Expression of antimicrobial peptides in recurrent adenotonsillitis

Kilic, Murat/0000-0002-1377-2021; aydin, sedat/0000-0003-4939-5026; demir, mehmet/0000-0002-0609-6782WOS: 000393197500008Background: Recurrent acute tonsillitis is one of the most frequent otorhinolaryngology clinic referrals, yet its pathogenesis remains poorly understood. Antimicrobial cationic peptides are components of the innate system. They are generally small, highly positively charged peptides with broad spectrum antimicrobial activity which function as the body's "natural antibiotics". Our aim is to investigate the role of antimicrobial cationic peptides in the susceptibility of patients to recurrent acute tonsillitis. Materials and methods: The study is done with 100 children who had a history of recurrent adenotonsillitis as subject group and 100 children with adenotonsillar hypertrophy as control group. Tonsillar and adenoid tissues are dissected into parts as deep and surface epithelium and investigated semiquantitatively with immunohistochemistry. Human beta defensin (hBD) 1-3 and cathelecidin (LL-37) levels are compared with microscopically. Results: Immunohistochemistry revealed a strong expression of hBD-1, hBD-2 and hBD-3 in tonsillar tissue. Quantification of hBD-1, hBD-2 and hBD-3 expressions are shown more in tonsillar tissue than in adenoids. LL-37 is one of the antimicrobial peptides found in human tonsillar tissue and adenoids, that participates in the innate immune system of these tissues. Statistically, hBD-1, hBD-3 and LL-37 expressions were different in recurrent tonsillitis tissue than control (p < 0.05). Moreover hBD-2 expression was different in adenoid tissue than control (p < 0.05). Conclusion: Antimicrobial peptides have key role in adenotonsillar infections and this defense mechanism increases susceptibility to recurrent infections in upper respiratory tract

Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells.

The aim of this study was to observe the cytotoxicity and apoptotic effects of nickel oxide nanoparticles on human cervix epithelioid carcinoma cell line (HeLa). Nickel oxide precursors were synthesized by an nickel sulphate-excess urea reaction in boiling aqueous solution. The synthesized NiO nanoparticles

MicroRNA 603 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting elongation factor 2 kinase

Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of defined molecular targets, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and is associated with high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC represents an unmet therapeutic challenge. Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent serine/threonine kinase that promotes TNBC tumorigenesis, progression, and drug resistance, representing a potential novel molecular target. However, the mechanisms regulating eEF2K expression are unknown. Here, we report that eEF2K protein expression is highly up-regulated in TNBC cells and patient tumors and it is associated with poor patient survival and clinical outcome. We found that loss/reduced expression of miR-603 leads to eEF2K overexpression in TNBC cell lines. Its expression results in inhibition of eEF2K by directly targeting the 3-UTR and the inhibition of tumor cell growth, migration and invasion in TNBC. In vivo therapeutic gene delivery of miR-603 into TNBC xenograft mouse models by systemic administration of miR-603-nanoparticles led to a significant inhibition of eEF2K expression and tumor growth, which was associated with decreased activity of the downstream targets of eEF2K, including Src, Akt, cyclin D1 and c-myc. Our findings suggest that miR-603 functions as a tumor suppressor and loss of miR-603 expression leads to increase in eEF2K expression and contributes to the growth, invasion, and progression of TNBC. Taken together, our data suggest that miR-603-based gene therapy is a potential strategy against TNBC

Comparison of GST Isoenzyme Expression in Normal and Neoplastic Breast Tissue: Correlation with Clinical and Prognostic Factors

Sak, Serpil/0000-0003-3666-3095WOS: 000266892000001Glutathione S-transferases in breast tissue play an important role in the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. In this study the immunohistochemical staining characteristics of glutathione S-transferase isoenzymes (alpha, mu, pi, and theta) were investigated in invasive duct carcinomas and in normal breast tissue of 43 patients. The relationships between the expression of the GST isoenzymes and some clinicopathological features were also examined. Diffuse cytoplasmic staining of varying intensity was observed for GST alpha, theta, and pi in normal and tumorous breast tissue in 100% of the samples. In normal epithelium there was a stronger intensity of staining for GST alpha, mu. and pi expression than in invasive tumor tissues (P 0.05). In this study significant relationships were observed between microcalcification status and GST mu, between menopause status and GST alpha, and between tumor grade and GST mu expression (P 0.05).Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); British CouncilThis study was supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK), and the British Council

Immunohistochemical Expressions of the Antimicrobial Peptides (hBD-3 and hCAP-18/LL-37) in Colon, Stomach and Lung Adenocarcinomas

Kilic, Murat/0000-0002-1377-2021WOS: 000362622100001This study investigated the immunohistochemical staining characteristics of human beta defensin-3 (hBD-3) and human cationic antimicrobial peptide-18/cathelicidin (hCAP-18/LL-37) in colon, stomach and lung adenocarcinomas and normal tissues (periphery to tumor tissues) from 22, 24 and 24 patients, respectively. Expressions of hBD-3 and hCAP-18/LL-37 were assessed by immunohistochemistry for colon, stomach and lung adenocarcinomas of 70 patients from Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital and Kecioren Training and Research Hospital. both located in Ankara, Turkey. The differences between the expressions of hBD-3 and hCAP-18/LL-37 in normal and carcinoma tissues were analyzed by Mann-Whitney U Test. When the normal and tumor tissues of these cases were compared according to their staining intensity of positive staining, the hBD-3 and hCAP-18/LL-37 expressions in colon, stomach and lung adenocarcinomas cells were significantly higher than those in normal cells (p<0.05). Immunostaining of HBD-3 and hCAP-18/LL-37 was found to be a marker of malignancy in colon, stomach and lung adenocarcinomas. The expressions of hBD-3 and hCAP-18/LL-37 were, for the first time, shown to be significantly altered in colon, stomach and lung adenocarcinomas as compared to controls. In conclusion, the present findings suggest that beside the antimicrobial activity of Antimicrobial Peptides (AMPs), hBD-3 and hCAP-18/LL-37 can also play a role in the pathogenesis of colon, stomach and lung adenocarcinomas

Usefulness of CA 15-3 for breast or ovarian primary sites in metastatic adenocarcinoma of pleural fluid

Kilic, Murat/0000-0002-1377-2021WOS: 000302197000005This study was conducted to evaluate the diagnostic value of CA 15-3, mammaglobin, c-erbB-2, estrogen receptor (ER), progesterone receptor (PR), CK 20, and CA 125 for detecting metastatic breast and ovarian carcinoma in pleural fluids. The material under study consisted of 26 pleural effusions from invasive breast and ovarian cancer patients from the Hannover Cytopathology Institute. Expressions of these markers were studied using immunocytochemistry. All of the breast cancer cases studied showed a positive reaction with CA 15-3, while only 36% with mammaglobin, 21% with c-erbB-2, 36% with ER, and 7% with PR were positive. The sensitivities of CK 20, CA 15-3, and CA 125 as markers for metastatic ovarian carcinoma were 43%, 88%, and 55%, respectively. Our results indicate that CA 15-3 has a higher sensitivity than other tumor markers for diagnosing metastatic breast and ovarian carcinoma in pleural fluids

Apoptotic and necrotic effects of plant extracts belonging to the genus Alchemilla L. species on HeLa cells in vitro

WOS: 000299778500027Apoptotic and necrotic effects of plant extracts belonging to the genus Alchemilla on HeLa cells were investigated. The ratio of viable cells was determined by cell counter. Double staining method for the determination of apoptotic and necrotic index was carried out. The lowest apoptotic effect was found in Alchemilla oriturcica with the ratio of around 14% and the highest apoptotic effect found in Alchemilla trabzonica was 24%. Apoptotic effect was additionally determined by caspase-3 immunostaining. Increasing the concentrations of the extracts, especially in the level of 150 to 200 mu g/mL caused the increase of necrotic effect on cancer cells. Particularly, the effects of A. oriturcica and A. trabzonica extracts with the density of 200 mu g/mL were very high compared to the other species. The flavonoid components were detected in extracts of the species used for this study. The flavonoids identified are orientin (luteolin-8-C-glucoside), hyperoside (quercetin-3-O-galactoside) and isoquercetin (quercetin-3-glucoside) in Alchemilla erythropoda; rutin (quercetin-3-rutinoside), orientin, vitexin (apigenin-8-C-glucoside), hyperoside in Alchemilla ikizdereensis; rutin, hyperoside, isoquercetin (quercetin-3-glucoside) in A. oriturcica, and hyperoside, isoquercetin and quercitrin (quercetin-3-O-rhamnoside) in A. trabzonica.Science Research Foundation of Kirikkale University of TurkeyKirikkale University [2007/44]This work was supported by Science Research Foundation of Kirikkale University of Turkey (project number: 2007/44)

Apoptotic and necrotic effects of carboxylated quercetin/polyethylenimine complex on HeLa cells

WOS: 000295799500013The effects of quercetin (Q), carboxylated quercetin (CQ) and carboxylated quercetin/polyethylenimine (CQ/PEI) complex on HeLa cell cultures were investigated. Firstly, carboxylated quercetin was acquired through hydroxyl groups of quercetin, using chloroacetic acid. The complex of CQ/PEI was acquired by electron cooperation path over polietilenimine amine groups and quercetin carboxyl groups. CQ and CQ/PEI obtained were characterised by FTIR and H-1-NMR methods. Cytotoxicity was determined by MTT assay. Apoptotic and necrotic indexes were obtained by immunocytochemical staining with the M30 antibodies and double staining and double staining, respectively. It was determined that quercetin caused lower rates of necrosis and apoptosis on HeLa cells by itself, but CQ/PEI complex resulted in high levels. As a result, it was observed that transition of quercetin to HeLa via binding it to polyethylenimine increased its anticarcinogenic effects.Kirikkale University Science Research FoundationKirikkale University [2007/70]; Kirikkale University of TurkeyKirikkale UniversityThis work was supported by Kirikkale University Science Research Foundation Project (number; 2007/70) of Kirikkale University of Turkey

Expression of glutathione-S-transferases isoenzymes and p53 in exfoliated human bladder cancer cells

WOS: 000295609000011PubMed: 19926314Objectives: This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 immunostaining as a marker of malignancy in urinary cytology, and evaluates their potential effect in increasing diagnostic accuracy in a series of urine cytologic samples. They are also correlated with cytopathology diagnosis and histopathologic diagnosis. Materials and methods: In this study, the slides from 124 bladder carcinoma patients prepared by the cytocentrifugation method were observed. The cytomorphologic properties of these cancer cells were determined. Moreover, the immunocytochemical distributions of GST alpha (GSTA), pi (GSTP), mu (GSTM4), theta (GSTT1) isoenzymes and p53 protein were studied for the patients. Results: The urothelial cancer cells had small cytoplasm and rough nuclear membrane. The chromatin granules were heterogeneously distributed in each malignant cell's nucleus. There was a pleomorphism of the malignant cells' nuclei. According to immunocytopathologic observations, the urothelial cancer cells had stronger staining intensity than the benign cells had in 48% of cases for GSTA, 46% of cases for GSTP, 38% of cases for GSTM4, and 42% of cases for GSTT1. For all papillary cases, the malignant cells were stained negative, while the benign cells were positive. For 83% of patients, the malignant cells were stained positive for p53. There was a significant difference in GSTA (P = 0.006), GSTT1 (P = 0.004), GSTP (P = 0.000) and p53 (P = 0.000) expressions for benign cells whereas, a non-statistical difference in the malignant cells for GSTA, GSTT1, GSTP, GSTM4, and p53 expressions (P > 0.05). Conclusions: GST isoenzymes and p53 immunostaining were not found to be markers of malignancy in urinary cytology. (C) 2011 Elsevier Inc. All rights reserved.Kirikkale UniversityKirikkale University [02/03.04.04]This work was supported by the Research Fund of the Kirikkale University, project number: 02/03.04.04