PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33446509-3 2021 We recently demonstrated that an etoposide-resistant K562 clonal subline, K/VP.5, with reduced levels of TOP2alpha/170, expresses high levels of a novel C-terminal truncated TOP2alpha isoform (90 kDa, TOP2alpha/90). Etoposide 33-42 DNA topoisomerase II alpha Homo sapiens 105-118 34550633-7 2022 Enriched etoposide-induced TOP2A cleavage in the relevant MAML2 genomic region supports a TOP2A DNA damage mechanism. Etoposide 9-18 DNA topoisomerase II alpha Homo sapiens 27-32 34550633-7 2022 Enriched etoposide-induced TOP2A cleavage in the relevant MAML2 genomic region supports a TOP2A DNA damage mechanism. Etoposide 9-18 DNA topoisomerase II alpha Homo sapiens 90-95 35617303-2 2022 For rapidly multiplying malignancies, this has made TOP2alpha/170 an important target for etoposide and other clinically active anticancer drugs. Etoposide 90-99 DNA topoisomerase II alpha Homo sapiens 52-65 35617303-4 2022 Our laboratory recently demonstrated reduced levels of TOP2alpha/170 and overexpression of a C-terminal truncated 90-kDa isoform, TOP2alpha/90, due to intronic polyadenylation (IPA; within intron 19) in an acquired etoposide-resistant K562 clonal cell line, K/VP.5. Etoposide 215-224 DNA topoisomerase II alpha Homo sapiens 130-142 35617303-5 2022 We previously reported that this isoform heterodimerized with TOP2alpha/170 and was a determinant of acquired resistance to etoposide. Etoposide 124-133 DNA topoisomerase II alpha Homo sapiens 62-75 35617303-9 2022 TOP2alpha/170 mRNA/protein expression levels were attenuated in the TOP2alpha gene-edited clones which resulted in resistance to etoposide as assessed by reduced etoposide-induced DNA damage (gammaH2AX, Comet assays) and growth inhibition. Etoposide 129-138 DNA topoisomerase II alpha Homo sapiens 0-13 35617303-9 2022 TOP2alpha/170 mRNA/protein expression levels were attenuated in the TOP2alpha gene-edited clones which resulted in resistance to etoposide as assessed by reduced etoposide-induced DNA damage (gammaH2AX, Comet assays) and growth inhibition. Etoposide 129-138 DNA topoisomerase II alpha Homo sapiens 68-77 35617303-9 2022 TOP2alpha/170 mRNA/protein expression levels were attenuated in the TOP2alpha gene-edited clones which resulted in resistance to etoposide as assessed by reduced etoposide-induced DNA damage (gammaH2AX, Comet assays) and growth inhibition. Etoposide 162-171 DNA topoisomerase II alpha Homo sapiens 0-13 35617303-9 2022 TOP2alpha/170 mRNA/protein expression levels were attenuated in the TOP2alpha gene-edited clones which resulted in resistance to etoposide as assessed by reduced etoposide-induced DNA damage (gammaH2AX, Comet assays) and growth inhibition. Etoposide 162-171 DNA topoisomerase II alpha Homo sapiens 68-77 35617303-11 2022 Forced expression of TOP2alpha/90 in the gene-edited K562 cells further decreased etoposide-induced DNA damage in support of a dominant negative role for this truncated isoform. Etoposide 82-91 DNA topoisomerase II alpha Homo sapiens 21-33 35596703-6 2022 In addition, patients with adverse clinical outcomes were more sensitive to three small molecule inhibitors (bortezomib, doxorubicin, and etoposide), and their targets (PSMB5 and TOP2A) also have elevated expression levels among these patients. Etoposide 138-147 DNA topoisomerase II alpha Homo sapiens 179-184 34031359-2 2021 Here we show that the long non-coding satellite III RNA (SatIII) generates resistance against the topoisomerase IIa (TOP2A) inhibitor etoposide in lung cancer. Etoposide 134-143 DNA topoisomerase II alpha Homo sapiens 117-122 34031359-5 2021 In response to stress, SatIII recruits TOP2A to nuclear stress bodies, which protects TOP2A from a complex formation with etoposide and results in decreased DNA damage after treatment. Etoposide 122-131 DNA topoisomerase II alpha Homo sapiens 39-44 34031359-5 2021 In response to stress, SatIII recruits TOP2A to nuclear stress bodies, which protects TOP2A from a complex formation with etoposide and results in decreased DNA damage after treatment. Etoposide 122-131 DNA topoisomerase II alpha Homo sapiens 86-91 33941661-4 2021 In this study, we show that inhibition of VCP/p97 leads to the prolonged accumulation of etoposide-induced TOP2A- and TOP2B- DNA complexes in a manner that is epistatic with the proteasomal pathway. Etoposide 89-98 DNA topoisomerase II alpha Homo sapiens 107-112 35565244-2 2022 Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). Etoposide 5-14 DNA topoisomerase II alpha Homo sapiens 68-73 35565244-2 2022 Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). Etoposide 16-20 DNA topoisomerase II alpha Homo sapiens 68-73 33446509-3 2021 We recently demonstrated that an etoposide-resistant K562 clonal subline, K/VP.5, with reduced levels of TOP2alpha/170, expresses high levels of a novel C-terminal truncated TOP2alpha isoform (90 kDa, TOP2alpha/90). Etoposide 33-42 DNA topoisomerase II alpha Homo sapiens 105-114 33446509-3 2021 We recently demonstrated that an etoposide-resistant K562 clonal subline, K/VP.5, with reduced levels of TOP2alpha/170, expresses high levels of a novel C-terminal truncated TOP2alpha isoform (90 kDa, TOP2alpha/90). Etoposide 33-42 DNA topoisomerase II alpha Homo sapiens 201-213 32414923-7 2020 Treatments with drugs used to poison/inhibit TOP2A function, such as etoposide and ICRF-193, do not phenocopy the effects on chromosome structure of TOP2A degradation by AID. Etoposide 69-78 DNA topoisomerase II alpha Homo sapiens 45-50 31836624-12 2020 SIGNIFICANCE STATEMENT: Results presented here indicate that miR-9-3p and miR-9-5p decrease TOP2alpha/170 expression levels in acquired resistance to etoposide. Etoposide 150-159 DNA topoisomerase II alpha Homo sapiens 92-101 32193368-5 2020 Using Top2alpha inhibitor (ICRF193 or Etoposide)-treated primary T cells as a model, we demonstrated that disrupting the DNA topology promoted DNA damage and T cell apoptosis via Top2cc accumulation that is associated with protein-DNA breaks (PDB) at genomic DNA. Etoposide 38-47 DNA topoisomerase II alpha Homo sapiens 6-15 27974636-4 2017 We show here that myeloperoxidase activity leads to elevated accumulation of etoposide- and mitoxantrone-induced TOP2A and TOP2B-DNA covalent complexes in cells, which are converted to DNA double-strand breaks. Etoposide 77-86 DNA topoisomerase II alpha Homo sapiens 113-118 33747282-0 2021 Effect of TOP2A and ERCC1 gene polymorphisms on the efficacy and toxicity of cisplatin and etoposide-based chemotherapy in small cell lung cancer patients. Etoposide 91-100 DNA topoisomerase II alpha Homo sapiens 10-15 33747282-4 2021 We undertook this retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on the efficiency and toxicity of chemotherapy with platinum and etoposide in SCLC Caucasian patients. Etoposide 218-227 DNA topoisomerase II alpha Homo sapiens 76-81 31271486-6 2019 Furthermore, we show that HMGA2 significantly reduced genotoxic DNA damage in each tested cancer cell model during treatment with the TOP2A poison etoposide or the catalytic TOP2A inhibitor merbarone. Etoposide 147-156 DNA topoisomerase II alpha Homo sapiens 134-139 28110185-4 2017 In this study, we constructed human topoisomerase II alpha (hTop2alpha) homology model docked with Amsacrine based on crystal structure of human Top2beta in complex with etoposide. Etoposide 170-179 DNA topoisomerase II alpha Homo sapiens 60-70 27974648-2 2017 Using antibody specific for the N-terminal of TOP2alpha, immunoassays indicated the existence of two TOP2alpha isoforms, 170 and 90 kDa, present in K562 leukemia cells and in an acquired etoposide (VP-16)-resistant clone (K/VP.5). Etoposide 187-196 DNA topoisomerase II alpha Homo sapiens 46-55 27974648-2 2017 Using antibody specific for the N-terminal of TOP2alpha, immunoassays indicated the existence of two TOP2alpha isoforms, 170 and 90 kDa, present in K562 leukemia cells and in an acquired etoposide (VP-16)-resistant clone (K/VP.5). Etoposide 187-196 DNA topoisomerase II alpha Homo sapiens 101-110 27974648-2 2017 Using antibody specific for the N-terminal of TOP2alpha, immunoassays indicated the existence of two TOP2alpha isoforms, 170 and 90 kDa, present in K562 leukemia cells and in an acquired etoposide (VP-16)-resistant clone (K/VP.5). Etoposide 198-203 DNA topoisomerase II alpha Homo sapiens 46-55 27974648-2 2017 Using antibody specific for the N-terminal of TOP2alpha, immunoassays indicated the existence of two TOP2alpha isoforms, 170 and 90 kDa, present in K562 leukemia cells and in an acquired etoposide (VP-16)-resistant clone (K/VP.5). Etoposide 198-203 DNA topoisomerase II alpha Homo sapiens 101-110 27974648-3 2017 TOP2alpha/90 expression was dramatically increased in etoposide-resistant K/VP.5 compared with parental K562 cells. Etoposide 54-63 DNA topoisomerase II alpha Homo sapiens 0-9 27974648-9 2017 Immunodetection of complex of enzyme-to-DNA and single-cell gel electrophoresis (Comet) assays demonstrated that K562 cells transfected with a TOP2alpha/90 expression plasmid exhibited reduced etoposide-mediated TOP2alpha-DNA covalent complexes and decreased etoposide-induced DNA damage, respectively, compared with similarly treated K562 cells transfected with empty vector. Etoposide 193-202 DNA topoisomerase II alpha Homo sapiens 143-152 27974648-9 2017 Immunodetection of complex of enzyme-to-DNA and single-cell gel electrophoresis (Comet) assays demonstrated that K562 cells transfected with a TOP2alpha/90 expression plasmid exhibited reduced etoposide-mediated TOP2alpha-DNA covalent complexes and decreased etoposide-induced DNA damage, respectively, compared with similarly treated K562 cells transfected with empty vector. Etoposide 193-202 DNA topoisomerase II alpha Homo sapiens 212-221 27974648-9 2017 Immunodetection of complex of enzyme-to-DNA and single-cell gel electrophoresis (Comet) assays demonstrated that K562 cells transfected with a TOP2alpha/90 expression plasmid exhibited reduced etoposide-mediated TOP2alpha-DNA covalent complexes and decreased etoposide-induced DNA damage, respectively, compared with similarly treated K562 cells transfected with empty vector. Etoposide 259-268 DNA topoisomerase II alpha Homo sapiens 143-152 27974648-11 2017 Further studies are underway to characterize the mechanism(s) by which TOP2alpha/90 plays a role in acquired resistance to etoposide and other TOP2alpha targeting agents. Etoposide 123-132 DNA topoisomerase II alpha Homo sapiens 71-80 29514855-0 2018 The Novel C-terminal Truncated 90-kDa Isoform of Topoisomerase IIalpha (TOP2alpha/90) Is a Determinant of Etoposide Resistance in K562 Leukemia Cells via Heterodimerization with the TOP2alpha/170 Isoform. Etoposide 106-115 DNA topoisomerase II alpha Homo sapiens 72-81 29514855-0 2018 The Novel C-terminal Truncated 90-kDa Isoform of Topoisomerase IIalpha (TOP2alpha/90) Is a Determinant of Etoposide Resistance in K562 Leukemia Cells via Heterodimerization with the TOP2alpha/170 Isoform. Etoposide 106-115 DNA topoisomerase II alpha Homo sapiens 182-191 29514855-2 2018 We previously characterized a C-terminally truncated isoform (TOP2alpha/90), detectable in human leukemia K562 cells but more abundantly expressed in a clonal subline, K/VP.5, with acquired resistance to the anticancer agent etoposide. Etoposide 225-234 DNA topoisomerase II alpha Homo sapiens 62-71 29514855-7 2018 Forced expression of TOP2alpha/90 in K562 cells suppressed, whereas siRNA-mediated knockdown of TOP2alpha/90 in K/VP.5 cells enhanced, etoposide-mediated DNA strand breaks compared with similarly treated cells transfected with empty vector or control siRNAs, respectively. Etoposide 135-144 DNA topoisomerase II alpha Homo sapiens 96-105 29514855-8 2018 In addition, forced expression of TOP2alpha/90 in K562 cells inhibited etoposide cytotoxicity assessed by clonogenic assays. Etoposide 71-80 DNA topoisomerase II alpha Homo sapiens 34-43 28611105-7 2017 Then, we show that despite being more cytotoxic, F14512 is less efficient than etoposide at producing TOP2alpha cleavage-complex (TOP2alphacc) in cells. Etoposide 79-88 DNA topoisomerase II alpha Homo sapiens 102-111 28611105-8 2017 Finally, we report that compared with TOP2alphacc mediated by etoposide, those generated by F14512 persist longer in the genome, are not dependent on TDP2 for cleaning break ends from TOP2alpha, are channeled to a larger extent to resection-based repair processes relying on CtIP and BRCA1 and promote RAD51 recruitment to damaged chromatin. Etoposide 62-71 DNA topoisomerase II alpha Homo sapiens 38-47 25605014-9 2015 Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. Etoposide 169-178 DNA topoisomerase II alpha Homo sapiens 60-65 26421495-5 2015 Moreover, we established in a chromatin context that following treatment with ETO, TDP1kd cells accumulate increased amounts of Top2alpha cleavage complexes, removing them with an altered kinetics. Etoposide 78-81 DNA topoisomerase II alpha Homo sapiens 128-137 24336569-5 2014 A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, whereas another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. Etoposide 191-200 DNA topoisomerase II alpha Homo sapiens 177-182 24327541-4 2014 Using a leukemia cell line model, we show that TOP2 beta (TOP2B) is required for induction of RUNX1 chromosomal breaks by the TOP2 poison etoposide and that, while TOP2 alpha (TOP2A) and TOP2B proteins are both present on RUNX1 and RUNX1T1 chromatin, only the TOP2B enrichment reached significance following etoposide exposure at a region on RUNX1 where translocations occur. Etoposide 138-147 DNA topoisomerase II alpha Homo sapiens 164-174 24103454-2 2013 The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). Etoposide 144-153 DNA topoisomerase II alpha Homo sapiens 112-128 24103454-2 2013 The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC). Etoposide 144-153 DNA topoisomerase II alpha Homo sapiens 130-135 22841979-6 2012 Additional consideration of our TOP2A model in light of an etoposide-inhibited complex of human topoisomerase IIbeta (TOP2B) suggests possible modification points for developing paralog-specific inhibitors to overcome the tendency of topoisomerase II-targeting chemotherapeutics to generate secondary malignancies. Etoposide 59-68 DNA topoisomerase II alpha Homo sapiens 32-37 23163762-5 2013 Ataxia telangiectasia-derived cell lines showed high levels of TOP2A that were associated with hypersensitivity to the TOP2 inhibitor etoposide. Etoposide 134-143 DNA topoisomerase II alpha Homo sapiens 63-68 22285073-10 2012 TOP2A, MSH2 and MLH1 expressions decreased in etoposide resistant sublines relative to MCF7/S cells. Etoposide 46-55 DNA topoisomerase II alpha Homo sapiens 0-5 22528119-6 2012 It was recently shown that the antitumor activity of etoposide was due primarily to the inhibition of Top2alpha, whereas inhibition of Top2beta was responsible for the development of secondary malignancies, pointing to the need for more selective Top2alpha inhibitors. Etoposide 53-62 DNA topoisomerase II alpha Homo sapiens 102-111 22528119-9 2012 We further confirmed that Top2alpha inhibition was due to a catalytic inhibition of the enzyme because it did not induce DNA double-strand breaks in CEM-treated cells but prevented the formation of Top2alpha- rather than Top2beta-DNA covalent complexes induced by etoposide. Etoposide 264-273 DNA topoisomerase II alpha Homo sapiens 26-35 22528119-9 2012 We further confirmed that Top2alpha inhibition was due to a catalytic inhibition of the enzyme because it did not induce DNA double-strand breaks in CEM-treated cells but prevented the formation of Top2alpha- rather than Top2beta-DNA covalent complexes induced by etoposide. Etoposide 264-273 DNA topoisomerase II alpha Homo sapiens 198-207 22285073-2 2012 Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Etoposide 0-9 DNA topoisomerase II alpha Homo sapiens 39-44 22285073-4 2012 In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to understand the relationship between differential expression of these genes and drug resistance against etoposide. Etoposide 237-246 DNA topoisomerase II alpha Homo sapiens 37-42 22285073-14 2012 CONCLUSIONS: Decrease in the expression levels of TOP2A, MSH2 and MLH1 may play significant roles in the development of chemotherapeutic resistance to etoposide in breast cancer. Etoposide 151-160 DNA topoisomerase II alpha Homo sapiens 50-55 19003983-10 2009 The potential therapeutic value in targeting TOP2A by Etoposide, as a single agent, and in combination with Doxorubicin was also explored. Etoposide 54-63 DNA topoisomerase II alpha Homo sapiens 45-50 17089011-6 2006 SK-Br3 cells cultured in the presence of topoisomerase IIalpha (TOP2A) inhibitors doxorubicin and etopoxide (VP-16) demonstrated a 2- to 3-fold increase in FAS promoter activity when compared with control cells growing in drug-free culture conditions. Etoposide 109-114 DNA topoisomerase II alpha Homo sapiens 64-69 20824055-3 2010 In this report, by using knock down experiments, we demonstrated that Top2alpha was largely responsible for the induction of gammaH2AX and cytotoxicity by the Top2 poisons idarubicin and etoposide in normal human cells. Etoposide 187-196 DNA topoisomerase II alpha Homo sapiens 70-79