Yukiko Ono

Clinicopathologic significance of laminin‐5 γ2 chain expression in squamous cell carcinoma of the tongue

The laminin‐5 γ2 chain plays an important role in cell migration during tumor invasion and tissue remodeling.

Epidermal growth factor receptor gene amplification is correlated with laminin-5 γ2 chain expression in oral squamous cell carcinoma cell lines

Abstract Both epidermal growth factor receptor (EGFR) gene amplification and laminin (Ln)-5 γ2 chain overexpression have been reported to be poor prognostic factors in patients with squamous cell carcinoma (SCC) of the head and neck. Here we report our investigation of the relationship between EGFR gene amplification and Ln-5 γ2 chain expression in seven SCC cell lines, since both epidermal growth factor (EGF) signaling and Ln-5 γ2 have been reported to be involved in cell motility. The degree of correlation between EGFR gene amplification and Ln-5 γ2 chain expression was evaluated by Southern and Western blot analyses. EGFR gene amplification was detected in all SCC cell lines at levels 5–50 times those in DNA from normal liver tissue. EGFR gene amplification increased with Ln-5 γ2 chain protein expression in seven cell lines, showing close correlation between EGFR gene amplification and Ln-5 γ2 chain protein expression. In order to show the causal relationship, we analyzed the effects of transforming growth factor-α (TGF-α), tyrosine kinase inhibitor of EGFR, and neutralizing antibody against EGFR, on the expression of Ln-5 γ2 in these cell lines. In two cell lines in which EGFR gene amplification was low , expression of both protein and mRNA of the Ln-5 γ2 chain increased in the presence of TGF-α, and Ln-5 γ2 chain expression was inhibited by neutralizing antibody against EGFR. In all cell lines, Ln-5 γ2 chain expression was inhibited by tyrosine kinase inhibitor which acts selectively on the EGFR signal transduction pathway under the stimulus of TGF-α. These results suggest that EGFR gene amplification and the EGFR signaling pathway can act as positive regulators on the induction of the Ln-5 γ2 chain secreted by tumor cells.

Keratinocytes of Tissue-Engineered Human Oral Mucosa Promote Re-Epithelialization After Intraoral Grafting in Athymic Mice

PURPOSE The objective of this study was to investigate the role of grafted oral keratinocytes in a transplanted ex vivo-produced oral mucosa equivalent (EVPOME) in the regeneration and/or healing process of the oral mucosa at the recipient site. MATERIALS AND METHODS The EVPOME was developed in a serum-free defined culture system without a feeder layer. EVPOME is composed of a stratified layer of human oral keratinocytes that are seeded onto a human cadaveric dermis, AlloDerm (LifeCell, Branchburg, NJ). Intraorally grafted EVPOMEs in athymic mice (BALB/c) were excised, contiguous with the surrounding oral mucosa, on days 5, 7, 14, and 21 after grafting. Serial sections were stained with hematoxylin-eosin and immunohistochemically analyzed for cytokeratin 17 (CK17) expression to distinguish the human-cultured EVPOME epithelial keratinocytes from murine oral keratinocytes. RESULTS All EVPOME epithelial cells showed intense immunoreactivity for CK17, whereas mouse buccal mucosal epithelial cells did not show CK17 immunoreactivity. The grafted EVPOME maintained a stratified epithelial layer for up to 5 days after grafting. By day 7 after grafting, a portion of the EVPOME epithelial layer peeled away from the AlloDerm, and a thin, CK17-immunonegative epithelial layer extended from the adjacent thick epithelial layer of the mouse and contacted the CK17-immunopositive EVPOME epithelium. From days 14 to 21 after grafting, the stratification of the CK17-immunonegative continuous mouse epithelium increased compared with earlier time points and showed a similar appearance to the epithelium of the adjacent mouse mucosa. In contrast, no epithelial coverage of the AlloDerm that was grafted without keratinocytes was observed for up to 21 days after grafting. The grafted AlloDerm without cells resulted in tissue necrosis that was accompanied by a dramatic infiltration of inflammatory cells by day 14. CONCLUSIONS These findings suggest that grafting of EVPOME with viable oral keratinocytes onto an intraoral mucosal wound plays an active role in promotion of re-epithelialization of the oral wound during the subsequent healing process.

A Case of Bone Resorption Following Augmentation Genioplasty with a Silicone Implant

There are two types of operation for chin augmentation. One is augmentation genioplasty by means of horizontal osteotomy, and the other is implantation with alloplastic materials, such as silicone implants and hydroxyapatite blocks. Augmentation genioplasty with silicone implants is easy and can be performed under local anesthesia. However, augmentation genioplasty with silicone implants tends to produce post-operative infection, bone resorption of the chin, and malposition of implants. We report a case of mandibular resorption and infection following augmentation genioplasty with a silicone implant.A 50-year-old female underwent augmentation genioplasty with silicone implantation about 8 years ago in Korea. At 7 years post-operation she noticed swelling and paresthesia in the mental region and so consulted our department. An abscess and an operative scar were observed in the intraoral mandibular incisor region. An implant was observed in the mental region, and some absorption of the bone beneath the implant radiographically. The implant was removed surgically. The implant surrounded by granulation tissue caved in the surface of the chin bone which was absorbed irregularly. These findings suggested that the resorption of surface bone under silastic implant was caused by the continuous pressure of musculus mentalis.