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Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors, in particular MMP-7, which is mainly produced by the cancer cell itself. We examined the expression of MMP-2, 7 and 9, and tissue inhibitors of metalloproteinase (TIMP)-1 and 2 in uterine endometrial carcinoma, and compared the expression with clinicopathological characteristics in uterine endometrial carcinoma (UEC). A group of 256 patients with UEC received surgery at the Osaka City University Medical School Hospital, and 196 tumor samples were immunohistochemically stained to examine the expression of MMP-2, 7 and 9, and TIMP-1 and 2. Additionally, the invasion ability of cell stain established from UEC was examined using an in vitro invasion assay. The expression of MMP-2, 7 and 9, and TIMP-1 and 2 was observed in the cytoplasm, and the expression of MMP-2 and 7, and TIMP-1 and 2 was observed in stromal cells around the tumor cells. The expression of MMP-7 was significantly stronger in higher-grade than lower-grade tumors (P<0.05). The invasion assay showed that the invasion of cells derived from UECs was significantly inhibited by TIMP-1 and 2. The disease-free interval was significantly shorter when MMP-7 expression was intense. This increased expression of MMP-7 in high grade UECs may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC.

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase as well as a cofactor of aromatic amino acid hydroxylases. However, its role in pregnancy is not yet understood. We evaluated the concentrations of BH4 throughout normal pregnancy and puerperium, and compared them with those of non-pregnant women by measuring its oxidation product biopterin. In addition, we also measured 6-pyruvoyl tetrahydropterin synthase (PTPS) activities, the rate-limiting enzyme in synthesizing BH4, in pregnant women at the 30th gestational week and non-pregnant women. Although the urinary biopterin levels did not remarkably change, plasma biopterin levels significantly decreased from the 10th gestational week to the 1st day of postpartum compared with those of non-pregnant women. There was no significant difference in PTPS activities between pregnant and non-pregnant women. However, the proportion of reticulocytes, which have been shown to possess high PTPS activity, is significantly higher in pregnant women than in non-pregnant women. Our results suggest that decreased plasma BH4 levels in pregnancy is caused by impaired PTPS activity.