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Öğe The anticancer potential of chlorine dioxide in small-cell lung cancer cells(CUREUS INC, 2022) Yıldız, Salih Zeki; Bilir, Cemil; Eskiler, Gamze Güney; Bilir, FilizBackground Chlorine dioxide (ClO2) is an effective disinfectant consisting of oxygen, chloride, and potassium. Because of its high oxidative capacity, ClO2 exerts antimicrobial, antiviral, and antifungal effects. However, its anticancer effects remain to be elucidated. Methodology The anticancer activity of ClO2 was assessed on DMS114 small-cell lung cancer (SCLC) cells and human umbilical vein endothelial cells (HUVEC) as control by WST-1, Annexin V, cell cycle analysis, and acridine orange staining. We for the first time investigated the possible therapeutic effects of long-term stabilized ClO2 solution (LTSCD). Results Our preliminary findings showed that LTSCD significantly inhibited the proliferation of SCLC cells (p < 0.01) with less toxicity in HUVEC cells. Additionally, LTSCD induced apoptotic cell death in SCLC cells through nuclear blehhing and vacuolar formation. However, LTSCD treatment did not induce cell cycle arrest in both cell lines. Conclusions LTSCD can be a therapeutic potential for the treatment of SCLC. However, further investigations are required to assess the LTSCD-induced cell death in SCLC both in vitro and in vivo.Öğe By 2022, cancer is now a more chronic disease with chronic difficulties to go along with It(Turkiye Klinikleri, 2022) Sümbül, Ahmet Taner; Sedef, Ali Murat; Karaçin, Cengiz; Bilir, Cemil; Akagündüz, BaranCancer is a disease in which some body cells with genetic or epigenetic changes become capable of replicating and invading other regions of the body uncontrollably. Numerous functional abilities and features are acquired by these cells during this multistage neo¬plastic process. In the last 20 years, many agents have been discovered and used in the fight against cancer. However, the use of these drugs in appropriate patient groups is still a serious problem. Many cancer types are on the way to becoming chronic diseases; conscientious physi¬cians who are unable to provide appropriate treatment due to economic factors and other reasons face an additional burden. © 2022 by Turkish Society of Medical Oncology.Öğe By 2022, cancer is now a nore chronic disease with chronic difficulties to go along with It(Turkiye Klinikleri, 2022) Sümbül, Ahmet Taner; Sedef, Ali Murat; Karaçin, Cengiz; Bilir, Cemil; Akagündüz, BaranCancer is a disease in which some body cells with genetic or epigenetic changes become capable of replicating and invading other regions of the body uncontrollably. Numerous functional abilities and features are acquired by these cells during this multistage neoplastic process. In the last 20 years, many agents have been discovered and used in the fight against cancer. However, the use of these drugs in appropriate patient groups is still a serious problem. Many cancer types are on the way to becoming chronic diseases; conscientious physicians who are unable to provide appropriate treatment due to economic factors and other reasons face an additional burden.Öğe Determinants of Cancer-Related Online Information-Seeking Intentions of Cancer Patients Receiving Chemotherapy(2023) Eskiler, Ersin; Bilir, Cemil; Altunışık, RemziObjective: In this research, we aimed to determine the factors affecting cancer patients' intention to seek cancer-related information online. Materials and Methods: The research was carried out in the context of the cross-section approach and relational survey model among the general survey models. Data were collected by a face-to-face survey from people treated at Sakarya University Faculty of Medicine, Oncology Department between April and November 2021. Total of 240 people voluntarily participated in the research, including 140 females (Age:47.10±10.78) and 100 males (Age:53.88±13.58) diagnosed with cancer in the 18-84 age range (Age:49.93±12.45). Results: As a result of the stepwise regression analysis, the factors of attitude, ISA, and ISQ had a statistically significant positive effect on the patient's intention to search for health information on the Internet, whereas facilitating conditions did not have a statistically significant effect. Conclusion: It is anticipated that the research results will provide guidance for understanding and successfully managing the information-seeking behaviours of cancer patients.Öğe Effect of the MiR-99b and MiR-135b on peritoneal carcinomatosis and liver metastasis in colorectal cancer(Elsevier Espana, 2023) Aziret, Mehmet; Eskiler, Gamze Guney; Cakar, Gozde Cakirsoy; Ozkan, Asuman Deveci; Ercan, Metin; Bilir, Cemil; Polat, ErdalAim: This study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. Materials and methods: Changes in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. Results: The expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues < 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p < 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p = 0.045, p = 0.006, and p = 0.012, respectively). Conclusion: While the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.Öğe The efficacy of indoximod upon stimulation with pro-inflammatory cytokines in triple-negative breast cancer cells(Taylor & Francis Online, 2021) Guney Eskiler, Gamze; Bilir, CemilBackground: Indoleamine 2,3-dioxygenase (IDO) inhibition has received much attention in cancer immunotherapy due to its role in immune escape in cancer cells. Additionally, changes in the pro-inflammatory cytokine levels can affect tumor growth and metastasis as well as the effectiveness of immunotherapy. The purpose of this study was for the first time to determine the effects of indoximod as an IDO inhibitor on triple-negative breast cancer (TNBC) and to assess the link between the efficacy of indoximod and IFN-? or TNF-? stimulation. Methods: The cytotoxic and apoptotic effects of indoximod alone or IFN-? or TNF-? induction to mimic an inflammatory environment were evaluated by WST-1, Annexin V, cell cycle analysis, and acridine orange (AO)/ethidium bromide (EtBr) staining. Furthermore, the expression levels of IDO1 and PD-L1 expression were analyzed by RT-PCR. Results: Our results demonstrated that indoximod significantly decreased the TNBC cell viability through apoptotic cell death (p < .05). The combination of indoximod and TNF-? was more effective than indoximod and IFN-? stimulation or indoximod alone in TNBC cells. Additionally, PD-L1 expression level was significantly up-regulated after treatment with indoximod and TNF-? or IFN-? combinations (p < .05). Conclusions: Indoximod exhibited a therapeutic potential in TNBC cells and pro-inflammatory cytokines could affect the effectiveness of indoximod. However, further studies are required to identify the role of the IDO-associated signaling pathways, the molecular mechanisms of indoximod induced apoptotic cell death, and the relationship between IDO inhibition by IDO inhibitors and pro-inflammatory cytokine levels.Öğe Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro(Elsevier, 2022) Güney Eskiler, Gamze; Deveci Özkan, Asuman; Hacıefendi, Ayten; Bilir, CemilThe therapeutic effects of abemaciclib (ABE), an inhibitor of cyclin- dependent kinases (CDK) 4/6, on the proliferation of two types of prostate cancer (PC) cells were revealed. In this study, in vitro cytotoxic and apoptotic effects of ABE on metastatic castration-resistant prostate cancer (mCRPC) androgen receptor (AR) negative PC-3 and AR mutant LNCaP PC cells were analyzed with WST-1, Annexin V, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential, RT-PCR, western blot, and apoptosis protein array. ABE considerably inhibited the growth of PC cells in a dose-dependent manner (p<0.01) and caused significant apoptotic cell death through the suppression of CDK4/6-Cyclin D complex, ROS generation and depolarization of mitochondria membrane potential. However, PC-3 cells were more sensitive to ABE than LNCaP cells. Furthermore, the expression levels of several pro-apoptotic and cell cycle regulatory proteins were upregulated by ABE in especially PC-3 cells with the downregulation of apoptotic inhibitor proteins. Our results suggest that ABE inhibits PC cell growth and promotes apoptosis and thus ABE treatment may be a promising treatment strategy in especially mCRPC. Further preclinical and clinical studies should be performed to clarify the clinical use of ABE for the treatment of PC.Öğe The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy(Springer Science and Business Media Deutschland GmbH, 2022) Güney Eskiler, Gamze; Kazan, Nur; Hacıefendi, Ayten; Deveci Özkan, Asuman; Özdemir, Kayhan; Özen, Miraç; Koçer, Havva Belma; Yılmaz, Fahri; Kaleli, Süleyman; Şahin, Elvan; Bilir, CemilPurpose: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. Methods: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. Results: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. Conclusion: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.
