PubMed Kapalı Erişimli Yayınlar
Permanent URI for this collectionhttps://hdl.handle.net/11727/10764
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Item Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study(2022) Ak, Guntulu; Metintas, Selma; Taskin, Ayse Naz; Sener, Melahat Uzel; Soyler, Yasemin; Yilmaz, Meltem; Turna, Akif; Kabalak, Pinar Akin; Bilaceroglu, Semra; Koksal, Deniz; Demirci, Nilgun Yilmaz; Sogukpinar, Ozlem; Boga, Sibel; Ercelik, Merve; Karadeniz, Gulistan; Polat, Gulru; Guldaval, Filiz; Akturk, Ulku Aka; Yilmaz, Senay; Ogan, Nalan; Yilmaz, Saliha; Esendagli, Dorina; Caglayan, Benan; Zeybek, Arife; Kocak, Nagihan Durmus; Mutlu, Pinar; Baytemir, Cansel Atinkaya; Mutlu, Pinar; Baytemir, Cansel Atinkaya; Sarbay, Ismail; Yilmaz, Ulku; Metintas, Muzaffer; 36173482Purpose The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. Methods This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. Results The mean age +/- SD of the 777 patients was 62.0 +/- 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). Conclusion The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.Item Small Cell Lung Cancer Stem Cells Display Mesenchymal Properties And Exploit Immune Checkpoint Pathways In Activated Cytotoxic T Lymphocytes(2021) Kursunel, M. Alper; Taskiran, Ekim Z.; Tavukcuoglu, Ece; Yanik, Hamdullah; Demirag, Funda; Karaosmanoglu, Beren; Ozbay, Feyza Gul; Uner, Aysegul; Esendagli, Dorina; 0000-0002-6619-2952; 34228218; ABF-9398-2020Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44(+)CD90(+) CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8(+) cytotoxic T lymphocytes (CTL) responses. The interaction between CD44(+)CD90(+) CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44(+) SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-gamma expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44(+)CD90(+) CSC-like cells. Moreover, especially through IFN-gamma secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-gamma-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .