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Öğe Alterations of cell cycle genes in cancer: unmasking the role of cancer stem cells(Springer, 2020) Caglar, Hasan Onur; Biray Avci, CigirThe cell cycle is a complex and strictly controlled process, consisting of different phases. Cell cycle regulation depends on phase-specific transcriptions of cell cycle genes. the alterations of cell cycle genes can predispose normal cells to have a cancerous phenotype. Indeed, several mechanisms underlying the deregulation of the cell cycle have been identified in different types of cancer. Cancer stem cells (CSCs), a fraction of tumor cells, are selectively capable of initiating tumor development. However, the deregulation of the cell cycle progression in CSCs still remains incompletely understood. This review describes epigenetic alterations and aberrant transcriptional regulation of cell cycle genes in CSCs as well as cell cycle patterns of CSCs.Öğe Application of Next-Generation Sequencing in Neurodegenerative Diseases: Opportunities and Challenges(Humana Press Inc, 2020) Shademan, Behrouz; Biray Avci, Cigir; Nikanfar, Masoud; Nourazarian, AlirezaGenetic factors (gene mutations) lead to various rare and prevalent neurological diseases. Identification of underlying mutations in neurodegenerative diseases is of paramount importance due to the heterogeneous nature of the genome and different clinical manifestations. An early and accurate molecular diagnosis are cardinal for neurodegenerative patients to undergo proper therapeutic regimens. the next-generation sequencing (NGS) method examines up to millions of sequences at a time. As a result, the rare molecular diagnoses, previously presented with "unknown causes", are now possible in a short time. This method generates a large amount of data that can be utilized in patient management. Since each person has a unique genome, the NGS has transformed diagnostic and therapeutic strategies into sequencing and individual genomic mapping. However, this method has disadvantages like other diagnostic methods. Therefore, in this review, we aimed to briefly summarize the NGS method and correlated studies to unravel the genetic causes of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, epilepsy, and MS. Finally, we discuss the NGS challenges and opportunities in neurodegenerative diseases.Öğe CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2(Frontiers Media Sa, 2022) Shademan, Behrouz; Nourazarian, Alireza; Hajazimian, Saba; Isazadeh, Alireza; Biray Avci, Cigir; Oskouee, Mahin AhangarOutbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.Öğe Detection of miRNA Expression Alteration in Diffuse and High Grade Glial Tumors(Journal Neurological Sciences, 2015) Yilmaz Susluer, Sunde; Biray Avci, Cigir; Dogan Sigva, Zeynep Ozlem; Balci, Tugce; Kayabasi, Cagla; Akalin, Taner; Dalbasti, Tayfun; Gunduz, CumhurObjective: It was aimed to determine the expression profiles of miRNAs in patients with diffuse and anaplastic brain tumors. Methods: miRNA expression profiles of 50 cases (19 Female, 31 Male) diagnosed with brain tumor [32 Glioblastoma (GBM), 10 diffuse astrocytoma (DA), 8 anaplastic oligodendroglioma (AO)] in Ege University, Department of Neurosurgery and of brain tumor cell lines (U-87 MG, U-118 MG and LN18) studied by the microarray method. Results: In all cases miR-21 expression level was high and no miR-124 expression was detected. In GBM, miR-495 and miR-432 expression showed significant 2-fold increase, and miR-708-3p, mir-339-5p and miR-4286 expressions 4-fold, mir-331-3p, miR-625-3p, and miR-20a-3p showed 5-fold reduction compared to cell lines. miRNA expressions compared GBM and AO, it was detected that miR-34c-3p, miR-132-5p, mir-605, miR-3130-3p, miR3127, mir-517a-pre, mir-548b-3p, miR-921, miR-769-5p were significantly increased. mir-204 expression was significantly decreased in AO compared to cell lines. In DA, miRNA expression was significantly increased in 18 and decreased in 7. There was no significant miRNA expression changes in AO compared with DA. miRNA expressions of DA, AO and GBM cases were compared and significant alterations were found in 29 miRNA expressions. Conclusion: miRNA expression profiles of GBM were significantly different from AO. It was emphasized that, new genes could be effective in tumor development supposed to be regulated by miRNAs. New specific gene targets regulated by miRNA expression could be predicted good clinical outcome in brain tumors.Öğe Distribution and Phylogenetic Analysis of Subtypes and Alleles of Blastocystis sp. in the Stool Samples Collected from Patients with Gastrointestinal Complaints in Izmir, Turkey(Springer Int Publ Ag, 2023) Aykur, Mehmet; Kurt, Cansu Caliskan; Erdogan, Derya Dirim; Biray Avci, Cigir; Vardar, Rukiye; Aydemir, Sohret; Girginkardesler, NogayPurposeBlastocystis sp. is one of the most prevalent intestinal protozoa found in humans and many other animals. The present study aimed to examine the distribution and genetic diversity of Blastocystis sp. in stool samples from patients with gastrointestinal complaints in Izmir, Turkey.MethodsAll stool samples of 439 patients with gastrointestinal complaints were examined by native-Lugol and trichrome staining. To investigate the presence of Blastocystis sp. in stool samples, DNA was isolated, and PCR was performed with the barcode region in the SSU rRNA gene. PCR positive samples were sequenced to identify subtypes and alleles of Blastocystis sp.ResultsThe prevalence of Blastocystis sp. was found to be 16.6% (73/439) in patients with gastrointestinal complaints in Izmir, Turkey. Three different Blastocystis sp. subtypes were identified. ST3 (28/55; 51.0%) was the most common subtype followed by ST2 (19/55; 34.5%) and ST1 (8/55; 14.5%). Itching and diarrhea were the most prominent clinical symptoms in Blastocystis sp. positive patients. When clinical symptoms and subtypes were compared, diarrhea was found in 62.5%, 47.4%, and 46.4% of patients with ST1, ST2, and ST3 subtypes, respectively. In addition, itching was found in 37.5%, 32.1%, and 21.1% of patients with ST1, ST3, and ST2, respectively. Six distinct alleles were identified by allele analysis of Blastocystis 18S rRNA gene: allele 4 for ST1, alleles 9, 11, and 12 for ST2, and alleles 34 and 36 for ST3. In this study, Blastocystis sp. was detected in 16 of 21 districts, including the central and rural districts of Izmir. Although ST1 was detected in central districts, it was not found in rural districts.ConclusionThis study provides comprehensive data on the prevalence and molecular epidemiology of the genetic diversity at the level of subtypes and alleles of Blastocystis sp. in different districts of Izmir province in Turkey. To the best of our knowledge, this is the first study which evaluates the distribution of subtypes and alleles of Blastocystis sp. according to PCR and SSU rRNA gene sequencing in patients with gastrointestinal complaints in different districts of Izmir province in Turkey.Öğe Evaluation of the anticancer effect of telomerase inhibitor BIBR1532 in anaplastic thyroid cancer in terms of apoptosis, migration and cell cycle(Humana Press Inc, 2023) Turkmen, Ecem; Sogutlu, Fatma; Erdogan, Mehmet; Biray Avci, CigirAnaplastic thyroid cancer (ATC) represents the type with the worst prognosis among thyroid cancers. In ATC with a highly invasive phenotype, selective targeting of TERT with BIBR1532 may be a goal-driven approach to preserving healthy tissues. In present study, it was aimed to investigate the effects of treatment of SW1736 cells with BIBR1532 on apoptosis, cell cycle progression, and migration. The apoptotic effect of BIBR1532 on SW1736 cells was examined using the Annexin V method, the cytostatic effect using cell cycle test, migration properties using wound healing assay. Gene expression differences were determined by real-time qRT-PCR and differences in protein level by ELISA test. BIBR1532-treated SW1736 cells had 3.1-fold increase in apoptosis compared to their untreated counterpart. There was 58.1% arrest in the G(0)/G(1) phase and 27.6% arrest in the S phase of the cell cycle in untreated group, treatment with BIBR1532 increased cell population in G(0)/G(1) phase to 80.9% and decreased in S phase to 7.1%. Treatment with the TERT inhibitor resulted in a 50.8% decrease in cell migration compared to the untreated group. After BIBR1532 treatment of SW1736 cells, upregulation of BAD, BAX, CASP8, CYCS, TNFSF10, CDKN2A genes, and downregulation of BCL2L11, XIAP, CCND2 genes were detected. BIBR1532 treatment resulted in an increase in BAX and p16 proteins, and a decrease in concentration of BCL-2 protein compared to untreated group. Targeting TERT with BIBR1532 as a mono drug or using of BIBR1532 at priming stage prior to chemotherapy treatment in ATC may present a novel and promising treatment strategy.Öğe ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation(Nature Portfolio, 2024) Saglam Metiner, Pelin; Yanasik, Sena; Odabasi, Yusuf Caglar; Modamio, Jennifer; Negwer, Moritz; Biray Avci, Cigir; Yesil Celiktas, OzlemPropofol and midazolam are the current standard of care for prolonged sedation in Intensive Care Units (ICUs). However, the effects and mechanism of these sedatives in brain tissue are unclear. Herein, the development of an ICU patient-on-a-chip platform to elucidate those effects is reported. The humanized neural tissue compartment combines mast cells differentiated from human induced pluripotent stem cells (hiPSCs) with cerebral organoids in a three-dimensional (3D) matrix, which is covered with a membrane populated with human cerebral microvascular endothelial cells (hCMEC/D3) that separates the tissue chamber from the vascular lumen, where sedatives were infused for four days to evaluate neurotoxicity and cell-mediated immune responses. Subsequent to propofol administration, gene expressions of CD40 and TNF-alpha in mast cells, AIF1 in microglia and GFAP/S100B/OLIG2/MBP in macroglia were elevated, as well as NOS2, CD80, CD40, CD68, IL6 and TNF-alpha mediated proinflammation is noted in cerebral organoids, which resulted in higher expressions of GJB1, GABA-A and NMDAR1 in the tissue construct of the platform. Besides, midazolam administration stimulated expression of CD40 and CD203c+ reactivated mast cell proliferation and compromised BBB permeability and decreased TEER values with higher barrier disruption, whereas increased populations of CD11b+ microglia, higher expressions of GFAP/DLG4/GJB1 and GABA-A-/NMDAR1- identities, as well as glutamate related neurotoxicity and IL1B, IFNG, IFNA1, IL6 genes mediated proinflammation, resulting in increased apoptotic zones are observed in cerebral organoids. These results suggest that different sedatives cause variations in cell type activation that modulate different pathways related to neuroinflammation and neurotoxicity in the ICU patient-on-chip platform.Öğe Investigating the Effects of a Synthetic Cannabinoid on the Pathogenesis of Leukemia and Leukemic Stem Cells: A New Therapeutic Approach(Mary Ann Liebert, Inc, 2022) Salcin, Hilal; Goker Bagca, Bakiye; Alcitepe, Ilayda; Biray Avci, Cigir; Aslan, Rukiye; Annette Akgur, Serap; Tezcanli Kaymaz, BurcinThe popularity and usage of synthetic cannabinoids (SCs) are increasing due to their easy accessibility and psychoactive effects worldwide. Studies on cannabinoids on leukemic stem cells (LSC) and hematopoietic stem cells (HSCs), which are the precursors of leukemia cells, generally depend on the natural cannabinoid delta-9-THC. As there is only a limited number of studies focusing on the results of SC applications, the reflections upon LSCs have to be clarified. In this study, biological responses and antileukemic effects of JWH-018-one of the first produced and widely used SCs-were evaluated upon leukemia cells. Whether JWH-018 exhibited a preventive effect on both leukemic and HSCs was evaluated by presenting a therapeutic approach for the first time in the literature. Cells were analyzed in case of cell proliferation, apoptosis, and transcriptional expression profiling of some significant JAK/STAT and AKT/mTOR pathways, apoptotic, cell cycle regulation, and epigenetic chromatin remodeling-related genes following JWH-018 treatment. In conclusion, however, further studies are still needed upon both HSCs and LSCs to illuminate the effects of SCs on leukemogenesis on chronic myeloid leukemia (CML) more clearly; we consider that the JWH-018 can provide a therapeutic effect on the pathogenesis of leukemia and particularly upon LSCs and SCs might have therapeutic potential in addition to current therapy.Öğe Molecular perspective on targeted therapy in breast cancer: a review of current status(Humana Press Inc, 2022) Demir Cetinkaya, Busra; Biray Avci, CigirBreast cancer is categorized at the molecular level according to the status of certain hormone and growth factor receptors, and this classification forms the basis of current diagnosis and treatment. The development of resistance to treatment and recurrence of the disease have led researchers to develop new therapies. In recent years, most of the research in the field of oncology has focused on the development of targeted therapies, which are treatment methods developed directly against molecular abnormalities. Promising advances have been made in clinical trials investigating the effect of these new treatment modalities and their combinations with existing therapeutic treatments in the treatment of breast cancer. Monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, PI3K/Akt/mTOR pathway inhibitors, cyclin-dependent kinase 4/6 inhibitors, anti-angiogenic drugs, PARP inhibitors are among the targeted therapies used in breast cancer treatment. In this review, we aim to present a molecular view of recently approved target agents used in breast cancer.Öğe Ponatinib and STAT5 Inhibitor Pimozide Combined Synergistic Treatment Applications Potentially Overcome Drug Resistance via Regulating the Cytokine Expressional Network in Chronic Myeloid Leukemia Cells(Mary Ann Liebert, Inc, 2024) Tezcanli Kaymaz, Burcin; Gumus, Nurcan; Celik, Besne; Alcitepe, Ilayda; Biray Avci, Cigir; Aktan, CagdasChronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCRÖğe Targeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemia(Humana Press Inc, 2022) Ozel, Buket; Kipcak, Sezgi; Biray Avci, Cigir; Sabour Takanlou, Maryam; Sabour Takanlou, Leila; Tezcanli Kaymaz, Burcin; Karatekin, IlknurChronic myeloid leukemia (CML) is a myeloproliferative disease that mediated by BCR/ABL oncogenic signaling. CML can be targeted with the imatinib, dasatinib, and nilotinib TKI inhibitors, the latter two of them have been approved for imatinib-resistant or -intolerant CML patients. The TKIs resistance occurs by different molecular mechanisms, including overexpression of BCR-ABL, mutations in the TKI binding site of BCR/ABL, and ER-stress. Unfolded protein responses (UPR) is a cytoprotective mechanism which is activated by ER-stress. The IRE1, PERK, and ATF6 are three main arms of the UPR mechanism and are activated by a common mechanism involving the dissociation of the ER-chaperone BiP/GP78. There is a correlation between ER-stress, CML progression, and response to TKI treatment. In the present study, we aimed to determine alterations of the expression levels of genes related to UPR pathway signaling after treatment with dasatinib in K562 chronic myeloid leukemia cell line by quantitative RT-PCR relatively. The array-data revealed that treatment with dasatinib significantly decreased the UPR mechanism-related genes (including HSPA1B, HSPA2, HSPA4L, ATF6, ATF6B, CEBPB, PERK, TRIB3, DNAJB, ERN1, and UHRF1) in K562 cells. In conclusion, the results showed that dasatinib regulates the UPR mechanism that plays a significant role in cancer progression and therapy resistance in CML. Thus, dasatinib-induced dysfunction of the UPR mechanism may promise encouraging therapy for CML. [GRAPHICS] .