ABSTRACT
In the present study, the effects of bulb type palatal lift prosthesis (bulb-PLP) therapy on nasality and velopharyngeal function (VPF) of patients with velopharyngeal incompetence (VPI) following palatoplasty were longitudinally assessed.The subjects included 18 patients (3 to 52 years of age) who had shown persistent VPI following palatoplasty and who had received bulb-PLP therapy. Nasality and VPF were assessed by perceptual voice analysis, nasometer test, blowing test, and cephalometric radiographic examination. Based on the outcomes of bulb-PLP therapy, the subjects were classified into two groups: the effective group and the ineffective group. Furthermore, the obturating and VPF-activating effects by bulb-PLP therapy were analyzed, and factors relating to different VPF activities were determined.All subjects achieved adequate VPF by wearing a bulb-PLP. After treatment, 10 patients (55.6%) achieved successful activation of VPF without bulb-PLP (the effective group), while persistent VPI remained in 8 patients (the ineffective group). The beginning-blowing ratio of the effective group was significantly greater than that of the ineffective group (P < 0.05) and the velopharyngeal distance (V-P distance) of the effective group tended to be smaller (P = 0.07). Regarding the shape of the bulb head, the angular type was dominant in the ineffective group, while the round type was dominant in the effective group.Bulb-PLP therapy was useful for providing adequate VPF activation. Possible signs of the subsequent effective activation of VPF are considered to be: 1) preexisting adequate VPF on blowing, 2) smaller V-P distance, and 3) synchronized palatopharyngeal movement.
ABSTRACT
A modification of the surgical technique for extracting impacted lower third molars is required to decrease the rate of complications including inferior alveolar nerve injury. In this study, a new two-stage extraction method for the horizontally impacted lower third molar was developed. During the first stage, only the crown was removed after separating the impacted tooth at the neck. Thereafter, the root(s) was pulled toward the anterior direction with an elastic band at 130-150 g over a 7-day period. Next, the root(s) was extracted. This method was firstly attempted for 20 horizontally impacted lower third molars, the roots of which had been close to the mandibular canal in panoramic radiographs and were pulled for 20.8 ± 11.5 (n = 20) days. The roots in 17 of 20 cases (85%) were loosened from the sockets and extracted easily without any complications. These outcomes suggest that this two-stage method is useful for the extraction of a horizontally impacted lower third molar in order to decrease the rate of inferior alveolar nerve injury.
ABSTRACT
We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (<i>p</i> < 0.001, <i>p</i> < 0.001, and <i>p</i> < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (<i>p</i> < 0.05 and <i>p</i> < 0.001, respectively), while both were associated with tumor size (<i>p</i> < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (<i>p</i> < 0.01) and PAI-1 (<i>p</i> < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.
ABSTRACT
Keratocystic odontogenic tumors have a high level of proliferative activity in epithelial cells and they tend to grow aggressively in the jaw. The tumor dramatically decreases in size by decompression of the intracystic fluid pressure. We herein focused on the roles of interleukin (IL)-1α and demonstrated the biochemical mechanisms of the tumor growth. We found that IL-1α is strongly expressed in the lining epithelial cells of the tumors, and the intracystic fluid levels of IL-1α are significantly higher than the levels of the other inflammatory cytokines of IL-6 and tumor necrosis factor-α (TNF-α). The expression of IL-1α in the epithelial cells decreases after the marsupialization of the tumor. <i>In vitro</i> experiments also reveal that positive pressure enhances the expression of IL-1α in the tumor epithelial cells in culture. IL-1α stimulates the production of matrix metalloproteinase (MMP)-9, and activates the released proMMP-9 by increasing the expression of proMMP-3 and plasminogen activator urokinase (u-PA) in the tumor epithelial cells. In the fibroblasts isolated from the tumors, IL-1α increases the expression of proMMP-1, proMMP-2, and proMMP-3. IL-1α also activates proMMP-2 by inducing the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) synergistically with type I collagen. Furthermore, IL-1α increases the expression of macrophage colony-stimulating factor (M-CSF) and cyclooxygenase (COX)-2 in the fibroblasts. The COX-2 synthesizes prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), and the secreted PGE<sub>2</sub> stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL), while neither IL-1α nor PGE<sub>2</sub> affects the expression of osteoprotegerin (OPG) in the fibroblasts. The fibroblasts express Ca<sup>2+</sup>-sensing receptor (CasR) on the cell surface, and extracellular Ca<sup>2+</sup> activates COX-2 expression via the CasR. A strong relationship may thus be present between the intracystic fluid pressure and IL-1α expression in epithelial cells, and the released IL-1α may play a crucial role in the growth of keratocystic odontogenic tumors by stimulating proteolytic enzyme production and osteoclastogenesis.
ABSTRACT
Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α<sub>2</sub> integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α<sub>2</sub> integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.
ABSTRACT
Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α<sub>2</sub> integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α<sub>2</sub> integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.
ABSTRACT
Adenoid cystic carcinoma (AdCC) is characterized by frequent recurrence and distant metastasis. Although lung metastasis in AdCC is very common, the mechanism by which this occurs is uncertain. When five AdCC cell lines (ACCS, ACCT, ACCH, Acc-3, and Acc-M) were screened for metastatic ability by injecting tumor cells into nude mice via the tail vein, lung metastases were found in mice injected with Acc-M (15/16 mice) but not in mice injected with any of the other four cell lines (0/10 mice with each line). To determine why Acc-M metastasizes to the lung but the others do not, we examined the biological characteristics of Acc-M and compared them with those of the other lines.Nuclear factor-κB (NF-κB) may play a key role in malignant tumor behaviors such as invasion and metastasis. Thus, we examined these cell lines for response to tumor necrosis factor (TNF-α), one of the typical stimulators of NF-κB. Although treatment with TNF-α stimulated matrix metalloprotease 9 (MMP-9) expression in all cell lines, the response to TNF-α varied between cell lines; the greatest stimulation was observed in Acc-M. Acc-M expressed higher levels of TNF receptors (both TNF-R1 and TNF-R2) than did the other AdCC lines. Judging from inhibitor-κBα degradation and nuclear translocation and DNA binding by NF-κB, the degree of activation of NF-κB in response to TNF-α in Acc-M cell lines was very high compared to the other lines. Moreover, the ability of Acc-M cells to adhere to endothelial cells, which was greater than that of the other cell lines, was further enhanced by pretreatment with TNF-α. Acc-M cells also expressed higher levels of sialyl Lewis<sup>x</sup> than did the other AdCC cell lines. These findings suggest that lung metastasis is mediated by tumor-endothelial cell interaction, which is probably associated with the NF-κB activation pathway. Further experiments are required to identify the molecules that mediate both lung metastasis and NF-κB activation.