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Saglam O.,Kocaeli University | Unal Z.S.,Kocaeli University | Subas C.,Kocaeli University | Ulukaya E.,Uludag University | Karaoz E.,Center for Regenerative Medicine and Stem Cell Research & Manufacturing LivMedCell
Tumor Biology | Year: 2015

Tumor microenvironment is an important factor, which sustains and promotes the tumors by inflammatory signals. Interleukin-6 (IL-6) is known as a multifunctional cytokine, which is a major activator of the signaling pathway of Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3). In this study, we aimed to investigate the effect of IL-6 in the tumor microenvironment on carcinogenesis. For this purpose, healthy breast tissue-derived stromal cells (HBT-SCs) and malign breast tissue-derived stromal cells (MBT-SCs) were co-cultured with MCF-7 (human breast adenocarcinoma cell line) cells using semipermeable membranes. The cell proliferation was monitored with water-soluble tetrazolium (WST) and carboxyfluorescein succinimidyl ester (CFSE) assays. Protein levels were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot hybridization, while gene expressions were measured by real-time PCR. The results demonstrated that IL-6 protein levels increased significantly in the supernatants of MBT-SCs when they were co-cultured with MCF-7 cells. In accordance with this, the expression of IL-6 was significantly higher in MBT-SCs. Additionally, the expression of STAT3 in MCF-7 cells increased slightly when they were co-cultured with MBT-SCs. Considering together, there is an important interaction between tumor microenvironment and tumor cells mediated by IL-6 signaling. Thereby, the targeting on IL-6 signaling in the treatment of cancer might effectively prevent the tumor progression. © 2015, International Society of Oncology and BioMarkers (ISOBM).


Yuksel S.,Trabzon Kanuni Training and Research Hospital | Gulec M.A.,BagcLar Training and Research Hospital | Gultekin M.Z.,BagcLar Training and Research Hospital | Adanr O.,BagcLar Training and Research Hospital | And 7 more authors.
Connective Tissue Research | Year: 2016

Introduction: This study aims to histopathologically, biomechanically, and immunohistochemically compare the fourth-week efficiencies of local platelet-rich plasma (PRP) and bone marrow-derived mesenchymal stem cell (rBM-MSC) treatments of the Achilles tendon ruptures created surgically in rats. Materials and Methods: The study included 35 12-month-old male Sprague Dawley rats, with an average weight of 400–500 g. Five rats were used as donors for MSC and PRP, and 30 rats were separated into MSC, PRP, and control groups (n = 10). The Achilles tendons of the rats were cut transversely, the MSC from bone marrow was administered to the MSC group, the PRP group received PRP, and the control group received physiological saline to create the same surgical effect. In previous studies, it was shown that this physiological saline does not have any effect on tendon recovery. Thirty days after the treatment, the rats were sacrificed and their Achilles tendons were examined histopathologically, immunohistochemically, and biomechanically. Results: The use of rBM-MSC and PRP in the Achilles tendon ruptures when the tendon is in its weakest phase positively affected the recovery of the tendon in histopathologic, immunohistochemical, and biomechanical manners compared to the control group (p < 0.05). While the levels of pro-inflammatory cytokines TNF-α, IFNγ, and IL 1β were significantly low, the levels of anti-inflammatory cytokines and growth factors playing key roles in tendon recovery, such as IL2, VEGF, transforming growth factor-beta, and HGF, were significantly higher in the MSC group than those of the PRP and control groups (p < 0.05). In the MSC group, the (Formula presented.) (mm) value was significantly higher (p ˂ 0.05) than that in the PRP and control groups. Conclusion: rBM-MSC and PRP promote the recovery of the tendon and increase its structural strength. The use of PRP and MSC provides hope for the treatment of the Achilles tendon ruptures that limit human beings’ functionalities and quality of life, particularly for athletes. It is thought that the use of MSC can be more effective for tendon healing; hence, more extensive and advanced studies are needed on this topic. © 2016 Taylor & Francis


Cinik R.,Diyarbakir Bismil State Hospital | Yuksel N.,Kocaeli University | Pirhan D.,Kocaeli University | Aslan M.S.,Arnavutkoy State Hospital | And 2 more authors.
Current Eye Research | Year: 2016

Purpose: To investigate the efficiency of everolimus on the prevention of postoperative scar in a rabbit model of glaucoma filtering surgery in comparison with mitomycin-C (MMC).Materials and Methods: Thirty New Zealand albino rabbits were randomly assigned into 3 groups, each including ten rabbits: an everolimus group (Group 1), a MMC group (Group 2), and a sham group (Group 3). A limbal-based trabeculectomy was performed on the right eyes of all the rabbits. For 28 days following surgery, the eyes were evaluated in terms of intraocular pressure (IOP), morphological and biomicroscopic changes, and complications in the bleb. On the 28th day, four eyes randomized from each group were enucleated and histologically and immunohistochemically analyzed. Transforming growth factor-β1 (TGF-β1), metalloproteinase (MMP-2, MMP-9), and proliferative cell nuclear antigen (PCNA) expressions in each group were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis.Results: Bleb survival was statistically significantly longer for a period in Group 1 compared to Group 2. When postoperative IOPs of three groups were measured, it was seen that there is significant IOP reduction in all three groups. However, there were increases in the mean IOP values beginning from the 5th day in Group 2 and from the 3rd day in Group 3 while in Group 1 mean IOP values began to increase beginning from 10th day and the mean IOP values in Group 1 remained at a lower level in comparison to the other groups for 28 days (p < 0.05). The expressions of TGF-β1, MMP-2, MMP-9, and PCNA were reduced in Group 1 compared to other groups. TUNEL positive apoptotic cells were significantly increased in Group 1 compared to other groups (p < 0.05).Conclusion: Everolimus appears to suppress the proliferation of fibroblast and thus may provide an effective treatment strategy in glaucoma filtering surgery. © 2016 Taylor & Francis

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