Ryo Kawata

Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: Implications for lymph node metastasis

We measured the production levels of seven different matrix metalloproteinases (MMP-1, 2, 3, 7, 8, 9 and 13) and two tissue inhibitors of metalloproteinases (TIMP-1 and 2) in the homogenates of human oral squamous cell carcinomas and control normal squamous epithelia by the corresponding sandwich enzyme immunoassay systems. The levels of MMP-1, 2, 3, 8, 9, 13 and TIMP-1 were significantly higher in the carcinoma samples than in the control. Among them, only the production level of MMP-2 was significantly higher in the carcinomas with cervical lymph node metastasis than in those without metastasis (P < 0.05). Gelatin zymography demonstrated that activation ratio of the zymogen of MMP-2 (proMMP-2) is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or normal control (P < 0.01). Quantitative RT-PCR for membrane-types 1, 2 and 3 MMPs (MT1, 2 and 3-MMPs), which activate proMMP-2 in vitro, demonstrated that MT1-MMP is predominantly expressed in the carcinoma tissues, and the expression level is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or the control samples (P < 0.05). Although MT2-MMP and MT3-MMP were detected in approximately 30% of the carcinoma cases, their expression levels were extremely lower compared with that of MT1-MMP. There was a direct correlation between the MT1-MMP expression level and proMMP-2 activation ratio (r = 0.62, P < 0.01). In situ hybridization and immunohistochemistry indicated that carcinoma cells and stromal cells adjacent to carcinoma cell nests express MT1-MMP transcripts and protein. MMP-2 and TIMP-2 were also immunolocalized to the carcinoma cells in the carcinoma samples. By in situ zymography, gelatinolytic activity was demonstrated in the carcinoma cell nests and abolished by the treatment with an MMP inhibitor, BB94. These results suggest that among seven different MMPs, the production of proMMP-2 and its activation mediated by MT1-MMP play an important role in the cervical lymph node metastasis of the human oral squamous cell carcinomas.

Enhanced Production of Matrix Metalloproteinase-2 in Human Head and Neck Carcinomas is Correlated with Lymph Node Metastasis

Matrix metalloproteinase (MMP)-2 and -9 degrade type IV collagen, which is one of the major components of the basement membrane in normal tissue and expressed in the surroundings of the cancer nest in squamous cell carinoma. The degeneration of type IV collagen is an essential step in the metastasis to lymph nodes and distant organs. In this study, we examined MMP-2 and -9 levels of cancer tissue and serum obtained from patients with head and neck squamous cell carcinoma (HNSCC) in order to evaluate the relationship between the clinicopathologic features and MMPs. We examined the production of MMP-2 and -9 in cancer tissue homogenates of 73 patients who had HNSCC and the serum MMP levels of 16 patients with HNSCC and 8 healthy volunteers. We also studied the localization of MMP-2 in the carcinoma using an immunohistochemical approach. The concentrations of MMP-2 and -9 in the tissue homogenates and serum were measured by means of a sandwich enzyme immunoassay using a monoclonal antibody. Immunohistochemical analyses were performed with monoclonal antibody to MMP-2. The concentration of MMP-2 in the tumor tissue homogenates was unrelated to tumor size, but that in patients with lymph node metastases was significantly higher than in those without lymph node metastases. The concentration of MMP-9 was unrelated to lymph node metastasis and tumor size. The levels of both MMP-2 and -9 in serum were unrelated to lymph node metastasis. Immunohistochemistry indicated that MMP-2 was mainly expressed in cancer cells. Because MMP-2 degrades type IV collagen, the level of MMP-2 in carcinomas may be a useful indicator of the degree of invasion and metastasis.

Prostaglandin content in human middle ear effusions.

SummaryThe concentrations of prostaglandins (PGs) were measured by a radioimmunoassay in human middle ear effusions (MEEs) obtained from patients with otitis media with effusions. Each sample of MEE was divided into two groups: serous effusions and mucoid ones. The main PG in both the serous and mucoid effusions was TXB2 (375 and 857pg/ml, respectively), followed by PGE2 (173 and 459pg/ml, respectively). Smaller quantities of PGD2 (35 and 64 pg/ml, respectively), PGF2a (139 and 183 pg/ml, respectively), and 6keto PGF1a (129 and 201 pg/ml, respectively) were also found in the MEEs. The amounts of each PG in the mucoid effusions were 2 or 3 times higher than those found in the serous effusions, while protein concentrations and the profile of these PGs in the MEEs were almost the same in the mucoid and serous groups. These results suggest that PGs may play an important role as a mediator of the inflammatory responses in the pathogenesis of MEEs.

Longitudinal Median Sternotomy for Extirpation of Cervical Tumors Extended to the Upper Mediastinum

The cervical tumor observed in five cases extending to the upper mediastinum was extirpated in our department by using a combination of a neck dissection and a longitudinal median sternotomy.These tumors were originated from thyroid,thymus,and cervical nerve. The longitudinal median sternotomy is a useful approach to the upper mediastinum in order to keep a good operation view,to decrease bleeding volume,and to shorten operation time. Therefore,this approach should be adapted more for the extirpation of cervical tumor which extends to the upper mediastinum and for a mediastinal dissection.