Prenatal sonographic markers of the outcome in fetuses with bronchopulmonary sequestration.

PURPOSE: To evaluate the prenatal sonographic predictive markers of the outcome in fetuses with bronchopulmonary sequestration (BPS). METHODS: BPS size and diameter of the feeding artery (FA) were measured prenatally and postnatally. Velocity of the FA and the left ventricular-modified myocardial performance index (LV mod-MPI) were also evaluated prenatally. RESULTS: Forty-seven women were included in the study. Mean gestational age, mass size, diameter and velocity of the FA, and LV mod-MPI at prenatal diagnosis were 23.5 ± 2.2 weeks, 3.6 ± 8.3 cm, 2.3 ± 0.6 mm, 46.6 ± 15.4 cm/s, and 0.46 ± 0.06, respectively. Mean mass diameter and FA diameter measured on postnatal CT examinations were 3.8 ± 1.0 cm and 2.3 ± 0.7 mm, respectively. Five patients had respiratory symptoms after birth. Twenty children (43%) underwent or were scheduled to undergo mass excision, and the remaining 27 (57%) were doing well without any intervention. There was no neonatal death. LV mod-MPI at diagnosis, the FA diameter after birth and the serial change in the FA size were significantly associated with postnatal mass excision. CONCLUSION: The FA diameter and LV mod-MPI may be additional markers for predicting whether fetuses with BPS should undergo mass excision in early childhood or conservative care.

First reported case of fetal aortic valvuloplasty in Asia.

Prenatal intervention of severe fetal aortic valve stenosis by ultrasound-guided percutaneous balloon valvuloplasty has been performed to prevent the progression to hypoplastic left heart syndrome, and achieve biventricular circulation in neonates. Here we report a case of fetal aortic valvuloplasty prenatally diagnosed with aortic stenosis at 24 weeks of gestation and showed worsening features on a follow-up echocardiography. Prenatal aortic valvuloplasty was performed at 29 weeks of gestation, and was a technical success. However, fetal bradycardia sustained, and an emergency cesarean delivery was performed. To the best of our knowledge, this is the first reported case of fetal aortic valvuloplasty which was performed in Asia.

Overexpression of c-myc induces epithelial mesenchymal transition in mammary epithelial cells.

The c-myc gene is frequently overexpressed in human breast cancer and its target genes are involved in tumorigenesis. Epithelial mesenchymal transitions (EMT), where cells undergo a developmental switch from a polarized epithelial phenotype to a highly motile mesenchymal phenotype, are associated with invasion and motility of cancer cells. Basal E-cadherin expression was down-regulated in c-myc overexpressing MCF10A (c-myc-MCF10A) cells compared to GFP-overexpressing MCF10A (GFP-MCF10A) cells, while N-cadherin was distinctly increased in c-myc-MCF10A cells. Given that glycogen synthase kinase-3beta (GSK-3beta) and the snail axis have key roles in E-cadherin deregulation during EMT, we investigated the role of GSK-3beta/snail signaling pathways in the induction of EMT by c-myc overexpression. In contrast to GFP-MCF10A cells, both the transcriptional activity and the ubiquitination-dependent protein stability of snail were enhanced in c-myc-MCF10A cells, and this was reversed by GSK-3beta overexpression. We also found that c-myc overexpression inhibits GSK-3beta activity through activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK by dominant negative mutant transfection or chemical inhibitor significantly suppressed snail gene transcription. These results suggest that c-myc overexpression during transformation of mammary epithelial cells (MEC) is involved in EMTs via ERK-dependent GSK-3beta inactivation and subsequent snail activation.

Oltipraz regenerates cirrhotic liver through CCAAT/enhancer binding protein-mediated stellate cell inactivation.

Liver cirrhosis (LC) is a chronic disease with high mortality rate. In the United States and Western world as well as Asian countries, LC is the major leading cause of death by disease. Yet, no effective therapeutic agent is available for LC treatment. Laboratory cirrhotic rats produced by dimethylnitrosamine administrations simulate the clinical features of human LC such as mortality, ascites, hepatic parenchymal cell destruction, and formation of connective tissue and nodular regeneration, providing a preclinical model to evaluate therapeutic efficacy of drugs and the underlying mechanisms. Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] has been used clinically and is of little toxicity. Comprehensive mechanistic and phase IIa clinical studies supported the notion that oltipraz exerts chemopreventive effects against chemical carcinogenesis. We report here that oltipraz within the clinical dose range regenerates cirrhotic liver in the established LC rats as a result of reduction of the intensities of cirrhotic nodules, elimination of accumulated extracellular matrix, and inactivation of stellate cells, thereby improving survival rate. We also reveal that activation of CCAAT/enhancer binding protein by oltipraz inhibits transforming growth factor b1 gene expression in stellate cells, which provides a molecular target for pharmacological treatment of LC. Oltipraz is the first therapeutic agent that regenerates cirrhotic liver.