Browsing by Subject "transforming growth factor beta2"
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Item Histopathological and ultrastructural effects of Losartan on embryonic rat kidney(Elsevier GmbH, 2005) Akil I.; Inan S.; Gurcu B.; Nazikoglu A.; Ozbilgin K.; Muftuoglu S.The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10 mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-β (TGF-β 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-β's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p<0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system. © 2005 Elsevier GmbH. All rights reserved.Item Immunolocalizations of VEGF, its receptors flt-1, KDR and TGF-β's in epithelial ovarian tumors(2006) Inan S.; Vatansever S.; Celik-Ozenci C.; Sanci M.; Dicle N.; Demir R.Objective: Angiogenesis is an essential factor for growth, differentiation, invasion and metastasis of tumors. In this study, we aimed to evaluate the immunolocalizations of vascular endothelial growth factor (VEGF), its receptors flt-1, KDR/flk-1, and transforming growth factor-beta's (TGF-β) in epithelial ovarian tumors, utilizing indirect immunohistochemistry to understand the role of the angiogenic events in ovarian neoplasia. Methods: Tissue blocks from 40 patients who had ovarian pathology (borderline serous-mucinous tumor and malignant serous-mucinous adenocarcinoma of the ovary) were included in this study. All formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against VEGF, flt-1, KDR/flk-1, TGF-β1, TGF-β2 and TGF-β3 using the avidin-biotin-peroxidase method. H-SCORE, a semi-quantitative grading system, was used to compare immunohistochemical staining intensities. Results: Positive VEGF immunoreactivity was concentrated in the epithelial and stromal parts of all the ovarian samples and the endothelial cells in the stroma were also stained. Increased immunoreactivity of VEGF was observed in malignant ovarian adenocarcinomas compared to the borderline tumors of the ovary. VEGF receptors, flt-1 and KDR/flk-1 immunoreactivities were detected not only in vascular endothelial cells, but also in tumor cells at malignant sites. Immunoreactivities of VEGF and its receptors were coexpressed in tumor cells of the ovarian carcinoma. While immunoreactivities of TGF-β1 and TGF-β2 were both overexpressed in malignant ovarian carcinomas, immunoreactivity of TGF-β3 was still mild. Conclusion: Our results suggest that overexpression of VEGF, its receptors flt-1, KDR/flk-1 and TGF-β interaction may play an important role in the ovarian cancer biology, with potential effects on tumor growth and angiogenesis. New therapeutic strategies using VEGF and TGF-β antagonists could obtain an additional approach to the treatment ovarian carcinoma by inhibiting angiogenesis.Item Distribution of furin, TNF-α, and TGF-β2 in the endometrium of missed abortion and voluntary first trimester termination case(Science Printers and Publishers Inc., 2015) Ozbilgin K.; Turan A.; Kahraman B.; Atay C.; Vatansever S.; Uluer E.T.; Özçakir T.Objective: To identify the role of furin, TNF-a, and TGF-b2 in human missed abortion pathogenesis. STUDY DESIGN: Decidual materials were collected from patients diagnosed with a missed abortion (n=10) (missed abortion group) and from legal voluntary termination cases at ≪ 10 gestational weeks (n=10) (normal pregnancy group). Tissue samples were collected from each group by dilation and curettage under mask anesthesia. For all tissue samples, furin, TNF-α, and TGF-β2 primary antibodies were performed by immunohistochemical staining. The number of stained cells was evaluated by using the H-score technique. Results: In immunohistochemical examination, the immunoreactivities of furin, TNF-α, and TGF-β2 were found to be higher in syncytiotrophoblastic cells in the missed abortion group than in the normal pregnancy group (p<0.005). Additionally, high immunoreactivity of TNF-α and TGF-β2 molecules was established only in cytotrophoblastic cells of missed abortions (p<0.005) in examination at decidual cells of the missed abortion group; furin immunoreactivities were detected higher in the missed abortion group than in the control group, but TNF-α and TGF-β2 immunoreactivity were increased in number in the normal pregnancy group (p<0.005). Conclusion: It is considered that high levels of furin and the 2 furin-related proteins (TNF-α and TGF-β2), which play important roles in proliferation, invasion, migration, differentiation, and survival of cells, may be the reason of proceeding decidualization, placentation, and prevention from abortion, in spite of terminating the fetal life. © Science Printers and Publishers, Inc.Item Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells(Taylor and Francis Ltd., 2022) Kayabasi C.; Yilmaz Susluer S.; Balci Okcanoglu T.; Ozmen Yelken B.; Mutlu Z.; Goker Bagca B.; Caliskan Kurt C.; Saydam G.; Durmuskahya C.; Kayalar H.; Ozbilgin A.; Biray Avci C.; Gunduz C.Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G0/G1, S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML. © 2022 Taylor & Francis Group, LLC.