Browsing by Author "Yildirim, N"
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Item Investigation of cytotoxic and apoptotic effects of disodium pentaborate decahydrate on ovarian cancer cells and assessment of gene profilingGunel, NS; Yildirim, N; Ozates, NP; Oktay, LM; Bagca, BG; Sogutlu, F; Ozsaran, A; Korkmaz, M; Avci, CBAfter revealing the anti-cancer properties of boron, which is included in the category of essential elements for human health by the World Health Organization, the therapeutic potential of boron compounds has been begun to be evaluated, and its molecular effect mechanisms have still been among the research subjects. In ovarian cancer, mutations or amplifications frequently occur in the PI3K/Akt/mTOR pathway components, and dysregulation of this pathway is shown among the causes of treatment failure. In the present study, it was aimed to investigate the anti-cancer properties of boron-containing DPD in SKOV3 cells, which is an epithelial ovarian cancer model, through PI3K/AKT/mTOR pathway. The cytotoxic activity of DPD in SKOV3 cells was evaluated by WST-1 test, apoptotic effect by Annexin V and JC-1 test. The gene expressions associated with PI3K/AKT/mTOR pathway were determined by real-time qRT-PCR. In SKOV3 cells, the IC50 value of DPD was found to be 6.7 mM, 5.6 mM, and 5.2 mM at 24th, 48th and 72nd hour, respectively. Compared with the untreated control group, DPD treatment was found to induce apoptosis 2.6-fold and increase mitochondrial membrane depolarization 4.5-fold. DPD treatment was found to downregulate PIK3CA, PIK3CG, AKT2, IGF1, IRS1, MAPK3, HIF-1, VEGFC, CAB39, CAB39L, STRADB, PRKAB2, PRKAG3, TELO2, RICTOR, MLST8, and EIF4B genes and upregulate TP53, GSK3B, FKBP8, TSC2, ULK1, and ULK2 genes. These results draw attention to the therapeutic potential of DPD, which is frequently exposed in daily life, in epithelial ovarian cancer and show that it can be a candidate compound in combination with chemotherapeutics.Item Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy (vol 23, 136, 2023)Karacin, C; Oksuzoglu, B; Demirci, A; Keskinkiliç, M; Baytemür, NK; Yilmaz, F; Selvi, O; Erdem, D; Avsar, E; Paksoy, N; Demir, N; Göksu, SS; Türker, S; Bayram, E; Çelebi, A; Yilmaz, H; Kuzu, ÖF; Kahraman, S; Gökmen, I; Sakin, A; Alkan, A; Nayir, E; Ugrakli, M; Acar, Ö; Ertürk, I; Demir, H; Aslan, F; Sönmez, Ö; Korkmaz, T; Celayir, ÖM; Karadag, I; Kayikçioglu, E; Sakalar, T; Öktem, IN; Eren, T; Erul, E; Mocan, EE; Kalkan, Z; Yildirim, N; Ergün, Y; Akagündüz, B; Karakaya, S; Kut, E; Teker, F; Demirel, BÇ; Karaboyun, K; Almuradova, E; Ünal, OÜ; Oyman, A; Isik, D; Okutur, K; Öztosun, B; Gülbagci, BB; Kalender, ME; Sahin, E; Seyyar, M; Özdemir, Ö; Selçukbiricik, F; Kanitez, M; Dede, I; Gümüs, M; Gökmen, E; Yaren, A; Menekse, S; Ebinç, S; Aksoy, S; Imamoglu, GI; Altinbas, M; Çetin, B; Uluç, BO; Er, Ö; Karadurmus, N; Erdogan, AP; Artaç, M; Tanriverdi, Ö; Çiçin, I; Sendur, MAN; Oktay, E; Bayoglu, IV; Paydas, S; Aydiner, A; Salim, DK; Geredeli, Ç; Yavuzsen, T; Dogan, M; Hacibekiroglu, IItem Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapyKaracin, C; Oksuzoglu, B; Demirci, A; Keskinkiliç, M; Baytemür, NK; Yilmaz, F; Selvi, O; Erdem, D; Avsar, E; Paksoy, N; Demir, N; Göksu, SS; Türker, S; Bayram, E; Çelebi, A; Yilmaz, H; Kuzu, ÖF; Kahraman, S; Gökmen, I; Sakin, A; Alkan, A; Nayir, E; Ugrakli, M; Acar, Ö; Ertürk, I; Demir, H; Aslan, F; Sönmez, Ö; Korkmaz, T; Celayir, ÖM; Karadag, I; Kayikçioglu, E; Sakalar, T; Öktem, IN; Eren, T; Urul, E; Mocan, EE; Kalkan, Z; Yildirim, N; Ergün, Y; Akagündüz, B; Karakaya, S; Kut, E; Teker, F; Demirel, BÇ; Karaboyun, K; Almuradova, E; Ünal, OÜ; Oyman, A; Isik, D; Okutur, K; Öztosun, B; Gülbagci, BB; Kalender, ME; Sahin, E; Seyyar, M; Özdemir, Ö; Selçukbiricik, F; Kanitez, M; Dede, I; Gümüs, M; Gökmen, E; Yaren, A; Menekse, S; Ebinç, S; Aksoy, S; Imamoglu, GI; Altinbas, M; Çetin, B; Uluç, BO; Er, Ö; Karadurmus, N; Erdogan, AP; Artaç, M; Tanriverdi, Ö; Çiçin, I; Sendur, MAN; Oktay, E; Bayoglu, IV; Paydas, S; Aydiner, A; Salim, DK; Geredeli, Ç; Yavuzsen, T; Dogan, M; Hacibekiroglu, IBackground There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.Item Asthma-chronic obstructive pulmonary disease overlap: Results from a national-multicenter studyÇelik, GE; Aydin, O; Sen, E; Demir, T; Gemicioglu, B; Kiyan, E; Mungan, D; Kivilcim Oguzülgen, I; Polatli, M; Göksel, Ö; Sayiner, A; Yildirim, N; Yildiz, F; Yorgancioglu, A; Elhan, AH; Yildiz, Ö; Basyigit, I; Börekçi, S; Havlucu, Y; Okumus, G; Türk, M; Saryal, SIntroduction: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have a greater disease burden than those with COPD or asthma alone. In this study, it was aimed to determine the prevalence, risk factors, and clinical features of ACO because there are limited national data in T & uuml;rkiye. Materials and Methods: The study was conducted in a cross-sectional design in nine tertiary-care hospitals. The patients followed with a diagnosis of asthma or COPD for at least one year were enrolled in the study. The frequency of ACO and the characteristics of the patients were evaluated in the asthma and COPD groups Results: The study included 408 subjects (F/M= 205/203, mean age= 56.24 +/- 11.85 years). The overall prevalence of ACO in both groups was 20.8% (n= 85). The frequency was higher in the COPD group than in the asthma group (n= 55; 33.3% vs. n= 22; 9.8%), respectively (p= 0.001). Patients with ACO had similarities to patients with COPD in terms of advanced age, sex, smoking, exposure to biomass during childhood, being born in rural areas, and radio-logic features. Characteristics such as a history of childhood asthma and allergic rhinitis, presence of chronic sinusitis, NSAID hypersensitivity, atopy, and high eosinophil counts were similar to those of patients with asthma (p< 0.001). The annual decline in FEV1 was more prominent in the ACO group (mean= -250 mL) than in the asthma (mean change= -60 mL) and COPD (mean change= -230 mL) groups (p= 0.003). Conclusion: This study showed that ACO was common among patients with asthma and COPD in tertiary care clinics in our country. ACO should be considered in patients with asthma and COPD who exhibit the above mentioned symptomsItem Asthma-COPD overlap syndromeSen, E; Oguzülgen, K; Bavbek, S; Günen, H; Kiyan, E; Türktas, H; Yorgancioglu, A; Polatli, M; Yildiz, F; Çelik, G; Demir, T; Gemicioglu, B; Mungan, D; Saryal, S; Sayiner, A; Yildirim, NAsthma and chronic obstructive pulmonary disease (COPD) are common lung diseases characterized by chronic airway inflammation and airway obstruction. Among patient with COPD and asthma; there is a group of patients with an overlap between clinical, functional characteristics and airway inflammation patterns, named Asthma-COPD Overlap Syndrome (ACOS). ACOS is a syndrome characterized by reversible but persistant airflow limitation (postbronchodilator FEV1/FVC < 70%) which has some features of both asthma and COPD. ACOS should be suspected in a patient > 40 years, with smoking history, previous asthma diagnosis or history of childhood asthma who has persistant airflow limitation and reversible ariway obstruction (defined by an increase of > % 12 of FEV1 pred or increase of FEV1 > 200 mL after inhalation of 400 mcg salbutamol or 1000 mcg terbutaline). The prevalence for ACOS has been reported 11-55% in different case series to date and increases by age and is more frequent in females in different age groups. Patients with ACOS are younger than COPD patients and older than asthma patients. Frequent and severe exacerbations and related hospitalization and emergency room visits are common in ACOS and this causes an impaired quality of life. Current recommendations of guidelines for pharmacologic treatment of ACOS have been composed of a combination with optimal COPD and asthma treatment. Future therapeutic approaches should be based on endotypes. Clinical phenotype and underlying endotype driven clinical studies may be the base of ACOS guidelines.Item Acute exacerbation in COPD and asthmaYildirim, N; Demir, T; Gemicioglu, B; Kiyan, E; Oguzülgen, K; Polatli, M; Saryal, S; Sayiner, A; Yorgancioglu, A; Bavbek, S; Çelik, GE; Günen, H; Mungan, D; Sen, E; Türktas, H; Yildiz, FChronic obstructive pulmonary disease (COPD) and asthma are airway diseases with acute exacerbations. Natural course of both disease are affected by exacerbations. COPD exacerbations may be caused by infections and other causes; indoor and outdoor pollution, cardiovascular diseases, asthma-COPD overlap syndrome, COPD-obstructive sleep apnea syndrome, pulmonary embolism, gastro-oesophageal reflux, anxiety-depression, pulmonary hypertension. Exposure to triggering factors, viral infections, treatment insufficiency may cause asthma exacerbations. Smoking cessations, prevention of infections, long-acting anticholinergics, long-acting beta 2 agonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, mucolytics, prophilactic antibiotics can be effective on the prevention of COPD exacerbations. Asthma exacerbations may be decreased by the avoidance of allergens, viral infections, occupational exposures, airpollution, treatment of comorbid diseases. Effective treatment of asthma is required to prevent asthma exacerbations. Inhaled steroids and combined treatments are the most effective preventive therapy for exacerbations. Patient education and cooperation is an element of the preventive measures for asthma attacks. Compliance to therapy, inhalation techniques, written asthma plans are required. The essential of COPD and asthma exacerbation treatment is bronchodilator therapy. Steroids are also implemented to the therapy, targeting the inflammation. Specific treatments of the cause (infection, airpollution, pulmonary embolism etc.) should be administered.Item Treatment of Severe Asthma: Expert OpinionTürktas, H; Bavbek, S; Çelik, G; Demir, T; Gemicioglu, B; Günen, H; Kiyan, E; Mungan, D; Oguzulgen, IK; Polatli, M; Saryal, S; Sayiner, A; Sen, E; Yildirim, N; Yildiz, F; Yorgancioglu, ASevere asthmatics account 10% of the all asthmatic population. Those asthmatics whose disease is inadequately controlled account for up to half of the cost for asthma, because they have more emergency room visits, more hospital admission and greater absenteeism from work. New therapeutic options were tried in those patients whose asthma was uncontrolled with standart high dose inhaled corticosteroid and long acting beta-2 agonsit combination therapy. In this paper taking into account the conditions of our country, current literature was reviewed and treatment options was discussed and graded recommendations are made for daily clinical practice in patients with severe treatment-refractory asthma.Item Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG studyBeypinar, I; Demir, H; Yaslikaya, S; Köseci, T; Demir, B; Çolak, G; Agaoglu, AB; Sahbazlar, M; Sanci, PC; Cabuk, D; Isik, U; Sahin, E; Coskun, A; Caner, B; Aykut, T; Artac, M; Duygulu, ME; Sever, N; Öksüz, S; Turan, N; Aykan, MB; Tüzün, EK; Uysal, M; Ugurlu, I; Sakin, A; Acar, C; Özaskin, D; Sakalar, T; Keskinkilic, M; Yavuzsen, T; Köse, N; Ertürk, I; Yildirim, N; Balçik, OY; Alkan, A; Selvi, O; Ercin, E; Ünal, OU; Karaçin, CPurpose In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. Method The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. Results One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. Conclusion This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.Item The prognostic impact of Her2 status in early triple negative breast cancer: a Turkish Oncology Group (TOG) studyÖzyurt, N; Alkan, A; Gülbagci, B; Seyyar, M; Aydin, E; Sahbazlar, M; Türker, M; Kinikoglu, O; Yerlikaya, T; Dinç, G; Aytaç, A; Kalkan, Z; Ebinç, S; Gültürk, I; Keskinkiliç, M; Isleyen, ZS; Çaglayan, D; Türkel, A; Aydin, E; Sakalar, T; Sekmek, S; Yildirim, N; Koçak, S; Okutur, K; Özveren, A; Dursun, B; Kitapli, S; Eren, OÖ; Beypinar, I; Hacibekiroglu, I; Çabuk, D; Karaman, E; Acar, Ö; Paydas, S; Eryilmaz, MK; Demir, B; Oruç, Z; Yilmaz, M; Biricik, FS; Salim, DK; Tanriverdi, Ö; Dogan, MThe studies evaluating the impact of Her2 levels in neoadjuvant setting have conflicting data. The aim of the study was to evaluate the prognostic impact of Her2 status in early triple negative breast cancer(TNBC). In the study TNBC patients who were treated with neoadjuvant chemotherapy (NAC) and surgery were analyzed retrospectively. The primary aim of the study was to analyze the impact of Her2 status(Her2-0 and Her2-low) on pathological complete response (pCR). The secondary objectives were disease free survival (DFS) and overall survival (OS). 620 female triple negative breast cancer patients were evaluated. 427 patients (68.9%) had Her2-0 and 193(31.1%) had her2-low pathology. The pCR rates were similar between Her2-0 and Her2-low patients (33.0% vs. 27.5%, p = 0.098). Although Her2-0 group has better DFS (106 vs. 50 months, p = 0.002), in multivariate analysis it had a HR of 0.74 (p = 0.06). In addition, OS was similar (131 vs. 105 months, p = 0.13) with a HR of 0.88 (p = 0.61). In multivariate analysis; presence of LVI (HR:2.2 (95% CI 1.1-3.5) p = 0.001), Clinical stage T1/T2 (HR:0.39 (95% CI 0.2-0.6) p < 0.001) and lymph node negativity (HR:0.35 (95% CI 0.1-0.9) p = 0.03) were independent factors for OS. Although there were pathological and clinical differences, the pCR, DFS and OS were similar between Her2-0 and Her2-low TNBC patients. The importance of Her2 status of TNBC in neoadjuvant setting should be further studied.Item Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) studyYildirim, HC; Kapar, C; Koksal, B; Seyyar, M; Sanci, PC; Guliyev, M; Perkin, P; Buyukkor, M; Yaslikaya, S; Majidova, N; Keskinkilic, M; Ozaskin, D; Avci, T; Gunes, TK; Arcagok, M; Topal, A; Keskin, GSY; Kavgaci, G; Yildirim, N; Celayir, OM; Avci, N; Aslan, F; Alkan, A; Erciyestepe, M; Cengiz, M; Pehlivan, M; Gulmez, A; Beypinar, I; Tuylu, TB; Kayikcioglu, E; Chalabiyev, E; Turhal, S; Guzel, HG; Ayas, E; Sahbazlar, M; Dulgar, O; Demir, H; Yavuzsen, T; Bayoglu, V; Salim, DK; Ozturk, B; Ozdemir, F; Kara, O; Oksuzoglu, B; Bal, O; Demirci, NS; Yilmaz, M; Cabuk, D; Aksoy, SThe only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.