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  • Küçük Resim
    Öğe
    Chloroquine used in combination with chemotherapy synergistically suppresses growth and angiogenesis in vitro and in vivo
    (Int Inst Anticancer Research, 2018) Gürel-Gürevin, Ebru; Kıyan, Hülya Tuba; Esener, Osman Behzat Burak; Aydınlık, Şeyma; Üvez, Ayça; Ulukaya, Engin; Dimas, Konstantinos; Armutak, Elif İlkay
    Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. Materials and Methods: The cytotoxic effect of doxorubicin (0.1-1 mu M), chloroquine (0.25-32 ,mu M) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 mu g/pellet) and chloroquine (15 mu g/pellet), their combination, and standards (50 mu g/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Results: The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (+/-)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay. Conclusion: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.
  • Küçük Resim
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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.