Androgen downregulates desmocollin-2 in association with induction of mesenchymal transition of breast MDA-MB-453 cancer cells.

Desmosomes are cellular structures that are critical in cell-cell adhesion and in maintaining tissue architecture. Changes in the expression of desmocollin-2 (DSC2) have been noted during tumor progression into an invasive phenotype and as cells undergo epithelial-mesenchymal transition. We have previously reported that breast MDA-MB-453 cancer cells, a luminal androgen receptor (AR) model of triple-negative breast cancer, acquire mesenchymal features when treated with the AR agonist, dihydrotestosterone (DHT). We have therefore investigated androgen regulation of the expression and cellular localization of DSC2 in MDA-MB-453 cells. Treatment of the cells with DHT resulted in a dose-dependent reduction in DSC2 protein levels and dispersion of its membrane localization concomitant with AR- and ß-catenin-mediated mesenchymal transition of cells. A significant correlation was revealed between decreased expression of AR and increased expression of DSC2 in patient samples. In addition, whereas lower expression of AR was associated with a reduced overall and recurrence-free survival of breast cancer patients, higher expression of DSC2 was found in invasive breast tumors than in normal breast cells and was correlated with lower patient survival. Upon knocking down DSC2, the cells became elongated, mesenchymal-like, and slightly, but insignificantly, more migratory. The addition of DHT further stimulated cell elongation and migration. DSC2 siRNA-transfected cells reverted to a normal epithelial morphology upon inhibition of ß-catenin. These results highlight the role of DSC2 in maintaining the epithelial morphology of MDA-MB-453 cells and the negative regulation of the desmosomal protein by DHT during stimulation of the androgen-induced, ß-catenin-mediated mesenchymal transition of the cells.

PD-L1 Expression Is a Favorable Prognostic Marker in Gastric Carcinoma.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Although multidisciplinary therapeutic strategies have improved treatment outcomes, the overall prognosis for patients with GC remains poor. Recently, immunotherapeutic agents targeting immunosuppressive proteins such as anti-programmed death-1 receptor and anti-programmed death ligand-1 (PD-L1) have emerged as effective treatment options for various cancers, including GC. In addition to their therapeutic role, the expression of PD-L1 has been used as a predictive biomarker for programmed death-1/PD-L1 treatment response and has been shown to have a prognostic role in certain cancers. This study aims to evaluate the expression of PD-L1 in GC samples from Jordanian patients and assess its prognostic role as well as its correlation with clinicopathologic variables. Gastrectomy samples from 96 patients diagnosed with gastric adenocarcinoma were included in the study. Immunohistochemistry assay was employed for PD-L1 testing, and the scoring was based on a combined positive score (CPS). It was found that 66.7% of the study samples were positive for PD-L1 (CPS≥1). The expression of PD-L1 was not significantly associated with any of the assessed clinicopathologic variables; however, it was found to be an independent favorable prognostic factor for overall survival (hazard ratio: 0.481; 95% confidence interval: 0.231-1.001; P=0.050).

Application of Gas Chromatography-Mass Spectrometry for the Identification and Quantitation of Three Common Synthetic Cannabinoids in Seized Materials from the Jordanian Market.

Synthetic cannabinoids (SCs) were developed to mimic the effects of Δ9-tetrahydrocannabinol on humans. SCs were distributed in the form of herbal blends, with smoking being the main method of consumption. These synthetic compounds have a wide range of physical, behavioral, and harmful effects on the body. However, this study aimed to identify and quantify three common SCs including AB-FUBINACA, AB-CHMINACA, and XLR-11 in the seized materials from the Jordanian market by gas chromatography coupled with mass spectrometry (GC-MS). A liquid-liquid extraction sample preparation technique was applied to 100 different seized samples obtained from the Anti-Narcotics Department of Public Security in a period between 2017 and 2018. Profiling of the seized samples revealed different distributions of the targeted SCs in the obtained samples. Upon quantitation, concentrations of these SCs varied greatly within and among the samples. The use of GC-MS analysis provided a powerful technique in the detection and identification of SCs. This study revealed the current and trends of SC use in the Jordanian illicit substance market, which was previously unclear. Future studies are required to explore new SCs and their influence in different biological samples.

A low-cost paper-based platform for fast and reliable screening of cellular interactions with materials.

A paper-based platform was developed and tested for studies on basic cell culture, material biocompatibility, and activity of pharmaceuticals in order to provide a reliable, robust and low-cost cell study platform. It is based upon a paper or paperboard support, with a nanostructured latex coating to provide an enhanced cell growth and sufficient barrier properties. Wetting is limited to regions of interest using a flexographically printed hydrophobic polydimethylsiloxane layer with circular non-print areas. The nanostructured coating can be substituted for another coating of interest, or the regions of interest functionalized with a material to be studied. The platform is fully up-scalable, being produced with roll-to-roll rod coating, flexographic and inkjet printing methods. Results show that the platform efficiency is comparable to multi-well plates in colorimetric assays in three separate studies: a cell culture study, a biocompatibility study, and a drug screening study. The color intensity is quantified by using a common office scanner or an imaging device and the data is analyzed by a custom computer software without the need for expensive screening or analysis equipment.

Topical mitomycin C can effectively alleviate dysphagia in children with long-segment caustic esophageal strictures.

Caustic ingestion in children and the resulting long esophageal strictures are usually difficult to be managed, and eventually, esophageal replacement was required for cases refractory to frequent dilatation sessions. Topical mitomycin C (MMC) application has been used recently to improve the results of endoscopic dilatation for short esophageal strictures. The study aims to assess the role of MMC application in management of long-segment caustic esophageal strictures. From January 2009 to June December 2013, patients presented with long caustic esophageal stricture (>3 cm in length) were included in this study and subjected to topical MMC application after endoscopic esophageal dilatation on multiple sessions. Regular follow-up and re-evaluation were done. A dysphagia score was used for close follow-up clinically; verification was done radiologically and endoscopically. During the specified follow-up period, 21 patients with long caustic esophageal stricture were subjected to topical MMC application sessions. Clinical, radiological, and endoscopic resolution of strictures occurred in 18 patients (85.7% cure rate). Number of dilatation sessions to achieve resolution of dysphagia was (n = 14.3 ± 5.7) with application of mitomycin two to six times. There was no recurrence in short- and mid-term follow-up. No complications were encountered related to topical MMC application. MMC is a promising agent in management of long-segment caustic esophageal strictures. Long-term follow-up is needed to prove its efficacy and to evaluate potential long-term side-effects of MMC application.

Preparation of niosomes as an ocular delivery system for naltrexone hydrochloride: physicochemical characterization.

Recent reports have demonstrated that topical and systemic application of naltrexone markedly improves the characteristic signs of diabetic keratopathy; most notably, impaired corneal sensation and delayed wound repair. The aim of this study was to prepare and characterise non-ionic surfactant vesicles (niosomes) for the ocular drug delivery of naltrexone hydrochloride. The niosomes were prepared using the thin film hydration method and characterised using polarized light microscopy, cryo-scanning electron microscopy (Cryo-SEM), percent drug entrapment efficiency (EE %), laser light diffraction and differential scanning calorimetry (DSC). Two classes of non-ionic surfactants (sorbitan esters and polyoxyethylene alkyl ethers) were investigated. The results revealed that tuning of cholesterol concentrations can significantly alter the niosome's physical properties including sizes, EE% and membrane fluidity (thermo-responsiveness). The prepared vesicles were in the range of 7.0 +/- 1.0 to 14.6 +/- 0.8 microm in size. The prepared niosomes showed different abilities to accommodate cholesterol. This was highly dependent on the structure and continuity of the hydrophobic chains of the used surfactants. Span 60-based vesicles containing 30% mol/mol of cholesterol showed the highest EE%. The microstructure and lamellarity of the niosomes were studied using Cryo-SEM. Typical concentric multilayered structures (onion or rose-like) were seen suggesting the formation of multilamellar vesicles. DSC-studies conducted on Span 60-based niosomes containing 30% mol/mol cholesterol revealed liquid-gel transition (T(m) and entropy of 43.5 degrees C and 0.82 kcal/mol, respectively). Such transition reflects potential thermo-responsive properties, which is desirable for ocular delivery.

Assessment of biological changes of continuous whole body exposure to static magnetic field and extremely low frequency electromagnetic fields in mice.

The question whether static magnetic fields (SMFs) and extremely low frequency electromagnetic fields (ELF-EMF) cause biological effects is of special interest. We investigated the effects of continuous whole body exposure to both fields for 30 days on some liver and blood parameters in mice. Two exposure systems were designed; the first produced a gradient SMF while the second generated uniform 50 Hz ELF-EMF. The results showed a gradual body weight loss when mice were exposed to either field. This is coupled with a significant decrease (P<0.05) in the levels of glucose, total protein and the activity of alkaline phosphatase in serum. A significant increase in lactate dehydrogenase activity was demonstrated in serum and liver paralleled with a significant elevation in hepatic γ-glutamyl transferase activity. The glutathione-S-transferase activity and lipid peroxidation level in the liver were significantly increased while a significant decrease in hepatic gluthathione content was recorded. A significant decrease in the counts of monocytes, platelets, peripheral lymphocytes as well as splenic total, T and B lymphocytes levels was observed for SMF and ELF-EMF exposed groups. The granulocytes percentage was significantly increased. The results indicate that there is a relation between the exposure to SMF or ELF-EMF and the oxidative stress through distressing redox balance leading to physiological disturbances.