Constitutively active Ras proteins, their regulatory components, and overexpressed tyrosine kinase receptors that activate Ras, are frequently associated with cell transformation in human tumors. This suggests that functional Ras antagonists may have anti-tumor activity. Studies in rodent ®broblasts have shown that S-trans, transfarnesylthiosalicylic acid (FTS) acts as a rather speci®c nontoxic Ras antagonist, dislodging Ras from its membrane anchorage domains and accelerating its degradation. FTS is not a farnesyltransferase inhibitor, and does not a ect Ras maturation. Here we demonstrate that FTS also acts as a functional Ras antagonist in human pancreatic cell lines that express activated KRas (Panc-1 and MiaPaCa-2). In Panc-1 cells, FTS at a concentration of 25 ± 100 mM reduced the amount of Ras in a dose-dependent manner and interfered with serumdependent and epidermal growth factor-stimulated ERK activation, thus inhibiting both anchorage-dependent and anchorage-independent growth of Panc-1 cells in vitro. FTS also inhibited tumor growth in Panc-1 xenografted nude mice, apparently without systemic toxicity. Daily FTS treatment (5 mg/kg intraperitoneally) in mice with tumors (mean volume 0.07 cm 3 ) markedly decreased tumor growth (after treatment for 18 days, tumor volume had increased by only 23+30-fold in the FTStreated group and by 127+66-fold in controls). These ®ndings suggest that FTS represents a new class of functional Ras antagonists with potential therapeutic value.
Objective To evaluate the outcome of pregnancies with proven and well-dated primary cytomegalovirus (CMV) infection with and without abnormal fetal ultrasound and magnetic resonance imaging (MRI) findings.
Methods
SummaryBackgroundTo compare maternal and neonatal outcomes of term macrosomic and adequate for gestational age (AGA) pregnancies.Material/MethodsA retrospective analysis was performed on all term singleton macrosomic (birth weight ≥4000 g) and AGA (birth weight >10th percentile and <4000 g) pregnancies delivered at our hospital between 2004 and 2008. Data collected included maternal age, gestational age at delivery, mode of delivery, birth weight, fetal gender, maternal and neonatal complications. Comparisons were made between macrosomic and AGA pregnancies and between different severities of macrosomia (4000–4250 g, 4250–4500 g and ≥4500 g).ResultsThe study population comprised of 34,685 pregnancies. 2077 neonates had birth weight ≥4000 g. Maternal age and gestational age at delivery were significantly higher for macrosomic neonates. Significantly more macrosomic neonates were born by cesarean section, and were complicated with shoulder dystocia, neonatal hypoglycemia, and had longer hospitalization period (both in vaginal and cesarean deliveries). Specifically, the odds ratio (OR) relative to AGA pregnancies for each macrosomic category (4000–4250 g, 4250–4500 g and ≥4500 g) of shoulder dystocia was 2.37, 2.24, 7.61, respectively, and for neonatal hypoglycemia 4.24, 4.41, 4.15, respectively. The risk of post partum hemorrhage was statistically increased when birth weight was >4500 g (OR=5.23) but not for birth weight between 4000–4500 g. No differences were found in the rates of extensive perineal lacerations between AGA and the different macrosomic groups.ConclusionsMacrosomia is associated with increased rate of cesarean section, shoulder dystocia, neonatal hypoglycemia, and longer hospitalization, but not associated with excessive perineal tears. Increased risk of PPH was found in the >4500g group.
Objective To describe our management of pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence.Methods This was a retrospective study involving all cases of TRAP sequence referred to our fetal medicine unit in a 3-year period (2000)(2001)(2002)
Diagnosis of isolated hemivertebra might be associated with a favorable outcome. The 3 key factors in achieving an optimal spine at maturity, early diagnosis, anticipation, and prevention of deterioration, might be enhanced by our joint multidisciplinary approach to the diagnosis of skeletal anomalies.
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