It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

In cancers of the oral cavity, high histological malignancy grade is associated with higher risk of cervical lymph nodes, lung and bone metastases, which have great impact on the prognosis. Furthermore, early detection of these cancers is desirable so that treatment can aim at conserving oral functions and improving prognosis. It is known that several percent of leukoplakia that develop in the tongue become cancerous. Leukoplakia is a clinical diagnostic term, and histopathologically most cases show hyperkeratosis with epithelial dysplasia or hyperkeratosis without epithelial dysplasia. On the other hand, difficulties in histopathological diagnosis of severe epithelial dysplasia and carcinoma in situ are often encountered. In recent years, immunohistochemical staining of cytokeratins (CK), p53 and Ki-67 for precancerous lesions and squamous cell carcinoma (SCC) of the oral cavity has been reported. However, few reports have applied a combination of several immunohistochemical stainings to diagnosis. In the present study, with the objective to achieve a higher precision in histopathological diagnosis, we conducted and compared the immunohistochemical stainings of CK13, CK17, CK14 and p53 in 10 cases each of hyperkeratosis without epithelial dysplasia, hyperkeratosis with epithelial dysplasia, carcinoma in situ, and SCC in the tongue. The following results were obtained. CK13 was positive in all 10 cases of hyperkeratosis without epithelial dysplasia, and negative in all cases of hyperkeratosis with epithelial dysplasia, carcinoma in situ, and SCC. CK17 was negative in all 10 cases of hyperkeratosis without epithelial dysplasia, and was positive in all 10 cases of hyperkeratosis with epithelial dysplasia as well as 10 cases of carcinoma in situ and 9 of 10 cases of SCC. CK14 was negative or positive only in the basal cell layer or a few rows of cells in spinous layer adjacent to the basal cell layer in cases of hyperkeratosis without epithelial dysplasia, but was positive in all the epithelial layers in all 10 cases of hyperkeratosis with epithelial dysplasia, and also positive in the tumor in all 10 cases each of carcinoma in situ and SCC. For p53, positive reaction was observed in some cells of the basal cell layer in 2 of 10 cases of hyperkeratosis without epithelial dysplasia, while high positive rates were found in hyperkeratosis with epithelial dysplasia (10 of 10 cases) and SCC (9 of 10 cases). On the other hand, only 5 of 10 cases of carcinoma in situ were positive for p53. In conclusion, although the histopathological diagnosis of epithelial dysplasia and carcinoma in situ is based on hematoxylin-eosin stained sections, immunostaining and evaluation of CK13, CK17, CK14 and p53 are useful as an adjunct to histopathological diagnosis.

Tumors of the oral maxillofacial region consist of odontogenic and non-odontogenic tumors, and one often encounters tumor-like diseases that require differentiation from these tumors. When performing histopathological diagnoses of surgically resected tissues (surgical specimens), accurate evaluation of the extent of tumor expansion and the presence or absence of tumor in the surgical margin; as well as differentiation from similar diseases are necessary. Hence sectioning at the appropriate position is important. The present study

Actinomycosis is a specific inflammatory disorder infected by actinomycetes, one of oral resident flora. Although actinomycosis frequently arises as gnathitis or perignathitis in the oral and maxillofacial region, it is rarely localized in the oral soft tissue. This report deseribes a rare case of actinomycosis in the buccal region . A 43-year-old man visited our hospital because of a soft mass in the left buccal region, which had gradually increased in size 2 weeks before admission. We clinically diagnosed the lesion as a fibroma or abscess of the left buccal region. Excision of the mass was performed, and antibiotics were given. Since various sizes of drusen were histopathologically observed in the specimens, the final diagnosis was actinomycosis . As for pathogenesis, actinomycetes seems to cause infection by decubital ulcers due to bite injuries. In addition to oral and dental hygienic guidance, adequate treatments for peripheral periodontitis, apical periodontitis, tooth malalignment, and tooth loss were performed. Then, the prognosis is good.