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Rafael Rios - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms in xenobiotic transporters abcb1 abcg2 abcc2 abcc1 ABCC3 and multiple myeloma risk a case control study in the context of the international multiple myeloma research immense consortium
Leukemia, 2012Co-Authors: Alessandro Martino, Daniele Campa, Gabriele Buda, Juan Sainz, Krzysztof Jamroziak, Rui Manuel Reis, Niels Weinhold, Manuel Jurado, Ramon Garciasanz, Rafael RiosAbstract:Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
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Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
Leukemia, 2011Co-Authors: Alessandro Martino, Daniele Campa, Gabriele Buda, Juan Sainz, Ramón García-sanz, Krzysztof Jamroziak, Rui Manuel Reis, Niels Weinhold, Manuel Jurado, Rafael RiosAbstract:Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
Omer Faruk Karatas - One of the best experts on this subject based on the ideXlab platform.
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Differential expression of ABCB1, ABCG2, and KLF4 as putative indicators for paclitaxel resistance in human epithelial type 2 cells
Molecular Biology Reports, 2021Co-Authors: Mehmet Bugrahan Duz, Omer Faruk KaratasAbstract:Laryngeal squamous cell carcinoma (LSCC) is the second most common malignancy of the head and neck region in the USA with a declining 5-year survival rate. Paclitaxel resistance of tumors including LSCC still stands as a vital cause for poor clinical outcome in patients. In the current study, our aim was to explore the expressions of ATP-binding cassette transporters and stemness associated genes in human epithelial type 2 (Hep-2) cells with paclitaxel resistance. Resistant cells were developed via treatment with increasing doses of paclitaxel to acquire four sub-lines resistant to one-, two-, four-, and eightfold concentrations of paclitaxel (1×, 2×, 4×, 8×). Then, we profiled the expressions of ten selected ABC transporters (ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, ABCF2, and ABCG2) and four stem cell markers (SOX2, OCT4, KLF, and CXCR4) using quantitative real time polymerase chain reaction in paclitaxel resistant cells to look for a link between these markers and chemoresistance. We demonstrated that ABCB1 and ABCG2 expressions gradually elevated and reached a maximum level in Taxol 8× cells. Considering stem cell markers, KLF4 expression elevated significantly, as soon as parental cells acquired resistance to the lowest dose of paclitaxel and its expression elevated stepwise. Expression levels of other tested ATP-binding cassette transporters and stem cell markers also elevated, although at different steps of paclitaxel resistance acquisition. Our findings suggest that higher expressions of ABCB1, ABCG2, and KLF4 might be considered as putative indicators for paclitaxel resistance in LSCC patients.
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Expression profile of stem cell markers and ABC transporters in 5-fluorouracil resistant Hep-2 cells
Molecular Biology Reports, 2020Co-Authors: Omer Faruk KaratasAbstract:Resistance of laryngeal squamous cell carcinoma cells to traditional therapeutic regimens still remains to be a major reason for therapeutic failure in patients. In this study, we aimed at investigating the expression profiles of ATP-binding cassette (ABC) transporters and stem cell markers in 5-fluorouracil (5-FU) resistant laryngeal Hep-2 cells. We treated parental Hep-2 cells, with stepwise increased doses of 5-FU for almost 1 year to develop 5-FU resistant sub-lines with resistance against varying levels of 5-FU concentrations (4 sub-lines resistant to 1, 2, 4, and eightfold of 5-FU). Then, we measured the expression levels of 10 genes from ABC transporters family and 4 stem cell associated markers using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to find out a potential relationship between these markers and chemoresistance. We found that stemness-associated markers had elevated expressions from the beginning of 5-FU resistance acquisition. Their expressions elevated stepwise while parental Hep-2 cells got resistance to higher doses of 5-FU. Expressions of tested ABC transporters (ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10 and ABCF2, and ABCG2) were also deregulated in 5-FU resistant Hep-2 cells. Although their expressions remained unaltered at the beginning of acquisition of resistance, expressions of ABC transporters except from ABCB6 increased significantly when cells became resistant to higher doses of 5-FU. Our results suggest that enrichment of cells with stemness characteristics and upregulation of ABC transporters might be amongst the crucial contributors of chemoresistance in laryngeal cancer cells.
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Expression profile of stem cell markers and ABC transporters in 5-fluorouracil resistant Hep-2 cells
Molecular Biology Reports, 2020Co-Authors: Omer Faruk KaratasAbstract:Resistance of laryngeal squamous cell carcinoma cells to traditional therapeutic regimens still remains to be a major reason for therapeutic failure in patients. In this study, we aimed at investigating the expression profiles of ATP-binding cassette (ABC) transporters and stem cell markers in 5-fluorouracil (5-FU) resistant laryngeal Hep-2 cells. We treated parental Hep-2 cells, with stepwise increased doses of 5-FU for almost 1 year to develop 5-FU resistant sub-lines with resistance against varying levels of 5-FU concentrations (4 sub-lines resistant to 1, 2, 4, and eightfold of 5-FU). Then, we measured the expression levels of 10 genes from ABC transporters family and 4 stem cell associated markers using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to find out a potential relationship between these markers and chemoresistance. We found that stemness-associated markers had elevated expressions from the beginning of 5-FU resistance acquisition. Their expressions elevated stepwise while parental Hep-2 cells got resistance to higher doses of 5-FU. Expressions of tested ABC transporters (ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10 and ABCF2, and ABCG2) were also deregulated in 5-FU resistant Hep-2 cells. Although their expressions remained unaltered at the beginning of acquisition of resistance, expressions of ABC transporters except from ABCB6 increased significantly when cells became resistant to higher doses of 5-FU. Our results suggest that enrichment of cells with stemness characteristics and upregulation of ABC transporters might be amongst the crucial contributors of chemoresistance in laryngeal cancer cells.
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The role of ATP‐binding cassette transporter genes in the progression of prostate cancer
The Prostate, 2015Co-Authors: Omer Faruk Karatas, Mehmet Bugrahan Duz, Esra Guzel, Michael Ittmann, Mustafa OzenAbstract:BACKGROUND Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related death among men in developed countries. There is no clear evidence showing the success of current screening tests in reducing mortality of PCa. In this study, we aimed to profile expressions of nine ABC transporters, ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, and ABCF2, in recurrent, non-recurrent PCa and normal prostate tissues. METHODS A total of 77 (39 recurrent, 38 non-recurrent) radical prostatectomy and 20 normal prostate samples, obtained from Baylor College of Medicine Prostate Cancer program, were included into the study and divided into two independent groups as test and validation sample sets. Differential expression of selected ABC transporters was assessed using quantitative real-time PCR (qRT-PCR). Pearson's correlation test, receiver operating characteristics (ROC) analysis and Kaplan–Meier test were used for statistical analysis. RESULTS QRT-PCR results demonstrated the elevated expression of ABCA5, ABCB1, ABCB6, ABCC1, and ABCC2 as well as reduced expression of ABCC3 in PCa samples compared to normal prostate tissues. In addition, we found deregulation of ABCB1, ABCB6, ABCC3, and ABCC10 in recurrent PCa samples and validated differential expression of ABCB6, ABCC3, and ABCC10 in recurrent PCa compared to non-recurrent PCa. Pearson's correlation, ROC and Kaplan–Meier analysis revealed the power of these three ABC transporters for estimating prognosis of PCa. CONCLUSIONS We demonstrated differential expression of ABC transporters both in tumor versus normal and recurrent versus non-recurrent comparisons. Our data suggest ABCB6, ABCC3, and ABCC10 as valuable predictors of PCa progression. Prostate © 2015 Wiley Periodicals, Inc.
Pavlina Konstantinova - One of the best experts on this subject based on the ideXlab platform.
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adenosine triphosphate binding cassette transporter genes up regulation in untreated hepatocellular carcinoma is mediated by cellular micrornas
Hepatology, 2012Co-Authors: Florie Borel, Allerdien Visser, Harald Petry, Sander Van Deventer, Peter L M Jansen, Pavlina KonstantinovaAbstract:Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired HCC patient samples (16 untreated, 3 treated by chemotherapeutics). Twelve ABC transporters showed up-regulation in HCC compared with adjacent healthy liver. These include ABCA2, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, and ABCE1. The expression profile and function of some of these transporters have not been associated with HCC thus far. Because cellular microRNAs (miRNAs) are involved in posttranscriptional gene silencing, we hypothesized that regulation of ABC expression in HCC might be mediated by miRNAs. To study this, miRNAs were profiled and dysregulation of 90 miRNAs was shown in HCC compared with healthy liver, including up-regulation of 11 and down-regulation of 79. miRNA target sites in ABC genes were bioinformatically predicted and experimentally verified in vitro using luciferase reporter assays. In total, 13 cellular miRNAs were confirmed that target ABCA1, ABCC1, ABCC5, ABCC10, and ABCE1 genes and mediate changes in gene expression. Correlation analysis between ABC and miRNA expression in individual patients revealed an inverse relationship, providing an indication for miRNA regulation of ABC genes in HCC. Conclusion: Up-regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down-regulation. Up-regulation of five ABC genes appears to be mediated by 13 cellular miRNAs in HCC patient samples. miRNA-based gene therapy may be a novel and promising way to affect the ABC profile and overcome clinical multidrug resistance. (Hepatology 2012)
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Adenosine triphosphate‐binding cassette transporter genes up‐regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs
Hepatology, 2012Co-Authors: Florie Borel, Allerdien Visser, Harald Petry, Peter L M Jansen, Ruiqi Han, Sander J. H. Van Deventer, Pavlina KonstantinovaAbstract:Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired HCC patient samples (16 untreated, 3 treated by chemotherapeutics). Twelve ABC transporters showed up-regulation in HCC compared with adjacent healthy liver. These include ABCA2, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, and ABCE1. The expression profile and function of some of these transporters have not been associated with HCC thus far. Because cellular microRNAs (miRNAs) are involved in posttranscriptional gene silencing, we hypothesized that regulation of ABC expression in HCC might be mediated by miRNAs. To study this, miRNAs were profiled and dysregulation of 90 miRNAs was shown in HCC compared with healthy liver, including up-regulation of 11 and down-regulation of 79. miRNA target sites in ABC genes were bioinformatically predicted and experimentally verified in vitro using luciferase reporter assays. In total, 13 cellular miRNAs were confirmed that target ABCA1, ABCC1, ABCC5, ABCC10, and ABCE1 genes and mediate changes in gene expression. Correlation analysis between ABC and miRNA expression in individual patients revealed an inverse relationship, providing an indication for miRNA regulation of ABC genes in HCC. Conclusion: Up-regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down-regulation. Up-regulation of five ABC genes appears to be mediated by 13 cellular miRNAs in HCC patient samples. miRNA-based gene therapy may be a novel and promising way to affect the ABC profile and overcome clinical multidrug resistance. (Hepatology 2012)
Alessandro Martino - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms in xenobiotic transporters abcb1 abcg2 abcc2 abcc1 ABCC3 and multiple myeloma risk a case control study in the context of the international multiple myeloma research immense consortium
Leukemia, 2012Co-Authors: Alessandro Martino, Daniele Campa, Gabriele Buda, Juan Sainz, Krzysztof Jamroziak, Rui Manuel Reis, Niels Weinhold, Manuel Jurado, Ramon Garciasanz, Rafael RiosAbstract:Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
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Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
Leukemia, 2011Co-Authors: Alessandro Martino, Daniele Campa, Gabriele Buda, Juan Sainz, Ramón García-sanz, Krzysztof Jamroziak, Rui Manuel Reis, Niels Weinhold, Manuel Jurado, Rafael RiosAbstract:Polymorphisms in xenobiotic transporters ABCB1 , ABCG2 , ABCC2 , ABCC1 , ABCC3 and multiple myeloma risk: a case–control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
Michelle Haber - One of the best experts on this subject based on the ideXlab platform.
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ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux
Journal of the National Cancer Institute, 2011Co-Authors: Michelle J. Henderson, Claudia Flemming, Michelle Haber, Antonio Porro, Marcia A Munoz, Nunzio Iraci, Chengyuan Xue, Jayne Murray, Janice Smith, Jamie I. FletcherAbstract:Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the “poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001).
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Expression of the multidrug transporter genes ABCC1/MRP1, ABCC3/MRP3, and ABCC4/MRP4 are powerful predictors of clinical outcome in childhood neuroblastoma
Journal of Clinical Oncology, 2007Co-Authors: Murray D. Norris, Janine Smith, Alan Kwek, Claudia Flemming, Susan L. Cohn, Wendy B. London, Allen Buxton, Glenn M. Marshall, Michelle HaberAbstract:9524 Background: We have previously shown, both retrospectively and prospectively, that high-level expression of the multidrug transporter gene ABCC1/MRP1, is strongly predictive of poor outcome in the childhood cancer neuroblastoma (NEJM, 334:231–8, 1996; JCO, 24:1546–53, 2006), and that ABCC1/MRP1 can be regulated by the MYCN oncogene. The contribution of other ABCC family genes to clinical outcome in this disease has now been examined. Methods: Real-time quantitative PCR was used to determine ABCC gene expression in a large prospectively accrued cohort (n=209) of primary untreated neuroblastomas from patients enrolled on POG biology protocol 9047. Results: Older age, advanced stage, and MYCN amplification were all predictive of poor outcome in the cohort. Amongst the ABCC family, high levels of ABCC1 and ABCC4, but low levels of ABCC3, were strongly associated with reduced survival and event-free survival (P
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expression of the multidrug transporter genes abcc1 mrp1 ABCC3 mrp3 and abcc4 mrp4 are powerful predictors of clinical outcome in childhood neuroblastoma
Journal of Clinical Oncology, 2007Co-Authors: Murray D. Norris, Janine Smith, Alan Kwek, Claudia Flemming, Susan L. Cohn, Wendy B. London, Allen Buxton, Glenn M. Marshall, Michelle HaberAbstract:9524 Background: We have previously shown, both retrospectively and prospectively, that high-level expression of the multidrug transporter gene ABCC1/MRP1, is strongly predictive of poor outcome in the childhood cancer neuroblastoma (NEJM, 334:231–8, 1996; JCO, 24:1546–53, 2006), and that ABCC1/MRP1 can be regulated by the MYCN oncogene. The contribution of other ABCC family genes to clinical outcome in this disease has now been examined. Methods: Real-time quantitative PCR was used to determine ABCC gene expression in a large prospectively accrued cohort (n=209) of primary untreated neuroblastomas from patients enrolled on POG biology protocol 9047. Results: Older age, advanced stage, and MYCN amplification were all predictive of poor outcome in the cohort. Amongst the ABCC family, high levels of ABCC1 and ABCC4, but low levels of ABCC3, were strongly associated with reduced survival and event-free survival (P<0.005) in the overall study population, and also in subgroups of patients lacking MYCN amplific...