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Article ; Online: Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.

Demir, Ayse Banu / Baris, Elif / Kaner, Umay Bengi / Alotaibi, Hani / Atabey, Nese / Koc, Ahmet

2023 Volume 50, Issue 10, Page(s) 8551–8563

Abstract: Background: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly ... ...

Abstract	Background: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. Methods and results: The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment. Conclusions: Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.
MeSH term(s)	Humans ; Apoptosis ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Saccharomyces cerevisiae ; Intracellular Signaling Peptides and Proteins/genetics
Chemical Substances	Doxorubicin (80168379AG) ; TOLLIP protein, human ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-08-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-023-08737-2
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Zs.A 1140: Show issues

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Article: Türkiye’den Bildirilen Sars-CoV-2 İzolatlarında RT-PCR Primer/Prob Bağlanma Bölgelerindeki Nükleotit Değişimlerinin Analizi.

Demir, Ayşe Banu / Bulgurcu, Alihan / Appak, Özgür / Sayıner, Ayça Arzu

Mikrobiyoloji bulteni

2021 Volume 55, Issue 3, Page(s) 311–326

Abstract: The SARS-CoV-2 virus, which caused the COVID-19 epidemic, caused more than 55 million cases and nearly 1.5 million deaths worldwide. For the microbiological diagnosis of the disease, the most valid method is detecting the presence of the viral genome by ... ...

Title translation	Analysis of Nucleotide Changes in RT-PCR Primer/Probe Binding Regions in SARS-CoV-2 Isolates Reported from Turkey.
Abstract	The SARS-CoV-2 virus, which caused the COVID-19 epidemic, caused more than 55 million cases and nearly 1.5 million deaths worldwide. For the microbiological diagnosis of the disease, the most valid method is detecting the presence of the viral genome by real-time reverse transcription polymerase chain reaction (rRT-PCR). However, due to the nature of the RNA viruses, frequent mutations may affect the sensitivity of the analyses made on the genetic material of the virus, such as PCR. In this study, we aimed to investigate the mutations in the primer-probe binding regions of the rRT-PCR panels used in COVID-19 diagnosis. SARS-CoV-2 whole genome sequence data (n= 194) isolated from COVID-19 cases in Turkey and uploaded on GISAID database from the centers in İstanbul (n= 78), Ankara (n= 58), Kars (n= 47), Bursa (n= 2), Adıyaman (n= 2), Erciyes (n= 1) and Kocaeli (n= 1) between March 17-September 14, 2020 were analyzed. In order to determine the nucleotide changes, SARS-CoV-2 sequences from Turkey were compared to the reference genome sequence (NC_045512.1) present in "GenBank" website. The constructed data set was aligned using the MAFFT program and was checked manually if the sequences were in the same frame by using the AliView program. Primer-probe binding sites of the thirteen SARS-CoV-2 rRT-PCR panels from seven different institutes (US CDC, China CDC, Charite CDC, Pasteur, HKU, Thailand, NIID) that are being used in COVID-19 diagnosis were evaluated in terms of nucleotide changes within the corresponding regions compared to the reference genome. Sequence diversities in the viral genomes were determined via positional nucleotide numerical calculator and entropy calculator modules and nucleotide and entropy changes in primer-probe binding regions for each rRT-PCR panel were examined. Among thirteen different primer-probe panels, nucleotide changes in the target regions of the seven primer-probe panels were determined. When viral sequences with nucleotide changes in the primer-probe binding regions were examined, the most common changes were observed in the "China CDC" N-forward primer and "US CDC" N3-forward primer binding regions. It is important that the kits to be used as diagnostic tests are designed specific to the regions with less nucleotide changes. Nucleotide changes may not be critical for DNA amplification for most PCR panels, but should be carefully monitored as they may affect the sensitivity of the assay. If the risk of alteration of the designed region is high, the primer - probe binding sites should be checked frequently and updated when necessary.
MeSH term(s)	COVID-19 ; COVID-19 Testing ; Humans ; Nucleotides ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2 ; Sensitivity and Specificity ; Turkey
Chemical Substances	Nucleotides
Language	Turkish
Publishing date	2021-08-20
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	985146-x
ISSN	0374-9096
ISSN	0374-9096
DOI	10.5578/mb.20219803
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Zs.A 3943: Show issues

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Article ; Online: Analysis of Three Mutations in Italian Strains of SARS-CoV-2: Implications for Pathogenesis.

Benvenuto, Domenico / Benedetti, Francesca / Demir, Ayse Banu / Ciccozzi, Massimo / Zella, Davide

Chemotherapy

2021 Volume 66, Issue 1-2, Page(s) 33–37

Abstract: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries ... ...

Abstract	Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries around the world, with >80 million cases registered and >1.8 million deaths. Objective: As several vaccines are still being developed and 2 have been approved, it is particularly important to perform evolutionary surveillance to identify mutations potentially affecting vaccine efficacy. Methods: DynaMut server has been used to evaluate the impact of the mutation found on SARS-CoV-2 isolates available on GISAID. Results: In this article, we analyze whole genomes sequenced from Italian patients, and we report the characterization of 3 mutations, one of which presents in the spike protein. Conclusion: The mutations analyzed in this article can be useful to evaluate the evolution of SARS-CoV-2.
MeSH term(s)	COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/virology ; Epidemiological Monitoring ; Humans ; Italy/epidemiology ; Mutation ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Spike Glycoprotein, Coronavirus/genetics ; Whole Genome Sequencing/methods
Chemical Substances	Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-03-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	6708-8
ISSN	1421-9794 ; 0009-3157
ISSN (online)	1421-9794
ISSN	0009-3157
DOI	10.1159/000515342
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Article ; Online: High-Copy Overexpression Screening Reveals PDR5 as the Main Doxorubicin Resistance Gene in Yeast.

Demir, Ayse Banu / Koc, Ahmet

PloS one

2015 Volume 10, Issue 12, Page(s) e0145108

Abstract: Doxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms and its cytotoxicity. In this study, we performed a high-copy screening ... ...

Abstract	Doxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms and its cytotoxicity. In this study, we performed a high-copy screening analysis to find genes that play a role in doxorubicin resistance and found several genes (CUE5, AKL1, CAN1, YHR177W and PDR5) that provide resistance. Among these genes, overexpression of PDR5 provided a remarkable resistance, and deletion of it significantly rendered the tolerance level for the drug. Q-PCR analyses suggested that transcriptional regulation of these genes was not dependent on doxorubicin treatment. Additionally, we profiled the global expression pattern of cells in response to doxorubicin treatment and highlighted the genes and pathways that are important in doxorubicin tolerance/toxicity. Our results suggest that many efflux pumps and DNA metabolism genes are upregulated by the drug and required for doxorubicin tolerance.
MeSH term(s)	ATP-Binding Cassette Transporters/biosynthesis ; ATP-Binding Cassette Transporters/genetics ; Doxorubicin/pharmacology ; Drug Resistance, Fungal/physiology ; Gene Expression Regulation, Fungal/drug effects ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/biosynthesis ; Saccharomyces cerevisiae Proteins/genetics
Chemical Substances	PDR5 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Doxorubicin (80168379AG)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0145108
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Article: Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line.

Demir, Ayse Banu / Benvenuto, Domenico / Karacicek, Bilge / Erac, Yasemin / Spoto, Silvia / Angeletti, Silvia / Ciccozzi, Massimo / Tosun, Metiner

Journal of personalized medicine

2022 Volume 12, Issue 12

Abstract: Elevated levels of STIM1, an endoplasmic reticulum ... ...

Abstract	Elevated levels of STIM1, an endoplasmic reticulum Ca
Language	English
Publishing date	2022-12-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm12122065
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Article: Prenatal detection of Peters plus-like syndrome.

Canda, Mehmet Tunç / Doğanay Çağlayan, Latife / Demir, Ayşe Banu / Demir, Namık

Turkish journal of obstetrics and gynecology

2019 Volume 15, Issue 4, Page(s) 273–276

Abstract: Peters plus syndrome is a rare congenital disorder that includes ocular anterior segment defects of the classic Peter's anomaly, and is mostly associated with craniofacial and skeletal defects. A 21-week fetus was referred for further evaluation due to a ...

Abstract	Peters plus syndrome is a rare congenital disorder that includes ocular anterior segment defects of the classic Peter's anomaly, and is mostly associated with craniofacial and skeletal defects. A 21-week fetus was referred for further evaluation due to a suspicion of fetal hydrocephalus. An ultrasound examination revealed hyperechogenic lenses, microphthalmia, hypotelorism, retrognathia, mild ventriculomegaly, absence of the cavum septum pellucidum, and short stature. Amniocentesis and further microarray analysis revealed normal chromosomal copy numbers including the gene
Language	English
Publishing date	2019-01-09
Publishing country	Turkey
Document type	Case Reports
ISSN	2149-9322
ISSN	2149-9322
DOI	10.4274/tjod.45649
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Article: Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension.

Molin, Mikael / Demir, Ayse Banu

International journal of cell biology

2014 Volume 2014, Page(s) 913071

Abstract: Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, ... ...

Abstract	Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.
Language	English
Publishing date	2014-02-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2536742-0
ISSN	1687-8884 ; 1687-8876
ISSN (online)	1687-8884
ISSN	1687-8876
DOI	10.1155/2014/913071
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Article: Prenatal Diagnosis of Osteogenesis Imperfecta Type III.

Canda, Mehmet Tunc / Ceylaner, Serdar / Doganay Caglayan, Latife / Demir, Ayşe Banu / Demir, Namik

Journal of obstetrics and gynaecology of India

2019 Volume 69, Issue 4, Page(s) 374–376

Language	English
Publishing date	2019-04-22
Publishing country	India
Document type	Case Reports
ZDB-ID	410688-x
ISSN	0971-9202 ; 0022-3190
ISSN	0971-9202 ; 0022-3190
DOI	10.1007/s13224-019-01230-6
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Article ; Online: Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission.

Benvenuto, Domenico / Demir, Ayse Banu / Giovanetti, Marta / Bianchi, Martina / Angeletti, Silvia / Pascarella, Stefano / Cauda, Roberto / Ciccozzi, Massimo / Cassone, Antonio

Journal of medical virology

2020 Volume 92, Issue 10, Page(s) 2232–2237

Abstract: Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and disease impact after coronavirus disease-2019 pandemia started in China. Even though the presence of mutations on spike ... ...

Abstract	Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and disease impact after coronavirus disease-2019 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS-CoV-2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three nonsynonymous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bioinformatics tools. Amino acid analysis and changes in three-dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favor virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.
MeSH term(s)	Amino Acid Substitution ; COVID-19/epidemiology ; COVID-19/pathology ; COVID-19/transmission ; COVID-19/virology ; China/epidemiology ; Coronavirus Nucleocapsid Proteins/chemistry ; Coronavirus Nucleocapsid Proteins/genetics ; Evolution, Molecular ; Genome, Viral ; Humans ; Italy/epidemiology ; Models, Molecular ; Molecular Epidemiology ; Mutation ; Pandemics ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phylogeny ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; Severity of Illness Index ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Travel ; Virus Replication
Chemical Substances	Coronavirus Nucleocapsid Proteins ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.26104
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Article ; Online: The role of cancer stem cells in immunotherapy for bladder cancer: An in vitro study.

Özcan, Yegane / Çağlar, Fulya / Celik, Serdar / Demir, Ayşe Banu / Erçetin, Ayşe Pınar / Altun, Zekiye / Aktas, Safiye

Urologic oncology

2020 Volume 38, Issue 5, Page(s) 476–487

Abstract: Objective: Bladder cancer is characterized by frequent recurrence and progression. CD44+ cancer stem cells (CSCs) might be one of the main reasons for recurrence. Although Bacillus Calmette Guerin (BCG) has become a gold standard immunotherapy, after ... ...

Abstract	Objective: Bladder cancer is characterized by frequent recurrence and progression. CD44+ cancer stem cells (CSCs) might be one of the main reasons for recurrence. Although Bacillus Calmette Guerin (BCG) has become a gold standard immunotherapy, after treatment recurrence frequently occur. Based on this knowledge, the aim of this study was to evaluate the changes in cytokine and chemokine expressions in bladder cancer and CSCs cultures in vitro with BCG only and in combination with IL2 and lymphocyte (MNCs) applications. Material and methods: In this study, 3 cell lines of human bladder cancer cells with different characteristics (T24, 5637, and JMSU-1) and CD44+ bladder CSCs isolated by magnetic bead isolation (Miltenyl Magtech) were used. Bladder cancer cell lines and bladder CSCs in complete medium were cultured under humidified conditions of 37°C temperature in 5% CO Results: BCG treatment with 7.32 µg/ml dose alone and in combination with IL2 (1000 IU/ml) and MNCs (1000 cells/ml) were found to be most effective on bladder cancer cells. When BCG and its combinations were applied to CSCs of the 3 cell lines, BCG treatment showed cytotoxic effect on CSCs as well as cancer cells. CSCs of 3 cell lines over expressed CXCL5, CCL8, CNTF, and CSF2 compared with cancer cells. Cancer cells over expressed IL6, TNSFF11, FASLG, and CXCL9 compared with CSCs. In all 3 cell lines, BCG application increased expression of CXCL5 and LTB and also decreased CCL20 and IL6. When BCG was combined with IL2 and MNCs, CXCL10, CXCL5, and IFNG were increased and CXCL12, IL6, and TNSF11 were decreased. BCG treatment of CSCs caused increases in ADIPOQ, CXCL10, and XCL1 and a decrease in CCL8. When IL2 and MNCs were combined with BCG, the expression of many cytokines and chemokines decreased. Conclusion: BCG treatment changes the expression of many cytokines and chemokines in bladder cancer. The expression differs in 3 different cell lines and their CSCs. Immune modulation of each case differs from each other. The effectivity of BCG-based immunotherapy in bladder cancer on CSCs might decrease in combination with IL2. Our results indicate that recurrence after BCG treatment for bladder cancer may not occur mainly based on the CSCs hypothesis considering bladder cancer occurs at different loci of surface epithelium.
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Adjuvants, Immunologic/pharmacology ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; BCG Vaccine/administration & dosage ; BCG Vaccine/pharmacology ; Cell Line, Tumor ; Chemokines/biosynthesis ; Cytokines/biosynthesis ; Humans ; Immunotherapy ; Interleukin-2/administration & dosage ; Interleukin-2/pharmacology ; Lymphocytes ; Male ; Middle Aged ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/physiology ; Urinary Bladder Neoplasms/immunology ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/therapy
Chemical Substances	Adjuvants, Immunologic ; Antineoplastic Agents ; BCG Vaccine ; Chemokines ; Cytokines ; Interleukin-2
Language	English
Publishing date	2020-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2020.02.021
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