Seiki Mogi

Expression of cIAP-1 correlates with nodal metastasis in squamous cell carcinoma of the tongue

Cellular inhibitor-of-apoptosis protein 1 (cIAP-1) is a member of the inhibitor-of- apoptosis protein family, which predominantly regulates apoptosis. It has been suggested that expression of cIAP-1 correlates with certain clinicopathological features. The possible significance of cIAP-1 expression in cervical lymph node metastasis of tongue squamous cell carcinoma (SCC) is investigated. Seventy-five tongue SCCs were analyzed by immunohistochemistry. cIAP-1 immunoreactivity patterns were nuclear in 38 (51%), cytoplasmic in 47 (63%), and concurrent in 37 (49%) cases. Nuclear, cytoplasmic and concurrent cIAP-1 immunoreactions were significantly correlated with lymph node metastasis in tongue SCCs (P=0.0011, 0.0012, and 0.0006, respectively). The cleaved caspase-3, which is a marker of tumor apoptosis, and Ki-67 index, which is a marker of tumor proliferation, were immunohistochemically examined in 21 tongue SCCs with concurrent nuclear and cytoplasmic cIAP-1 expression and with metastasis, and in 23 tongue SCCs without concurrent nuclear and cytoplasmic cIAP-1 expression and without metastasis. Concurrent cIAP-1 expression was inversely correlated with caspase-3 (P=0.0066), but was positively correlated with Ki-67 expression (P=0.0028). The mode of invasion was associated with lymph node metastasis (P=0.014) and differentiation (P=0.013), but was not correlated with cIAP-1 expression. There was no statistically significant correlation between nuclear or cytoplasmic cIAP-1 expression and the clinicopathological factors of gender, age, clinical stage or differentiation. These results suggest that both patterns of cIAP-1 are useful markers for predicting cervical lymph node metastasis in tongue SCC.

Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4–1BB) costimulation

We investigated the cytolytic mechanism by CD4+ T cells in anti‐CD3 mAb‐induced redirected cytotoxicity against a murine Fc receptor‐bearing mastocytoma (P815) transfected with eitherCD80 or CD137 ligand (CD137L). CD137 costimulation preferentially induced anti‐CD3‐induced redirected cytotoxicity within 4 h. This cytotoxicity was efficiently abrogated by the addition of anti‐CD137L or anti‐CD95L mAb, or by treatment with a broad caspase inhibitor, Z‐VAD, suggesting that the induced cytotoxicity against CD137L‐P815 is dependent on CD95L‐mediated apoptosis. In contrast, the cytotoxicity against CD80‐P815, but not CD137L‐P815 was efficiently inhibited by an inhibitor of perforin‐dependent cytotoxicity, concanamycin A. Involvement of CD95L in the CD137L‐dependent cytotoxicity was confirmed by a failure of induction of cytotoxicity by CD4+ T cells from CD95L‐gene mutated gld mice. A rapid and remarkable induction of CD95L transcription within 1 h was observed by CD137L costimulation. These results demonstrated that CD137L costimulation induces a rapid induction of CD95L on CD4+ T cells and leads to apoptosis of CD95‐sensitive target cells. This biological function of CD137 in CD4+ T cells may play an important role for immune homeostasis.

Cementoblastoma Arising in the Maxilla of an 8-Year-Old Boy: A Case Report

Cementoblastoma is an uncommon disease, representing only 1–8% of all odontogenic tumours. Furthermore, this tumour is especially uncommon in children, as only five cases have been reported in this age group. Here, we describe a case of cementoblastoma arising in the maxilla of an 8-year-old boy, that was treated with a partial maxillectomy. The patients facial appearance has remained satisfactory, and the tumour has not recurred in the 9 years after the operation.

Congenital Unilateral Absence of the Submandibular Gland

Abstract Congenital absence of the major salivary glands is infrequent. This report is of a patient with congenital unilateral absence of the submandibular gland accompanied by squamous cell carcinoma of the buccal mucosa.

The Abnormal Expression of p53 Protein is a Predictive Prognostic Marker in Oral Leukoplakia

Abstract Objectives: The p53 tumour suppresser gene has been studied as a prognostic marker of oral squamous cell carcinoma. This study was conducted to search for a p53 predictive prognostic marker in oral premalignant leukoplakia using p53 immunostaining. Patients and Methods: Oral leukoplakia with epithelial dysplasia (60 patients) and healthy oral mucosa (15 patients) were immunohistochemically stained for the p53 protein. The healthy oral mucosa were obtained from a separate group of patients. Results: Fifty percent of the leukoplakia lesions were positive for p53 protein. Among the 60 lesions, 13 developed into squamous cell carcinoma, of which 10 showed p53 positive staining even before malignant transformation. Conclusion: Overexpression of p53 protein may be a useful diagnostic procedure for oral leukoplakias that have a high probability of developing into oral squamous cell carcinoma.

The Effect of Recombinant CD80-Adenovirus and Interleukin-12 on Generation of Cytotoxic T Lymphocytes Against Autologous Tumour in Patients with Oral Squamous Cell Carcinoma

Abstract Objectives: The combined effect of a costimulatory molecule, CD80 and interleukin-12, on generation of cytotoxic T lymphocytes against autologous tumour cells was investigated using peripheral blood lymphocytes from patients with oral squamous cell carcinoma. Materials and Methods: The use of recombinant adenovirus enabled efficient transduction of CD80 into all primary cultured squamous cell carcinoma cells. Peripheral blood mononuclear lymphocytes from patients with oral squamous cell carcinoma were co-cultured with CD80-transduced autologous tumour cells in the presence of interleukin-12. Results: The levels of cytotoxicity against autologous tumour in patients with squamous cell carcinoma were individually variable. However, the cytotoxicity against autologous tumour cells, but not against allogeneic tumour cells, was efficiently inhibited by the addition of either anti-CD3, anti-CD8, or anti-MHC class I mAb, suggesting that the induced cytotoxicity was specific for autologous tumour cells. Conclusion: The results suggest that generation of tumour-specific cytotoxic T lymphocytes using a combination with CD80 costimulation and interleukin-12 is effective in oral squamous cell carcinoma patients. However, a further approach for expanding the number of specific effector cells will be required for clinical application.