Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.

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.

Long-term effects of Ag-containing alloys on mucous tissue present in biopsy samples.

The aim of this study was to investigate the long-term effects of alloys containing silver (mainly Ag-Sn alloy) on oral mucous tissue. We observed biopsy tissue specimens from patients diagnosed as having amalgam tattoo and/or metal pigmentation by light and electron microscopy and electron-probe microanalysis (EPMA). In most cases, Ag-Sn alloy was present in the tissue but it could not be confirmed if the alloy originated from amalgam. Distributions of both Ag-S and Ag-Sn have typical patterns. Most Ag forms Ag2S and is stably deposited in three patterns along the collagen, basement membrane, and fibrous cells without inducing any host reaction. On the other hand, Sn forms large granules that contain Ag, S, C, N, P, and Ca, and is in soft state in the tissue. Tissue reactions to the alloy become weaker as time passes.

Immunohistochemical localization of parathyroid hormone-related protein (PTHrP) and serum PTHrP in normocalcemic patients with oral squamous cell carcinoma.

Cancer cells produce parathyroid hormone-related protein (PTHrP) in the early phase of malignancy development, before hypercalcemia occurs. The relationship between PTHrP and the clinicopathologic features of oral squamous cell carcinoma is poorly understood. We studied 60 patients (43 men, 17 women; mean age, 64.8 +/- 11.2 years) with primary oral squamous cell carcinoma, from whom pretreatment biopsy specimens were obtained. We examined the relationship among immunohistochemical PTHrP expression, serum PTHrP levels, clinical characteristics of the tumor, and histopathologic aspects of the tumor. The mean calcium concentration for the 60 patients was 9.1 +/- 0.4 mg/dl. No patients had laboratory evidence of hypercalcemia before treatment. Six patients had serum levels of C-terminal (C)-PTHrP higher than the normal level of 55.3 pmol/l. There were no significant differences in serum C-PTHrP levels according to TNM stages. Abundant positive immunoreactivity for anti-PTHrP (1-34) antibody was recognized diffusely in the whole cytoplasm of many tumor cells. Anti-PTHrP (38-64) antibody staining tended to localize as small granules in the cytoplasm, especially close to the nuclear periphery. There was no correlation between the serum C-PTHrP concentration and the intensity of either immunostain. The intensity of PTHrP was proportionally related to the degree of differentiation or extent of keratinization (P < 0.05) and the histologic malignancy grade of the tumor (P < 0.05), when using antibody against PTHrP (1-34), but not when using antibody against PTHrP (38-64). Serum C-PTHrP levels did not correlate with the intensity of cellular PTHrP expression and characteristics of the tumor at the initial patient visit. The fragment that includes PTHrP (1-34) may be involved in the differentiation of oral squamous cell carcinoma. The differences between immunoreactivities may have been due to differing tissue malignancies and the use of different antibodies. The results suggest the need for caution when interpreting immunoreactivities of PTHrP in malignancies.

Magnetic resonance imaging findings of nodular fasciitis in the mental region.

Nodular fasciitis (NF) is a benign reactive lesion of the soft tissues related to the fascia and characterized by fibroblastic proliferation. The most common site is the upper extremities (46%), followed by the head and neck region (20%). In the orofacial region, the lesion typically develops within the subcutaneous structures overlying the angle and inferior border of the mandible and the zygoma. Magnetic resonance imaging (MRI) findings of NF in the orofacial region are almost unreported in the literature. In the present case report, we describe MRI findings of mental NF in a 19-year-old woman. MRI revealed a well-defined, round soft-tissue mass lying on the mentum. On T1-weighted MRI, the lesion was isointense to skeletal muscle; it was hyperintense to skeletal muscle on T2-weighted MRI, and was enhanced by Gd-diethylenetriamine pentaacetic acid (DTPA). Histologic examination revealed abundant myxoid degeneration dispersed in the lesion. The T2-weighted higher heterogeneous signal intensity was likely due to abundant myxoid degeneration or the cellular component of the lesion. A strong bright signal intensity belt appeared in the periphery of the lesion on Gd-DTPA enhancement. This rim enhancement appeared to represent small arterioles and venules that were visible in the peripheral area on histologic examination.