BackgroundRecently, medical rapid prototyping (MRP) models, fabricated with computer-aided design and computer-aided manufacture (CAD/CAM) techniques, have been applied to reconstructive surgery in the treatment of head and neck cancers. Here, we tested the use of preoperatively manufactured reconstruction plates, which were produced using MRP models. The clinical efficacy and esthetic outcome of using these products in mandibular reconstruction was evaluated.MethodsA series of 28 patients with malignant oral tumors underwent unilateral segmental resection of the mandible and simultaneous mandibular reconstruction. Twelve patients were treated with prebent reconstruction plates that were molded to MRP mandibular models designed with CAD/CAM techniques and fabricated on a combined powder bed and inkjet head three-dimensional printer. The remaining 16 patients were treated using conventional reconstruction methods. The surgical and esthetic outcomes of the two groups were compared by imaging analysis using post-operative panoramic tomography.ResultsThe mandibular symmetry in patients receiving the MRP-model-based prebent plates was significantly better than that in patients receiving conventional reconstructive surgery.ConclusionsPatients with head and neck cancer undergoing reconstructive surgery using a prebent reconstruction plate fabricated according to an MRP mandibular model showed improved mandibular contour compared to patients undergoing conventional mandibular reconstruction. Thus, use of this new technology for mandibular reconstruction results in an improved esthetic outcome with the potential for improved quality of life for patients.

BackgroundCell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC.MethodsWe evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system.ResultsThe CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21Cip1, p27Kip1, p15INK4B, and p16INK4A) in the knockdown cells.ConclusionThe current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors.

Background Abnormal miRNA expression was recently implicated in the metastasis of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation of the invasion‐metastasis cascade involves epithelial‐mesenchymal transition (EMT). Our aim was to clarify how miRNA, especially miR‐155‐5p misexpression contributes to OSCC metastasis through EMT. Methods We collected tumor samples from 73 subjects with OSCC. The samples were analyzed by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), and correlations between miR‐155‐5p levels and clinical characteristics were investigated. OSCC cell lines were analyzed by miRNA microarray and by transfection with a miR‐155‐5p mimic or inhibitor, followed by proliferation and wound‐healing migration assays. qRT‐PCR analyses of EMT makers in cells transfected with miR‐155‐5p inhibitor were performed. Results We found high miR‐155‐5p expression in tissue samples from subjects with OSCC that had metastasized to cervical lymph nodes. HSC‐3 cells also strongly expressed miR‐155‐5p. The epithelial marker E‐cadherin was strongly expressed in HSC‐3 cells transfected with miR‐155‐5p inhibitor, and we observed elevated SOCS1 and decreased STAT3 expression in these cells. Conclusions Our results suggest that miR‐155‐5p causes OSCC to metastasize, and could serve as a novel therapeutic target for OSCC.

Cell division cycle associated 2 (CDCA2) recruits protein phosphatase 1 to chromatin to antagonize activation of ataxia telangiectasia mutated (ATM)-dependent signal transduction. ATM kinase plays a critical role in the DNA damage response and its phosphorylation cascade to inhibit the p53-MDM2 interaction, which releases p53 to induce p21 and G1 cell-cycle arrest. However, the relevance of CDCA2 to human malignancy including oral squamous cell carcinoma (OSCC) is unknown. In the current study, we found that CDCA2 expression was up-regulated in OSCC cell lines. Functional studies with shRNA system showed that knockdown of CDCA2 significantly (P<0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase and up-regulating the cyclin-dependent kinase inhibitors (p21Cip1, p27Kip1, p15INK4B, and p16INK4A). CDCA2 knockdown also promoted apoptosis after treatment with the DNA damage reagent, cisplatin. In clinical samples, the CDCA2 protein expression level in primary OSCCs was significantly (P<0.05) greater than in matched normal oral tissues (67/85, 79%). Furthermore, CDCA2-positive cases were correlated significantly (P<0.05) with high cancer progression. Our results showed for the first time that CDCA2 frequently is overexpressed in OSCCs and might be associated closely with OSCC progression by preventing cell-cycle arrest and apoptosis.

Background and purposePeriodontal disease is closely related to lifestyle-related diseases and obesity. It is widely known that moderate exercise habits lead to improvement in lifestyle-related diseases and obesity. However, little research has been undertaken into how exercise habits affect periodontal disease. The purpose of this study was to examine the effect of exercise habits on periodontal diseases and metabolic pathology.MethodsWe conducted a prospective intervention research for 12 weeks. The subjects were 71 obese men who participated in an exercise and/or dietary intervention program. Fifty subjects were assigned to exercise interventions (exercise intervention group) and 21 subjects were assigned to dietary interventions (dietary intervention group). This research was conducted before and after each intervention program.ResultsIn the exercise intervention group, the number of teeth with a probing pocket depth (PPD) ≥4 mm significantly decreased from 14.4% to 5.6% (P<0.001), and the number of teeth with bleeding on probing (BOP) significantly decreased from 39.8% to 14.4% (P<0.001). The copy counts of Tannerella forsythia and Treponema denticola decreased significantly (P=0.001). A positive correlation was found between the change in the copy count of T. denticola and the number of teeth with PPD ≥4 mm (P=0.003) and the number of teeth with BOP (P=0.010). A positive correlation was also found between the change in the copy count of T. denticola and body weight (P=0.008), low-density lipoprotein cholesterol (P=0.049), and fasting insulin (P=0.041). However, in the dietary intervention group the copy count of T. denticola decreased significantly (P=0.007) and there was no correlation between the number of periodontal disease-causing bacteria and PPD and BOP.ConclusionOur results are the first to show that exercise might contribute to improvements in periodontal disease.

While circulating tumor-derived molecules have been identified in a variety of malignant tumors, it is sometimes difficult to detect the molecular targets due to the lower serum concentration. We report that evaluation of circulating tumor-derived mitochondrial DNA (mtDNA) seems to have novel efficiency for detecting tumoral micrometastasis. In murine xenografting human oral cancer cells, human mtDNAs could be quantitatively detected from multiple organs and blood samples whereas human nucleic DNAs could not. We also determined if this mtDNA blood test was relevant for patients with oral cancer with no histologic evidence of tumoral cells in their surgical margins. For this, mtDNA from normal and tumorous tissues and serum mtDNA obtained pre and postoperatively was examined at three different regions including the displacement loop, 12S-rRNA, and 16S-rRNA. All recurring patients had significantly higher amounts of mutant mtDNAs in the tumoral tissues compared with the non-recurring group. More importantly, on the blood test with the cut-off point by receiver operating characteristic (ROC) curve analysis, while the vast majority of serum mtDNA samples obtained postoperatively in the recurring cases maintained significantly higher amounts of mutant mtDNAs, the non-recurring cases did not, and they showed good prognosis. This is the first report of this approach for managing patients after resection of oral tumors, and may have substantial diagnostic potential for other tumoral types.

MicroRNAs (miRNAs or miRs) play important roles in carcinogenesis. The miRNA, miR-205-5p, has been reported to suppress the growth of various types of tumor; however, its functional contribution to oral squamous cell carcinoma (OSCC) is not yet clear. Thus, this study was conducted to determine the miRNA expression signatures in OSCC and to investigate the functional role of miR‑205‑5p in OSCC cells. We measured miR‑205‑5p expression by RT-qPCR, and examined the function of miR‑205‑5p by transfecting a miR‑205‑5p mimic or inhibitor into OSCC cells and measuring cell proliferation, migration and invasiveness. Genes targeted by miR‑205‑5p were identified using the TargetScan database and verified by western blot analysis, luciferase reporter assay and ELISA. We found that miR‑205‑5p was significantly downregulated in OSCC cell lines and tissue specimens. Following transfection of miR‑205‑5p mimic or inhibitor into the cancer cell lines, miR‑205‑5p overexpression significantly suppressed cancer cell migration and invasion. We further demonstrated that miR‑205‑5p directly targeted and regulated the tissue inhibitor of metalloproteinases‑2 (TIMP‑2) gene. The silencing of TIMP‑2 suppressed cancer cell invasion and the activation of pro‑matrix metalloproteinase‑2 (pro‑MMP‑2). These results suggest that TIMP‑2 promotes tumor progression, and that miR‑205‑5p directly regulates TIMP‑2, thereby suppressing pro‑MMP‑2 activation and inhibiting OSCC cell invasiveness. Our data describing the pathways regulated by miR‑205‑5p provide new insight into the mechanisms responsible for OSCC development and metastasis.

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