Browsing by Author "Uluer E.T."
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Item Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathway(2012) Uluer E.T.; Aydemir I.; Inan S.; Ozbilgin K.; Vatansever H.S.Aberrant activation of the JAK/STAT pathway may predispose to malignancy as a consequence of the deregulation of cell proliferation, differentiation or apoptosis such as in cancer of the blood, head and neck, and breast. In our study we aimed to investigate the effects of 5-fluorouracil (5-FU) and gemcitabine on a breast cancer cell line (MCF-7 cells) via the JAK/STAT pathway. Distribution of JAK1, JAK2, JAK3 and STAT2, STAT3, STAT4, STAT5 were evaluated on MCF-7 cells following gemcitabine and 5-FU treatment and in the absence of drug treatment by an indirect immunohistochemical method. It was observed that JAK1, JAK3, STAT5 and particularly STAT2 activation were more effective than the other JAK/STATs in breast cancer progression. Following treatment with 5-FU, JAK1 and STAT5 immunoreactivities were decreased in MCF-7 cells in comparison with both gemcitabine-treated and non-treated groups. These results suggest that the JAK/STAT pathway plays an important role in breast cancer pathogenesis and may be more affected after 5-FU treatment rather than gemcitabine. Drugs which block STAT5 may provide a novel therapeutic approach for the treatment of breast cancer. © 2011 Elsevier GmbH.Item EVect of lisinopril on renal tissue damage in unilateral ureteral obstruction in rats(2012) Karabuga Ä.; Akbay K.; Turna B.; Vatansever H.S.; Altay B.; Güzel E.; Uluer E.T.; Ustun G.; Ekren F.; Nazli O.; Muftuoglu S.; Apaydin E.In this study, it was aimed to investigate apoptosis in renal injury and the eVect of lisinopril in rat model, which constitute unilateral ureteral obstruction. The retroperitoneal ureter was ligated with a 4.0 silk for the experimental model of ureteral obstruction in Wistar albino rats. Untreated group (n = 20) received no treatment. For the lisinopril-treated group (n = 20), 20 mg/kg/day of drug was given orally. Ultrastructural diVerences were analyzed using electron microscopic technique; apoptotic distribution was analyzed using the TUNEL method. After electron microscopic evaluation, on the 4th and 14th day in the untreated group, edema in the glomeruli, loss of microvillus and apoptotic cells in proximal tubule cells and sclerosis in the glomeruli were detected. On the 4th day in the lisinopril-treated group, the kidney was ultrastructurally normal and a less number of apoptotic cells were only observed on the 14th day. On light microscopic examination on the 4th and 14th day in the untreated group, while the glomeruli were normal in structure, the boundary of the proximal tubule was disrupted and some picnotic cells in both the proximal and collecting tubules were observed. In both 4th and 14th day of the lisinopril-treated group, kidney showed normal structure, although in some places picnotic cells in the collecting tubules were observed. In conclusion, lisinopril was eVective and it may prevent early renal damage in the direct obstruction model. © Springer-Verlag 2011.Item Analysis of transferred keratinocyte-like cells derived from mouse embryonic stem cells on experimental surgical skin wounds of mouse(2013) Vatansever H.S.; Uluer E.T.; Aydede H.; Ozbilgin M.K.Autologous/allogenic skin grafts constituted from differentiated adult or embryonic stem cells can be used in treatment of skin disorders. In our study we aimed to differentiate keratinocytes from mouse embryonic stem cells and the transfer of viable keratinocyte-like cells to a model of surgical skin wound of mouse. Embryoid bodies, derived from mouse embryonic stem cells, were cultured on basement membrane matrix with added BMP-4 for 10 days. The identification of differentiated keratinocyte-like cells was done by detection of cytokeratin-8 and cytokeratin-14 localization using an indirect immunoperoxidase technique and transmission electron microscopy evaluation. Distribution of BrdU, cytokeratin-8 and cytokeratin-14 were evaluated using an indirect immunoperoxidase technique from the experimental (dressing including BrdU labelled cells applied after the surgical wound was created on mouse), control (only the surgical wound was created on mouse) and sham (only the dressing applied after the surgical wound was created on mouse) in groups after 3, 5 and 7 days. Immunohistochemically and ultrastructurally, cells derived from mouse embryonic stem cells were similar to differentiated keratinocyte-like cells. Differentiated keratinocyte-like cells were demonstrated by positive BrdU, cytokeratin-8 and cytokeratin-14 staining after transfer to the wound area. In the experimental group wound healing was better after transferring differentiated keratinocytes when compared to the sham and control groups. In vivo continuity and usability of derived cells are very important issues. In wound repair mechanisms, keratinocyte-like cells could provide positive effects during the wound healing and could be used in clinical treatments of wound repair process. © 2012 Elsevier GmbH.Item The role of hypoxia related angiogenesis in uterine smooth muscle tumors(Informa Healthcare, 2015) Uluer E.T.; Inan S.; Ozbilgin K.; Karaca F.; Dicle N.; Sanci M.Mechanisms of hypoxia-related angiogenesis are important for uterine smooth muscle tumors. Factors that are related to angiogenesis during hypoxia include vascular endothelial growth factor (VEGF), hypoxia inducible factor 1α (HIF1α), T-cell intracellular antigen1 (TIA1), eukaryotic translation initiation factor 2α (eIF2α) and thrombospondin 1 (TSP1). We investigated immunoreactivities of VEGF, HIF1α, TIA1, eIF2α and TSP1 using an indirect immunoperoxidase method for formalin fi xed, paraffi n embedded tumors that had been diagnosed as leiomyoma (LMY), cellular leiomyoma (CLM) or leiomyosarcoma (LMS). TSP1 immunoreactivity was scored as moderate, mild or minimal, while VEGF, eIF2α and TIA1 immunoreactivities were scored as mild, moderate and strong in LMY, CLM and LMS samples, respectively. HIF1α immunoreactivity was scored as mild to minimal in LMY, CLM and LMS samples, but showed no statistically signifi cant differences among samples. Although angiogenic factors showed strong immunohistochemical staining intensity in LMS, anti-angiogenic factors showed minimal immunohistochemical intensity. There was no difference in HIF-1α immunoreactivity compared to LMY, CLM and LMS samples. We suggest that HIF1α protein synthesis could be suppressed by eIF2α and TIA1. Furthermore, VEGF could be activated by pathways such as COX2, Ras, NF-κB or c-myc instead of HIF1α. Angiogenesis could trigger and accelerate tumor development; therefore, anti-angiogenic therapy could be useful for treatment of tumors. © 2014 The Biological Stain Commission.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 POMC expression of the urothelium of the urinary bladder of mice submitted to pelvic radiation(SAGE Publications Inc., 2016) Ozbilgin M.K.; Aktas C.; Temel M.; Önal T.; Uluer E.T.; Vatansever H.S.; Kurtman C.Objective: Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder injury. The acute changes that the urothelium undergo after radiation are known, but the healing mechanism of the urothelium of the urinary bladder after pelvic radiotherapy is not clearly understood. Proopiomelanocortin (POMC) peptides, which have immunomodulatory effects, are produced locally in sites outside of the central nervous system. This study aims to determine the role of POMC expression in the urothelium during radiation injury. Methods: Twenty-four male Swiss Albino mice were divided into four groups. A single-fractioned 10 Gy of ionizing radiation was applied to the pelvic zone of all mice with Cobalt-60 radiotherapy. The first group 1, which consisted intact animal and not irradiated was the control group, and the second, third, and fourth groups were euthanized after 24 h (Group 2), 48 h (Group 3), and 7 days (Group 4) after irradiation. All bladders were prepared for histochemical analysis using hematoxylin eosin (H&E) and immunohistochemical analysis using anti-POMC antibody. Results: No morphological differences were seen in all the group samples stained with H&E. POMC expression of the urothelium of bladder tissue samples shows different staining levels. Group 1 (96.7 ± 7.68), Group 2 (88.3 ± 8.04), and Group 3 (85.10 ± 10.9) were very weakly stained, but the POMC immunoreactivity of Group 4 (113.0 ± 12.8) was observed to be strong. Conclusion: Expression of POMC from urothelium seems to prevent bladder damage from radiation supplying differentiation and restoration of the urothelium. © 2016 The Author(s).Item Effects of cyclooxygenase on the urothelium of the urinary bladder of mice exposed to pelvic radiation(Science Printers and Publishers Inc., 2016) Ozbilgin M.K.; Onal T.; Ozcan C.; Temel M.; Aktas C.; Gareveran M.S.; Uluer E.T.; Inan S.; Kurtman C.OBJECTIVE: To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. STUDY DESIGN: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. RESULTS: In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation ex-posed groups than in the normal control group (group 1) (p<0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p<0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p<0.005). CONCLUSION: COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radi-ation, supplying differentiation and restoration of the urothelium. © Science Printers and Publishers, Inc.Item Influence of radiation exposure during radiotherapy: Evidence for the increase of versican and heparin-binding EGF-like growth factor concentrations(Science Printers and Publishers Inc., 2016) Ozbilgin M.K.; Aktas C.; Uluer E.T.; Buyukuysal M.C.; Gareveran M.S.; Kurtman C.OBJECTIVE: To investigate the reaction of versican and heparin-binding EGF-like growth factor (HB-EGF) molecule concentrations to acute radiation exposure in normal bladder and rectal tissue samples in order to gain more insight into the effects of cancer radiotherapy. STUDY DESIGN: Four groups with 6 male adult Swiss Albino mice per group were investigated. The mice bladder and rectum tissue samples were subjected to a 10-Gy single-dose radiation exposure in the pelvic region with a Co-60 teletherapy device and investigated 1, 2, and 7 days after radiation exposure, with 1 reference group which was not exposed to radiation. RESULTS: In the immunohistochemical examination of the tissue samples with anti-versican and anti-HB-EGF primary antibodies was observed a statistically significant increase 7 days after radiation exposure. CONCLUSION: The observed increase of versican and HB-EGF concentrations in the normal tissue matrix after radiation exposure may play a role in the side effects of radiotherapy. © Science Printers and Publishers, Inc.Item Role of proopiomelanocortin in preventing miscarriage(Journal of Reproductive Medicine, Inc., 2017) Ozbilgin K.; Kahraman B.; Atay C.; Vatansever S.; Uluer E.T.; Özçakır T.OBJECTIVE: To compare the distribution of proopiomelanocortin (POMC) in decidua and placenta samples from missed abortion and voluntary termination cases in order to research the effects in the etiology of missed abortion. STUDY DESIGN: Decidual materials were collected from patients who were diagnosed with missed abortion (n=19) and legal voluntary termination cases (n=15) under 10 gestational weeks. Materials were divided into 2 groups for examination. For all samples, POMC primary anti body was performed by immunohistochemical staining. The number of stained cells was calculated by using the Hscore technique. RESULTS: In the missed abortion group the mean age was 28.7 (18–41), and in the control group the mean age was 27.5 (21–37). POMC immunoreactivity was determined to be lower in the parenchyma and placenta of the missed abortion group than those of the control group. POMC immunoreactivities were found to be higher in both the syncytiotrophoblast and cytotrophoblast cells of the missed abortion group than those of the control group (p<0.005). CONCLUSION: POMC has become a paradigmatic polypeptide precursor and has a role in the parturition process. Local production of POMC in placenta and decidua may influence pregnancy and may have a role in missed abortion pathogenesis. © Journal of Reproductive Medicine®, Inc.Item A Study on the Anticarcinogenic Effects of Calcium Fructoborate(Humana Press Inc., 2017) Tepedelen B.E.; Korkmaz M.; Tatlisumak E.; Uluer E.T.; Ölmez E.; Değerli İ.; Soya E.; İnan S.Evidences about the preventive and therapeutic effects of boron compounds on cancer have been increasing in the last years. Although calcium fructoborate (CaFB) is used as a nutritional supplement, data about its preventive and therapeutic effects on neoplastic transformations are limited. In the present study, the various concentrations of CaFB were applied to the MDA-MB-231 metastatic breast cancer cell line. First, we examined the cytotoxic effect and IC50 value of CaFB by MTT assay. For the evaluation of the DNA damage, apoptosis and metastatic potential, expression levels of ATM, pATM, PARP, p53, p-p53, caspase-3, caspase-9, and VEGF were investigated by using immunoblotting and immunohistochemical methods. Cell viability was significantly reduced at 50 μM CaFB treatment. pATM, p-p53, and caspase-9 levels increased significantly in all groups; furthermore, there was approximately 12.5-, 2.4-, and 10.7-fold increase, respectively, for 100 μM CaFB treatment. ATM and p53 levels did not change with CaFB treatment, but PARP levels significantly 2.5-fold decreased. While VEGF immunoreactivity decreased in all groups, significant increase in caspase-3 immunoreactivity was observed only in the group treated with 50 μM CaFB (p < 0,001). Our results imply that CaFB may have therapeutic potential as well as preventive benefits in cancer. © 2016, Springer Science+Business Media New York.Item Role of Bone Marrow-Derived Stem Cells in Wound Healing(Wiley Blackwell, 2018) Kurt F.O.; Vatansever H.S.; Uluer E.T.Wound healing is a complex process and some conditions such as diabetes is difficult to treat. In these conditions external cell support is required where mesenchymal stem cells can be functional and useful. One of the main sources for these cells is bone marrow. These cells can be separated from hematopoietic precursors by adhesive properties where they can proliferate, differentiate, and expand for clinical use. Their effect on wound healing depends on their interaction with other cells, in which their production of cytokine and growth factors play an important role during the healing process, especially for immune modulation. In this review, the effect of stem cells on wound healing with cell interaction, regulation of the matrix, and adhesion with secretion of cells will be discussed in order to understand the mechanisms used by these cells to achieve a better quality of life for the patient suffering from a non-healing wound. © 2018 John Wiley & Sons, Inc. All rights reserved.Item Wound Healing and Microenvironment(Wiley Blackwell, 2018) Uluer E.T.; Vatansever H.S.; Kurt F.O.The wound healing process includes activation of signaling pathways that work together to restore a tissue microenvironment consisting of cells and extracellular matrix (ECM) with enzymes, cytokines, and growth factors. Wound healing consists of a dynamic process including various overlapping stages that include hemostasis and inflammation, cell proliferation, and maturation together with remodeling. In this chapter, we focus on wound healing types and the importance of the microenvironment. We then discuss the mechanism of wound healing and the interactions between molecules, cells, and extracellular matrix in the microenvironment during wound healing. © 2018 John Wiley & Sons, Inc. All rights reserved.Item May zonula occludens proteins regulate the pathogenesis of allergic rhinitis?(Istanbul University Press, 2019) Yılmaz Ö.; Kanık E.T.; Pınar E.; Türkeli A.; Uluer E.T.; İnan S.; Yüksel H.Objectives: This study aims to investigate the expression pattern of zonula occludens (ZO) proteins, namely occludin, claudin-1, tricellulin, junctional adhesion molecules (JAM), and ZO-1,-2, and-3 in nasal mucosal biopsies of individuals with and without allergic sensitization. Patients and Methods: Between August 2011 and August 2012, a total of 69 patients (38 males, 31 females; mean age 28.0 years, range, 18 to 61 years) who underwent surgery for nasal septum deviation were included in this cross-sectional study. All patients underwent skin prick test with environmental allergen mixtures. Cup forceps biopsy samples were obtained from the inferior turbinate during septoplasty. These samples were stained immunohistochemically for occludin, claudin-1, tricellulin, JAM, and ZOs. Staining intensity was graded semi-quantitatively using the H-Score. Results: Of all patients, 14 were atopic. Occludin, claudin-1, and JAM scores were significantly lower in the mucosal samples from atopic patients, compared to the non-atopic patients (median 142.5 vs. 288, 153 vs. 296, and 156 vs. 312, respectively; p<0.001 for all). The ZO-1,-2, and-3 proteins were significantly lower in atopic patients (p<0.001 for all). The tricellulin, located at the intersection of three epithelial cells, was not significantly different between the two groups (208.5 vs. 195, respectively; p=0.686). Conclusion: Expression of the structural proteins of ZO decreases in the upper airways of asymptomatic atopic patients. These findings indicate that ZO may be an important determinant of atopic sensitization and, therefore, may be a potential target in the treatment of allergic rhinitis. © 2019 Behbut Cevanşir Otorhinolaryngology-Head and Neck Surgery Society. All rights reserved.Item Keratinocytes derived from embryonic stem cells induce wound healing in mice(Taylor and Francis Ltd, 2019) Uluer E.T.; Vatansever H.S.; Aydede H.; Ozbilgin M.K.The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson’s trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages. © 2018, © 2018 The Biological Stain Commission.Item Investigation of the effects of rapamycin on the mTOR pathway and apoptosis in metastatic and non-metastatic human breast cancer cell lines(Comenius University, 2020) Ekizceli G.; Uluer E.T.; Inan S.AIM: The aim of this study was to analyze the effects of rapamycin treatment on apoptosis via mTOR pathway in metastatic and non-metastatic human breast cancer cell lines by immunohistochemical and TUNEL analysis. METHOD: MCF-7 and MDA-MB 231 cell lines were incubated under standard conditions forming Rapamycin and control groups. In immunohistochemical evaluation; mTOR pathway was evaluated with anti-IGF1, anti-PI3K, anti-pAKT1/2/3, anti-mTORC1, anti-mTORC2 and anti-ERK1 antibodies. The effect of apoptosis was also confi rmed by TUNEL method. RESULTS: In this study, activation of PI3K/AKT/mTOR and related molecular pathways in the MDA-MB 231 and MCF-7 breast cancer cell line was evaluated and it was observed that these pathways could play a key role in cancer development. Increased apoptotic cells were observed in mTORC1 inhibition by Rapamycin administration. CONCLUSION: Targeting the mTOR pathway in breast cancer treatment may be a treatment option. In addition, the demonstration and confi rmation of increased apoptosis in Rapamycin treated groups suggested that Rapamycin, an inhibitor of mTOR, is promising in the treatment of breast cancer (Tab. 2, Fig. 3, Ref. 66). © 2020, Comenius University.Item Adjuvant effects of chemotherapeutics and metformin on MFE-319 endometrial carcinoma cell line(Editura Academiei Romane, 2020) Aydemir I.; Uluer E.T.; Korkmaz O.; Tuglu M.I.; Inan S.We aimed to investigate the cytotoxicity of Metformin, Cisplatin, and Paclitaxel on MFE-319 endometrial carcinoma cell line using 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry assays. Half maximal inhibitory concentration (IC50) doses of three drugs alone and in the dual combinations were applied to the cells. Immunocytochemical method was performed for the cell survival and for phosphatidylinositol 3-kinase (PI3K), phosphorylated extracellular regulated kinases (pErk)-1/2, Akt-1, phosphorylated Akt (pAkt)-1/2/3 cell growth markers and angiogenic vascular endothelial growth factor (VEGF). Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was found that these drugs caused a decrease in the immunoreactivities of these markers. Particularly, dual combination of Paclitaxel and Cisplatin decreased the immunoreactivities of PI3K, pErk-1/2, Akt-1, and pAkt-1/2/3. Cisplatin and Paclitaxel were more effective than Metformin; on the other hand, Metformin has been shown to enhance the efficacy of these two drugs. In vitro or in vivo further studies are needed to investigate the efficacy of these three drugs via PI3K/Akt signal pathway. © 2020, Editura Academiei Romane. All rights reserved.Item Do Wortmannin and Thalidomide induce apoptosis by autophagy inhibition in 4T1 breast cancer cells in vitro and in vivo?(E-Century Publishing Corporation, 2021) Uluer E.T.; Sonmez P.K.; Akogullari D.; Onal M.; Tanriover G.; Inan S.The aim of this study was to show the effects of autophagy inhibitor Wortmannin and antiangiogenic-proapoptotic Thalidomide on autophagy and apoptosis markers in 4T1 breast cancer cells in vitro and in vivo. The half-maximal inhibitory concentration (IC50) values of 4T1 cells for Wortmannin and Thalidomide were evaluated by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. After cancer formation in 28 BALB/C female mice, drugs were administered for seven days. Cells and tissue sections were evaluated for anti-phosphoinositide 3-kinase (PI3K), anti- the microtubule-associated protein 1 light chain3 (MAPLC3β), anti-caspase 8, anti-caspase 9, and anti-caspase 3 immunoreactivities by immunohistochemical staining and apoptosis by Terminal Transferase dUTP Nick End Labeling (TUNEL) assay. Both PI3K and MAPLC3β immunoreactivities decreased in all treatments when compared to control group except Thalidomide treatment in primary cancer tissue. The caspase 3, 8, and 9 immunoreactivities were increased in all treatment groups and TUNEL positive cells were the highest in the Wortmannin and Thalidomide group. Our findings suggest that autophagy is an important mechanism for 4T1 cells and both Wortmannin and Thalidomide treatments inhibit autophagy and induce apoptosis. In primary cancer tissues, autophagy was not effective as in vitro. The treatment of Wortmannin and Thalidomide increased the apoptotic cells in vivo independent from autophagy inhibition. Different results may be because of microenvironment. Further studies must be done to elucidate the effect of microenvironment. © 2021 E-Century Publishing Corporation. All rights reserved.Item Investigation of Ototoxicity of Intratympanic 5-fluorouracil in Rats(Istanbul University Press, 2022) Çevikkan M.D.; Aslan A.; Uluer E.T.; Taş D.D.Objective: Although 5-fluorouracil is beneficial in treating cholesteatoma in people, it is unknown if this drug harms the inner ear. We are planning to contribute to the literature by investigating the effects of the intratympanic administration of 5-fluorouracil solution form to the middle ear on the inner ear in rats. Materials and Methods: The study was conducted on 11 Wistar albino male rats: a positive control group was treated with amikacin, a study group was treated with 5-FU, and a negative control group received no treatment. One week after intratympanic drug administration, the rats were sacrificed, and ototoxicity was histopathologically examined by light microscopy and TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling) method. Results: There was a significant difference between the two groups treated with amikacin and 5-fluorouracil in terms of apoptosis (p<0.05). The difference in stria vascularis thicknesses was significant between the amikacin group and the 5-fluorouracil group and the negative control group (p<0.05). Conclusion: The intratympanic administration of 5-fluorouracil to rats did not have any ototoxic effects, according to the results of the histological analysis that looked at apoptosis. © 2022, Istanbul University Press. All rights reserved.Item Continuous and intermittent parathyroid hormone administration promotes osteogenic differentiation and activity of programmable cells of monocytic origin(Taylor and Francis Ltd., 2022) Kir M.C.; Onal M.O.; Uluer E.T.; Ulman C.; Inan S.Bone healing deficiencies are challenging for orthopedic practice. The use of stem cells with scaffolds to treat bone tissue losses currently is popular for promoting regeneration of tissue. Programmable cells of monocytic origin (PCMO) may differentiate into three germ layers and may be a promising alternative treatment due to their stem cell-like properties. Parathyroid hormone (PTH) participates in bone metabolism. Intermittent administration of PTH promotes osteogenic activity of mesenchymal stem cdells (MSC). We investigated the osteogenic effects of continuous and intermittent administration of PTH on PCMO. Mononuclear cells were harvested from the peripheral blood of healthy donors. Isolated cells were cultured for six days in a de-differentiation medium. Indirect immunocytochemistry using anti-CD14, anti-CD45 and anti-CD90 primary antibodies, as well as electron microscopy were used to detect PCMO. PCMO then were cultured in an osteogenic differentiation medium supplemented with continuous or intermittent 50 ng/ml PTH. The PTH-free control group (CG), intermittent PTH treated group (IPG) and continuous PTH treated group (CPG) were cultured and assessed for their differentiation into osteogenic lineage cells by indirect immunocytochemistry using anti-collagen I, anti-osteonectin and anti-osteocalcin primary antibodies. Osteoblast-like cells obtained by continuous or intermittent PTH administration exhibited increased levels of collagen I, osteonectin and osteocalcin immunoreactivity. We found that continuous and intermittent PTH administration to PCMO enhanced their differentiation to osteogenic lineage cells and increased osteoblastic activity. © 2022 The Biological Stain Commission.