Yazar "Develi, Elif Sedef" seçeneğine göre listele

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    Evidence for heterogeneity in response to treatment in mammary tumors of dogs as happens in humans
    (NCI CPTAC Assay Portal, 2022) Turna, Özge; Üvez, Ayça; Baykal, Aslıhan; Develi, Elif Sedef; Dıramalı, Murat; Sönmez, Kıvılcım; Karakaş, Didem; Kaşıkçı, Güven; Armutak, Elif İlkay; Ulukaya, Engin
    Tumors are formed by various clones developed over a long time. This gives rise to a heterogeneous nature. This heterogeneity is the hardest challenge in the treatment of cancers because it is the main reason for drug resistance. This is a well-known fact in human cancer. Therefore, we have reasoned that if the tumor heterogeneity in canine mammary gland tumors (CMGTs) could be shown by an ex vivo assay, which will be used first time in veterinary oncology practice, this could be used further in clinics. To achieve this, twenty-six patients were included in the study. Tumor tissues were obtained from animals during routine surgery. Tumor cells were isolated and seeded ex vivo. The cells were exposed to anticancer drugs that are clinically used. Seven days after the treatment, chemosensitivity has luminometrically been assayed by ATP-tumor chemosensitivity assay (ATP-TCA). It has clearly been shown that all the tumor tissues have responded to treatment differently, implying that heterogeneity exists in mammary tumors. There has also been found that there was a weak to moderate statistically significant correlation between tumor size and drug index. However, there has been no correlation between drug index and metastasis to lymph nodes. Hyperplasic areas had relatively higher PCNA values. The results of our study demonstrate the heterogeneity in responses to in vitro drugs. Clinical trials based on test results and follow-up studies with large numbers of animals are needed to prove that such chemotherapeutic activity assessment tests can be clinically useful in predicting drug responses in CMGTs.
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    Protoflavone-chalcone hybrids exhibit enhanced antitumor action through modulating redox balance, depolarizing the mitochondrial membrane, and inhibiting ATR-dependent signaling
    (Mdpi, 2020) Latif, Ahmed Dhahir; Jernei, Tamas; Podolski-Renic, Ana; Kuo, Ching-Ying; Vagvolgyi, Mate; Girst, Gabor; Zupko, Istvan; Develi, Elif Sedef; Ulukaya, Engin; Wang, Hui-Chun; Pesic, Milica; Csampai, Antal; Hunyadi, Attila
    Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC(50)values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou-Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.
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    Yeni protoflavon bazlı hibrid bileşiklerin meme kanseri hücre soylarında sitotoksik/apoptotik etkilerinin araştırılması
    (İstinye Üniversitesi / Sağlık Bilimleri Enstitüsü, 2019) Develi, Elif Sedef
    Meme kanseri, kadınlar arasında en sık görülen kanser olup, her yıl 2,1 milyon kadını etkilemektedir, kadınlarda kansere bağlı ölümlerde önde gelen nedenler arasındadır. 2018'de 627.000 kadının meme kanserinden öldüğü tahmin edilmektedir ki bu kadınlarda tüm kanser ölümlerinin yaklaşık % 15'idir. Tedavisinde yeni yaklaşımlara rağmen etkin bir başarı sağlanamamaktadır. Bu tez çalışması kapsamında; dört yeni hibrid protoflavon bileşiğin MCF-7 ve MDA-MB-231 hücre hatları üzerinde anti-kanser etkileri incelenecektir. MCF-7 hücre hattı ER? -pozitif meme kanseri için temsili model olarak ve MDA-MB-231 hücre hattı üçlü negatif meme kanseri (TNBC) için model olarak kullanılacaktır