Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of Snail, Slug, Twist, and MMP1/9.

Arginine deprivation is currently being evaluated for its efficacy and safety in clinical trials aimed at combating tumors. However, the cellular signaling and molecular changes in response to such deprivation have not been systematically deciphered. Here, we evaluate the effect of arginine deprivation on human pancreatic cancer cells, with respect to their migratory and invasive potentials and their ability to undergo epithelial-mesenchymal transition (EMT). The transcription factors Snail, Slug, and Twist are regulators of EMT, as indicated by the suppression of E-cadherin and other epithelial markers and adhesion molecules. Our data indicated that arginine starvation inhibited the migration and impaired the adhesion and invasion of the pancreatic cancer cells, decreased Snail, Slug, and Twist expression, and increased E-cadherin expression without altering the expression of vimentin. It is well known that matrix metalloproteinases (MMPs) are important for the events that underlie tumor dissemination. Arginine starvation inhibited the expression of MMP-1 and MMP-9. Furthermore, the PI3K/Akt pathway was altered when the pancreatic cancer cells underwent arginine deprivation as exhibited by the decreased Akt phosphorylation. Thus, these data reveal that arginine deprivation has the potential to decrease the metastatic ability of pancreatic cancer cells.

Evaluation of the Aries Bordetella Assay for Detection and Identification of Bordetella pertussis in Nasopharyngeal Swab Specimens.

The Aries Bordetella assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP). The Aries BA was evaluated using retrospective, remnant nasopharyngeal swabs (NPS), previously tested by FilmArray RP. Performance characteristics evaluated included positive percent agreement (PPA) and negative percent agreement (NPA) with the FilmArray RP. Discordant analysis was performed using bidirectional sequencing. A time and motion study was performed to compare the laboratory workflow of the two tests. Three hundred samples were included in the study. There were no samples positive for B. parapertussis The PPA and NPA of the Aries BA were 61.1% (95% confidence interval [CI], 35.8 to 82.7%) and 100% (95% CI, 98.7 to 100%). Discordant results included five Bordetella bronchiseptica results that were incorrectly identified as B. pertussis by the FilmArray RP and one false-negative result for both the Aries BA and the FilmArray RP. The overall agreement between the Aries BA and FilmArray RP for the detection of B. pertussis was considered good at 97.7% with a kappa value of 0.71 (95% CI, 0.51 to 0.9). The Aries BA offers a new diagnostic option for the rapid and targeted approach to the diagnosis of pertussis. Unlike the FilmArray RP, the Aries BA did not cross-react with B. bronchiseptica in our study, although a larger sample set should be tested to confirm this finding.

Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer.

p21-activated kinases (Paks) play an important role in oncogenic signaling pathways and have been considered as potential therapeutic targets in various cancers. Most studies of Pak function employ gene knock-out or knock-down methods, but these approaches result in loss of both enzymatic and scaffolding properties of these proteins, and thus may not reflect the effects of small molecule inhibitors. Here we use a transgenic mouse model in which a specific peptide inhibitor of Group I Paks is conditionally expressed in response to Cre recombinase. Using this model, we show that inhibition of endogenous Paks impedes the transition of adenoma to carcinoma in an Apc-driven mouse model of colorectal cancer. These effects are mediated by inhibition of Wnt signaling through reduced ß-catenin activity as well as suppression of an epithelial-mesenchymal transition program mediated by miR-200 and Snai1. These results highlight the potential therapeutic role of Pak1 inhibitors in colorectal cancer.

Acute calcific tendinitis of the hip: case report with magnetic resonance imaging findings.

The clinical presentation of acute calcific tendinitis can be quite dramatic. This report describes a patient with this entity who had calcification in an unusual area, accompanied by abnormalities seen on radiography and magnetic resonance imaging. Clinical aspects of acute calcific tendinitis are also reviewed. With recognition of this entity, treatment can be initiated promptly, with dramatic resolution.

Cardiovascular effects of Gardenia florida L. (Gardeniae Fructus) extract.

Intravenous injection of Gardeniae Fructus extract in rats significantly lowered the systemic arterial pressure which was related to a decreased cardiac output with decreased stroke volume. Gareniae Fructus extract decreased the myocardial contractility of perfused isolated rat heart. Electrocardiogram revealed evidence of myocardial damage and atrioventricular block after a large dose of the extract.