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We examined production and tissue localization of 7 different matrix metalloproteinases (MMP‐1, ‐2, ‐3, ‐7, ‐8, ‐9 and ‐13) and 2 tissue inhibitors of metalloproteinases (TIMP‐1 and ‐2) in human endometrial‐carcinoma tissues. Sandwich enzyme immunoassays showed enhanced production of MMP‐7, MMP‐8 and MMP‐9 as well as TIMP‐1 in the carcinoma tissues compared with non‐carcinoma endometrial tissues. Among these MMPs, only the amount of MMP‐7 correlated with clinicopathological factors of the carcinomas. The level was significantly 6.8‐fold higher in the patient group with lymph‐node metastases than in that without metastases (p < 0.05), and also increased with the progress of the clinical stage. MMP‐7 was immunolocalized predominantly to the carcinoma cells in 73% of the cases, while MMP‐8 and MMP‐9 were immunostained in the inflammatory cells infiltrated in the carcinoma tissues. Immunoblotting revealed a definite band for the zymogen of MMP‐7 (proMMP‐7) of 28 kDa in 82% of the carcinoma samples, while only a faint band for proMMP‐7 was seen in 57% of the non‐carcinoma endometrial samples. Active MMP‐7 species of 19 kDa and its activity were demonstrated in the carcinoma samples with proMMP‐7 production by immunoblotting and zymography, respectively. RT‐PCR using a specific primer pair for MMP‐7 demonstrated expression in 86% of the carcinoma tissue and in 57% of the control tissue samples. In situ hybridization showed carcinoma cells selectively expressing MMP‐7 mRNA. These data suggest that, among the 7 MMPs examined, MMP‐7 may play a key role in invasion and lymph‐node metastasis of human endometrial carcinomas. Int. J. Cancer (Pred. Oncol.) 84:470–477, 1999. © 1999 Wiley‐Liss, Inc.

High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.

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