Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells

Bulut, Gulcan/0000-0001-7382-0972WOS: 000533256900008PubMed: 31829029Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. in this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: the trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: the trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113S055]This project was supported by the Scientific and Technological Research Council of Turkey (TUBITAK, Project Number 113S055). the authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Does peri-implant bone loss affect the LL-37 and proteinase 3 levels in peri-implant sulcus fluid?

WOS: 000555979600001PubMed: 32748292Background Inactive human cathelicidin antimicrobial peptide is present in neutrophils, and proteinase 3 activates this peptide by producing active LL-37 peptide. LL-37 acts as a defensive peptide in the oral tissues. in the present study, the aim was to evaluate LL-37 and proteinase 3 levels in peri-implant sulcus fluid (PISF) in implants with and without peri-implantitis. Methods Patients who simultaneously had dental implants with peri-implantitis and without peri-implantitis were included in the study. Forty-four samples with peri-implantitis and 34 samples without peri-implantitis from 16 patients were obtained. Intraoral evaluations such as pocket depth, modified sulcus bleeding index, and modified plaque index were noted. Enzyme-linked immunosorbent assay was used for the evaluation of PISF LL-37 and proteinase 3 levels. Results PISF volume was significantly increased in the implants with peri-implantitis than those without peri-implantitis (p 0.05). Pocket depths and PISF LL-37 and proteinase 3 levels were not correlated in the groups (p> 0.05). Conclusions PISF volume might be increased in response to peri-implant bone destruction. However, peri-implant tissue destruction caused by peri-implantitis does not seem to affect PISF LL-37 and proteinase 3 levels.Ege University Research FoundationEge University [2017-DIS-010]This study was supported by Ege University Research Foundation (2017-DIS-010)

Glioblastoma tümörlerinde çoklu ilaç direnci

Merkezi sinir sisteminin gerek yapı ve fonksiyonunu gerekse patolojisini hücresel düzeyde anlamada nöronal ve glial paradigma olmak üzere iki yaklaşım öne çıkmaktadır. Nöronal paradigma nöronları, glial paradigma ise glia hücrelerini vurgulayarak patolojiyi açıklamakta ve anlamlandırmaktadır. Beyin tümörlerinin en yaygın türlerinden biri olan glioblastoma, konumu, sağ kalım süresinin kısalığı ve ilacın hedef dokuya ulaşabilirliğinin zorluğu noktalarından özgün bir tümördür. Glioblastomalarda kemoterapötik tedavi- de gözlenen ilaç direnci, diğer tümörlerde gözlenen direnç mekanizmalarıyla uyumludur. Bu direnç mekanizmaları, tümör hücreleri- nin ilaca hassasiyetini azaltan kan beyin bariyeri ve membran transport proteinlerine bağlı olarak hücre içine ilaç girişinin azalması, DNA tamir sistemlerindeki adaptif cevap ve hedef molekülün ilaca bağlanma etkinliğinin azaltılması ve ilaçların hedef dokudaki et- kin konsantrasyonunu azaltan mekanizmalar detoksifikasyonda rol alan proteinlerdeki değişimler, tümör mikroçevresinde meydana gelen hipoksik bölgeler olmak üzere iki alt başlıkta incelenebilir. Ayrıca, onkogenlerin aktivasyonu ve apoptozisle ilişkili Bcl-2 ailesi proteinlerinin ifadesindeki düzensizliklerin de ilaç direncinin ortaya çıkışında rol aldığı bilinmektedir. Bu derlemede glioblastoma tümörlerinde görülen çoklu ilaç direncinin olası mekanizmalarını güncel literatür ışığında tanımlanarak sistemik ve bütüncül bir bakış açısı ortaya konulmaya çalışılmıştı

Synthesis of silver nanoparticles using Alpinia officinarum rhizome extract induces apoptosis through down-regulating Bcl-2 in human cancer cells

In this study, silver nanoparticles were synthesized using Alpinia officinarum rhizome extract via an eco-friendly green synthesis method. The silver nanoparticles (AO-AgNPs) were characterized by UV–Vis spectrometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and dynamic light scattering. Further, the cytotoxic and apoptotic effects of AO-AgNPs were investigated in human cancer cells with different tissue origins via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe- nyl-2H-tetrazolium bromide (MTT) assay and flow cytometric analyses, respectively. The expression levels of anti-apoptotic Bcl-2 protein were evaluated via a real-time polymerase chain reaction. The synthesized AO-AgNPs induced a significant cytotoxic effect in all tested cancer cells but not in normal cells. AO-AgNPs induced the percentage of apoptotic cells and reduced the levels of anti-apoptotic Bcl-2 mRNA levels in cancer cells. These results demonstrate the potential application of AO-AgNPs in cancer treatment

Preparation, Characterization, and Drug Delivery of Hexagonal Boron Nitride-Borate Bioactive Glass Biomimetic Scaffolds for Bone Tissue Engineering

In this study, biomimetic borate-based bioactive glass scaffolds containing hexagonal boron nitride hBN nanoparticles (0.1, 0.2, 0.5, 1, and 2% by weight) were manufactured with the polymer foam replication technique to be used in hard tissue engineering and drug delivery applications. To create three-dimensional cylindrical-shaped scaffolds, polyurethane foams were used as templates and covered using a suspension of glass and hBN powder mixture. Then, a heat treatment was applied at 570 °C in an air atmosphere to remove the polymer foam from the structure and to sinter the glass structures. The structural, morphological, and mechanical properties of the fabricated composites were examined in detail. The in vitro bioactivity of the prepared composites was tested in simulated body fluid, and the release behavior of gentamicin sulfate and 5-fluorouracil from glass scaffolds were analyzed separately as a function of time. The cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. The findings indicated that the hBN nanoparticles, up to a certain concentration in the glass matrix, improved the mechanical strength of the glass scaffolds, which mimic the cancellous bone. Additionally, the inclusion of hBN nanoparticles enhanced the in vitro hydroxyapatite-forming ability of bioactive glass composites. The presence of hBN nanoparticles accelerated the drug release rates of the system. It was concluded that bioactive glass/hBN composite scaffolds mimicking native bone tissue could be used for bone tissue repair and regeneration applications

Novel ferrocenyl pyrazoles inhibit breast cancer cell viability via induction of apoptosis and inhibition of PI3K/Akt and ERK1/2 signaling

Despite the advances in early detection and targeted therapies, chemotherapy is still of vital importance in breast cancer treatment. However, development of drug resistance and serious side effects limits their usage. Thus, there is an urgent need for safer and more effective agents against breast cancer. We have previously described the synthesis of a number of pyrazole derivatives, and in the current study, we have investigated the effects of two different ferrocenyl pyrazole (FP) derivates, 5-ferrocenyl-1-phenyl-1H-pyrazole (FP-Ph) and 5-ferrocenyl-IH-pyrazole (FP-H), on breast cancer cells. First, we investigated the effects of both FPs on cell viability and induction of cell death in breast cancer cells and benign MCF-10A cells by XTT and DNA fragmentation assays, respectively. Morphological changes in human breast cancer cells after FPs treatment were detected by both phase contrast microscope and atomic force microscopy (AFM). Then, we tested whether FPs exert their cytotoxic effect through inhibiting PI3K/Akt and/or ERK1/ 2 signaling pathways by using specific inhibitors. Both FPs induced cytotoxicity in a time and concentration-dependent manner in breast cancer cells; however, MCF-10A benign breast epithelial cells were much less susceptible to the cytotoxic effect of both FPs. FPs inhibited both PI3K/Akt and ERK 1/2 signaling pathways in breast cancer cells. The ultra structure images of MCF-7 cells by AFM showed that the cell surface was smooth in untreated cells, but it was rough with protrusions in treated cells. Both FPs induced apoptotic cell death in MDA-MB-231 cells; however, necrotic cell death was induced in caspase-3 lack MCF-7 cells, which implies that the synthesized FPs may induce apoptosis through caspase-3 dependent mechanism. In summary, these results suggest that FPs might be promising agents for the breast cancer therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Evaluation of gingival crevicular fluid cyclophilin a and extracellular matrix metalloproteinase inducer levels in different periodontal diseases

WOS: 000379369600022PubMed ID: 27176139Objective: Cyclophilin A (CypA) is able to regulate inflammatory responses and matrix metalloproteinase production via its interaction with extracellular matrix metalloproteinase inducer (EMMPRIN). EMMPRIN is the cell surface receptor of CypA. The aim of the present study was to evaluate the gingival crevicular fluid (GCF) CypA and EMMPRIN levels in patients with chronic periodontitis (CP), generalized aggressive periodontitis (G-AgP) and periodontally healthy controls. Methods: Twenty CP patients, 19 G-AgP patients and 20 healthy control subjects were included in the present study. All study participants were non-smokers. Full mouth clinical periodontal parameters including probing depth, clinical attachment level, plaque index, and papilla bleeding index were recorded. GCF CypA and EMMPRIN levels were analyzed by enzyme-linked immunosorbent assay. Data were analyzed statistically with parametric and non-parametric tests. Results: GCF CypA total amount was higher in the G-AgP group compared to healthy controls (p 0.05). No significant difference in GCF CypA total amount between CP and G-AgP was observed (p > 0.05). Also, there was no significant difference in GCF EMMPRIN total amounts among the study groups (p > 0.05). Conclusion: Higher levels of GCF CypA in patients with G-AgP might demonstrate that CypA is associated with the inflammatory infiltrate and alveolar bone destruction of G-AgP. However, GCF CypA level does not seem to be affected by CP. Similar GCF EMMPRIN levels in diseased and healthy groups might suggest that EMMPRIN has role in the turn over of connective tissues in physiological conditions as well as pathological state. (C) 2016 Elsevier Ltd. All rights reserved