Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: A mechanism mediated by IL-8 signaling pathway

<p>Abstract</p> <p>Background</p> <p>Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer characterized by invasion of carcinoma cells into dermal lymphatic vessels where they form tumor emboli over expressing adhesion molecule E-cadherin. Although invasion and metastasis are dynamic processes controlled by complex interaction between tumor cells and microenvironment the mechanisms by which soluble mediators may regulate motility and invasion of IBC cells are poorly understood. The present study investigated the effect of media conditioned by human monocytes U937 secreted cytokines, chemokines and growth factors on the expression of adhesion molecules E-cadherin and fibronectin of human IBC cell line SUM149. Furthermore, cytokines signaling pathway involved were also identified.</p> <p>Results</p> <p>U937 secreted cytokines, chemokines and growth factors were characterized by cytokine antibody array. The major U937 secreted cytokines/chemokines were interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1/CCL2). When SUM149 cells were seeded in three dimensional (3D) models with media conditioned by U937 secreted cytokines, chemokines and growth factors; results showed: 1) changes in the morphology of IBC cells from epithelial to migratory spindle shape branched like structures; 2) Over-expression of adhesion molecule fibronectin and not E-cadherin. Further analysis revealed that over-expression of fibronectin may be mediated by IL-8 via PI3K/Akt signaling pathway.</p> <p>Conclusion</p> <p>The present results suggested that cytokines secreted by human monocytes may promote chemotactic migration and spreading of IBC cell lines. Results also indicated that IL-8 the major secreted cytokine by U937 cells may play essential role in fibronectin expression by SUM149 cells via interaction with IL-8 specific receptors and stimulation of PI3K/Akt signaling pathway.</p

Hydrographical conditions and benthic assemblages in the Suez Gulf, Egypt

The coastal development and human activities along the Suez Gulf leading to sedimentation, degrade the quality of water, disturbing the natural structure and functions of aquatic communities. The Suez Gulf is a large semi-closed area with a 346 km long coastline on the western beach side. The prevailing physicochemical parameters in shallow intertidal waters were measured seasonally over the year. Benthic faunas in the sampling sites were studied indicating their regional distribution in relation to the impact of different environmental parameters in the intertidal region. The concentration of copper in seawater reached high level at St. IV (4.57 ug/1), which is exposed to sewage and petroleum hydrocarbons. The grain size of the sediment is a determining factor for the organic carbon concentration and the sandy substrate enhances organic matter degradation processes. A large number of oil fields are present along the western coast of the Suez Gulf, therefore, cadmium and organic matter appeared to be high. The values of pH did not vary greatly among the different sampling sites. It was high at EI-Ein, El-Sukhna and Ras-Shukeir due to the disposal of mainly acidic sewage and industrial effluents of the two stations Adabiya and Ras-Gharib respectively. The macrobenthos included 71 species embraced mainly from Mollusca (53.5% Gastropoda and 12.7% Bivalvia) and the other invertebrates included 7 groups namely, Rhizostoma, Polychaeta, Cirripedia, Amphipoda, Isopoda, Decapoda and Echinodermata. The distribution of benthos is affected by the temperature and salinity of seawater. The concentration of organic matter in seawater and in sediments in shallow waters shows high values in the central part of the Gulf of Suez

Impacts of environmental conditions on macrobenthic distribution along the Suez Gulf, Egypt

Increases in coastal development and human activities leading to sedimentation degrade the quality of water; disturb the natural structure and functions of aquatic communities. The Suez Gulf is a large semi-closed area (~625 km long coastline).The assemblages of bottom fauna were studied qualitatively and quantitatively in the shallow intertidal waters along the western coast of the Suez Gulf. The quality of seawater and sediment structures were analyzed. The distribution of macro-benthos included a total of 38 species of Gastropoda and 9 Bivalvia; and 25 species from the other invertebrates included 7 groups namely, Rhizostoma, Polychaeta, Cirripedia, Amphipoda, Isopoda, Decapoda and Echinodermata. The most dominant group among invertebrate groups was the Polychaeta which included 4 species: Hydroides elegans, Perinereis cultilifera, Perinereis nuntia and Ophelina acuminata. The Cirripedia were represented by 3 species namely, Balanus amphitrite, Chithamalus challengeri and Tetraclita squamosa. The variations in the numerical abundance and biomass of bottom fauna studied between the observation periods and at sampling sites. There was a marked increase in benthos biomass at St. IV (Ras Gharib) yielding an average of 318.8 g/m² in which the gastropod community represented the dominant species in collected samples reaching 270.28 g/m² (84.4% of the total biomass) and numerically numbered 116 ind./m². Veliger larvae of bivalves and gastropods appeared to be present in the plankton for long periods and their production seems to be continuous throughout the year. In the intertidal zone of the Suez Gulf, the values of pH varied within narrow limits. Water temperature and salinity seemed to be important in the distribution and abundance of the macro-benthos communities in the study areas. The organic content in shallow intertidal waters and sediments indicated high values in the central part of the Gulf of Suez

Direct Enantiomeric Resolution of Betaxolol with Application to Analysis of Pharmaceutical Products

A high-performance liquid chromatographic (HPLC) method has been developed for the separation and determination of S- and R-enantiomers of betaxolol in tablets and ophthalmic preparations. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T with fluorescence detection at excitation/emission wavelengths 275/305 nm. The polar ionic mobile phase (PIM) consists of methanol-glacial acetic acid-triethylamine, (100:0.020:0.025, v/v/v) has been used at a flow rate of 1.5 ml/min. All analytes with S-(–)-atenolol as internal standard were conducted at ambient temperature. The method is highly specific where another coformulated compounds did not interfere. The stability of betaxolol enantiomers under different degree of temperature also studied. The results showed that it is stable for at least 7 days at 70°C. The method validated for its linearity, accuracy, precision and robustness. Experimental design was used during validation to evaluate method robustness. Using the chromatographic conditions described, S- and R-betaxolol were well resolved with mean retention times of 11.3 and 12.6 min, respectively. Linear response (r > 0.997) was observed over the range of 10–500 ng/ml of betaxolol enantiomers, with detection limit of 5 ng/ml. The recoveries of S- and R-betaxolol from tablets and ophthalmic preparation ranged from 97.4 to 101.4% and 98.0 to 102.0%, respectively. The mean relative standard deviation (R.S.D.%) for both enantiomers were 1.1–1.4% and 1.3–1.7% in tablets and ophthalmic solution, respectively

Risk Assessment Approaches in Banking Sector –A Survey

Prediction analysis is a method that makes predictions based on the data currently available. Bank loans come with a lot of risks to both the bank and the borrowers. One of the most exciting and important areas of research is data mining, which aims to extract information from vast amounts of accumulated data sets. The loan process is one of the key processes for the banking industry, and this paper examines various prior studies that used data mining techniques to extract all served entities and attributes necessary for analytical purposes, categorize these attributes, and forecast the future of their business using historical data, using a model, banks\u27 business, and strategic goals

Cathepsin b: a potential prognostic marker for inflammatory breast cancer

<p>Abstract</p> <p>Background</p> <p>Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.</p> <p>Methods</p> <p>In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups.</p> <p>Results</p> <p>Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC.</p> <p>Conclusions</p> <p>CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.</p

Promoter Hypermethylation and Suppression of Glutathione Peroxidase 3 Are Associated with Inflammatory Breast Carcinogenesis

Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients’ in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients’ clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract: [Figure not available: see fulltext.

Insulin Growth Factor-1 in Egyptian Children with Juvenile Idiopathic Arthritis: Correlation with Growth Pattern and Disease Activity

Background: Juvenile idiopathic arthritis (JIA) is a systemic, chronic, inflammatory disease that affects patients under 18 years. Interactions between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the immune system are complex. Many studies found that chronic inflammation suppresses GH/IGF-1 axis.Objective: To assess if there is correlation between the serum level of IGF-1 and the growth pattern in children with JIA in Egypt, and to evaluate the correlation between the serum level of IGF-1 and disease activity among these patients. Patients and Method: The study was a case control study which included 80 patients with JIA and 40 normal children as a control. Their ages ranged from 5-15 years. All patients were subjected to full history taking from their care givers, clinical examination, growth assessment, and laboratory measurement of serum IGF-1 level, CRP, ESR, and CBC.Results: There was a statistically significant decrease in serum level of IGF-1 among patients with JIA. There was a statistically significant positive correlation between serum level of IGF-1 with height, weight and BMI. There was a statistically significant difference between patients and controls regarding Height-for-Age-Z-Score (HAZ), 35% of patients had short stature. There was a statistically significant decrease in weight and BMI, 90% of patients were underweight. There was no statistically significant correlation between serum level of IGF-1 and the disease activity. Conclusion: There was a statistically significant positive correlation between IGF-1 with height, weight and BMI. Short stature and underweight were common among JIA patients. There was no significant correlation between serum level of IGF-1 and the disease activity among JIA patients

Nutritional Analysis and Enzyme Activities of Pleurotus Ostreatus Cultivated on Citrus Limonium and Carica Papaya Wastes

Abstract: Utilization of three food processing wastes (lemon pulp, papaya fruit waste and rice straw) for the production of fruit bodies mushroom with edible fungi Pleurotus ostreatus NRRL-0366 was done using solid state fermentation technique. Rice straw supplemented with different concentrations of the other two wastes forming eight substrates was used in this study. The highest mushroom harvested was with a substrate no. 2 (equal concentration of lemon pulp and rice straw ) giving 957.80 g/Kg fresh fruit bodies with biological efficiency 26.98% followed by substrate no. 7 (double amounts of papaya fruit waste supplemented with one amount of rice straw ) giving 431.1g/Kg fresh fruit bodies with biological efficiency 13.50%. The results revealed that the fruit bodies containing 26.0-31.5% digestible protein, 20.9 -33.0% total soluble carbohydrates and 2.0-5.9% fat (on dry basis). Calorific values for the eight fruit bodies ranged189-253 Kcal per 100 g of dry mushrooms. GLC analysis of the eight fatty acids of the fruit bodies has revealed that the unsaturated fatty acids were at higher concentration (68.2-75.2%) than the saturated one. Studies were carried out on the activities of amylase, cellulase, invertase, polygalacturonase and pectinlyase enzymes of Pleurotus ostreatus fruit bodies cultivated in the previous eight substrates. T he substrates affect the enzyme activities of Pleurotus ostreatus fruit bodies. A higher activity of amylase was observed in the unsupplemented lemon pulp and papaya waste. No significant change was obtained in cellulase and invertase activities within the eight substrates except substrate no. 7 using papaya waste. This fungus is able to produce high levels of pectinlyase in fruit bodies during solid state fermentation on lemon pulp