Fakülteler / Faculties
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Item Copy Number Variations Of Stepwise-Selected Doxorubicin-Resistant Mcf-7 Cell Lines(GENE, 2025-02) Acinan, Irem Sinem; Kazan, Hasan Huseyin; Kandemir, Basak; Karahan, Ceyhan Piril; Kayhan, Guelsuem); Iseri, Ozlem DarcansoyElimination of cytotoxic effect in cells with multidrug resistance (MDR) phenotype is a situation that is gradually acquired over time and develops through multiple pathways resulting in global phenotypic changes of cells. Although molecular background of the resistance phenotype has widely been studied in the gene expression level, segmental and gene copy number variations (CNVs) have limitedly been documented. Thus, in the present study, we aimed to analyze the CNVs using DNA microarray in the sensitive and two doxorubicin-resistant MCF-7 breast cancer cell lines which had different resistance indices. In the present study, we performed conventional karyotyping and array comparative genomic hybridization (aCGH). Then, results of aCGH data were studied with genomic profiling, comparison analysis and ideogram plotting to evaluate genomic profiles, and the loss and gains of heterozygosity profiles. Next, gene lists for each cell line were compared with the 66-breast cancer- related genes and the multidrug resistance-related genes. aCGH analyses showed that CNV profiles and the copy number of specific genes were dramatically different between these three cell lines. Totally, 6212, 6558, and 11,201 genes were found to be altered in MCF-7, MCF-7/400DOX, and MCF-7/1000DOX genomes, respectively. Amongst the MCF-7/1000DOX had the highest number of altered genes, and doxorubicin resistance may cause differential chromosomal changes depending on the resistance status. DNA microarray would be one of the informative methods used in the studies on the cancer drug resistance in addition to transcriptomic and proteomic level high throughput analysis to define molecular mechanisms of the resistance status.Item Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients with Stage IV Non-Small Cell Lung Cancer Previously Treated with Radical Chemoradiation Therapy(2015) Topkan, Erkan; Yildirim, Berna Akkus; Guler, Ozan Cem; Parlak, Cem; Pehlivan, Berrin; Selek, Ugur; 0000-0001-8120-7123; 0000-0001-6170-0383; 0000-0001-6661-4185; 0000-0001-6908-3412; 0000-0001-8087-3140; 25752391; AAG-2213-2021; B-3671-2014; V-5717-2017; AAC-5654-2020; O-5474-2014Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a >= 2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P < .001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P < .001), absence of anemia (P = .001), and fewer metastatic sites (1-2; P < .001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans. (C) 2015 Elsevier Inc.Item Potential for Tumor Volume and Site in Prediction of the Outcomes in Recurrent or Second Primary Head and Neck Cancers(2018) Yildirim, Berna Akkus; Topkan, Erkan; 0000-0001-6661-4185; 0000-0001-8120-7123; 30012532; V-5717-2017; AAG-2213-2021Item Prevalence of Endometrial Cancer or Atypical Hyperplasia Diagnosed Incidentally in Infertility Clinic(2018) Tohma, Yusuf Aytac; Zeyneloglu, Hulusi Bulent; Aslan, Oner Deniz; Haberal, Asuman Nihan; Onalan, Gogsen; Ayhan, Ali; 0000-0001-9418-4733; 0000-0002-0289-2642; 0000-0003-0386-7614; 0000-0001-9852-9911; 30118694; AAE-6482-2021; B-6487-2009; AAK-4587-2021; GZG-9810-2022; AAJ-5802-2021Item Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated With Radical Concurrent Chemoradiation Therapy(2018) Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A.; Guler, Ozan C.; Ciner, Fuat; Besen, A. A.; Findikcioglu, Alper; Ozyilkan, Ozgur; https://orcid.org/0000-0001-8120-7123; https://orcid.org/0000-0002-2218-2074; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-7862-0192; https://orcid.org/0000-0001-8825-4918; 29887509; AAG-2213-2021; AAG-5629-2021; V-5717-2017; AAC-5654-2020; AAD-6910-2021; AFT-2303-2022; AAD-2817-2021Purpose: To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT). Methods and Materials: Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors. Results: Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P < .001), weight loss >5% (20.9% vs 7.1%; P < .001), and hemoptysis (27.1% vs 6.4%; P <. 001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P > .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P < .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss > 5% (P < .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P < .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P < .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P < .001 for each of these covariates), and PFS (P < .001 for each of these covariates), respectively. Conclusions: Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT. (C) 2018 Elsevier Inc. All rights reserved.Item Postchemoradiotherapy Neutrophil-to-Lymphocyte Ratio Predicts Distant Metastasis and Survival Results in Locally Advanced Pancreatic Cancers(2022) Topkan, Erkan; Selek, Ugur; Haksoyler, Veysel; Kucuk, Ahmet; Durankus, Nulifer Kilic; Sezen, Duygu; Bolukbasi, Yasemin; Pehlivan, Berrin; https://orcid.org/0000-0001-8120-7123; 35685603; AAG-2213-2021Background and Objectives. In the absence of similar research, we endeavored to investigate the prognostic usefulness of posttreatment neutrophil-to-lymphocyte ratio (NLR) in patients treated with definitive concurrent chemoradiotherapy (CCRT) for locally advanced pancreatic adenocarcinoma (LAPAC). Materials and Methods. Our retrospective research included a sum of 126 LAPAC patients who received CCRT. The NLR was calculated for each patient based on the complete blood count test results obtained on the last day of the CCRT. The availability of optimal cutoff(s) that might dichotomize the whole cohort into two groups with significantly different clinical outcomes was searched using receiver operating characteristic (ROC) curve analysis. Primary and secondary endpoints were the potential association between the post-CCRT NLR measures and distant metastasis-free survival (DMFS) and overall survival (OS) outcomes. Results. The median follow-up duration was 14.7 months (range: 2.4-94.5). The median and 3-year OS and DMFS rates for the whole group were 15.3 months (95% confidence interval: 12.4-18.2) and 14.5%, and 8.7 months (95% CI: 6.7-10.7) and 6.3% separately. The ROC curve analysis findings separated the patients into two groups on a rounded NLR cutoff of 3.1 (area under the curve (AUC): 75.4%; sensitivity: 74.2%; specificity: 73.9%) for OS and DMFS: NLR < 3.1 (N = 62) and NLR >= 3.1 (N = 64), respectively. Comparisons between the NLR groups displayed that the median OS (11.4 vs. 21.4 months; P < 0.001) and DMFS (6.0 vs. 16.0 months; P < 0.001) lengths were significantly shorter in the NLR >= 3.1 group than its NLR < 3.1 counterparts, as well as the 3-year actuarial DM rate (79.7% vs. 50.0%; P=0.003). The N1-2 nodal stage, CA 19-9 > 90 U/mL, and NLR > 3.1 were found to be independent predictors of poor prognosis in the multivariate analysis. Conclusion. The present study found that the posttreatment NLR >= 3.1 was independently linked with a higher risk of DM and subsequent degraded survival outcomes in unresectable LAPAC patients managed with exclusive CCRT.Item Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol(2020) Topkan, Erkan; Kucuk, Ahmet; Ozdemir, Yurday; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezen, Duygu; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-7862-0192; 0000-0001-8120-7123; 0000-0002-2218-2074; 0000-0002-1932-9784; 33274245; AAD-6910-2021; AAG-2213-2021; AAG-5629-2021; M-9530-2014Objectives. We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. Methods. The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI=NeutrophilsxMonocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. Results. The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI <= 1.78 (N=96) and SIRI>1.78 (N=85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI <= 1.78 cohort had altogether significantly superior median PFS (16.2 versus 6.6 months; P<0.001) and OS (22.9 versus 12.2 months; P<0.001) than its SIRI>1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (P<0.001) and OS (P<0.001) durations, respectively. Conclusions. Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.Item The Influence of Systemic Inflammation Response Index on Survival Outcomes of Limited-Stage Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy(2020) Kucuk, Ahmet; Ozkan, Emine Elif; Eskici Oztep, Sukran; Mertsoylu, Huseyin; Pehlivan, Berrin; Selek, Ugur; Topkan, Erkan; 0000-0002-1932-9784; 0000-0001-8120-7123; 33381177; M-9530-2014; AAG-2213-2021Background. Recent studies have indicated that the systemic inflammation response index (SIRI) can efficiently predict survival outcomes in various tumor types. Thusly, in absence of comparable investigations in limited-stage small-cell lung cancers (LS-SCLCs), we aimed to retrospectively evaluate the prognostic utility of SIRI in LS-SCLC patients treated with concurrent chemoradiotherapy (CRT). Patients and Methods. Present multi-institutional retrospective analysis incorporated LS-SCLC patients treated with CRT at three academic radiation oncology centers between January 2007 and December 2018. The SIRI was calculated by using the peripheral blood neutrophil (N), monocyte (M), and lymphocyte (L) counts acquired in the last <= 7 days before the commencement of the CRT: SIRI = N x M/L. Accessibility of pretreatment SIRI cutoff that may stratify the study population into two gatherings with distinctive overall survival (OS) results was evaluated by utilizing the receiver operating characteristic (ROC) curve analysis. Primary objective was the association between the SIRI values and the OS results. Results. Search for the availability of an ideal SIRI cutoff that may stratify the entire patients' population into two particular groups with distinctive OS outcomes identified the 1.93 value (area under the curve (AUC): 72.9%; sensitivity: 74.6%; specificity: 70.1%): Group 1: SIRI <1.93 (N = 71) and Group 2: SIRI >= 1.93 (N = 110), respectively. At a median follow-up of 17.9 (95% CI: 13.2-22.6) months, 47 (26.0%) patients were still alive (47.9% for SIRI p<0.001). Kaplan-Meier comparisons between the two SIRI groups showed that the SIRI <1.93 cohort had significantly longer median OS (40.5 versus 14.2 months; p<0.001) than the SIRI >= 1.93 cohort. Similarly, the 3- (54% versus 12.6%) and 5-year (33% versus 9.9%) OS rates were also numerically superior in the SIRI Conclusions. The results of this retrospective multi-institutional cohort analysis suggested that a pre-CRT SIRI was a strong and independent prognostic biomarker that reliably stratified LS-SCLC patients into two cohorts with significantly different OS outcomes.Item Oncological outcome of surgical management in patients with recurrent uterine cancer-a multicenter retrospective cohort study-CEEGOG EX01 Trial(2019) Dursun, Polat; 31064862Objectives To assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome. Methods A retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up. Results The median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; p<0.001). The site of recurrence did not significantly influence survival in cervical or in endometrial cancer. Cancer stage at first diagnosis, tumor grade, lymph node status at recurrence, progression-free interval after first diagnosis, and free resection margins were associated with improved overall survival on univariate analysis. On multivariate analysis, the stage at first diagnosis and resection margins were significant independent predictive parameters of an improved oncologic outcome. Conclusion Long-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection.Item Prognostic significance of lymphovascular space invasion in low-risk endometrial cancer(2019) Ayhan, Ali; Sahin, Hanifi; Sari, Mustafa Erkan; Yalcin, Ibrahim; Haberal, Ali; Meydanli, Mehmet Mutlu; 30665899Objective The purpose of this study was to assess the prognostic significance of lymphovascular space invasion in women with low-risk endometrial cancer. Methods A dual-institutional, retrospective department database review was performed to identify patients with 'low-risk endometrial cancer' (patients having <50% myometrial invasion with grade 1 or 2 endometrioid endometrial cancer according to their final pathology reports) at two gynecologic oncology centers in Ankara, Turkey. Demographic, clinicopathological and survival data were collected. Results We identified 912 women with low-risk endometrial cancer; 53 patients (5.8%) had lymphovascular space invasion. When compared with lymphovascular space invasion-negative patients, lymphovascular space invasion-positive patients were more likely to have post-operative grade 2 disease (p<0.001), deeper myometrial invasion (p=0.003), and larger tumor size (p=0.005). Patients with lymphovascular space invasion were more likely to receive adjuvant therapy when compared with lymphovascular space invasion-negative women (11/53 vs 12/859, respectively; p<0.001). The 5-year recurrence-free survival rate for lymphovascular space invasion-positive women was 85.5% compared with 97.0% for lymphovascular space invasion-negative women (p<0.001). The 5-year overall survival rate for lymphovascular space invasion-positive women was significantly lower than that of lymphovascular space invasion-negative women (88.2% vs 98.5%, respectively; p<0.001). Age >= 60 years (HR 3.13, 95% CI 1.13 to 8.63; p=0.02) and positive lymphovascular space invasion status (HR 6.68, 95% CI 1.60 to 27.88; p=0.009) were identified as independent prognostic factors for decreased overall survival. Conclusions Age >= 60 years and positive lymphovascular space invasion status appear to be important prognostic parameters in patients with low-risk endometrial cancer who have undergone complete surgical staging procedures including pelvic and para-aortic lymphadenectomy. Lymphovascular space invasion seems to be associated with an adverse prognosis in women with low-risk endometrial cancer; this merits further assessment on a larger scale with standardization of the lymphovascular space invasion in terms of presence/absence and quantity.