Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma

BACKGROUND: Fascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters. METHODS: Fascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed. RESULTS: The expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters. CONCLUSIONS: Our findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899

In vitro and in silico assessment of DNA interaction, topoisomerase I and II inhibition properties of Chrysosplenetin

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Chrysosplenetin is a methoxyflavone with reported anti-cancer effect. We tested its cytotoxic effect on the MCF-7 breast cancer cell line, and determined its effect on DNA intercalation and on the activity of topoisomerases I and II. The compound inhibited proliferation MCF-7 with an IC50 value of 0.29 µM. Chrysosplenetin did not initiate plasmid DNA cleavage but, in a concentration-dependent manner, protected plasmid DNA against damage induced by Fenton reagents. Furthermore, it possessed dual Topoisomerase I and II inhibitory properties. Especially, it inhibited topoisomerase II by 83-96% between the range 12.5-100 µM. In the light of these experimental findings, molecular docking studies were performed to understand binding mode, interactions and affinity of chrysosplenetin with DNA, and with topoisomerases I and II. These studies showed that of 4-chromone core and the hydroxyl and methoxy groups important for both intercalation with DNA and topoisomerase I and II inhibition

Histological Subgroups in Classic Kaposi Sarcoma: A Preliminary Study

Background and Design: Kaposi sarcomas (KS) are vascular tumors with a low malignant potential which include overlapping infectious, immunologic, and neoplastic processes. Recently, many histological subtypes have been defined. Material and Method: In the present study, 151 cutaneous classic KS lesions in 56 patients were retrospectively evaluated with regard to histological subtypes. Determination of the subtypes was based on the predominant histopathological component in the lesion. We examined changes in epidermis and dermis along with intratumoral inflammatory response characteristics in the lesions. By defining histopathological variants of the cases, differences regarding subtypes were investigated. Results: Cases that bear the ordinary characteristics of KS and those that can not be classified otherwise, comprised 82..8% of the study group. Twenty-six cases showed consistency with the subtypes outlined in the literature in terms of their histopathological properties. The most common histological subtype was the lymphangiectatic variant in 7.3% of the cases. Bullous (2.6%), lymphangioma like (2.6%), intravascular (2%), and pyogenic granuloma like (2%) variants were less common. The most uncommon histological subtype was micronodular (0.6%) type. Lymphangiectatic, bullous, intravascular, and pyogenic granuloma like variants were frequently observed in the nodular stage of KSs. Lympangioma like changes were seen to be present in the early KS lesions. Lymphangiectatic type was oftenly associated with bullous component, whereas pyogenic granuloma like type demonstrated superficial ulceration and intense inflammatory response. Lymphangioma like and intravascular types exhibited a characteristic appearance, while other variants were accompanied by components belonging to different subtypes. Conclusion: In KS, histopathological subtypes can develop as a result of different pathological processes. The next stage of the current study, which is one of the largest case series in the literature, will be investigation of the clinical and prognostic characteristics of the variants

Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico.

Collaboration between DMU-Leicester School of Pharmacy (UK), Hacettepe University, Faculty of Pharmacy, Ankara (Turkey) and Karadeniz Technical University, Faculty of Pharmacy, Trabzon (Turkey).Introduction – Tyrosinase is a multifunctional copper-containing oxidase enzyme that catalyzes the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture. Objective – To develop an analytical method that allows identification of drug-like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition. Method – Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations. Results - All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with IC50 values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were noncompetitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B-ring of these flavones faced the catalytic site in the enzyme. Conclusions – The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design

The Elements, Lawrence University Flute Ensemble, January 30, 2017

Harper Hal

Günlük diyette tüketilen bazı meyvelerin ve bitki çaylarının antioksidan kapasiteleri ile Staphylococcus aureus üzerinde antimikrobiyal etkilerinin araştırılması.

Staphylococcus aureus is one of the major causes of food-borne pathogenesis. Antibiotic consumption for these pathogens has been increasing year by year world-wide. In order to decrease the use of synthetic antibiotics, fresh fruits and dry herbs consumed as beverages in regular diets were examined as potential natural antibiotics for the treatment of food based infections against Staphylococcus aureus. Herbs consumed as tea infusions including Pimpinella anisum L. (anise), Anthemis arvensis L. (camomile), Rosa canina L. (rosehip), Salvia fruticosa Mill (sage) and fresh fruit juices including Vitis vinifera L. (grape), Citrus sinensis L. (orange), Prunus persica L. (peach) and Punica granatum L. (pomegranate) were selected as samples of hot or cold consumed beverages in our daily diets. Extracts of fresh fruit juices were prepared in methanol, on the other hand, tea infusions of herbs were filtered and lyophilized. Antioxidant capacities of the plant samples were investigated by radical scavenging methods, namely 2’2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as determination of total phenolic and flavonoid contents. Furthermore, antimicrobial activities of plant samples were determined by minimum inhibitory concentration and minimum bactericidal concentration methods along with disc diffusion method. Trolox equivalent antioxidant capacities (TEAC) of the herbal tea infusions obtained by ABTS radical scavenging method were ranged between 48.38 ± 1.242 and 715.73 ± 4.265 (μmol Trolox equivalent (TE)/g of extract) while, TEAC values of fresh fruits juices were between 26.86 ± 0.217 and 73.55 ± 0.973 (μmol Trolox equivalent (TE)/g of extract). Moreover, EC50 values of the tea infusions obtained by DPPH radical scavenging method were ranged between 0.05 ± 0.001 and 1.53 ± 0.004 (mg/mL) while, EC50 values of the fruit juices were 1.6 ± 0.014 and 2 ± 0.093 (mg/mL). Total phenolic content of the plant samples tested in this study were varied from 1.383 (μg gallic acid equivalent (GAE)/mg of extract) to 159.167 (μg gallic acid equivalent (GAE)/mg of extract) and total flavonoid content varied from 0.111 (μg quercetin equivalent (QE)/mg of extract) to 201.15 (μg quercetin equivalent (QE)/mg of extract). Sage, orange and grape displayed higher antimicrobial activities with values of 1.5, 6 and 6 mg/mL minimum inhibitory concentrations and 1.5, 24 and 24 mg/mL minimum bactericidal concentrations, respectively. Inhibition zone diameters of sage, orange and grape were found to be 9, 9 and 11 mm.M.S. - Master of Scienc

9-11 Year Old Students’ Perception of Violence Reflected in Their Drawings

Violence, which can be defined as any threat towards the physical and psychological integrity of a human being, can result in fear, anxiety and severe behavior problems on children, whether exposed or witnessed. In this study, it is planned to achieve children’s perception of violence expressed by drawing and obtaining data in this way. In this study, the type of violence children portray in their drawings, how they determine to portray characteristics who perpetrate violence and are exposed to it as well as how is applied are analyzed. To measure how children perceive the violence, they were asked to draw a picture describing the ones who use violence and the ones who are exposed to violence. The pictures, drawn by children who participated in the study, were examined from a semantic perspective and content analysis method was adopted on the pictures. The research was conducted in Samsun province in the middle socio-economic level, with total of 53 students, 27 girls and 26 boys between the ages of 9-11 who were randomly selected representing two schools. Drawings were examined according to the issues they portrayed and then, semantic and content analysis was applied. In the children’s drawings, it is shown that the violence of adults is reflected more. These findings indicate that child to child violence, domestic violence, war, adult to child violence, adults to animal violence and terrorism is portrayed respectively. Generally, males are portrayed in the drawings. Drawn illustrations show that children are aware of the growing violence in their environmental. Raising the children in nonviolent social environment seems important for their healthy development. We can say that drawing, which is a simple tool for exploring the children’s inner world, can be used by all professionals responsible for children education

Design, synthesis and biological evaluation of water soluble and non-aggregated silicon phthalocyanines, naphthalocyanines against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines as potential anticancer agents

Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated silicon (IV) phthalocyanines and naphthalocyanines containing (3,5-bis{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy groups have been synthesized and characterized to investigate their anticancer potential. Their DNA binding/nuclease, topoisomerases inhibition were investigated using UV-Vis absorption, thermal denaturation and agarose gel electrophoresis. The in vitro cytotoxic properties of the compounds on human lung (A549), breast (BT-20), liver (SNU-398), prostate (DU-145), melanoma (SK-Mel 128) carcinoma and human fibroblast (HFC) normal cell lines were evaluated by using MTT assay. In order to determine the mechanism of cancer cell growth suppression, cell cycle analysis was carried out using flow cytometer on A549 cell line. The Kb values of SiPc1a and SiNc2a were 6.85 +/- (0.35) x 10(6) and 1.72 +/- (0.16) x 10(4) M-1 and T-m values of ct-DNA were calculated as 82.02 degrees C and 78.07 degrees C, respectively in the presence of both compounds. The Delta(Tm), values of SiPc1a and SiNc2a were calculated as 6.45 and 2.50 degrees C, respectively. The nuclease effects of SiPc1a and SiNc2a with supercoiled plasmid pBR322 DNA demonstrated that both compounds did not trigger any DNA nuclease effects at the lowest concentrations without irradiation whereas both compounds in the presence of activating agent (H2O2) showed significant plasmid DNA nuclease actions under irradiation (22.5 J/cm(2)). SiPc1a and SiNc2a inhibited to topoisomerase I on increasing concentrations whilst they had lower inhibition action toward topoisomerase II that of topoisomerase I. The in vitro cytotoxicity studies displayed that SiPc1a had the highest cytotoxic effects among the tested compounds against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines with CC50 values ranged from 0.49 to 2.99 mu M. Furthermore, SiPc1a inhibited cell proliferation by cell cycle arrest in G(0)/G(1) phase. All of these results suggested that SiPcla is a promising candidate as an anticancer agent