinal cervical skin incision, the trachea was exposed and a rectangular defect (1 x 0.5 cm) was created on the cervical trachea by scalpel on six rabbits. Tissue-engineered cartilage using fibrin/HA composite was trimmed and fixed to defect boundaries with Tissucol (Baxter International, Deerfield, IL). Postoperatively, the site was evaluated endoscopically, histologically, radiologically, and functionally. RESULTS: Postoperatively, rigid telescopic examination showed that the implanted scaffolds in all cases were completely covered with regenerated mucosa without granulation or stenosis. Histologic data showed ciliated epithelium regenerated at the operated site from 2 months postoperatively. Ciliary beat frequency of ciliated epithelium on implants was very similar to normal respiratory mucosa. Computed tomography images revealed fine luminal contour of the regenerated site. However, allograft cartilage implanted was found to be partially preserved on the postoperative specimen. CONCLUSIONS: The tracheal luminal contour and functional epithelial regeneration without graft rejection and inflammation were observed after repair of a tracheal resection using allogeneic implants with chondrocytes cultured with fibrin/HA.

Epicatechin protects auditory cells against cisplatin-induced death.

Cisplatin, a chemotherapeutic drug that is widely used to treat various cancers, promotes ototoxicity at higher doses. In this study, the effect of epicatechin (EC) on cisplatin-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and in vivo in zebrafish. Cisplatin promoted apoptosis and altered mitochondrial membrane potential (MMP) in HEI-OC1 cells. EC inhibited cisplatin-induced apoptosis and intracellular reactive oxygen species (ROS) generation. Labeling of zebrafish lateral line hair cells by the fluorescent dye YO-PRO1 was lost upon exposure to cisplatin, and EC protected against this cisplatin-induced loss of labeling in a dose-dependent manner. Scanning and transmission electron micrographs showed that treatment with EC protected against cisplatin-induced loss of kinocilium and stereocilia in zebrafish neuromasts. These results suggest that EC prevents cisplatin-induced ototoxicity by blocking ROS generation and by preventing changes in MMP.