Takahiko Toyoshima

Identification of a truncated cystatin SA-I as a saliva biomarker for oral squamous cell carcinoma using the SELDI ProteinChip platform

New and more consistent biomarkers of oral squamous cell carcinoma (OSCC) are needed to improve early detection of the disease and to monitor patient management. The aim of this study was to detect new OSCC tumor markers in saliva. Unstimulated saliva, collected from patients with primary stage I OSCC as matched pre-and post-treatment samples, was used in the analysis. A surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF) ProteinChip system was used to screen for differentially expressed proteins in the saliva samples. This analysis revealed 26 proteins with significantly different expression levels in the pre-and post-treatment samples (P<0.05). A 14 kDa protein detected in pre-treatment saliva from the OSCC patients was identified as a truncated cystatin SA-I, with deletion of three amino acids from the N-terminus. The authors propose that ProteinChip analysis may provide a reliable screening test for early diagnosis of OSCC and that truncated cystatin SA-I might be a useful tumor biomarker for OSCC.

Inhibition of cyclooxygenase-2 suppresses the invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 production and activation.

Increased cyclooxygenase (COX-2) expression in tumors is known to be correlated with tumor invasion, angiogenesis, resistance to apoptosis, and suppression of host immunity. We previously reported that the invasiveness of human oral squamous cell carcinoma (OSCC) cell lines NA and HSC-4 was suppressed by treatment with either NS-398, a selective COX-2 inhibitor, or COX-2 antisense oligonucleotide (AS). In the present study, to explore the effects of COX-2 inhibition on the interaction between cancer cells and fibroblasts, we examined the effects of these anti-COX-2 reagents on the expression of matrix metalloproteinases (MMPs) in fibroblast cell lines WI-38 and MRC-5. Western blotting and enzyme-linked immunosorbent assay revealed that NS-398 and COX-2 AS down-regulated the expression and secretion of MMP-2 and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human fibroblast cell lines. Furthermore, invasion activity of OSCC cells was down-regulated by the addition of culture supernatant from fibroblasts treated with anti-COX-2 reagents in a Matrigel® invasion assay. These results suggest that selective COX-2 inhibition suppresses the invasion activity of OSCC cells via down-regulation of an MMP-2-activating mechanism involving TIMP-2 and production of the MMP-2 protein by an interaction between cancer cells and stromal fibroblasts. Genetic or pharmacological inhibition of COX-2 may therefore be a beneficial strategy in the treatment of OSCC.

Treatment of Mandibular Prognathism in an Acromegalic Patient: Report of a Case

A case of acromegaly accompanied by pituitary adenoma in a 35-year-old male is reported. The patient presented with mandibular protrusion, malocclusion and articulate disorder. Prior to oral surgery, a pituitary adenoma was resected at the Department of Neurosurgery. Pre-operative orthodontic treatment was started after growth hormone and insulin-like growth factor I had returned to normal levels. Orthognathic surgery by sagittal split ramus osteotomy (SSRO) was performed, and good occlusion was obtained. Articulate function also improved after orthognathic surgery.

A case of angioneurotic edema with C1 esterase inhibitor deficiency and repeated facial edema triggered by odontogenic inflammation

Angioneurotic edema is subcutaneous or mucosal swelling resulting from increased vascular permeability, which can be produced by a variety of conditions. There are two forms of angioneurotic edema: hereditary and non-hereditary. Deficiency of C 1 esterase inhibitor (C 1 INH) function is known to be associated with hereditary angioneurotic edema. Non-hereditary angioneurotic edema associated with deficiency of C 1 INH function is rare. We report a case of non-hereditary angioneurotic edema with facial edema triggered by odontogenic inflammation. The patient was a 58-year-old woman who was referred to our clinic because of facial swelling after pulpectomy of the right lower incisors. Marked edema was present in her face, lips, cheeks, and soft palate. Laboratory examination revealed a deficiency of C 1 INH. Because no member of her family had episodes of facial swelling or deficiency of C 1 INH, the diagnosis was non-hereditary angioneurotic edema with deficiency of C 1 INH. We describe the clinical course of the patient and the mechanism of angioneurotic edema.