Browsing by Author "Oktem, G."

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Cancer Stem Cells and Nitric Oxide
(Elsevier, 2023) Taskiran, A.; Demir, A.; Acikgoz, E.; Oktem, G.
Cancer stem cells (CSCs) forming the tumor heterogeneity are thought to be the main reason for ineffective and insufficient conventional cancer treatments including surgery, radiotherapy, and chemotherapy and, therefore, causing relapse, metastasis, and multidrug resistance in the long term. CSCs express specific biomarkers on their surface and, thus, differentiate from non-CSCs. The metabolic and signaling activities of CSCs have been shown to be different from those of non-CSCs, and there are still many unknown activities. CSCs share Wnt, Hedgehog, and Notch signaling pathways and many surface markers with embryonic and adult stem cells, indicating that CSCs are the starting point of tumor formation. Deregulation of intrinsic and extrinsic factors of cells induces altered metabolic activities, including the nitric oxide (NO) metabolism, that have a crucial role in the cell fate. CSCs produce high levels of NO and secrete it in the tumor microenvironment involving a wide range of components such as stromal cells, cancer-associated fibroblasts (CAFs), immune cells, nonimmune cells, and blood vessels. Studies have shown that cancer (stem) cell-derived NO promotes chronic inflammation in the tumor microenvironment, pro-tumorigenic activities of CAFs, drug resistance, invasion, and metastasis. These events are reversible by inhibiting cellular NO by NO-releasing drugs or NO donors in cancer therapy either alone or combined with other cytotoxic drugs. Thereby, NO is suggested to be a promising agent for cancer therapy, prevention of the metastatic cascade, and CSC transformation. Further research is needed to elucidate the highly sophisticated activities of NO and CSCs for the advancements of new therapeutic strategies targeting CSCs. © 2023 Elsevier Inc. All rights reserved.
Cross-Talk Between Ribosome Biogenesis, Translation, and Mtor in Cd133+4/Cd44+prostate Cancer Stem Cells
(Springer international Publishing Ag, 2020) Binal, Z.; Acikgoz, E.; Kizilay, F.; Oktem, G.; Altay, B.
Objective To investigate the gene expression profile of CSCs and to explore the key pathways and specific molecular signatures involved in the characteristic of CSCs. Materials and methods CD133+ /CD44+ CSCs and bulk population (non-CSCs) were isolated from DU-145 cells using fluorescence-activated cell sorting (FACS). We used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of CSCs and non-CSCs. Protein-protein interaction (PPI) network analysis was performed using the STRING database. Biomarkers selected based on gene expression profiling were visually analyzed using immunofluorescence staining method. An image analysis program, ImageJ (R), was used for the analysis of fluorescence intensity. Results In microarray analysis, we found that many ribosomal proteins and translation initiation factors that constitute the mTOR complex were highly expressed. PPI analysis using the 33 genes demonstrated that there was a close interaction between ribosome biogenesis, translation, and mTOR signaling. The fluorescence amount of mTOR and MLST8 were higher in CSCs compared to non-CSCs. Conclusions The increase in a number of genes associated with ribosome biogenesis, translation, and mTOR signaling may be important to evaluate prognosis and determine treatment approach for prostate cancer (PCa). A better understanding of the molecular pathways associated with CSCs may be promising to develop targeted therapies to prolong survival in PCa.
Nk Cells in Prostate Cancer
(Elsevier, 2021) Acikgoz, E.; Sati, L.; Soner, B.C.; Oktem, G.
Advanced modalities in the treatment of prostate cancer, an important health problem among men, draw attention to the field of cancer immunotherapy. Although the immune system holds promise for prostate cancer treatment, the biological processes associated with prostate cancer cells and immune cells have not yet been fully elucidated. The prostate cancer microenvironment is a complex system containing a large number of immune cells. Among multiple immune cells, natural killer (NK) cells have enormous potential in targeting various cancer cells. NK cells, which are an important part of the innate immune system, play a very important role as a first-line defense against prostate cancer cells. Various strategies have been adopted by researchers to increase the efficiency of NK cells. However, there are many difficulties to increase the therapeutic relevance of NK cells. This review will provide a perspective on the phenotypic and functional properties of NK cells, molecular links between NK cells and prostate cancer cells, and the therapeutic and prognostic significances of NK cells in both advanced hormone naïve prostate cancer and castration-resistant prostate cancer. © 2021 Elsevier Inc. All rights reserved.
The Rhythmicity of Life: a Review of the Circadian Clocks
(Begell House Inc., 2021) Acikgoz, E.; Karahuseyinoglu, S.; Ayla, S.; Oktem, G.
Physiology of the mammalian body has been adapted to diurnal cycles of around 24 h, an evolutionary situation that affects a wide spectrum of biological events including sleep-to-wake transitions, feeding/fasting, body temperature, and hormonal regulations. The patterns of the diurnal cycle occur due to rhythmic oscillations that arise from the suprachiasmatic nucleus of hypothalamus, which also can be defined as the pacemaker of the system. The clock can be defined as a molecular machinery driven by the core clock genes that encode clock proteins in a rhythmic oscillatory fashion maintained by the light/dark cycles of the environment. Although the well-established knowledge refers to the function of the circadian rhythm as maintenance of the normal physiology, growing evidence shows that disruptions in the system usually caused by genetic and/or epigenetic misregulations may have a direct effect to lead major pathological conditions, such as carcinogenesis. This review outlines the main molecular aspects of circadian physiology, and reveals the reasons for and results of the circadian disruptions at different levels. In spite of the fact that more proof is needed for a direct correlation between circadian disruptions and oncogenesis and other pathological events, data obtained from current research supports the role of circadian rhythms in malfunctioning of the normal cellular metabolism. © 2021 by Begell House, Inc.
Yy1 Involvement in Embryonic Development and Cancer
(Elsevier, 2020) Acikgoz, E.; Sati, L.; Oktem, G.
Despite numerous advances in the field of cancer cell biology, the origin of cancer cells and the systemic disruptions in the cancer process of normal cells have not yet been fully identified. However, we certainly know that cancer cells carry genetic and molecular similarities of the early embryonic development indicating an interesting relationship between “birth” and “death.” During the embryonic development process, the software of system codes to determine cell fate has been designed. Then, cells containing embryonic residues can be directed as a normal cell, cancer cell, or a stem cell. The transcription factor Yin Yang 1 (YY1) has been reported to play critical roles in many biological processes, such as the embryonic development, cell fate specification, regulation of pluripotency, and oncogenesis. In view of these activities, YY1 has been implicated in both the embryonic development and oncogenesis by acting as a bridge linking these two important biological processes. Therefore, in this review, we primarily focus on YY1 investigations linking the embryonic development, oncogenesis, and stem cell biology. © 2021 Elsevier Inc. All rights reserved.