Cetuximab, a specific anti-EGFR monoclonal antibody, is used in cancer treatment. Although development of resistance to cetuximab is well recognized, the underlying mechanisms remain unclear. In the present study, we characterized cetuximab-resistant oral squamous cell carcinoma (OSCC) cell lines. The human OSCC cell lines HSC3, HSC4, and SAS were studied to identify the characteristics of cell resistant to cetuximab. Cetuximab inhibited proliferation of HSC3 and HSC4 cells, but not SAS cells. Proliferation of all three cell lines was inhibited by the EGFR/ErbB2/ErbB4 inhibitor II. The EGFR inhibitor AG1478 strongly inhibited HSC3 and HSC4 proliferation, but inhibited SAS cells only moderately. EGFR proteins were localized on the cell surface and phosphorylated in all three cell lines. Thus, cetuximab-resistant SAS cells still expressed EGFR in the cell membrane and EGFR became phosphorylated when stimulated with a ligand.

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We analyzed the relationship between dental caries prevalence and the market share of fluoride toothpaste by birth year cohort. The dental caries experience was obtained from 10 Japanese national surveys of oral health over approximately 60 years. The market share of fluoride toothpaste was researched by the Lion Co. We analyzed the data by birth year cohort for 11 groups evaluated every five years. The DFT index of Japanese children stabilized during the prewar and immediate postwar generations, and then increased linearly over the next 30 years. During this period there was no relationship between changes in the DFT index and the market share of fluoride toothpaste. For those born between Showa 20 and 40 (1945 and 1965), the DFT and DMFT indices reached a plateau. A dramatic decrease in these indices was seen when there was a rapid increase in the market share of fluoride toothpaste. For children born between Showa 40 and 60 (1965 and 1985), the market share of fluoride toothpaste reached 50%, while the DFT and DMFT indices plateaued at the same time. These changes in dental caries experience were likely affected by the market share of fluoride toothpaste.

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In order to investigate the relationship between pronunciation function and prostheses, we compared and assessed the lip-tongue movements in young, healthy, dentulous dentists by measuring speech recognition error rates for written words and oral diadochokinesis using the continuous speech recognition software, AmiVoice Ex Dental, which enables chairside measurement. The study included groups of subjects wearing 1.5-mm or 3.0-mm experimental palatal plates and a group without the plate.
    Recognition error rates of 3.5±0.9% were observed for the non-palatal plate group, 4.8±1.6 % for the 1.5-mm palatal plate group, and 8.4±2.6% for the 3.0-mm palatal plate group. The speech recognition error rates increased with the thickness of the plate, and significant differences were noted among the groups. Additionally, all subjects showed a decrease in the oral diadochokinetic value for articulation of/ta/ and/ka/ as the plate thickness increased, exhibiting a statistically significant difference between the non-palatal plate group and the 1.5-mm/3.0-mm plate groups, thereby suggesting impaired tongue movement. The results of the assessment from the viewpoint of continuous speech recognition and oral diadochokinesis suggested that wearing the experimental palatal plate may decrease speech recognition rates.

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We investigated the efficiency of the objective structured clinical examination (OSCE) in basic training of operative dentistry. The training was done for 33 hours for third year dental students using manikins. An instructor guided the groups of 13 to 14 students. The training included demonstrations by the instructors. After the basic training, the students' skills were evalvated by OSCE. Placement of the Tofflemire matrix, spatulation of glass ionomer cement, placement of rubber dams and placement of composite resin fillings were included in the OSCE. Over 50% of the students failed to properly place the Tofflemire matrix, 54% of them properly spatulated the glass ionomer cement, and 48% properly punctured the rubber dam sheet. High success rates were recorded for the bonding procedures, composite resin placement, contour adjustment and light-activation of the resin. Low success rates were recorded for subjects where the procedures were performed on the manikin or where the demonstration of the procedures had not easily been observed by the students. This study indicated that OSCE could be used to evaluate the students' skills and that the demonstration method should be improved to increase the students' level of understanding.

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We prepared a novel LED curing light with an Ml-head and a small tip of 2.1 mm capable of irradiating light close to the gingival wall. This new light was then compared with a conventional LED light curing unit, the Pen Cure, to investigate the influence of the curing unit on adhesion applied to the gingival wall of class II cavities. We investigated the tensile bond strength (TBS), marginal leakage and light intensity. We found that improvements in the irradiation method and prolonged irradiation are necessary to achieve adequate bond strength of the bonding agent to class II cavities when using the MI-head.

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We evalvated the ablation efficiency of the Er: YAG laser using a new test tip that sprays the irrigation fluid as a mist. The tip was prepared by modifying the conventional irrigation mechanism with the cooperation of the J. Morita Corp. The ablated cross-sectional area was significantly greater in the mist spray group than in the controls at an irradiation distance of 0.5 mm in enamel and at 0.5 and 1.0 mm in dentin. Spraying the irrigation fluid as a mist during laser ablation of dental hard tissue improved the ablation efficiency.

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Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) were previously shown to be secreted in pulpitic tissue during the caries process. Matrix metalloproteinases (MMPs) such as MMP-1, 2, 3, and 14 were also shown to be expressed in inflamed dental pulp. Dental pulp destruction may be regulated, in part, by MMP-3. In addition, other MMPs activated by MMP-3 have been shown to regulate the degradation and regeneration of dental pulp. Ras-related C3 botulinum toxin substrate 1 (Rac1) is a pleiotropic regulator of many cellular processes, including cell growth, cytoskeletal reorganization, and the activation of protein kinases. We hypothesized that Rac1 may negatively regulate the production of MMP-3 from human pulp fibroblasts.

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During orthodontic therapy, osteoclast precursors such as monocytes and macrophages migrate from vessels into the periodontium and then differentiate into osteoclasts, causing bone resorption. Vascular cell adhesion molecule-1 (VCAM-1) is bound to very late antigen-4 (VLA-4) which is a kind of α4 β1-integrin. It recruits monocytic osteoclast progenitors and elevates local osteoclast activity. We focused on how VCAM-1/α4 integrin mediates the differentiation into osteoclasts and found that it was through FAK. Neutralizing antibodies against integrin α4 effectively inhibited the differentiation into osteoclasts and the phosphorylation of FAK. These findings confirmed that VCAM-1 regulates the differentiation of bone into osteoclasts.

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Dental treatment fees are regulated by the Japanese universal public health care system. However, it has been reported that there are differences in dental treatment expenditures between high and low income groups. We analyzed the current government data from a survey on family income and expenditures to investigate how income affects expenditures for dental treatment. We found that people with high income tend to spend a greater percentage of their total expenditures for medical and dental treatment on dentistry than do people with lower income. We would like to investigate how this gap can be reduced.

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We analyzed the relation between the number of missing teeth (MT) and the rate of market share of fluoride containing dentifrice (FRMS) by birth year cohort. We analyzed the date of 10 Japanese National Surveys of Oral Health between 1952 and 2011. The data for MT in those born from 1926 to 1973 were divided into 8 groups, one for each six year interval. The changes in MT and FRMS were analyzed for each birth year cohort. We found that MT increased with age, and that FRMS was lower in the earlier surveys. We found that the decrease in MT correlated with the increase in FRMS. These results suggest the goal that 80-years-old Japanese should have at least 20 teeth will be accomplished within 15 years.

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Titanium surfaces play an important role in affecting osseointegration of dental implants. Previous studies have shown that the titania nanotube promotes osseointegration by enhancing osteogenic differentiation. Only relatively recently have the effects been investigated that titanium surfaces with other nanostructures have on osteogenic differentiation. In this study, we used NaOH solutions with a concentration of 2.5, 5, 7.5, 10 and 12.5 M to develop a simple and useful titanium surface modification that introduces the nanonetwork structures with titania nanosheet (TNS) nanofeatures to the surface of titanium disks. Using different alkaline concentrations, we evaluated the effects of the modified nanonetwork structure on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMMSCs). The nanonetwork structures with TNS nanofeatures induced by alkali etching markedly enhanced the BMMSC functions of cell adhesion and osteogenesis-related gene expression. In addition, it significantly increased other cell behaviors such as proliferation, ALP activity, ECM deposition and mineralization. These effects were most pronounced when the concentration of NaOH was 10M. These results suggest that nanonetwork structures with TNS nanofeatures improve BMMSC proliferation and induce their osteogenic differentiation. In addition, the surfaces formed with 10 M NaOH seem to have the potential to improve the clinical performance of dental implants.

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We studied the cell survival and gene expression of three-dimensional in vitro human periodontal ligament-like tissue (HPdLLT) under various compressive stress conditions mimicking orthodontic force. HPdLLTs were subjected to 5, 15, 25, and 35 g/cm^2 compressive stress for 1, 3, 7 or 14 days. Similar extracellular matrix, spindle-shaped cells and its survival inside or on the surface of each in vitro HPdLLT with no relation to compressive stress duration or intensity. Genes showed their distinctive expressions according to compressive stress duration or intensity. This study indicated that in vitro HPdLLT effectively mimicked the reaction and gene expression of human PDL in response to orthodontic force.

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We evaluated the effects of synthesized collagen model polypeptides that consist of a proline-hydroxyproline-glycine (poly (PHG)) sequence combined with porous alpha-tricalcium phosphate (α-TCP) particles on bone formation in a canine tibia defect model. Micro-CT analysis showed the volume density of new bone was higher in the poly (PHG)/α-TCP group than in the group with poly (PHG) alone at 2 and 4 weeks. However, there was no difference at 8 weeks. Histological evaluation at 4 weeks after implantation revealed that the poly (PHG) had degraded and newly formed bone was present on the surface of the α-TCP particles. At 8 weeks, continuous cortical bone formation with Haversian structures covered the top of the bone defects in both groups.

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Interleukin-17A (IL-17A) is produced by leukocytes such as Th17 cells, γδT cells, and natural killer cells. IL-17A stimulates osteoclastic bone resorption via osteoblasts by inducing the expression of the receptor activator of NF-κB ligand (RANKL). However, little is known about the direct effects of IL-17A on the osteoclast precursors. We examined the role of IL-17A on osteoclast differentiation of RAW264.7 cells. We confirmed that IL-17A and SP600125 directly inhibit differentiation of osteoclasts, which was stimulated by RANKL. We found that IL-17A reduced JNK phosphorylation and c-Fos expression, which were enhanced by RANKL stimulation. These results suggest that JNK and c-Fos are involved in the inhibition of differentiation by IL-17A stimulation.

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The purpose of this study was to analyze the relationship between dental caries prevalence and the market share of fluoride toothpaste by birth year cohort. The dental caries experience was obtained from 10 Japanese national surveys of oral health over about 60 years. The market share of the fluoride toothpaste was researched by the Lion Co., Ltd. It was analyzed by birth year cohort for 11 groups evaluated every five years. DFT and DMFT indices tended to peak for the generations born after World War II, while the market share of fluoride toothpaste also increased rapidly at the same time. The decrease in caries experience was likely affected by the market share of the fluoride toothpaste.

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