Kültürlerarası iletişim: Makedonya'da yaşayan Türkler ve Makedonlar arasındaki iletişim

Tez (yüksek lisans) - Anadolu ÜniversitesiAnadolu Üniversitesi, Sosyal Bilimler Enstitüsü, Basın ve Yayın Anabilim DalıKayıt no: 433747Kültürlerarası etkileşimi anlamak için, iki veya daha fazla kültür arasındaki ilişki, aralarındaki iyi niyet veya çatışmalar, kültürlerin kendisi ve varsa sürdürdükleri iletişim incelenmelidir. Bu çalışmasının konusunu, Makedonya'da yaşayan Makedonlar ve Türkler arasındaki kültürlerarası iletişim oluşturmaktadır. Türk azınlık (Makedonya Türkleri) ve Makedonya Cumhuriyeti topraklarında yaşayan Makedon halk arasında varolan durumun belirlenmesi amacıyla, söz konusu insanların kültürel özellikleri, kimliği, kültürlerarası yaşam, daha da özelde kültürlerarası iletişim araştırılıp çözümlenmiştir. Çalışmada, veri toplama yöntemi olarak derinlemesine görüşmeler yapılmıştır. Görüşmeler, Makedonya'nın başkenti Üsküp'te yaşayan 10 Türk (5 kadın/ 5 erkek) ve 10 Makedon (5 kadın/ 5 erkek) ile gerçekleştirilmiştir. Her katılımcıya toplam 19 adet soru sorulmuştur. İlk 9 soru, iki kültürün genel kültürel karakteristiklerini araştırmak ve belirtmek için hem Türklere hem de Makedonlara aynı şekilde sorulmuştur. Sonraki 10 soru ise, Makedonların ve Makedonya'da yaşayan Türklerin kimlik özelliklerini, aidiyet ve kabullenme duygularını, ortak veya ayrışan sembolleri, gelenekleri ve yaşam tarzlarını tanımlamak için her bir gruba farklı olacak biçimde yöneltilmiştir. Ayrıca, toplam 19 sorudan her biri, Makedonlar ve Türkler arasında gerçekleştirilen kültürlerarası iletişimi daha iyi anlayabilmek için katkı sağlamıştır. Sonuçlara göre, Makedon ve Türk kültürlerinin yakın hatta benzer olduğu anlaşılmıştır. Bu toplumlar, sadece aynı topraklarda yaşamamaktadırlar, aynı ve benzer yaşam tarzıları, kültürleri, algıları, tutumları ve değerleri paylaşmaktadırlar. İkisi de özgür duyumsamakta, özgürce davranmakta, yaşamı aynı şekilde algılamaktadır. Makedonya'da iki kültürün aynı derecede güçlü ve belli bir kimliğe sahip olduğu, hiçbirinin kendini azınlık ya da çoğunluk olarak görmediği anlaşılmaktadır. Birlikte entegre olmaları dolayısıyla kültürel kimliklerinin de birbirine uyumlu olduğu ortaya çıkmıştır

Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy

The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1. Patients and methods: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured. Results: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events. Conclusions: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice

The Place of Chemotherapy in The Evolving Treatment Landscape for Patients With HR-positive/HER2-negative MBC

Endocrine therapy (ET) for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR-positive/HER2-negative) metastatic breast cancer (MBC) has changed markedly over recent years with the emergence of new ETs and the use of molecularly targeted agents. Cytotoxic chemotherapy continues, however, to have an important role in these patients and it is important to maximize its efficacy while minimizing toxicity to optimize outcomes. This review examines current HR-positive/HER2-negative MBC clinical guidelines and addresses key questions around the use of chemotherapy in the face of emerging therapeutic options. Specifically, the indications for chemotherapy in patients with HR-positive/HER2-negative MBC and the choice of optimal chemotherapy are discussed

Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial

Background. The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after >= 2 lines of treatment. Methods. Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort

Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts

Both of the sphingosine kinase (SK) subtypes SK-1 and SK-2 catalyze the production of the bioactive lipid molecule sphingosine 1-phosphate (S1P). However, the subtype-specific cellular functions are largely unknown. In this study, we investigated the cellular function of SK-2 in primary mouse renal mesangial cells (mMC) and embryonic fibroblasts (MEF) from wild-type C57BL/6 or SK-2 knockout (SK2ko) mice. We found that SK2ko cells displayed a significantly higher proliferative and migratory activity when compared to wild-type cells, with concomitant increased cellular activities of the classical extracellular signal regulated kinase (ERK) and PI3K/Akt cascades, and of the small G protein RhoA. Furthermore, we detected an upregulation of SK-1 protein and S1P3 receptor mRNA expression in SK-2ko cells. The MEK inhibitor U0126 and the S1P1/3 receptor antagonist VPC23019 blocked the increased migration of SK-2ko cells. Additionally, S1P3ko mesangial cells showed a reduced proliferative behavior and reduced migration rate upon S1P stimulation, suggesting a crucial involvement of the S1P3 receptor. In summary, our data demonstrate that SK-2 exerts suppressive effects on cell growth and migration in renal mesangial cells and fibroblasts, and that therapeutic targeting of SKs for treating proliferative diseases requires subtype-selective inhibitors

A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine

Background: Capecitabine and eribulin are widely used as single agents in metastatic breast cancer (MBC) and have nonoverlapping toxicities. Methods: In phase 1b (dose escalation), patients with advanced, treatment-refractory, solid tumours received eribulin mesilate intravenously in 21-day cycles according to schedule 1 (day 1) or schedule 2 (days 1, 8) with twice-daily oral capecitabine (1000 mg/m² days 1–14). In phase 2 (dose confirmation), women with advanced/MBC and ≤3 prior chemotherapies received eribulin mesilate at the maximum tolerated dose (MTD) per the preferred schedule plus capecitabine. Primary objectives were MTD and dose-limiting toxicities (DLTs; phase 1b) and objective response rate (ORR; phase 2). Secondary objectives included progression-free survival (PFS), safety, and pharmacokinetics. Results: DLTs occurred in 4/19 patients (schedule 1) and 2/15 patients (schedule 2). Eribulin pharmacokinetics were dose proportional, irrespective of schedule or capecitabine coadministration. The MTD of eribulin was 1.6 mg/m² day 1 for schedule 1 and 1.4 mg/m² days 1 and 8 for schedule 2. ORR in phase 2 (eribulin 1.4 mg/m² days 1, 8 plus capecitabine) was 43% and median PFS 7.2 months. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and lethargy. Conclusions: The combination of capecitabine and eribulin showed promising efficacy with manageable tolerability in patients with MBC

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY

Purpose The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data. Methods The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC. Results Of 563 patients screened, 256 (gBRCAm, n  = 253; sBRCAm, n  = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up. Conclusion The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC. Clinical trial registration Clinical trials registration number: NCT03286842AstraZenecahttp://dx.doi.org/10.13039/100004325Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US