Fakülteler / Faculties
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Item The Clinicopathological and Prognostic Significance of CD24, CD44, CD133, ALDH1 Expressions in Invasive Ductal Carcinoma of The Breast CD44/CD24 Expression in Breast Cancer(2015) Kapucuoglu, Nilgun; Bozkurt, Kemal Kursat; Baspinar, Sirin; Kocer, Murat; Eroglu, Hasan Erol; Akdeniz, Rasit; Akcil, Mehtap; 26298632Background: Recently, there are several studies about cancer stem cells (CSC), indicating that they are the cells that initiate the tumor, provide progression, metastasis and responsible for the aggressive tumor behavior. Materials and methods: The purpose of this study is to investigate the expressions of CD24, CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma. Their relationships with clinicopathologic parameters, such as tumor grade, lymphovascular invasion, tumor size, axillary lymph node involvement, stage, hormone receptors, HER2 expression, basal like tumors, triple negative status and prognosis were also investigated. Tissue microarray method was used to investigate immunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105 invasive ductal carcinoma cases. Results: CD 133 expression was significantly associated with tumor size (p = 0.023) and stage (p = 0.009). CD133 expression was decreased in tumors with larger tumor size, higher stage and lymphovascular invasion. CD133 expression was positively correlated with CD44 (r = 0.212, p = 0.032) and CD44(+)/CD24(+) (r = 0.202, p = 0.040) expressions. CD44, CD24 and ALDH1 expressions showed no significant relationship and correlation with clinicopathologic features. There was a significant relationship (p = 0.048) between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was positively correlated with CD44(+)/CD24(-/low) phenotype (r = 0.211, p = 0.036). Conclusions: Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low) phenotype. CD133 can detect a different population of CSC in breast carcinoma. (C) 2015 Elsevier GmbH. All rights reserved.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 .