Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition

Inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as a novel therapeutic strategy for the treatment of oral squamous cell carcinoma (OSCC). The EGFR-directed inhibitor cetuximab is currently the only approved targeted therapy for the treatment of OSCC. EGFR status may affect the patient response to cetuximab treatment. In the present study, via analysis of the immunomarker for EGFR, it was revealed that 58.3% of the total cases investigated stained positively for EGFR expression, and furthermore, that invasiveness was inversely correlated with EGFR expression. Expression levels of EGFR were quantified, and the correlation between EGFR expression and cetuximab sensitivity was investigated using three varying grades of invasive human OSCC line. EGFR expression in high-grade invasive cells was significantly downregulated compared with that of low-grade invasive cells. There was no significant antiproliferative effect in the high-grade invasive cells treated with various concentrations of cetuximab. The EMT-associated genes, N-cadherin, vimentin and Snail, were upregulated in the high-grade invasive cells. The low-grade invasive cells exhibited characteristics of typical epithelial cells, including the expression of E-cadherin and absence of the expression of N-cadherin, vimentin and Snail. Transforming growth factor-β induced low-grade invasive cells to undergo an epithelial-mesenchymal transition (EMT)-associated gene switch, which resulted in low levels of EGFR expression. The results of the present study suggested that loss of EGFR expression in OSCC was associated with EMT, and may have functional implications with regard to tumor invasiveness and the resistance to cetuximab treatment. © Spandidos Publications 2015. All rights reserved.Embargo Period 6 month

Loss of maspin is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma

金沢大学附属病院歯科口腔外科Objective: Maspin, a 42-kDa protein, belongs to the serpin family of protease inhibitors and is known to have tumor-suppressor function. In this study, we investigated the interrelationship between clinicopathologic findings and maspin expression in oral squamous cell carcinoma (OSCC). Methods: Using immunohistochemical techniques to examine the expression levels of maspin in OSCC, maspin expression in OSCC was detected in 46 (64.8%) of 71 cases. We also compared the clonicopathologic features of OSCC cases with maspin expression levels. Moreover, we examined expression of maspin in eight cell lines derived from OSCC using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Results: There was a significant correlation between decreased maspin expression and T-category (P < 0.01), lymph metastasis (P < 0.0001), and mode of invasion (P < 0.0001). Patients with positive maspin expression had a significantly better prognosis (P < 0.001). Lower expression of maspin was also seen in cell lines derived from grade 4D, which shows stronger invasive potential than other grades of OSCC. Conclusion: Maspin may be a useful marker to identify the potential for progression in OSCC. © 2008 Blackwell Munksgaard

Anti-cytokine autoantibodies are ubiquitous in healthy individuals

AbstractAnti-cytokine autoantibodies in healthy individuals have been widely reported but the occurrence is variable and inconstant. We hypothesized that cytokine-binding in vivo may explain their variable and infrequent detection. Therefore, we focused on the detection of the cytokine-autoantibody complexes and found that anti-cytokine autoantibody to IL-2, IL-8, tumor necrosis factor-α, vascular endothelial growth factor and granulocyte-colony stimulating factor were present in all 15 individuals evaluated, while those to IL-3, osteopontin and macrophage-colony stimulating factor were not detected in anyone. Autoantibodies against IL-4, IL-6, IL-10, and interferon-gamma were variously detected. Thus, we discovered that anti-cytokine autoantibodies to multiple cytokines are ubiquitous in healthy individuals

A case of mandibular fracture including coronoid process fracture

The incidence of mandibular fractures is the highest among facial bone fractures. Addi-tionally, most of mandibular fractures occur in the mandibular angle and condylar process. On the other hand, the incidence of fracture of coronoid process is extremely low. We experienced a case of mandibular fractures involving mandibular body, condylar process as well as the coronoid process in a man aged 3₉–years–old who had received strong direct external force to the mandible. Mandibular fractures usually occur in the condylar process and mandibular angle because direct external force is more likely to transmit to these re-gions. Based on the classification of mandibular fractures, the incidence of mandibularfractures involving coronoid process increases with an increased number of fractures lines that means complicated fracture. At the viewpoint of anatomical portion, direct external force dose not transmit to coronoid process; however, it is possible that direct external force may transmit coronoid process in the case of complicated fracture. In this case report, we considered the potential mechanism of fracture of coronoid process by using a three–dimensional finite element model of a human mandible stress distribution analysis

Shear wave speed structure beneath the South Pacific superswell using broadband data from ocean floor and islands

[1] We determined three-dimensional shear wave speed structure beneath the South Pacific superswell down to a depth of 200 km by analyzing Rayleigh wave records from broadband ocean bottom seismograph stations and island stations in the Pacific Ocean. The ocean bottom stations were deployed from 2003 to 2005 on the seafloor in the French Polynesian region, which enabled us to study the upper mantle structure beneath the Superswell with unprecedentedly high resolution. We measured the dispersions of fundamental mode Rayleigh waves at periods between 40 and 140 seconds by the two-station method. We found pronounced slow anomalies near the hot spots and in the Lau Basin. The slow anomalies beneath the hot spots have deeper-rooted than those associated with the Lau basin. The slow anomalies near the Society, Macdonald, Marquesas, and Pitcairn hot spots continue down to at least 200 km depth