Browsing by Author "Çakar B."

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    Cytotoxic and apoptotic effects of trabectedin on breast cancer stem cells; [Trabektedinin meme kanseri kök hücreleri üzerindeki sitotoksik ve apoptotik etkileri]
    (Turkiye Klinikleri, 2019) Atmaca İlhan H.; Çakar B.; İşseven M.; Karaca B.
    Objective: In this study, effect of trabectedin (ET743, Yondelis®) was investigated on the viability of MCF-7 cells and CD44+/CD24- breast cancer stem cells. Material and Methods: CD44+/CD24- breast cancer stem cells were isolated from MCF-7 cells by using flow cytometry. XTT test was used to investigate the effect of trabectedin on the viability of MCF-7 and CD44+/ CD24- breast cancer stem cells. Apoptotic effect of trabectedin was investigated by measuring DNA fragmentation and changes in mitochondrial membrane potential were determined by tetram-ethylrhodamine ethyl ester (TMRE) staining. Results: Trabectedin inhibited the cell viability of both MCF-7 breast cancer and CD44+/CD24- breast cancer stem cells in a concentration and time dependent manner. IC50 concentrations at 48 h was calculated as 4.52±0.7 nM for MCF-7 cells and 1.23±1.2 nM for CD44+/CD24- cells. It was found that breast cancer stem cells were more sensitive to trabectedin than MCF-7 cancer cells. Cells in control group were stained with fluorescent TMRE stain but the staining was less in the both cell groups that were treated with the IC50 concentrations of trabectedin. It was shown that trabectedin induced more apoptotic cells in CD44+/CD24- breast cancer stem cells. Conclusion: According to the current data, it was shown that trabectedin induced cytotoxicity and apoptosis in breast cancer stem cells as well as MCF-7 cancer cells in a concentration and time dependent manner. These data indicates that trabectedin might be a potential therapeutic for breast cancer. However, more detailed studies investigating the effects of trabectedin on breast cancer stem cells are needed. © 2019 by Türkiye Klinikleri.
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    Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab
    (Springer Japan, 2021) Tural D.; Ölmez Ö.F.; Sümbül A.T.; Özhan N.; Çakar B.; Köstek O.; Ekenel M.; Erman M.; Coşkun H.Ş.; Selçukbiricik F.; Keskin Ö.; Türköz F.P.; Oruç K.; Bayram S.; Bilgetekin İ.; Yıldız B.; Şendur M.A.N.; Paksoy N.; Dirican A.; Erdem D.; Selam M.; Tanrıverdi Ö.; Paydaş S.; Urakçı Z.; Atağ E.; Güncan S.; Ürün Y.; Alkan A.; Kaya A.O.; Özyükseler D.T.; Taşkaynatan H.; Yıldırım M.; Sönmez M.; Başoğlu T.; Gündüz Ş.; Kılıçkap S.; Artaç M.
    Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120–4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031–4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer. © 2021, Japan Society of Clinical Oncology.
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    Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences
    (Elsevier B.V., 2021) Tural D.; Ölmez Ö.F.; Sümbül A.T.; Artaç M.; Özhan N.; Akar E.; Çakar B.; Köstek O.; Ekenel M.; Erman M.; Coşkun H.Ş.; Selçukbiricik F.; Keskin Ö.; Türköz F.P.; Oruç K.; Bayram S.; Yılmaz U.; Bilgetekin İ.; Yıldız B.; Şendur M.A.N.; Paksoy N.; Dirican A.; Erdem D.; Selam M.; Tanrıverdi Ö.; Paydaş S.; Urakçı Z.; Atağ E.; Güncan S.; Ürün Y.; Alkan A.; Kaya A.O.; Özyükseler D.T.; Taşkaynatan H.; Yıldırım M.; Sönmez M.; Başoğlu T.; Gündüz Ş.; Kılıçkap S.
    Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47–28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25–5.49) and 9.8 mo (95% CI, 6.7–12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3–4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. © 2020 European Association of Urology
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    Thymoquinone glucuronide conjugated magnetic nanoparticle for bimo-dal imaging and treatment of cancer as a novel theranostic platform
    (Bentham Science Publishers, 2021) İnce İ.; Müftüler Z.B.; Medine E.İ.; Güldü Ö.K.; Takan G.; Ergönül A.; Parlak Y.; Yıldırım Y.; Çakar B.; Bilgin E.S.; Aras Ö.; Göker E.; Ünak P.
    Background: Theranostic oncology combines therapy and diagnosis and is a new field of medicine that specifically targets the disease by using targeted molecules to destroy the cancer-ous cells without damaging the surrounding healthy tissues. Objective: We aimed to develop a tool that exploits enzymatic TQ release from glucuronide (G) for the imaging and treatment of lung cancer. We added magnetic nanoparticles (MNP) to enable magnetic hyperthermia and MRI, as well as 131I to enable SPECT imaging and radionuclide thera-py. Methods: A glucuronide derivative of thymoquinone (TQG) was enzymatically synthesized and conjugated with the synthesized MNP and then radioiodinated with 131I. New Zealand white rab-bits were used in SPECT and MRI studies, while tumor modeling studies were performed on 6–7-week-old nude mice utilized with bioluminescence imaging. Results: Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectra confirmed the expected structures of TQG. The dimensions of nanoparticles were below 10 nm and they had rather polyhedral shapes. Nanoparticles were radioiodinated with 131I with over 95% yield. In imaging studies, in xenograft models, tumor volume was significantly reduced in TQGMNP-treated mice but not in non-treated mice. Among mice treated intravenously with TQGMNP, xenograft tumor models disappeared after 10 and 15 days, respectively. Conclusion: Our findings suggest that TQGMNP in solid, semi-solid and liquid formulations can be developed using different radiolabeling nuclides for applications in multimodality imaging (SPECT and MRI). By altering the characteristics of radionuclides, TQGMNP may ultimately be used not only for diagnosis but also for the treatment of various cancers as an in vitro diagnostic kit for the diagnosis of beta glucuronidase-rich cancers. © 2021 Bentham Science Publishers.
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    The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study
    (Springer, 2024) Yıldırım H.Ç.; Kutlu Y.; Mutlu E.; Aykan M.B.; Korkmaz M.; Yalçın S.; Şakalar T.; Celayir Ö.M.; Kayıkçıoğlu E.; Aslan F.; Hafızoğlu E.; Altıntaş Y.E.; Keskinkılıç M.; Chalabiyev E.; Çelebi A.; Dursun B.; Kapar C.; Özen M.; Acar Ö.; Dülgar Ö.; Kut E.; Biter S.; Kus F.; Almuradova E.; Erdoğan A.P.; Saray S.; Güven D.C.; Şimşek E.T.; Üskent N.; Kemal Y.; Çakar B.; Açıkgöz Ö.; Kılıçkap S.; Aksoy S.
    Introduction: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 −) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. Methods: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. Results: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92–27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70–37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51–37.42) vs 28.33 months (95% CI 14.77–41.88), respectively, p = 0.211). No new adverse events were reported. Discussion: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 − metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population. © The Author(s) under exclusive licence to Japan Society of Clinical Oncology 2024.