Jingo Kusukawa

Production onf matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study

Background. Matrix metalloproteinases (MMP) are a gene family of zinc enzymes capable of degrading almost all of the extracellular matrix macromolecules in vivo. Their enzymic activities are believed to be responsible for tumor invasion and metastasis.

Expression of matrix metalloproteinase-3 in stage I and II squamous cell carcinoma of the oral cavity☆

PURPOSE The object of this study was to evaluate the significance of matrix metalloproteinase-3 (MMP-3) in tumor invasion and metastasis of early squamous cell carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS Surgical specimens from 65 patients with stage I and II SCC of the oral cavity were the subjects of this study. Tissue specimens were fixed in formalin and embedded in paraffin, and the sections were stained with monospecific antibodies against human MMP-3 by the avidin-biotin-peroxidase complex method. RESULTS Of the 65 patients, 30 (46.2%) tested positive for MMP-3. Immunoreactivity revealed the expression of MMP-3 to be in the small cancer nests in the advancing front of invasion, but not in normal oral epithelium. MMP-3 expression was positively correlated with tumor size, depth of tumor invasion, diffuse invasive mode, and the high incidence of lymph node metastasis. CONCLUSION MMP-3-containing tumors will invade adjacent normal tissues more aggressively, including lymphatic and blood vessels. Therefore, the examination of MMP-3 expression in biopsy specimens should provide information useful in predicting the malignant potential of early SCC of the oral cavity.

The Significance of Epidermal Growth Factor Receptor and Matrix Metalloproteinase-3 in Squamous Cell Carcinoma of the Oral Cavity

Surgical specimens from 65 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistochemically. The clinicopathological significance of the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase-3 (MMP-3) was assessed. Among the 65 tumours, 20(30.8%) and 37(56.9%) tested positively for EGFR and MMP-3, respectively. A positive correlation between the expression of EGFR and MMP-3 was found. The expression of EGFR in oral SCCs was associated with an advanced T stage of the primary tumour, an advanced pathological stage, and a high incidence of neck metastasis. In addition, MMP-3 was primarily expressed at the advancing front of cancer with a diffuse invasive mode. Thus, overexpression of MMP-3 was associated with an advanced pathological stage, a diffuse invasive mode, and a high incidence of neck metastasis. The analysis of MMP-3 expression is useful to evaluate the pathological status of tumours. Because EGFR-overexpressed tumour should produce larger amounts of MMP-3 in vivo, a close examination of oral SCC for expression of EGFR and MMP-3 should be helpful to predict their malignant potential.

Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive human cancers, and novel treatment modalities are required. We investigated the therapeutic potential of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2L) in combination with the proteasome inhibitor bortezomib (Velcade) on human ESCC cell lines. Bortezomib enhanced the susceptibility to TRAIL in 12 of the 15 ESCC cell lines tested, although most showed low sensitivity to TRAIL as a single agent. The enhancement of TRAIL-induced apoptosis by bortezomib was caspase dependent. Increased processing of caspase-8 often accompanied enhancement of TRAIL-induced apoptosis by bortezomib. However, the increased cell surface expression of death receptors observed on bortezomib treatment did not seem to be crucial for this effect. For some ESCC, bortezomib treatment resulted in a more efficient recruitment of caspase-8 and the Fas-associated death domain to the death-inducing signaling complex. Additional downregulation of the cellular FLICE-inhibitory protein long isoform [c-FLIP(L)] could cooperate in the activation of the extrinsic pathway in some cases. For other ESCC, the crucial effect of bortezomib treatment seemed to be increased signaling via the intrinsic apoptotic pathway on subsequent exposure to TRAIL. Thus, bortezomib could sensitize ESCC to TRAIL apoptosis by multiple molecular mechanisms of action. Therefore, the combination of bortezomib and TRAIL might be a novel therapeutic strategy for ESCC patients who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. Mol Cancer Ther; 9(6); 1842–51. ©2010 AACR.

Usefulness of intra-oral ultrasonography to predict neck metastasis in patients with tongue carcinoma

OBJECTIVE To assess tissue characterization relating with neck metastasis of invasive tongue cancer, we investigate the usefulness of intra-oral ultrasonography (US). MATERIALS AND METHODS The patients with squamous cell carcinoma of the tongue (n = 110) were preoperatively evaluated with intra-oral US. The US images were compared with histological sections. The histological and ultrasonographic parameters were evaluated for their correlation with neck metastasis. RESULTS AND CONCLUSION High-quality ultrasonic images were obtained, and all lesions over 1 mm thickness by histology were detected. There was a significant correlation (P < 0.0001) between measurements of tumor thickness by US and histology. Univariate analysis showed that the histological parameters influencing neck metastasis were mode of invasion (P = 0.0006), muscular invasion (P < 0.0001), stromal reaction (P = 0.0002), and tumor thickness (P = 0.0004). Of the ultrasonographic parameters, shape of margin (P = 0.019), pattern of margin (P = 0.033), internal echo signal (P = 0.035), and tumor thickness (P < 0.0001) showed a significant correlation with neck metastasis. Ultrasound images of oral tongue cancer reflected the histological structures. Tumors with diffuse invasive mode shows an irregular and unclear tumor margins on US image. Thickness of 8 mm by ultrasound is useful as a cut-off point of predicting risk of neck metastasis of tongue cancer. Intra-oral US is a reliable tool in objectively predicting subclinical neck metastasis in tongue cancer.

Dentigerous cyst associated with a deciduous tooth. A case report.

A case of a dentigerous cyst associated with a deciduous tooth in a 2-year-old boy is presented. Radiologic examination revealed a well-defined radiolucency in the right maxilla associated with the crown of a maxillary second deciduous molar. The cyst cavity was lined with nonkeratinized squamous epithelium, and odontogenic epithelial islands were seen in subepithelial connective tissue.

Epithelial-myoepithelial carcinoma : Report of a case arising in the nasal cavity

We present an extremely rare case of epithelial-myoepithelial carcinoma (EMC) arising in the nasal cavity. The patient was a 56-year-old Japanese male with a polypoid tumour arising from the nasal septum. Histopathological examination revealed the tumour to consist of a solid proliferation of clear-cells and, in some areas, small or elongated duct structures with a double-layered arrangement of inner cuboidal cells and outer clear-cells. Dual differentiation toward myoepithelial and ductal cells were confirmed immunohistochemically. The occurrence of EMC in the nasal cavity is possible and this entity should be generally recognized by surgical pathologists, not only those engaged in head and neck surgery.

Osteochondroma in the mandibular condyle that caused facial asymmetry: A case report

Abstract Osteochondroma is the most common benign tumor of the axial skeleton, though it is rarely found in the oral and maxillofacial regions. Reported is a case of osteochondroma affecting the mandibular condyle of a 22-year-old Japanese woman. The patient visited the hospital with the chief complaint of facial asymmetry. She had pain with clicking on her right temporomandibular joint (TMJ), resulting in trismus and facial asymmetry with a chin deviation to the left side. Her maximum jaw opening was 34 mm, with moderate left TMJ tenderness. There was Class I occlusion without open bite. Panoramic radiography and computed tomography (CT) revealed an enlarged right mandibular condylar head. Magnetic resonance imaging (MRI) also showed an enlarged condyle with hyperintense bone marrow on a T2-weighted image. Condylectomy and condyloplasty were performed. Surgical specimen of the lesion revealed osteochondroma of the mandibular condyle head. Two months after the initial surgery, facial asymmetry was surgically corrected by Le Fort I osteotomy and chin reduction. The patient was discharged from the hospital with no subjective complaints. At the time of this report, the patient had been followed up for seven months, and there had been no evidence of recurrence.

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma (Review)

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.

Lateral cephalometric analysis of the pharyngeal airway space affected by head posture

To clarify the relationship between head posture and pharyngeal airway space (PAS), the cephalometric parameters at different head postures were examined. Twelve normal Japanese adults (6 males and 6 females) were examined. Lateral cephalometric radiographs were taken at five different head postures in each person. All radiographs were traced, and the measurements were analyzed statistically. PAS was significantly increased by forward inclination of the cervical spine. The most significant correlation was found between the change in CVT/NSL (cranio-cervical inclination in the second and fourth vertebrae) and the change in PAS-TP (the minimal pharyngeal airway space) (r(2)=0.79 in males, r(2)=0.67 in females). The mean CVT/NSL when the head was in the natural (neutral) position was 100.9 degrees in males and 103.5 degrees in females. Linear regression analysis revealed DeltaPAS (mm)=0.37DeltaCVT/NSL (degree) (r(2)=0.79, p<0.0001) in males, and DeltaPAS (mm)=0.33DeltaCVT/NSL (degree) (r(2)=0.51, p<0.0001) in females. The correlation equations were obtained as follows: the corrected PAS (mm)=the actual PAS (mm)+0.37[100.9-the actual NSL/CVT (degree)] in males, and the corrected PAS (mm)=the actual PAS (mm)+0.33[103.5-the actual NSL/CVT (degree)] in females. These results will contribute to obtaining an accurate assessment of the PAS that should be corrected by the cranio-cervical inclination.