Kuniyasu Moridera

Up-regulation of neutrophil gelatinase-associated lipocalin in oral squamous cell carcinoma: Relation to cell differentiation

Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin2, LCN2) is a secreted glycoprotein with increased expression in solid tumors. The expression and functions of NGAL in oral cancer, however, remain unclear. We investigated the expression of NGAL in oral cancer tissues and oral cancer cell lines. By immunohistochemical examinations, NGAL expression was strongly up-regulated in well-differentiated OSCC tissues and moderately to weakly up-regulated in moderately to poorly differentiated OSCC tissues. In contrast, NGAL expression was weak or very weak in normal mucosa and leukoplakia. By western blot analysis, NGAL expression levels positively correlated with cell morphology patterns and loss of E-cadherin. In addition, the enzymatic activity of the NGAL/MMP-9 complex significantly correlated with the results obtained by zymographic analysis. In conclusion, NGAL expression is high in well-differentiated cancer, suggesting that NGAL may be a useful diagnostic marker of tumor-cell differentiation.

Novel PTCH1 mutations in Japanese Nevoid basal cell carcinoma syndrome patients: two familial and three sporadic cases including the first Japanese patient with medulloblastoma

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is inherited in an autosomal dominant mode, and is characterized by a combination of developmental abnormalities and predisposition to form a variety of tumors. The hedgehog receptor Patched1 (PTCH1) has been identified as the gene mutated in NBCCS. We analyzed PTCH1 in two familial and three sporadic Japanese NBCCS cases, and identified five germline mutations in PTCH1. Two cases have a nonsense mutation (c.3058C>T and c.2760C>A), one a splice site mutation (c.584+2T>G), one a 1 bp insertion (c.2712_2713insA) and one a 1 bp deletion (c.980Gdel). All mutations induce truncation of the PTCH1 protein or could induce nonsense-mediated mRNA decay. The 11-year-old male patient with splice-site mutation (c.584+2T>G) had medulloblastoma (MB) at the age of 1 year. This is the first NBCCS patient with molecularly defined MB in Japan.

Establishment of a new cell line with neuronal differentiation derived from small cell neuroendocrine carcinoma of the maxillary sinus.

Objective: It is well known that small cell neuroendocrine carcinoma (SNEC) arising at extrapulmonary sites has a poor prognosis and an interesting biological characterization. To understand biological characterization and elucidation of the origin of the histogenesis of SNEC, we report the establishment of a new SNEC cell line and characteristics of neuroendocrine properties including neuronal differentiation by treatment with dibutyryl cyclic AMP (db-cAMP). Methods: We established a new cell line (SNEC-MI) derived from SNEC of the maxillary sinus by a modified spill-out method, and verified neuroendocrine properties including neuronal differentiation by immunocytochemical and immunoblotting methods. Results: The established cell line showed spherical or spindle shape in monolayer culture and was positive for neuron-specific enolase (NSE), neuronal cell adhesion protein (N-CAM, CD56) and gastrin-releasing peptide. NSE was also demonstrated in the cultured medium and dense-core neuroendocrine granules were detected ultrastructurally in the cytoplasm. Treatment of cells with db-cAMP markedly induced the development and elongation of neuronal processes, which formed a netlike arrangement. Characterization of these elongated neuronal processes revealed them immunoreacting intensely with high molecular-weight neurofilament, and a time-dependent increase of microtubule-associated protein-2 in cell lysates. Conclusions: These findings indicated that this cell line possesses the capability to differentiate into neuronal cells, and supported the hypothesis that extrapulmonary SNEC might be derived from a pluripotent stem cell.

Unicystic ameloblastoma metastasizing to multiple cervical lymph nodes

Ameloblastoma is the most common odontogenic tumor, but the incidence of its metastasis is extremely low. We report a case of unicystic ameloblastoma metastasizing to the cervical lymph nodes. This patient pointed out a radiolucent cystic lesion with impacted wisdom tooth in the left mandibular region, and recieved enucleation of the cystic lesion and removal of the wisdom tooth. Histopathogical diagnosis was unicystic ameloblastoma. Three years later, this patient complained of a swelling in the left submandibular region. A CT scan showed a bilobed cystic mass measuring 30 mm in diameter compressing the submandibular gland, and we performed extirpation of the mass with the submandibular gland and associated lymph nodes. Histologically, the lesion was cystic and lymph follicles were seen in the cyst-like wall. The laminated epithelium of cyst wall was ameloblastomatous epithelium, and two lymph nodes associated with cystic lesion also included ameloblastomatous epithelium. This is the first report of metastasizing unicystic ameloblastoma.

Osteonecrosis of the jaw in an AIDS patient: a case report

We report a rare case of osteonecrosis of the jaw following necrotizing gingivitis in a Japanese AIDS patient. Intraoral examination showed exposed necrotic bone in the left mandible and spontaneous loss of teeth. This patient was successfully treated with highly active anti-retroviral therapy combined with minimally invasive surgical procedures to remove the osteonecrosis of the jaw.

Malignant Fibrous Histiocytoma of the Mandible: Report of a Case

Abstract Malignant fibrous histiocytoma is the most common soft tissue sarcoma that is found to occur during late adult life; however, few cases have been documented in the mandible and oral cavity. A rare case of malignant fibrous histiocytoma, predominantly of the pleomorphic type, arising in the mandible is presented. The literature available on malignant fibrous histiocytoma of the oral cavity is reviewed and discussed.