Oral leukoplakia and its malignant transformation are reviewed in this article. Oral leukoplakia is defined as a predominantly white lesion of the oral mucosa that can not be characterized as any other definable lesion; however, the lesion must be confirmed histopathologically by biopsy in order to discuss malignant transformation of oral leukoplakia. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%, while the rates of five-year cumulative malignant transformation range from 1.2 to 14.5%. Some reports found a high incidence of malignant transformation in older patients. Chewing tobacco and smoking are distinct risk factors particularly among males in certain countries; however, other countries have noted that females or non-smokers may be at risk of malignant transformation. HPV has been detected in oral dysplasia lesions and cancer in non-smokers. Conflicting reports have been presented regarding the malignant transformation of oral leukoplakia with epithelial dysplasia; however, we and some authors believe that epithelial dysplasia is an important factor in the malignant transformation of oral leukoplakia. The majority of researchers showed non-homogenous leukoplakia as a risk factor, although different terms have been used to describe these lesions. There may be several routes to malignant transformation of oral leukoplakia, including transformations induced by carcinogenesis due to betel quid chewing or smoking, or by HPV infection. While no definite treatment modalities for oral leukoplakia have been established, we suggest surgical therapy with an adequate safety-margin and well-timed evaluation as an appropriate treatment in preventing malignant transformation.

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Normal human development requires the precise functioning and coordination of many complex pathways. Abnormalities in these signaling cascades often result in developmental perturbations, giving rise to congenital anomalies and cancers. There are 21,787 genes in each human nucleus, different gene subsets are expressed in different cell types, and different gene networks make different signal cascades. Among a large number of genes, in this review, we describe signaling disorders of sonic hedgehog and its receptor, patched-1; Tie2; fibroblast growth factor receptor in craniofacial anomalies and oral cancers.

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Periodontal tissue has a unique structure in that the human periodontal ligament (hPDL) lies between the hard tissues of cementum and alveolar bone. Although the role of cytokines in hPDL function is not clearly understood, we investigated the effect of mechanical stress as hydrostatic pressure (HP) on cytokine expression in hPDL cells.
The hPDL cells were obtained from a healthy maxillary third molar. After the 3rd to 4th passage, the cells were exposed to HP ranging from 1 MPa to 6 MPa as previously described. The expression of cytokine mRNA was determined by RT-PCR and cytokines in the culture supernatants were assessed by enzyme-linked immunosorbent assay (ELISA).
The exposure to 6 MPa of HP caused no morphological changes of hPDL cells, and did not affect cellular viability. No expression of IL-1β, IL-6, IL-8, TNF-α, RANK, RANKL or OPG mRNA was observed in the control cells under atmospheric pressure, whereas in hPDL cells treated with HP, enhancement of IL-6, IL-8, RANKL and OPG mRNA expression was observed between 10 and 60 minutes after the exposure to HP. After the exposure to HP, the production of IL-6 and TNF-α were induced significantly in hPDL cells, but IL-1β and IL-8 were not produced.
These results suggest that hPDL cells may play a role in the production of cytokines in response to mechanical stress in vivo.

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The aim of the present study was to clarify whether ATP binding cassette transporters are refractory factors in head and neck cancer chemotherapy. For in vitro and in vivo chemotherapeutic studies, we employed a human salivary gland adenocarcinoma cell line (HSY) and a human oral squamous cell carcinoma cell line (SCCSK) with vincristine (VCR) at clinically equivalent doses. Western blot analysis, reverse transcription-polymerase chain reaction, in vivo evaluation in xenograft models inoculated with cultured carcinoma cell line and drug efflux analysis were performed. VCR-treated SCCSK and HSY cells, as well as xenografted SCCSK and HSY cells in tumor-bearing nude mice, were found to express MDR1/ABCB1 and MRP1/ ABCC1. In addition to MDR1 and MRP1 mRNA, HSY/VCR and its cloned cells expressed MRP7/ABCC10 mRNA, but SCCSK/VCR did not express MRP7. Furthermore, drug resistance to VCR and docetaxel decreased in HSY/VCR in the presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D-glucuronide). These results indicate that MDR1 and MRP1 expression are refractory factors in head and neck cancer chemotherapy and suggest that induction of MRP7 expression is involved in drug resistance in salivary gland adenocarcinomas.

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Ets-1 is an Ets family transcription factor, can up-regulate the transcription of matrix metalloproteinase (MMP) genes and confers an invasive phenotype on human cancer cells. HSC3 is an oral squamous cell carcinoma-derived cell line, and it manifests high levels of Ets-1 and MMP-9 gene expression that are associated with invasive potential. In this study, we investigated the effect of Ets-1 on the invasive properties of oral cancer from a molecular biological perspective. We constructed an Ets-1 antisense (AS) expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express Ets-1 AS RNA. The expression of Ets-1 and MMP-9 was analyzed with RT-PCR. The invasive ability of the HSC3AS cells was determined using a matrigel invasion assay and MMP-9 production was measured using gelatin zymography. The amount of Ets-1 mRNA was significantly reduced in HSC3AS cells compared with parental HSC3 cells and the control transfected with empty vector. Matrigel invasion assay revealed that the HSC3AS cells had lower invasive ability. Gelatin zymography demonstrated that HSC3AS MMP-9 productions were decreased compared with those of parental HSC3 cells and the control. These results imply that transfection of AS Ets-1 inhibits oral cancer invasion by down-regulating MMP-9 genes.

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Symmetrical lipomatosis is characterized by symmetrical infiltration of adipose tissue into the head, neck, or upper trunk. By contrast, oral involvement is extremely rare. The present report describes a case of symmetrical lipomatosis of the tongue (SLT) presenting as macroglossia. The patient was a 63-year-old Japanese male who developed progressive dysarthria secondary to enlargement of the tongue. The patient's medical history was notable for alcoholic hepatitis and hyperlipidemia. Marginal glossectomy was performed on both sides of the tongue to achieve volume reduction and restore normal speech. Histopathologic examination of the resected tissue revealed diffuse infiltration with adipose tissue lacking a fibrous capsule. The patient's postoperative course was uneventful, and he remained free of recurrence or regrowth and functional deficits at the 6-year follow-up time point.

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