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Objective Oral squamous cell carcinoma is characterized by diverse histopathological features, tumorigenesis, and invasion. Gingiva squamous cell carcinoma (GSCC) is characterized by easily invading the jawbone. Epithelial–mesenchymal transition (EMT) is a crucial event for invasion of cancer cells and progression of carcinogenesis, inducing stem-like properties in epithelial cells. Here, expression of BMI1, which controls stem cell self-renewal, and ZEB1, a transcription factor that regulates EMT, was evaluated for its role in EMT and invasion of GSCC. Materials and methods We analyzed 36 gingival specimens (24 carcinomas and 12 dysplasias) by measuring protein and mRNA expression levels of BMI1, ZEB1, vimentin, and E-cadherin, and examining associations between their expression and clinicopathological parameters. Results Compared with adjacent normal squamous epithelium, E-cadherin expression was decreased significantly ( P P P = 0.027), and vimentin and BMI1 expression was significantly increased in grade 4 mode of invasion ( P P = 0.014) and between BMI1 and ZEB1 mRNA expression ( P = 0.034). Conclusion The present study shows that the expression levels of several biomarkers of gingiva carcinogenesis have unique characteristics that differ from those in tongue carcinogenesis. BMI1 and ZEB1 may be important factors associated with EMT in the invasion and progression of GSCC.

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment.

Cdc42, a member of the Rho subfamily of small GTPases, is known to be a regulator of multiple cellular functions, including cytoskeletal organization, cell migration, proliferation, and apoptosis. However, its tissue-specific roles, especially in mammalian limb development, remain unclear. To investigate the physiological function of Cdc42 during limb development, we generated limb bud mesenchyme-specific inactivated Cdc42 (Cdc42(fl/fl); Prx1-Cre) mice. Cdc42(fl/fl); Prx1-Cre mice demonstrated short limbs and body, abnormal calcification of the cranium, cleft palate, disruption of the xiphoid process, and syndactyly. Severe defects were also found in long bone growth plate cartilage, characterized by loss of columnar organization of chondrocytes, and thickening and massive accumulation of hypertrophic chondrocytes, resulting in delayed endochondral bone formation associated with reduced bone growth. In situ hybridization analysis revealed that expressions of Col10 and Mmp13 were reduced in non-resorbed hypertrophic cartilage, indicating that deletion of Cdc42 inhibited their terminal differentiation. Syndactyly in Cdc42(fl/fl); Prx1-Cre mice was caused by fusion of metacarpals and a failure of interdigital programmed cell death (ID-PCD). Whole mount in situ hybridization analysis of limb buds showed that the expression patterns of Sox9 were ectopic, while those of Bmp2, Msx1, and Msx2, known to promote apoptosis in the interdigital mesenchyme, were down-regulated. These results demonstrate that Cdc42 is essential for chondrogenesis and ID-PCD during limb development.

Objective We have searched for the factor to diagnose malignant potential of epithelial dysplasia. Recent studies have suggested that determination of the expression of cytokeratin 13 and 17 would be useful for the early diagnosis of oral squamous cell carcinoma. In this study, we focused on the diagnosis based on the malignant potential of epithelial dysplasia and evaluated the feasibility of combined assessment of cytokeratin 13 and 17. Patients and methods The expression of cytokeratin 13 and 17 observed in 8 patients with clinically diagnosed T1 or T2 tongue squamous cell carcinoma was analyzed using real-time PCR and immunohistochemical staining of resected specimens. Areas in each specimen were identified as Normal, Dysplasia and Cancer. Results Real-time PCR showed that the expression of cytokeratin 13 decreased beginning with Dysplasia, whereas the expression of cytokeratin 17 increased beginning with Dysplasia. Immunohistochemical staining revealed that cytokeratin 13-positive cells decreased beginning with Dysplasia, while there were almost no cytokeratin 13-positive cells in Cancer. Conversely, cytokeratin 17-positive cells increased beginning with Dysplasia, and almost all cells were cytokeratin 17-positive in Cancer. These results thus indicate that the expression of cytokeratin 13 and 17 is associated with carcinogenesis in epithelial dysplasia. Conclusions The findings of this study indicate that assessment of the expression of cytokeratin 13 and 17 might be useful in the diagnosis of malignant potential in epithelial dysplasia. Moreover, evaluating changes in the expression of cytokeratin 13 and 17 could be effective in evaluating surgical margins.

summary It has been reported recently that histone deacetylase inhibitors (HDACIs) can block the growth of a variety of malignant tumor cells by reversing the silencing of the tumor suppressor genes; these will be the anticancer agents of the next generation. In this study, we evaluated the antitumor effects of the HDACI suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and investigated its molecular mechanism. SAHA suppressed the in vitro proliferation of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells, accompanying a decrease in the percentage of S-phase cells. Western blot analyses demonstrated that the expression of p21 protein was remarkably augmented and hyperacetylation of p53 was induced after SAHA treatment. These results suggest that administration of SAHA suppresses OSCC growth through G1 phase arrest. Additionally, we observed that the growth of xenograft SAS tumors in nude mice was significantly blocked by the administration of SAHA without major adverse effects.

Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 ( P =0.033), 7q21.3 ( P P =0.013), 7q36 ( P =0.033), and 22q11.2 ( P =0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.

The product of the adenomatous polyposis coli (APC) tumor suppressor gene has been observed to regulate the Wnt signaling pathway through beta-catenin. In the present study, we attempted to clarify the relation between APC and the canceration of oral squamous epithelium. Each target tissue of normal squamous epithelium, epithelial dysplasia, and squamous cell carcinoma (SCC) was recovered the oral SCC case by laser microdissection. In recovered cells, we examined the change in expression of APC and beta-catenin gene transcription products, as well as the existence of mutations in APC gene. We analyzed the localization of each protein of APC and beta-catenin by immunohistochemical study. We found a clear change in the expression level of the gene transcription product of APC in canceration of oral squamous epithelium and the differentiation of oral SCC. In addition, there was some change in the localization of the APC protein in canceration. It was not clear, however, whether the APC was mutated. A change was also observed in the expression level of the beta-catenin gene transcription product during the differentiation of oral SCC. Our results suggest that the changes in the expression level and the intracellular localization of APC are related to the canceration of oral squamous epithelium, and in malignant characterization of oral SCC. Mutations of the APC gene might not be indispensable, however, in canceration of oral squamous epithelium.

Chondrolipoma is a rare form of lipoma with cartilaginous metaplasia. Chondrolipoma of the breast is well known, but only a few chondrolipomas involving the oral region have been reported. To the authors' knowledge, only 3 patients with chondrolipoma involving the lip have been reported in the literature. This report is of a 59-year-old man with chondrolipoma of the lip, who was referred with a painless mass on the left side of the lower lip.

We found that dimethyl-sulfoxide (DMSO) at concentrations of 2.5% induced apoptosis in SV40-immortalized human keratinocytes, while normal keratinocytes were arrested at the boundary of G1/S phase under the same conditions. DMSO-induced apoptosis in SV-40 immortalized keratinocytes was not associated with change in phosphorylated state of the retinoblastoma susceptibility gene. When SV40-immortalized cells were treated with 2.5% DMSO, dissociation of the complex was observed by immunoblotting of SV40 T antigen from immunoprecipitated p53 protein fraction.

Florid cemento-osseous dysplasia is an uncommon disease of cemento-osseous tissue calcification in the tooth-bearing area of the jaw. Although most patients with florid cemento-osseous dysplasia do not have a family history of the disease, a few familial cases have been reported. This report is of a 29-year-old Japanese woman with florid cemento-osseous dysplasia. The patient's wisdom tooth was extracted due to pericoronitis, which was followed by intensive intravenous antibiotic therapy, although surgical procedures are usually not recommended for patients with florid cemento-osseous dysplasia. Radiological examination of the patient's father, who had a history of prolonged osteomyelitis of the upper jaw, also revealed typical features of florid cemento-osseous dysplasia.

The purpose of this study was to histomorphometrically evaluate the use of hydroxylapatite (HA) implants in 60Co-irradiated bone. HA implants were installed in rabbit mandibles 3 months, 6 months, and 12 months after 15-Gy irradiation. Nonirradiated rabbits served as controls. The rabbits were killed 7, 14, 30, 60, and 90 days after the HA implantation. The histologic features of the healing process were examined and histomorphometric measurements were made to quantify the percentage of HA-bone contact and trabecular bone in the medullary cavity. In the irradiated groups, although HA-bone contact was observed later than that in the controls, recovery increased with time after irradiation and the rate of HA-bone contact bone-contacting implant surface ratio; BCSR exceeded 90% in all groups examined before 90 days. In the radiated groups, the average trabecular bone-specific volume was lower than that in the controls and began to decrease before BCSR exceeded 90%. Based on the present data, as well as data from the literature, it is suggested that the success rate of HA implants in irradiated bone increases with the interval after radiotherapy. It is also recommended that HA implants in irradiated bone be installed so that bearing by the cortical bone is increased.

Objective Breast cancer cells with CD44 + CD24-/low gene expression signature have been suggested to have stem cell-like tumor-initiating properties. The purpose of this study is to clarify the gene expression profiling of cells with CD44 + CD24-/low gene expression signature in the estrogen receptor (ER) positive tumors. Methods Laser-captured microdissection was used to select the isolation of cancer cells in 32 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT2 Profiler PCR Array was used for gene expression analysis in the groups of CD44 + CD24-/low and CD44 + CD24+ gene expression signature. Results Thirty-two tumors were divided into 2 groups. Group A was composed of the CD44 + CD24-/low type, in which the ratio of CD44/CD24 was >10.0. Group B was composed of the CD44 + CD24+ type, in which the ratio was >0.1 and ≦ 10.0. The number of tumors in group A and B were 4 and28, respectively. Regarding the correlation of CD44/CD24 status with tumor characteristics, the tumors of group A were significantly associated with axillary lymph node metastasis compared with those of group B (P = 0.009). There were no significant differences in tumor size, nuclear grade between the two groups. HER2 status in the tumors of group B was significantly higher than group A (P = 0.028). According to signaling pathways, the number of expression genes for the Notch pathway in group A was significantly greater than in group B (P = 0.028). Overexpressed genes for ALDH1 (P = 0.021) and SOX2 (P = 0.018) were noted in group A compared to group B. Conclusion This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44 + CD24-/low gene expression signature. In addition, either ALDH1or SOX2 may be a candidate marker for cancer stem cells in the ER positive breast cancer. Disclosure All authors have declared no conflicts of interest.

A new method has been devised for preparing artificial cecal pouches lined with mucous epithelium in the lower lips of Wistar and Sprague-Dawley rats in order to make carcinogens act continuously for a long time in the oral mucosa. When a 0.5 per cent mineral oil solution of DMBA, a crystal of MC, and a crystal of NG were administered, squamous-cell carcinoma, carcinoma in situ, papilloma, adenoma sebaceum. neurofibroma, fibroma, hemangiosarcoma, hemangiosarcoma, hemangioma, and lymphangioma were successfully produced in the oral mucosa of rats. In addition, interesting findings were obtained concerning tissue changes in the process of carcinogensis in the mucous epithelium.