An isolated SMA dissection is a rare entity that may be managed successfully in a variety of ways based on clinical presentation. Endovascular stenting can be performed with good results and may be the preferred treatment in patients with symptomatic isolated SMA dissections.

Liposarcomas are the most common type of soft tissue sarcoma but their genetics are poorly defined. To identify genes that contribute to liposarcomagenesis and serve as prognostic candidates, we undertook expression profiling of 140 primary liposarcoma samples, which were randomly split into training set (n ¼ 95) and test set (n ¼ 45). A multigene predictor for distant recurrence-free survival (DRFS) was developed by the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% versus 45% for high risk score patients (P ¼ 0.001). The HR for high versus low score, adjusted for histologic subtype, was 4.42 (95% CI, 1.26-15.55; P ¼ 0.021). The concordance probability for risk score was 0.732. In contrast, the concordance probability for histologic subtype, which had been considered the best predictor of outcome in liposarcoma, was 0.669. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multigene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. RNAi-mediated knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Taken together, our findings identify genes that seem to be involved in liposarcomagenesis and have promise as therapeutic targets, and support the use of this multigene predictor to improve risk stratification for individual patients with liposarcoma. Cancer Res; 71(7); 2697-705. Ó2011 AACR.

Placental growth factor (PGF, previously known as PlGF) is prominently expressed by trophoblasts in human placenta, whereas most nontrophoblast cells express low levels of PGF mRNA under normal physiological conditions. We have shown that hypoxia decreases PGF expression in the trophoblast, but little is known about transcriptional regulation of PGF gene expression. We sought to determine promoter regions of the human PGF gene that contribute to its restricted high constitutive expression in the trophoblast. Overlapping putative promoter regions of human PGF gene encompassing 2-1.5 kb were cloned into reporter vectors and co-transfected into trophoblast and nontrophoblast cell lines. Promoter activity generated by a 2-1.5-kb clone was significantly higher in trophoblasts than in nontrophoblasts. Selective deletion mutants showed that a clone encompassing the PGF (2-828/++34) region generated promoter activity similar to the 2-1.5-kb region in the trophoblast. However, deletion of another 131 bp from this subclone (2-698/++34) resulted in significantly less promoter activity in the trophoblast. The (2-828/2-698) region significantly enhanced activity of a minimal promoter construct in trophoblast but not in nontrophoblast cells, suggesting that this region contributes to regulating PGF transcription in the trophoblast. Site-directed mutagenesis of a glial cell missing 1 (GCM1) motif in the 131-bp region significantly decreased enhancer activity in the trophoblast. Furthermore, overexpression of GCM1 significantly increased PGF 2-1.5-kb promoter activity and PGF mRNA expression in trophoblast and nontrophoblast cells. Forced overexpression of GCM1 restored PGF expression in the hypoxic trophoblast. These data support a functional role for GCM1 contributing to constitutively high trophoblast PGF expression and is the first direct evidence of an oxygen-responsive, trophoblast-specific transcription factor contributing to the regulation of PGF expression.

Therapeutic, II.

Great variability exists in microsurgical postoperative care in the United States. Lack of standardized postoperative monitoring protocols and appropriate training of monitoring personnel leads to inefficiency and increased cost of providing microsurgical postoperative care. A 45-question survey was sent to all plastic surgery and plastic surgery-based microsurgery program directors in the United States. Questions focused on the number and type of flaps performed, length of stay, complications, postoperative monitoring setting, training provided to monitoring personnel, and limitations in flap monitoring. The response rate was 31% with 3407 microvascular free flaps performed annually at 26 centers. A total of 1533 flaps were monitored in the intensive care unit (ICU) for an average of 3.1 days. In 45% of responding centers patients were cared for in an ICU secondary to a lack of adequately trained nurses at alternative sites. Printed postoperative protocols were provided to nurses in 39% of centers. With a comparative increase cost of $2878 to $3345 per day for ICU care, this translates into an annual increased cost of $13.7 to $15.9 million to the responding centers. Improved nursing training and the use of standardized postoperative protocols may allow patients to be monitored in non-ICU settings postoperatively, thereby reducing the costs associated with providing postoperative microsurgical care.

Objective-To determine the mechanism for differential effects of low oxygen tension on human PlGF gene transcription in trophoblast and nontrophoblast cells.Study Design-Human PlGF reporter clones and real time RT-PCR were used to compare the effects of hypoxia on gene transcription in human trophoblast and nontrophoblast cell lines. Overexpression of HIF-1α, inhibition of HIF-1 function and biochemical assessments of HIF-1 cofactor interactions were used to characterize hypoxia response mechanisms regulating PlGF transcription.Results-PlGF transcription is specifically inhibited by low oxygen tension in trophoblast but is induced in some nontrophoblast cells. Overexpression of HIF-1α in normoxic cells or inhibition of HIF-1 function in hypoxic cells did not significantly alter transcription patterns of the PlGF gene in either cell type.Conclusions-These results suggest that transcriptional repression of PlGF gene expression occurs in human trophoblast exposed to low oxygen tension but that PlGF transcription is stimulated in certain hypoxic nontrophoblast cells. However, regulation of PlGF transcription is not mediated by functional HIF-1 activity in either cell types.

Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in critically ill patients. Here, we employed the broad antibacterial effects of sphingosine to prevent VAP by developing a novel method of coating surfaces of endotracheal tubes with sphingosine and sphingosine analogs. Sphingosine and phytosphingosine coatings of endotracheal tubes prevent adherence and mediate killing of Pseudomonas aeruginosa , Acinetobacter baumannii , and Staphylococcus aureus , even in biofilms. Most importantly, sphingosine-coating of endotracheal tubes also prevented P. aeruginosa and S. aureus pneumonia in vivo. Coating of the tubes with sphingosine was stable, without obvious side effects on tracheal epithelial cells and did not induce inflammation. In summary, we describe a novel method to coat plastic surfaces and provide evidence for the application of sphingosine and phytosphingosine as novel antimicrobial coatings to prevent bacterial adherence and induce killing of pathogens on the surface of endotracheal tubes with potential to prevent biofilm formation and VAP. Key messages Novel dip-coating method to coat plastic surfaces with lipids. Sphingosine and phytosphingosine as novel antimicrobial coatings on plastic surface. Sphingosine coatings of endotracheal tubes prevent bacterial adherence and biofilms. Sphingosine coatings of endotracheal tubes induce killing of pathogens. Sphingosine coatings of endotracheal tubes ventilator-associated pneumonia.

Liposarcomas are aggressive mesenchymal cancers with poor outcomes that exhibit remarkable histologic diversity, with five recognized subtypes. Currently, the mainstay of therapy for liposarcoma is surgical excision since liposarcomas are often resistant to traditional chemotherapy. In light of the high mortality associated with liposarcoma and the lack of effective systemic therapy, we sought novel genomic alterations driving liposarcomagenesis that might serve as therapeutic targets. ZIC1, a critical transcription factor for neuronal development, is overexpressed in all five subtypes of liposarcoma compared with normal fat and in liposarcoma cell lines compared with adipose-derived stem cells (ASC). Here we show that ZIC1 contributes to the pathogenesis of liposarcoma. ZIC1 knockdown inhibits proliferation, reduces invasion, and induces apoptosis in dedifferentiated and myxoid/round cell liposarcoma cell lines, but not in either ASC or a lung cancer cell line with low ZIC1 expression. ZIC1 knockdown is associated with increased nuclear expression of p27 protein, and the down-regulation of pro-survival target genes: BCL2L13, JunD, Fam57A, and EIF3M. Our results demonstrate that ZIC1 expression is essential for liposarcomagenesis and that targeting ZIC1 or its downstream targets may lead to novel therapy for liposarcoma.