OBJECTIVE: The purpose of this study was to assess the impact of vascular endothelial growth factor (VEGF) in pregnancies with mild and severe preeclampsia. METHODS: From January 1999 to June 2001, we studied the severity for pregnant women with pregnancy induced hypertension between 28 and 40 weeks gestation. In the mild (n=46) and severe preeclamptic women (n=28), the laboratory evaluation included liver function test, platelet counts, and serum creatinine. The systolic/diastolic (S/D) ratio of the fetal umbilical artery flow for placental resistance was measured by ultrasonographic doppler velocimetry. To detect the damage of vascular endothelial cells in all preeclamptic women, serum concentrations of VEGF were measured. RESULTS: Severe preeclampsia had more elevated liver enzymes, thrombocytopenia, high creatinine than mild preeclampsia. HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) was encountered in 8/28 (28.6%) of severe preeclampsia. Fifteen out of twenty-eight cases (53.6%) in severe preeclampsia had elevated S/D ratio from 3.0 to 4.5 including 6 cases with absent end diastolic velocity, whereas 4/46 (8.7%) was elevated SD ratio (>3.0) in mild preeclampsia. Serum concentrations of VEGF were elevated in both mild (7.5+/-4.9 ng/mL, p<0.05) and severe preeclampsia (19.3+/-8.8 ng/mL, p<0.05) compared to normal pregnancy (0.5~2.1 ng/mL). CONCLUSION: The higher serum concentration of VEGF and elevated S/D ratio of umbilical artery were responsible for the changes of the resistance of placental blood flow in severe preeclampsia. Furthermore, elevated S/D ratio of umbilical artery velocity was essential as a surveillance method of fetal health status with IUGR (Intrauterine growth restriction) by vascular declination of placenta.
Creatinine ; Endothelial Cells ; Female ; Fetal Growth Retardation ; HELLP Syndrome ; Humans ; Hypertension, Pregnancy-Induced ; Liver ; Liver Function Tests ; Placenta ; Platelet Count ; Pre-Eclampsia* ; Pregnancy ; Pregnant Women ; Rheology ; Thrombocytopenia ; Umbilical Arteries ; Vascular Endothelial Growth Factor A*

PURPOSE: The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process. MATERIALS AND METHODS: Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively. RESULTS: Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580. CONCLUSION: Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis.
Animals ; Antibodies ; Blotting, Northern ; Cats ; Gelatinases ; Humans* ; Matrix Metalloproteinases ; Neoplasm Metastasis ; p38 Mitogen-Activated Protein Kinases* ; Protein Kinases ; RNA, Messenger ; Stomach Neoplasms