Determining in vitro anticancer activity of mitomycin C loaded microemulsion

European Biotechnology Congress -- SEP 28-OCT 01, 2011 -- Istanbul, TURKEYWOS: 000295310800409European Biotechnol Themat Network Asso

Preparation and characterization of lipid nanoparticle/pDNA complexes for STAT3 downregulation and overcoming chemotherapy resistance in lung cancer cells

WOS: 000401112300012PubMed ID: 28428090Developments in the field of molecular oncology have revealed that resistance to chemotherapeutics is acqured through several mechanisms including overexpression of common oncogenic proteins. Signal Transducer and Activator of Transcription 3 (STAT3) is one of these oncogenes that is overexpressed in many cancer types. RNA interference (RNAi) is proven powerful tool for downregulating STAT3, allowing re-sensitization of resistant cancer cells. However, delivery of RNA interference-mediating molecules for STAT3 downregulation in lung cancer cells is limited to a small number of studies most of which employ commercially available transfection kits. The aim of this study was to develop and evaluate cationic solid lipid nanoparticles for delivery of RNAi-mediating plasmid DNA in order to down regulate STAT3 in cisplatin resistant lung cancer cells. We focused on obtaining cSLN:plasmid DNA complexes with size below or equal to 100 nm, and a positive zeta potential. Two successful candidate cSLN: plasmid DNA complexes (K2 and K3) were selected for in vitro tests and cell culture studies. These formulations have particle sizes of 98 and 93 nm, and zeta potential values of 10.5 and 8.9 mV, respectively. Plasmid DNA in these complexes was protected against DNaseI and serum-mediated degradation. Substantial part of DNA retained its supercoiled and circular conformation. TEM images showed nearly spherical complex structure. Both formulations reduced STAT3 expression by approx. 5-fold in cisplatin resistant Calu1 cell line and increased the sensitivity of cells to cisplatin. (C) 2017 Elsevier B.V. All rights reserved.Ege UniversityEge University [12-ECZ-006]This study was supported by the scientific fund of the Ege University (Project no. 12-ECZ-006). We thank to Dr. Tugba Erdogan from Transmission Electron Microscopy Facility of the Middle East Technical University for her help with TEM imaging experiments, and Assoc. Prof. Timur Kose from the Biostatistics Department, Ege University for providing consultancy with statistical analyses

Cytotoxicity of Dental Implants: The Effects of Ultrastructural Elements

WOS: 000417113300011PubMed ID: 29140372Purpose: In this in vitro study, the purpose was to assess the cytotoxicity profiles of seven commercial dental implant materials by using cell culture methods on an osteoblastic cell line. Materials and Methods: The microstructure of seven commercial dental implants (each given a letter code) was investigated via scanning electron microscopy and energy-dispersive x-ray analysis. Medium extracts were collected on the first and fifth days for each group and tested using MC3T3-E1 cell line. Cytotoxicity was evaluated with Xcelligance System and XTT reagent, and apoptosis was determined by Annexin-V staining. One-way analysis of variance (ANOVA) and Tukey's multiple range tests were used for statistical analyses. In all tests, P was set as .05. Results: ANOVA results disclosed that Ti (P = .001), Na (P = .001), Ca (P = .019), Al (P = .024), and P (P = .020) amounts were significantly different between test materials. Cytotoxicity and apoptosis analyses revealed that implant materials (C) and (E) were the materials with the lowest cell vitality and the highest apoptosis rates among the test materials. Phosphorus was the only element that presented the highest amount in C and E (14.23% and 12.29%, respectively) compared with the other implant materials tested. (F) and (G) had favorable results for all experiments. Conclusion: The results suggest that pure dental implant materials with a lower number of additional elements may possess fewer cytotoxic effects than the other implant materials tested in this study

Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells

WOS: 000334153000021PubMed ID: 24659656Purpose: Increased activation of the JAK-STAT signaling pathway is frequently observed in several primary cancers as well as cancer cell lines. Thus, targeting JAK-STAT pathway components by different molecular-biologic approaches in the search for new anticancer therapies has become widespread and resulted in encouraging outcomes. In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer. Methods: The parental NSCLC cell line Calu1 and its cisplatin-resistant subline CR-Calu1 were used to study the effects of STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and protein expressions were analyzed by real-time (RT) quantitative (q) PCR and Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and cell death assays. Results: STAT3 messenger (m)RNA and protein expression were significantly increased in CR-Calu1 cells and suppressing its expression with specific siRNAs increased the rate of apoptosis through Caspase-3 activation. STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and CR-Calu1 cells after transfection with STAT3 siRNAs. Conclusions: NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis

From a Molecular Biological Viewpoint, Does Endothelin Type A Receptor Antagonist Therapy Reduce Diabetes-induced Testicular Damage in Rats?

WOS: 000285778800079PubMed ID: 20630572OBJECTIVES To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)-induced diabetic rats. METHODS Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, diabetic rats treated with ERA-A, and healthy rats treated with ERA-A. Diabetes was induced in 40 rats by a single intraperitoneal injection of STZ and followed for 2 months. A total of 20 diabetic and 20 healthy rats were also intravenously treated with ERA-A at days 7 and 15. The remaining untreated healthy rats served as controls. Blood glucose levels of >= 250 mg/dL were considered to indicate diabetes and were measured at the end of the second month. Formalin-fixed paraffin-embedded testis tissue sections were analyzed after staining with hematoxylin and eosin or specific antibodies for apoptotic markers. mRNA expressions of genes involved in the apoptotic pathway or spermatogenesis were evaluated by real-time reverse transcription-polymerase chain reaction. RESULTS Major therapeutic effects of ERA-A could be achieved for damages caused by oxidative stress. Although a decrease in apoptotic cell death could be detected, no statistically meaningful results could be obtained for the duration of spermatogenesis. CONCLUSIONS ERA-A could prevent germ cell death by apoptosis and testicular damage in diabetic rats. UROLOGY 77: 250.e7-250.e13, 2011. (C) 2011 Elsevier Inc.Ege University, Izmir, TurkeyEge University [BAP2007TIP027]This work was supported by Ege University (BAP2007TIP027 to HA), Izmir, Turkey