Susumu Hashitani

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands

Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2‐dimensional differential in‐gel electrophoresis (2‐D‐DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix‐assisted laser desorption/ionization time‐of‐flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.

Prognostic significance of cyclooxygenase-2 and DNA topoisomerase IIα expression in oral carcinoma

Despite recent advances in the diagnosis and treatment of oral carcinoma, outcomes remain disappointing. The identification of new prognostic factors is necessary to improve survival. To determine the prognostic significance of cyclooxygenase (COX)‐2 and DNA topoisomerase (DNA‐Topo) IIα expression in patients with oral carcinoma, we immunohistochemically examined these enzymes and studied their relation to overall 5‐year survival.

Migration of a foreign body (staple) from the oral floor to the submandibular space: case report

We report a case of foreign bodies, staples, accidentally put in the oral cavity. One of the staples had migrated from the oral floor through the submandibular space and penetrated the submandibular gland. The staple was removed successfully using CT scan and fluoroscope imaging.

Effect of a nitric oxide synthase inhibitor and a CXC chemokine receptor-4 antagonist on tumor growth and metastasis in a xenotransplanted mouse model of adenoid cystic carcinoma of the oral floor

Nitric oxide (NO) is related to angiogenesis and tumor progression and chemokine receptor-4 (CXCR4) plays a central role in cell migration in metastasis and dissemination of cancer. The present study evaluated the effectiveness of a NOS inhibitor and a CXCR4 antagonist, given as single agents or in combination, in a xenotransplanted mouse model of adenoid cystic carcinoma (ACC) of the oral floor. A metastatic tumor (ACCIM) derived from a cervical metastatic lesion of human ACC that was transplantable in nude mice was used. ACCIM showed a high frequency of spontaneous metastasis to the lung when transplanted subcutaneously in nude mice. Mice with subcutaneous transplants of ACCIM were subdivided into six groups and intraperitoneally received one of the following treatments daily for 5 weeks: a) PBS (control), b) AMD3100 (CXCR4 antagonist), c) L-NAME (NOS inhibitor), d) 1400W (iNOS inhibitor), e) both AMD3100 and L-NAME (AMD3100+L-NAME) and f) both AMD3100 and 1400W (AMD3100+1400W). Tumor growth was evaluated during treatment and metastasis was assessed at 28 weeks. Single-agent treatment with AMD3100, L-NAME or 1400W inhibited tumor growth by 20.8, 26.5 and 54.5%, respectively. Combined treatment with AMD3100+L-NAME and AMD3100+1400W inhibited tumor growth remarkably by 48.0 and 50.2%, respectively. Immunohistochemical analysis revealed lower expression of CXCR4, iNOS and eNOS in tumor cells treated with AMD3100+L-NAME or AMD3100+1400W compared to control tumor cells and increased numbers of apoptotic tumor cells were demonstrated using the TUNEL method. CXCR4 expression decreased in 1400W-treated tumors using western blot analysis. When the effect of each agent on tumor-induced angiogenesis in tumor stroma was examined histologically, microvessel density was significantly lower in the groups treated with 1400W, AMD3100+L-NAME or AMD3100+1400W compared to the control, AMD3100 and L-NAME groups. Moreover, treatment with AMD3100 or 1400W markedly inhibited lung metastasis. Our results indicated that single-agent treatment with 1400W and combined treatment with AMD3100+L-NAME or AMD3100+1400W induced apoptosis and significantly inhibited tumor-induced angiogenesis and proliferation of ACCIM in vivo. Blockade of CXCR4 and iNOS was suggested to inhibit lung metastases from ACCIM. CXCR4 and iNOS may, thus, be important prognostic factors for long-term survival in ACC.

Allergy to metal caused by materials used for intermaxillary fixation: Case report

A 21-year-old man with no history of contact allergy developed eczema over his entire body 2 days after he had had intermaxillary fixation (IMF) of a mandibular fracture. Patch testing showed a strong reaction to nickel so the arch bars and wires that had been used for fixation were removed and replaced with resin brackets, elastic bands, and a chin cap. The eczema disappeared 2 days later.

Establishment of a nude mouse transplantable model of a human malignant fibrous histiocytoma of the mandible with high metastatic potential to the lung

Malignant fibrous histiocytoma (MFH) is one of the highest-grade sarcomas arising in bone and soft tissue. Its prognosis is poor because of chemoresistance and high metastatic potential to various organs. Few cases arising of MFH of the mandible or oral cavity have been documented. We established a tumor line in nude mice (MFH-N), which was derived from human MFH of the mandible and examined the characteristics of this tumor line. Histologically, MFH-N was identical to the original tumor and showed a storiform-pleomorphic pattern, but had low metastatic potential. Immunohistochemically, both the original and xenografted tumors expressed vimentin, S-100, α-SMA, and histiocytic marker CD68. Lysozyme was expressed by the original tumor, but only sporadically by the xenografted tumor. RT-PCR analysis demonstrated human β-actin in this tumor line, indicating the human origin. In a parallel experiment, we established a new MFH cell line (MFH-NC) from MFH-N. Tumor cells inoculated into the flanks and submandibular region of nude mice developed into tumors histologically similar to MFH-N and the original tumor; multiple lung metastases were detected approximately 5xa0months after inoculation. The expression levels of various metastasis-related molecules differed between MFH-N and MFH-NC on Western blotting. In MFH-NC, the expressions of MMP7, MMP9, MT1-MMP, CXCR4, COX-2 and integrin α4 were up-regulated, while those of MMP2 and TIMP1 were down-regulated. Expression of TIMP2, integrinαL and sialyl lewis X were not detected in either line. Our findings suggest that the MFH-N tumor line transplantable in nude mice is a useful model for studying the biological behavior of MFH.

Intramuscular Lipoma of the Cheek : Report of Two Cases

Abstract Two cases of intramuscular lipoma occurring in the cheek of a 39-year-old and of a 55-year-old Japanese males are presented. These were excised by the intraoral approach. Histopathologically, these lesions were composed of the adipose cell-like tumor cells infiltrating in the striated muscles. There has been no evidence of tumor recurrence after operation.

Benign Fibrous Histiocytoma of the Upper Lip: A Case Report

Abstract A rare case of benign fibrous histiocytoma arising in the upper lip in a 76-year-old female is presented. A well-defined tumor measuring 1 cm existed in the submucosal area of the right side of the upper lip. With the patient under local anesthesia, the tumor was excised. Microscopically, the excised tumor was diagnosed as a benign fibrous histiocytoma. There has been no evidence of tumor recurrence after the operation.

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.