Abstract. Squamous cell carcinomas (SCCs) of the gingiva frequently invade the mandible or maxilla; this invasion is associated with a worse prognosis. The bone destruction associated with carcinomal invasion is mediated by osteoclasts rather than directly by the carcinoma. Therefore, if the cellular and molecular mechanisms by which oral SCC regulates bone invasion were known, it could inform the development of new therapeutic targets. Recently, dysregulation of the functional equilibrium in the receptor activator of NF-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) triad has been shown to be responsible for osteolysis associated with the development of malignant tumors in bone sites. Furthermore, the administration of OPG or soluble RANK prevents bone metastasis by cancer cells. In this review, we discuss recent findings indicating that bone invasion by oral SCC is mediated via RANKL/RANK and may be successfully prevented by RANKL inhibition.
Oral squamous cell carcinoma (OSCC) cells display significantly augmented nuclear factor-κB (NF-κB) activity, and inhibiting this activity suppresses malignant tumor characteristics. Thus, we evaluated the effect of IMD-0560, a novel inhibitor of IκB kinase (IKK) β that is under assessment in a clinical trial of rheumatoid arthritis, on bone invasion by the mouse OSCC cell line SCCVII. We examined the inhibitory effects of IMD-0560 on NF-κB activity and tumor invasion using human OSCC cell lines and SCCVII cells in vitro. Using a mouse model of jaw bone invasion by SCCVII cells, we assessed the inhibitory effect of IMD-0560 on jaw bone invasion, tumor growth, and matrix degradation in vivo. IMD-0560 suppressed the nuclear translocation of NF-κB and the degradation of IκBα in OSCC cells. IMD-0560 also inhibited invasion by suppressing matrix metalloproteinase-9 (MMP-9) production in OSCC cells. IMD-0560 protected against zygoma and mandible destruction by SCCVII cells, reduced the number of osteoclasts by inhibiting receptor activator of NF-κB ligand (RANKL) expression in osteoblastic cells and SCCVII cells, increased SCCVII cell death and suppressed cell proliferation and MMP-9 production in SCCVII cells. Based on these results, IMD-0560 may represent a new therapeutic agent for bone invasion by OSCC cells.
PURPOSE: We examined the effects of sweet taste stimulation on pain tolerance threshold (PTT) of oral mucosa in children. SUBJECTS AND METHODS: Subjects comprised 10 children (mean age, 7.3±1.2 years) for whom PTT of oral mucosa was measured 2 min after oral administrations of sucrose or xylitol and water. Sine wave current stimulation (2 kHz, 250 Hz and 5 Hz, SWCS) which can stimulate sensory nerve fiber selectively (Aβ, Aδ and C) was used to measure PTT. RESULTS: Sweet taste stimulation with sucrose or xylitol increased oral mucosa PTT in children, but not in adults. No difference in the increased PTT was seen between sucrose and xylitol. CONCLUSIONS: Oral administration of sucrose and xylitol may potentially relieve pain associated with local anesthetic injections in children. effects of sweet taste stimulation on pain tolerance threshold (PTT) in the oral mucosa. The present study used sine wave current stimulation (SWCS) to test the effect of sweet taste stimulation by oral administration of sucrose and xylitol on PTT in the oral mucosa of children. We obtained similar measurements from adults in order to compare PTT of the oral mucosa with that of children. Subjects and Methods Subjects comprised 10 children between 6 and 9 years old (3 boys, 7 girls; mean age, 7.3±1.2 years) who provided consent and whose parent/guardian provided consent after receiving a sufficient explanation of the study purposes and 10 healthy adults (5 men, 5 women; mean age, 35.6±8.2 years) who gave similar consent. Subjects were orally administered three types of liquids: 0.5 ml of 24% sucrose solution (SS group) as the sweet taste stimulation substance; 0.5 ml of xylitol solution (XS group) at the same concentration as the S solution; and 0.5 ml of water (W group). PTT measurements were taken
Curcuma longa L Methods 1. Questionnaire-based survey of turmeric consumption by the patients 2. Measurement of the concentration of iron in turmeric
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