Usefulness of a fluorescence visualization system for the detection of oral precancerous and early cancerous lesions.

Early detection of precancerous and early cancerous lesions could greatly reduce both the mortality and morbidity of oral cancer. The objective of this study was to analyze a fluorescence visualization (FV) system for the detection of precancerous and early cancerous lesions in rat tongue carcinogenesis and human oral cancerous lesions using for the first time a 4NQO rat model and human tissue. Based on the results from the rat tongue carcinogenesis model, under direct FV, the normal oral mucosa emitted various shades of pale green autofluorescence. In the precancerous and early cancerous cases, the lesion appeared as an irregular dark area. Histological examination of the lesions showed that the VELscope system had a sensitivity of 95% and specificity of 100% in discriminating normal mucosa from dysplasia/carcinoma in situ (CIS) or invasive carcinoma. The proliferating cell nuclear antigen (PCNA) protein level was gradually increased with progression of carcinogenic transformation. Furthermore, the results of PCNA and FV loss (FVL) were correlated. Next, results from 17 patients were also presented. Histological examination of the lesions showed that the VELscope system had a sensitivity of 95% and specificity of 100% in discriminating normal mucosa from severe dysplasia/CIS or invasive carcinoma. There were no normal epithelium cells in any of the FVL regions. Furthermore, to clarify the usefulness of FV compared to vital staining with iodine, we investigated the surgical margins of early oral squamous cell carcinoma (OSCC) tissues and compared the FVL and iodine unstained area (IU). The percentage of various types of dysplasia were almost equal when comparing the FVL and IU. These results suggest that this direct FV device has the potential for simple, cost-effective screening, detection and margin determination of oral precancerous and early cancerous lesions.

Effects of CRM197, a specific inhibitor of HB-EGF, in oral cancer.

CRM197, a nontoxic mutant of diphtheria toxin, is a specific inhibitor of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family that has been implicated in the increased progression, proliferation, and metastasis of oral cancer. In this study, we analyzed the antitumor effects of CRM197, which represent possible chemotherapeutic agents for oral cancer. In the experiment, we used the oral squamous cell carcinoma cell lines HSC3 and SAS. Cells treated with CRM197 were analyzed based on cell viability, MTT assay, invasion assay, Western blot, and zymography. HSC3 cells were injected subcutaneously into female BALB/c nu/nu mice at 5 weeks of age. CRM197 and/or CDDP were injected intraperitoneally into tumor-bearing mice, and tumor volume was measured over time. HB-EGF expression in HSC3 and SAS cells treated with CRM197 was significantly reduced and cell proliferation was inhibited. The invasiveness of CRM197-treated cells was relatively low. MMP-9 and VEGF were suppressed in HSC3 treated with CRM197 on zymography and Western blot. Further, tumor growth in xenografted mice was suppressed by CRM197 or CDDP at 1 mg/kg/day. Also, the coadministration of CDDP and CRM197 at 1 mg/kg/day completely inhibited tumor formation. These results suggest that HB-EGF is a target for oral cancer and that CRM197 is effective in oral cancer therapy.