Published papers

Objectives: Increase of soft tissue attachment is a major concern for improving the design of novel dental implants. This study evaluated the use of mesh structures placed on the implant surface for the anchorage of fibrous tissues. Material and methods: Specimens were prepared by covering their surfaces with a nylon mesh. The following mesh spacings were used: 30, 46, 100, 200, and 500 μm. The specimens were retrieved along with the surrounding subcutaneous tissues at 4 weeks after their implantation into the dorsal subcutaneous tissues of rats. A tensile test was performed by using a material testing machine, and the load required to tear the tissue from the mesh was measured. Histological sections stained with hematoxylin-eosin or Azan were prepared and examined by performing light microscopy. The amount of fibrous tissue contributing to the mechanical attachment of the fibers to the mesh was qualitatively evaluated by performing image analysis. Results: The attachment strength was the greatest in the 200-μm mesh-spacing group and considerably greater than that in the 30-μm mesh-spacing group. In addition, the effective width of the anchoring fibrous tissues was the greatest in the 200-μm mesh-spacing group. As compared with the other groups, the 200- and 500-μm mesh-spacing groups exhibited a considerably greater width of the anchoring fibrous tissues. Conclusions: The efficiency of mesh structures for the attachment of soft tissues to implants was demonstrated. A mesh spacing of approximately 200 μm was observed to be favorable for the anchorage of fibrous tissues. © 2008 The Authors.

The targeting of antioxidant systems that allow stem-like cancer cells to avoid the adverse consequences of oxidative stress might be expected to improve the efficacy of cancer treatment. Here, we show that head and neck squamous cell carcinoma (HNSCC) cells that express variant isoforms of CD44 (CD44v) rely on the activity of the cystine transporter subunit xCT for control of their redox status. xCT inhibition selectively induces apoptosis in CD44v-expressing tumor cells without affecting CD44v-negative differentiated cells in the same tumor. In contrast to CD44v-expressing undifferentiated cells, CD44v-negative differentiated cells manifest EGF receptor (EGFR) activation and rely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR resulted in a synergistic reduction of EGFR-expressing HNSCC tumor growth. Thus, xCT-targeted therapy may deplete CD44v-expressing undifferentiated HNSCC cells and concurrently sensitize the remaining differentiating cells to available treatments including EGFR-targeted therapy. © 2012 AACR.

Soft tissue attachment is a major concern for the improved design of dental and maxillofacial implants. This study evaluated the efficacy of mesh structures for soft tissue attachment in a rat percutaneous model. Four kinds of implant specimens were prepared-TI implants made of titanium cylinders, HA implants of hydroxyapatite-coated titanium, TI-Mesh implants with a titanium mesh covering a groove machined around a titanium cylinder, and similar HA-Mesh implants with a hydroxyapatite-coated mesh. These specimens were implanted percutaneously into the skin tissue of rats. The detachments of the implants were examined during the experimental period of 4 weeks. Survived implants were subjected to mechanical tests for the attachment strength and histological examinations. TI and HA implants demonstrated 0% of survival rates, while TI-Mesh and HA-Mesh showed significantly higher rates of 93.3% and 100% respectively. The attachment strengths were 159 ± 47 kPa in the TI-Mesh and 135 ± 16 kPa in the HA-Mesh. Histological observations revealed that collagen fibers originating from surrounding subcutaneous tissues were anchored to the mesh structures of the TI- and HA-Mesh implants. The results demonstrated the efficacy of the mesh structures for the attachment of soft connective tissues to implants. © 2012 Wiley Periodicals, Inc.

© 2018, International & American Associations for Dental Research. This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient’s quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor’s cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

Introduction Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients’ activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. Materials and Methods We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. Results We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. Conclusions Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.

Objective: The aim of this study was to evaluate the risk of osteonecrosis of the jaw (ONJ) in patients with prostate cancer, particularly the relationship between prostate cancer progression and ONJ development. Study design: This single-center, retrospective, observational study included 113 patients who received zoledronic acid or denosumab for prostate cancer with bone metastasis between January 2012 and March 2020. The risk of ONJ was evaluated regarding age; antiresorptive drugs; duration of antiresorptive treatment; prostate cancer status, including castration-resistant prostate cancer (CRPC) and prostate-specific antigen level; chemotherapy; radium-223 treatment; corticosteroid treatment; diabetes mellitus; and dental extractions. Results: Overall, 28 patients had ONJ; 10 patients received zoledronic acid and 18 patients received denosumab. Multiple logistic regression analysis demonstrated that CRPC (odds ratio = 6.01; 95% confidence interval, 1.76-20.05; P = .004) and dental extractions (odds ratio = 12.40; 95% confidence interval, 3.42-44.70; P < .001) were significantly associated with ONJ. In addition, antiresorptive treatment lasting more than 1 year partially mediated between CRPC and development of ONJ. Conclusion: CRPC and dental extraction are risk factors for developing ONJ, and antiresorptive treatment lasting more than 1 year is a partial mediator between CRPC and ONJ.