Browsing by Subject "hypoxia inducible factor 1alpha"
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Item Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells(2013) Karaca B.; Atmaca H.; Bozkurt E.; Kisim A.; Uzunoglu S.; Karabulut B.; Sezgin C.; Sanli U.A.; Uslu R.We investigated the effects of AT-101/cisplatin combination treatment on the expression levels of apoptotic proteins and epigenetic events such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzyme activities in OVCAR-3 and MDAH-2774 ovarian cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were performed. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. DNMT and HDAC activities were evaluated by ELISA assay and mRNA levels of DNMT1 and HDAC1 genes were quantified by qRT-PCR. Combination of AT-101/cisplatin resulted in strong synergistic cytotoxicity and apoptosis in human ovarian cancer cells. Combination treatment reduced some pivotal anti-apoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, XIAP in OVCAR-3 cells, whereas p21, Bcl-2, cIAP-1, HSP27, Clusterin and XIAP in MDAH-2774 cells. Among the pro-apoptotic proteins, Bad, Bax, Fas, phospho-p53 (S46), Cleaved caspase-3, SMAC/Diablo, TNFR1 and Cytochrome c were induced in OVCAR-3 cells, whereas, Bax, TRAILR2, FADD, p27, phospho-p53 (S46), Cleaved caspase-3, Cytochrome c, SMAC/Diablo and TNFR1 were induced in MDAH-2774 cells. Combination treatment also inhibited both DNMT and HDAC activities and also mRNA levels in both ovarian cancer cells. AT-101 exhibits great potential in sensitization of human ovarian cancer cells to cisplatin treatment in vitro, suggesting that the combination of AT-101 with cisplatin may hold great promise for development as a novel chemotherapeutic approach to overcome platinum-resistance in human ovarian cancer. © 2012 Springer Science+Business Media Dordrecht.Item A comparison of the molecular distribution of proangiogenic factors in endometrium of missed abortions and of voluntary first trimester termination cases(S.O.G. CANADA Inc., 2015) Özçakir T.; Turan M.A.; Şimşek F.; Atay C.; Vatansever S.; Özbilgin K.Objective: The authors aimed to evaluate the angiogenic changes that occur in the cases with missed abortions compared with the voluntary termination of pregnancy as control group, with this controlled clinical study. Materials and Methods: The study included fifteen healthy volunteer women with unwanted pregnancy less than 10th gestational week in an academic research environment. The patients were 19 women between 6th and 11th gestational weeks diagnosed with missed abortion as the patient group. Immunohistochemistry was utilized to examine temporal and spatial expression of vascular endothelial growth factor (VEGF) and their two receptors: VEGF-R1 (Flt-1) and VEGF-R2 (Flk-l/KDR), and Trombospondin-1, eNOS, iNOS, and HIF-la in the both deciduas and placenta of the both groups. Results: This study discovered the significant difference (p < 0.005) between the groups of controlled and missed abortion in the decidual and placental cell components, and has put forward that thrombospondin and iNOS have an impact on abortion through antiangiogenic effect in cases of missed abortions. Conclusions: The potential role of molecules affecting angiogenesis in the etiology of missed abortion has been evaluated and the authors aimed for this to be a guide for studies on further treatments and on the prevention of the development of missed abortions.Item Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells(John Wiley and Sons Inc, 2020) Ozdemir Kutbay N.; Biray Avci C.; Sarer Yurekli B.; Caliskan Kurt C.; Shademan B.; Gunduz C.; Erdogan M.Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes: AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, and RICTOR genes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets. © 2020 Wiley Periodicals LLCItem Effect of non-surgical periodontal treatment on gingival crevicular fluid hypoxia inducible factor-1 alpha, vascular endothelial growth factor and tumor necrosis factor-alpha levels in generalized aggressive periodontitis patients(Wiley-Blackwell, 2020) Afacan B.; Keleş Yücel Z.P.; Paşali Ç.; Atmaca İlhan H.; Köse T.; Emingil G.Background: Hypoxia-inducible angiogenic pathway involving hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) may regulate several biological processes related to inflammation. The present study aimed to assess the effect of non-surgical periodontal treatment on gingival crevicular fluid (GCF) HIF-1α, VEGF, and TNF-α levels in generalized aggressive periodontitis (G-AgP). Methods: Twenty G-AgP patients and 20 periodontally healthy individuals were included. G-AgP patients received scaling and root planning (SRP), per quadrant at a 1-week-interval, performed with ultrasonic and periodontal hand instruments. GCF samples were collected and clinical periodontal parameters including probing depth, clinical attachment level, gingival index and plaque index were recorded at baseline, 1 and 3 months after treatment. Biomarker levels in GCF were analyzed by ELISA. Results: At baseline all clinical parameters and GCF HIF-1α, VEGF, and TNF-α levels were significantly higher in G-AgP patients compared to healthy control (P < 0.05). All clinical parameters improved over the 3-month-period in G-AgP patients (P < 0.05). GCF HIF-1α levels in G-AgP reduced at 1 and 3 months post-treatment, however, this did not reach to statistical significance (P > 0.05). GCF VEGF and TNF-α levels remained unchanged throughout the study period (P > 0.05). Conclusions: Within the limitations of the present study, although HIF-1α seems to possess a potential diagnostic value for G-AgP, it might not be a proper predictor of clinically favorable treatment outcome. SRP plus different adjunctive therapies could provide better information about the prognostic role of hypoxia-inducible angiogenic pathway in G-AgP. © 2020 The Authors. Journal of Periodontology published by Wiley Periodicals, Inc. on behalf of American Academy of PeriodontologyItem Effects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic Effects of Doxorubicin in Rats(Springer, 2021) Durdagi G.; Pehlivan D.Y.; Oyar E.O.; Bahceci S.A.; Ozbek M.The main disadvantage of doxorubicin (DOX) is that it has cardiotoxic side effects. Our aim is to evaluate the cardioprotective effects of adrenomedullin (ADM) and to compare these effects with melatonin (MEL), it’s cardioprotective effects are well known. Rats were divided into four groups: Control group (0.9% NaCl solution, intravenously), Doxorubicin group (45 mg/kg DOX, intravenously), Doxorubicin + Melatonin group (DOX + MEL, 10 mg/kg melatonin, intraperitoneally), Doxorubicin + Adrenomedullin group (DOX + ADM, 12 µg/kg adrenomedullin, intraperitoneally). A single dose of DOX was injected to the experimental groups on day 5, and a single dose of 0.9% NaCl solution was injected to the control group through the tail vein. The animals were anesthetized and ECG recordings were obtained on day 8. For the purpose of biochemical and histological analysis, cardiac tissue biopsy was obtained after ECG recordings. Compared to the control group, the DOX group had significantly increased duration of QRS complex, PR interval, QT interval and QTc interval. QRS complex, QT interval and QTc interval were prolonged with the administration of DOX and shortened with the administration of ADM. MEL weakened the toxic effects of DOX on the cardiac tissue and it is shown histologically. DOX increased interleukins (IL-1α, IL-6, IL-18), tumor necrosis factor-α (TNF-α), hypoxia-inducible factor 1-alpha (HIF-1α), malondialdehyde (MDA), nitric oxide (NO), creatine kinase myocardial band (CK-MB), and total oxidant status (TOS) levels in cardiac tissue, while reducing total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) levels. MEL administration decreased the levels of CK-MB, MDA, IL-1α, IL-6, IL-18, NO, and TNF-α, whereas ADM only decreased IL-1α, IL-18, MDA and TNF-α levels. In summary, these results show that DOX has toxic effects on rat cardiac tissue which is documented histologically, electrocardiographically and biochemically. MEL alleviated histological damage and showed improvement on the several biochemical parameters of cardiac tissue. ADM brought several electrocardiographic and biochemical parameters closer to normal values. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.Item Therapeutic effects of Lacosamide in a rat model of traumatic brain injury: A histological, biochemical and electroencephalography monitoring study(Elsevier Ltd, 2021) Mete M.; Alpay S.; Aydemir I.; Unsal U.U.; Collu F.; Özel H.F.; Duransoy Y.K.; Kutlu N.; Tuglu M.İ.Objective: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI can be classified based on severity, mechanism or other features. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophys-iological mechanisms underlying neuronal loss after TBI. Lacosamide (LCM) is an anticonvulsant compound approved for the adjunctive treatment of partial-onset seizures and neuropathic pain. This study aimed to investigate possible neuroprotective effects of LCM in a rat model of TBI. Material and methods: Twenty-eight adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the control group (n=7). Group 2 was the trauma group (n=7) where rats were treated with 100 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 6 (group 3, n=7) or 20 (group 4, n=7) mg/kg Lacosamide IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. In addition, electroencephalograpy monitoring results were compared. Results: The immunoreactivity of both iNOS and eNOS (oxidative stress markers) were decreased with LCM treatment compared to trauma group. The results were statistically significant (***P<0.001). The treatments of low (56,17±9,69) and high-dose LCM (43,91±9,09) were decreased the distribution of HIF-1α compared to trauma group (P<0.01). The number of apoptotic cells were decreased with LCM treatment the difference between the trauma group and 20mg/kg LCM treated group (9,55±1,02) was statistically significant (***P<0.001). Malondialdehyde level was reduced with LCM treatment. MDA level was significantly higher in trauma group compared to LCM treated groups (***P<0.001). The level of Superoxide dismutase in the trauma group was 1,86 U/ml, whereas it was 36,85 U/ml in 20mg/kg LCM treated group (***P<0.001). Delta strength of EEG in 20mg/kg LCM treated group were similar to control group values after LCM treatment. Conclusion: No existing study has produced results suggesting that different doses of LCM has therapeutic effect against TBI, using EEG recording in addition to histological and biochemical evaluations in rats. © 2021 Elsevier Ltd