Browsing by Author "Bozkurt E."
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Item Effects of Thymus serpyllum extract on cell proliferation, apoptosis and epigenetic events in human breast cancer Cells(2012) Bozkurt E.; Atmaca H.; Kisim A.; Uzunoglu S.; Uslu R.; Karaca B.Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDAMB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment. Copyright © 2012, Taylor & Francis Group, LLC.Item A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells(Elsevier Ireland Ltd, 2013) Atmaca H.; Bozkurt E.; Uzunoglu S.; Uslu R.; Karaca B.Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer. © 2013 Elsevier Ireland Ltd.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 Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drugresistant prostate cancer cell lines(Zerbinis Publications, 2014) Dirican A.; Erten C.; Atmaca H.; Bozkurt E.; Kucukzeybek Y.; Varol U.; Tarhan M.O.; Karaca B.; Uslu R.Purpose: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. Methods: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. Results: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DN A fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. Conclusion: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.Item Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway(Springer-Verlag Italia s.r.l., 2015) Dirican A.; Atmaca H.; Bozkurt E.; Erten C.; Karaca B.; Uslu R.Background: The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. Materials and Methods: The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways Results: We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Conclusion: Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC. © 2014, Federación de Sociedades Españolas de Oncología (FESEO).Item Trabectedin (ET-743) from marine tunicate for cancer treatment(Springer International Publishing, 2015) Atmaca H.; Bozkurt E.Trabectedin (Yondelis; ET-743) is a DNA binding agent that was originally derived from the marine tunicate Ecteinascidia turbinata and is currently prepared synthetically. Its mechanism of action is different from the conventional alkylating agents used in cancer chemotherapy. Two of the three fused rings of trabectedin molecule are involved in the minor groove binding to DNA; forming DNA adducts on N2 position of guanine, and bends DNA towards the major groove, while the third is known to interact with different transcription factors and DNA-binding proteins. Trabectedin has been found to inhibit the proliferation of various tumor cells in vitro and in vivo. It is the first anticancer marine derived drug that has been approved by the European Union, Russia and South Korea for the treatment of advanced or metastatic soft tissue sarcoma. Several Phase II clinical trials are also going on for several cancer types including breast and prostate. � Springer International Publishing Switzerland 2015.Item Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines(Springer Verlag, 2015) Karaca B.; Degirmenci M.; Ozveren A.; Atmaca H.; Bozkurt E.; Karabulut B.; Sanli U.A.; Uslu R.Purpose: Docetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines. Methods: The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISAPlus Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis. Results: DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone. Conclusions: These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects. © 2015 Springer-Verlag Berlin Heidelberg.Item Effects of Galium aparine extract on the cell viability, cell cycle and cell death in breast cancer cell lines(Elsevier Ireland Ltd, 2016) Atmaca H.; Bozkurt E.; Cittan M.; Dilek Tepe H.Ethnopharmacological relevance Galium species have been traditionally used for its anti-cancer, antioxidant, anti-inflammatory, antimicrobial and cardioprotective effects in the folk medicine. Galium aparine (GA) is a typical climbing plant growing widespread in Anatolia. Aim of the study To investigate the potential anti-proliferative and apoptotic effect of GA methanol (MeOH) extract on MCF-7 and MDA-MB-231 human breast cancer cells and MCF-10A untransformed breast epithelial cells. Materials and methods First, the extract was characterized by both liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) analyses. Then, cell viability and cell cycle distribution were investigated by XTT assay and PI staining by flow cytometry, respectively. Cell death was determined by Annexin V FITC/7-AAD staining. Results A total of 14 major phytochemicals were identified by LC/Q-TOF/MS and 34 volatile compounds were determined by GC-MS. The extract was cytotoxic in both breast cancer cell lines in a concentration and time dependent manner and showed G1 block after 72 h extract treatment. However, it was not cytotoxic to MCF-10A breast epithelial cells. Flow cytometry analyses revealed that apoptosis was induced in MDA-MB-231 cells; however, necrosis was induced in MCF-7 cells. Conclusion Our study suggests that GA MeOH extract may have potential anti-cancer effects against breast cancer cells without impairing normal breast epithelial cells. Ability to induction of non-apoptotic cell death besides apoptotic cell death by this complex plant-derived mixture may enable the killing of apoptosis resistant breast cancer cells but further studies should be conducted to investigate the bioavailability and metabolism of it in vivo. © 2016 Elsevier Ireland Ltd. All rights reserved.Item Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines; [İnsan kanser hücre hatlarında resveratrol sitotoksisitesinin XTT testi ve xCELLigence sistemi ile karşılaştırmalı analizi](Turkish Biochemistry Society, 2016) Atmaca H.; Bozkurt E.; Kısım A.; Uslu R.Objective: In vitro preliminary oncological and translational studies are mainly based on evaluating the cytotoxic effects of a specific compound on cultured cells. Resveratrol is a commercially available compound which is originally isolated from the roots of white hellebore and later from Polygonum cuspidatum. The objective of the study was to compare cytotoxicity data of Resveratrol from XTT end point assay with a real-time cell based xCELLigence system in terms of accuracy, sensitivity, speed and reproducibility in a panel of human cancer cell lines. Methods: XTT end point assay and real-time cell based xCELLigence system were used to evaluate cytotoxicity. Cytotoxicity results were verified by monitoring cells under phase-contrast microscope which were treated with IC50 values of resveratrol. Results: Resveratrol decreased cell viability in a timeand concentration-dependent manner in all cancer cell lines when tested by both the XTT assay and xCELLigence system. Standard deviations of the xCELLigence data were found to be lower than the data from XTT assay. Conclusion: The data from this study strongly imply that xCELLigence system has higher precision, more enlightening and more reproducible than XTT end point assay. © 2016 Turkish Biochemistry Society. All rights reserved.Item Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway(Springer Science and Business Media B.V., 2016) Surmeli Z.; Gursoy P.; Erdogan A.P.; Bozkurt E.; Atmaca H.; Uzunoglu S.; Sezgin C.; Şanlı U.A.; Uslu R.; Karaca B.The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells. © 2015, International Society of Oncology and BioMarkers (ISOBM).Item Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines(Springer Science and Business Media B.V., 2016) Atmaca H.; Bozkurt E.Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by −2.9, −3.7, −1.7, −1.7, −2.0 and −1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by −5.1, −2.0, −2.4, −3.1, −1.5, −2.0 and −2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer. © 2015, International Society of Oncology and BioMarkers (ISOBM).Item Evaluation of the gingival inflammation in pregnancy and postpartum via 25-hydroxy-vitamin D3, prostaglandin E2 and TNF-α levels in saliva(Elsevier Ltd, 2016) Gümüş P.; Öztürk V.Ö.; Bozkurt E.; Emingil G.Background Physiological changes and immunological modifications occur during pregnancy. The clinical and biological features of periodontal infections are affected by pregnancy. The aim of the present study was to evaluate saliva levels of 25-hydroxy-vitamin D3 (25(OH)D3), prostaglandin E2 (PGE2) and TNF-alpha (TNF-α) in pregnancy, postpartum and non-pregnant controls. Methods Whole saliva samples together with full-mouth clinical periodontal recordings were obtained from 59 pregnant, 47 post partum and 70 systemically healthy non-pregnant women. Groups were also evaluated according to the periodontal health status. 25(OH)D3, PGE2 and TNF-α levels in the saliva samples were determined by enzyme-linked immunoassays. Data were statistically tested by nonparametrical tests. Results Saliva TNF-α and PGE2 levels were significantly lower and 25(OH)D3 levels were significantly higher in the pregnant group than postpartum group (p < 0.0001). Saliva TNF-α and 25(OH)D3 levels were significantly higher and PGE2 levels were significantly lower in the control group than postpartum group (p < 0.0001). In the pregnant healthy, gingivitis and periodontitis groups saliva TNF-α levels were significantly lower than postpartum and control counterparts (p < 0.0001, p = 0.032, p = 0.003 and p = 0.013; p = 0.027; p = 0.007, respectively). In control healthy, gingivitis and periodontitis groups saliva 25(OH)D3 levels were significantly higher than the postpartum counterparts (p < 0.0001, p < 0.0001, p = 0.002, respectively). In the control healthy and gingivitis groups saliva 25(OH)D3 levels were significantly higher than pregnant healthy and gingivitis (p < 0.0001). Conclusions In conclusion, within the limits of the present study it seems that pregnancy have an effect on parameters in saliva in relation to the periodontal status of the women. Further studies are required for better understanding of the impact of periodontal diseases on pregnancy or otherwise. © 2015 Elsevier Ltd. All rights reserved.Item Gingival crevicular fluid and salivary resistin and tumor necrosis factor-alpha levels in Obese children with gingivitis(Wiley-Blackwell, 2018) Doğusal G.; Afacan B.; Bozkurt E.; Sönmez I.Background: This study aimed to evaluate the levels of resistin and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) and saliva of obese children with gingivitis. Methods: One-hundred and thirty children (65 obese and 65 normal weight; age range 8 to 12 years) were recruited for the study. The children were classified into four subgroups based on their body mass and periodontal status; 1) obese children with gingivitis (OG, n = 33); 2) obese children with healthy periodontium (OH, n = 32); 3) normal weight children with gingivitis (NWG, n = 32); 4) normal weight children with healthy periodontium (NWH, n = 33). Body mass index (BMI) percentile, probing pocket depth (PPD), gingival index (GI), and plaque index (PI) were recorded. Resistin and TNF-α were analyzed in GCF and saliva samples by ELISA. Results: Obese children had higher BMI percentiles than normal weight children (p < 0.0001). PPD, GI, PI, GCF volume, GCF, and salivary resistin and TNF-α levels were similar between obese and normal weight children (P > 0.05). OG and NWG subgroups had significantly higher GI, PI, GCF volume, GCF resistin total amounts, and salivary resistin concentrations but lower GCF resistin and TNF-α concentrations than OH and NWH (P < 0.0001 for all). GCF resistin total amounts were positively correlated with GI, PI, and GCF TNF-α total amounts (P < 0.05). Conclusions: To our knowledge, this is the first study evaluated the levels of resistin in GCF and saliva of children. Obesity is not associated with GCF and salivary resistin and TNF-α levels in children in the presence of gingival inflammation. © 2018 American Academy of Periodontology.Item The evaluation of peri-implant sulcus fluid osteocalcin, osteopontin, and osteonectin levels in peri-implant diseases(Wiley-Blackwell, 2018) Cakal O.T.; Efeoglu C.; Bozkurt E.Background: Peri-implant mucositis is an inflammation of the soft tissues surrounding an implant. Peri-implantitis refers to a process characterized by peri-implant bone loss along with an inflammation of the soft tissues. Osteocalcin, osteopontin, and osteonectin proteins are related to bone remodeling. The aim of the present study was to investigate peri-implant sulcus fluid (PISF) osteocalcin, osteopontin, and osteonectin levels in peri-implant mucositis and peri-implantitis. Methods: Fifty-two implants with peri-implantitis, 46 implants with peri-implant mucositis, and 47 control implants were included in the study. Clinical parameters including probing depth, modified sulcus bleeding index and modified plaque index were recorded. PISF osteocalcin, osteopontin, and osteonectin levels were analyzed by ELISA kits. Results: There were no significant differences in PISF osteocalcin, osteopontin, and osteonectin total amounts between healthy controls, peri-implant mucositis and periimplantitis groups (P > 0.05). Probing depths were not correlated with PISF osteocalcin, osteopontin, and osteonectin levels in the study groups (P > 0.05). Conclusions: Soft tissue inflammation around dental implants does not cause a change in osteocalcin, osteopontin, and osteonectin levels in PISF. Also, periimplantitis does not seem to give rise to an increase in PISF levels of osteocalcin, osteopontin, and osteonectin. © 2018 American Academy of Periodontology.Item AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells(Springer International Publishing, 2018) Yurekli B.S.; Karaca B.; Kisim A.; Bozkurt E.; Atmaca H.; Cetinkalp S.; Ozgen G.; Yilmaz C.; Uzunoglu S.; Uslu R.; Saygili F.Purpose: Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (−)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing’s disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods: Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results: AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion: AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells. © 2017, Italian Society of Endocrinology (SIE).Item Gingival crevicular fluid and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease(Wiley-Blackwell, 2019) Afacan B.; Öztürk V.Ö.; Paşalı Ç.; Bozkurt E.; Köse T.; Emingil G.Background: Hypoxia-inducible factor-1 alpha (HIF-1α) is expressed as an adaptive response to hypoxia, mediates angiogenesis through the expression of vascular endothelial growth factor (VEGF) and can be induced by tumor necrosis factor-alpha (TNF-α). This study aimed to investigate the gingival crevicular fluid (GCF) and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease. Methods: A total of 87 individuals, 20 generalized aggressive periodontitis (G-AgP), 20 chronic periodontitis (CP), 26 gingivitis patients, and 21 periodontally healthy individuals, were included. Clinical periodontal parameters were recorded; GCF and salivary samples were collected; and HIF-1α, VEGF, and TNF-α levels were measured by enzyme-linked immunosorbent assay. Nonparametric tests were used for the statistical analyses. Results: G-AgP and CP groups had significantly higher GCF HIF-1α, VEGF, and TNF-α total amounts than gingivitis and healthy groups (P < 0.05). GCF HIF-1α and TNF-α total amounts in gingivitis group were significantly higher than the healthy group (P < 0.05). GCF and salivary concentrations of biomarkers were similar in both periodontitis groups (P > 0.05). Salivary HIF-1α concentrations in gingivitis group were significantly higher than G-AgP and healthy groups (P < 0.05). GCF HIF-1α, VEGF, and TNF-α total amounts were positively correlated with the site-specific clinical periodontal parameters and with each other (P < 0.05). Conclusions: HIF-1α is detectable in GCF and saliva of periodontally diseased and healthy individuals, and the GCF levels of the biomarker can be affected by disease status. Increased GCF HIF-1α, VEGF, and TNF-α levels in both chronic and aggressive form of periodontitis might suggest the role of TNF-α/HIF-1α/VEGF pathway in the pathogenesis of periodontal diseases. © 2018 American Academy of PeriodontologyItem Nationwide prospective audit for the evaluation of appendicitis risk prediction models in adults: Right iliac fossa treatment (RIFT) - Turkey(Oxford University Press, 2024) Yalcinkaya A.; Yalcinkaya A.; Balci B.; Keskin C.; Erkan I.; Yildiz A.; Kamer E.; Leventoglu S.; Caglikulekci M.; Zarbaliyev E.; Sevmis M.; Ulgen Y.; Altinel Y.; Meric S.; Akbas A.; Hacim N.A.; Vartanoglu Aktokmanyan T.; Aktimur Y.E.; Calikoglu F.; Gullu H.F.; Durma A.G.; Acar S.; Ciftci E.; Balik E.; Kulle C.B.; Ozata I.H.; Tufekci T.; Tatar C.; Sevinc M.M.; Sevik H.; Ertürk C.; Kiraz I.N.; Ozben V.; Aytac E.; Aliyeva Z.; Mutlu A.U.; Tanal M.; Celayir M.F.; Bozkurt E.; Yetkin S.G.; Ergin E.; Attaallah W.; Uprak T.K.; Omak A.; Simsek O.; Bozkurt M.A.; Kara Y.; Bozdag E.; Yirgin H.; Ozcan A.; Okkabaz N.; Ozdenkaya Y.; Haksal M.C.; Pekuz C.K.; Duru S.; Sivrikoz E.; Ozdemir Y.; Tan N.; Yarbug Karayali F.; Taghiyeva A.; Tirnova I.; Erenler Bayraktar I.; Bayraktar O.; Emsal E.Z.; Dalkilic M.I.; Yesiltas M.; Tok H.; Karakas D.O.; Pusane A.; Demirer A.I.; Sahin H.B.; Gok A.F.K.; Bozkurt H.A.; Yildirim M.; Uzunyolcu G.; Yanar H.T.; Ergun S.; Kutluk F.; Uludag S.S.; Zengin A.K.; Ozcelik M.F.; Sanli A.N.; Altuntas Y.E.; Memisoglu E.; Sari R.; Akdogan O.; Kucuk H.F.; Ozkan O.F.; Ulgur H.S.; Kirkan E.F.; Yuksekdag S.; Rencuzogullari A.; Aktas M.K.; Aba M.; Demirel A.O.; Eray I.C.; Aydogan B.; Cetinkunar S.; Yener K.; Sozutek A.; Irkorucu O.; Bayrak M.; Altintas Y.; Alabaz O.; Atasever A.; Erdogrul G.; Kupeli A.H.; Muhammedoglu B.; Kokdas S.; Kaya M.; Uysal E.; Yildirim A.C.; Zeren S.; Ekici M.F.; Algin M.C.; Kucuk G.O.; Eraslan H.; Aybar E.; Polat S.; Ceylan A.; Isik O.; Kural S.; Aktas A.; Bakar B.; Uzunoglu M.Y.; Gulcu B.; Ozturk E.; Devay A.O.; Taspinar E.; Balcin O.; Aksoy F.; Garip G.; Yalkin O.; Iflazoglu N.; Yigit D.; Kaya R.B.; Ugur M.; Kilic E.; Dedemoglu A.; Arslan R.E.; Temiz M.; Aydin C.; Demirli Atici S.; Kaya T.; Ozturk S.; Calik B.; Kilinc G.; Acar T.; Acar N.; Cengiz F.; Ureyen O.; Tan S.; Ilhan E.; Turk Y.; Durak A.T.; Yilmaz M.; Mercan M.; Atci R.; Sokmen S.; Bisgin T.; Egeli T.; Yildirim Y.; Safak T.; Celik K.; Yilmaz E.M.; Kirnap M.; Demirkiran A.E.; Sekerci U.U.; Karacan E.; Bilgic E.; Ozmen M.M.; Guldogan C.E.; Gundogdu E.; Moran M.; Erol T.; Dincer H.A.; Kirimtay B.; Yilmaz S.; Cennet O.; Yildiz A.; Sahin C.; Akyol C.; Koc M.A.; Ersoz S.; Turhan A.; Konca C.; Tezcaner T.; Erkent M.; Aydin O.; Avci T.; Altiner S.; Osmanov I.; Emral A.C.; Cetinkaya G.; Lapsekili E.; Sakca M.; Cimen S.; Ozen D.; Kozan E.B.; Dogan L.; Haberal E.; Kayhan O.; Aksel B.; Karabacak H.; Azili C.; Yazici F.; Apaydin M.; Kaya I.O.; Cetinkaya E.; Akin T.; Gunes G.; Turap H.; Aslan D.; Demirbag A.E.; Bolukbasi B.; Karaca B.E.; Ozturk E.; Ozeller E.; Kayacan G.S.; Borcek A.O.; Ece I.; Yormaz S.; Colak B.; Calisir A.; Sahin M.; Arslan K.; Hasirci I.; Ulutas M.E.; Metin S.H.; Gultekin F.A.; Ozkan Z.; Ilhan O.; Gundogdu T.; Liman R.K.; Kanat B.H.; Aydin A.; Sungurtekin U.; Ozgen U.; Aykota M.R.; Altintoprak F.; Gonullu E.; Cakmak G.; Dulger U.C.; Mantoglu B.; Demir H.; Akin E.; Eroz E.; Nazli O.; Dere O.; Dadasoglu M.A.; Kara E.; Tutcu S.; Solak I.; Gencer I.; Dalkiran A.; Sevinc B.; Karahan O.; Damburaci N.; Sari E.; Akay T.; Calta A.F.; Ozdemir A.; Ohri N.; Ermis I.; Bozbiyik O.; Ozdemir M.; Goktepe B.; Demir B.; Kilincarslan O.; Gunduz U.R.; Olcum M.; Dincer O.I.; Cakir R.C.; Dinc B.; Sahin E.; Uludag E.; Arslan Y.; Posteki G.; Oktay A.; Tatar O.C.; Guler S.A.; Utkan N.Z.; Tayar S.; Copelci Y.; Kartal M.; Kalayci T.; Yeni M.; Buyukkasap A.C.; Vural S.; Kesicioglu T.; Aydin I.; Gulmez M.; Saracoglu C.; Topcu O.; Kurt A.; Soylu S.; Kurt B.; Serin M.; Basceken S.I.; Gundes E.; Savda M.; Balkan A.Z.A.; Yildiz M.N.; Uzunkoy A.; Karaca E.; Berkan A.; Isik A.; Yildiz Y.A.; Ergul Z.; Yasar N.F.; Badak B.; Ozen A.; Velipasaoglu M.; Ure I.Background: Appendicitis is the most prevalent surgical emergency. The negative appendicectomy rate and diagnostic uncertainty are important concerns. This study aimed to assess the effectiveness of current appendicitis risk prediction models in patients with acute right iliac fossa pain. Methods: A nationwide prospective observational study was conducted, including all consecutive adult patients who presented with right iliac fossa pain. Diagnostic, clinical and negative appendicectomy rate data were recorded. The Alvarado score, Appendicitis Inflammatory Response (AIR), Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) and Adult Appendicitis Score systems were calculated with collected data to classify patients into risk categories. Diagnostic value and categorization performance were evaluated, with use of risk category-based metrics including 'true positive rate' (percentage of appendicitis patients in the highest risk category), 'failure rate' (percentage of patients with appendicitis in the lowest risk category) and 'categorization resolution' (true positive rate/failure rate). Results: A total of 3358 patients from 84 centres were included. Female patients were less likely to undergo surgery than men (71.5% versus 82.5% respectively; relative risk 0.866, 95% c.i. 0.834 to 0.901, P < 0.001); with a three-fold higher negative appendicectomy rate (11.3% versus 4.1% respectively; relative risk 2.744, 95% c.i. 2.047 to 3.677, P < 0.001). Ultrasonography was utilized in 56.8% and computed tomography in 75.2% of all patients. The Adult Appendicitis Score had the best diagnostic performance for the whole population; however, only RIPASA was significant in men. All scoring systems were successful in females patients, but Adult Appendicitis Score had the highest area under the receiver operating characteristic curve value. The RIPASA and the Adult Appendicitis Score had the best categorization resolution values, complemented by their exceedingly low failure rates in both male and female patients. Alvarado and AIR had extremely high failure rates in men. Conclusion: The negative appendicectomy rate was low overall, but women had an almost three-fold higher negative appendicectomy rate despite lower likelihood to undergo surgery. The overuse of imaging tests, best exemplified by the 75.2% frequency of patients undergoing computed tomography, may lead to increased costs. Risk-scoring systems such as RIPASA and Adult Appendicitis Score appear to be superior to Alvarado and AIR. © 2024 The Author(s). Published by Oxford University Press on behalf of BJS Foundation Ltd.