PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 26598513-9 2016 Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Dexrazoxane 51-62 survival of motor neuron 1, telomeric Homo sapiens 76-79 26873546-8 2016 Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. Dexrazoxane 6-9 troponin T2, cardiac Mus musculus 49-53 23474841-0 2013 Dexrazoxane prevents the development of the impaired cardiac phenotype in caveolin-1-disrupted mice. Dexrazoxane 0-11 caveolin 1, caveolae protein Mus musculus 74-84 25955698-9 2015 The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol. Dexrazoxane 156-167 insulin like growth factor 1 receptor Homo sapiens 16-22 25955698-9 2015 The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol. Dexrazoxane 156-167 insulin like growth factor binding protein 3 Homo sapiens 39-46 25723884-1 2015 BACKGROUND: To evaluate the cardioprotective effect of dexrazoxane (DEX) on chemotherapy in patients with breast cancer with concurrent type 2 diabetes mellitus (DM2). Dexrazoxane 55-66 immunoglobulin heavy diversity 1-14 (non-functional) Homo sapiens 162-165 25723884-1 2015 BACKGROUND: To evaluate the cardioprotective effect of dexrazoxane (DEX) on chemotherapy in patients with breast cancer with concurrent type 2 diabetes mellitus (DM2). Dexrazoxane 68-71 immunoglobulin heavy diversity 1-14 (non-functional) Homo sapiens 162-165 25723884-11 2015 CONCULSIONS: DEX protects against cardiotoxicity induced by chemotherapy in patients with breast cancer with concurrent DM2. Dexrazoxane 13-16 immunoglobulin heavy diversity 1-14 (non-functional) Homo sapiens 120-123 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 ATR serine/threonine kinase Homo sapiens 130-133 25521189-0 2015 The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells. Dexrazoxane 41-52 activating transcription factor 3 Homo sapiens 73-77 25521189-2 2015 EXPERIMENTAL APPROACH: We investigated the DNA damage response and the role of the activating transcription factor 3 (ATF3) accumulation in tumour cells exposed to dexrazoxane. Dexrazoxane 164-175 activating transcription factor 3 Homo sapiens 83-116 25521189-2 2015 EXPERIMENTAL APPROACH: We investigated the DNA damage response and the role of the activating transcription factor 3 (ATF3) accumulation in tumour cells exposed to dexrazoxane. Dexrazoxane 164-175 activating transcription factor 3 Homo sapiens 118-122 25521189-3 2015 KEY RESULTS: Dexrazoxane exposure induced topoisomerase IIalpha (TOP2A)-dependent cell death, gamma-H2AX accumulation and increased tail moment in neutral comet assays. Dexrazoxane 13-24 DNA topoisomerase II alpha Homo sapiens 65-70 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 ATM serine/threonine kinase Homo sapiens 93-127 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 ATM serine/threonine kinase Homo sapiens 93-96 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 checkpoint kinase 1 Homo sapiens 158-162 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 checkpoint kinase 2 Homo sapiens 167-171 25521189-4 2015 Dexrazoxane induced DNA damage responses, shown by enhanced levels of gamma-H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane 0-11 tumor protein p53 Homo sapiens 196-199 25521189-5 2015 Dexrazoxane-induced gamma-H2AX accumulation was dependent on ATM. Dexrazoxane 0-11 ATM serine/threonine kinase Homo sapiens 61-64 25521189-6 2015 ATF3 protein was induced by dexrazoxane in a concentration- and time-dependent manner, which was abolished in TOP2A-depleted cells and in cells pre-incubated with ATM inhibitor. Dexrazoxane 28-39 activating transcription factor 3 Homo sapiens 0-4 25521189-6 2015 ATF3 protein was induced by dexrazoxane in a concentration- and time-dependent manner, which was abolished in TOP2A-depleted cells and in cells pre-incubated with ATM inhibitor. Dexrazoxane 28-39 DNA topoisomerase II alpha Homo sapiens 110-115 25521189-6 2015 ATF3 protein was induced by dexrazoxane in a concentration- and time-dependent manner, which was abolished in TOP2A-depleted cells and in cells pre-incubated with ATM inhibitor. Dexrazoxane 28-39 ATM serine/threonine kinase Homo sapiens 163-166 25521189-7 2015 Knockdown of ATF3 gene expression by siRNA triggered apoptosis in control cells and diminished the p53 protein level in both control and dexrazoxane -treated cells. Dexrazoxane 137-148 activating transcription factor 3 Homo sapiens 13-17 25521189-7 2015 Knockdown of ATF3 gene expression by siRNA triggered apoptosis in control cells and diminished the p53 protein level in both control and dexrazoxane -treated cells. Dexrazoxane 137-148 tumor protein p53 Homo sapiens 99-102 25521189-9 2015 ATF3 knockdown also delayed the repair of dexrazoxane -induced DNA double-strand breaks. Dexrazoxane 42-53 activating transcription factor 3 Homo sapiens 0-4 25521189-10 2015 CONCLUSIONS AND IMPLICATIONS: As with other TOP2A poisons, dexrazoxane induced DNA double-strand breaks followed by activation of the DNA damage response. Dexrazoxane 59-70 DNA topoisomerase II alpha Homo sapiens 44-49 25521189-11 2015 The DNA damage-triggered ATF3 controlled p53 accumulation and generation of double-strand breaks and is proposed to serve as a switch between DNA damage and cell death following dexrazoxane treatment. Dexrazoxane 178-189 activating transcription factor 3 Homo sapiens 25-29 25521189-11 2015 The DNA damage-triggered ATF3 controlled p53 accumulation and generation of double-strand breaks and is proposed to serve as a switch between DNA damage and cell death following dexrazoxane treatment. Dexrazoxane 178-189 tumor protein p53 Homo sapiens 41-44 25609833-4 2015 Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. Dexrazoxane 0-5 H2A.X variant histone Mus musculus 189-198 25609833-8 2015 DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Dexrazoxane 155-160 H2A.X variant histone Mus musculus 196-205 25609833-9 2015 Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. Dexrazoxane 14-19 RAC-alpha serine/threonine-protein kinase Callithrix jacchus 72-76 25609833-9 2015 Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. Dexrazoxane 14-19 caspase-9 Callithrix jacchus 97-106 25634181-0 2015 Cardiac protective effects of dexrazoxane on animal cardiotoxicity model induced by anthracycline combined with trastuzumab is associated with upregulation of calpain-2. Dexrazoxane 30-41 calpain 2 Rattus norvegicus 159-168 23474841-6 2013 We evaluated dexrazoxane treatment for 6 weeks in cav1 mice and wild-type controls. Dexrazoxane 13-24 caveolin 1, caveolae protein Mus musculus 50-54 23474841-7 2013 This study provides the first evidence for a reduced reactive oxygen species formation in the vessels of dexrazoxane-treated cav1 mice. Dexrazoxane 105-116 caveolin 1, caveolae protein Mus musculus 125-129 23474841-8 2013 This reduced oxidative stress resulted in a markedly reduced rate of apoptosis, which finally was translated into a significantly improved heart function in dexrazoxane-treated cav1 mice. Dexrazoxane 157-168 caveolin 1, caveolae protein Mus musculus 177-181 23474841-11 2013 Taken together, these novel findings indicate that dexrazoxane significantly reduces vascular reactive oxygen species formation cav1. Dexrazoxane 51-62 caveolin 1, caveolae protein Mus musculus 128-132 23474841-12 2013 Because this is paralleled by an improved cardiac performance in cav1 mice, our data suggest dexrazoxane as a novel therapeutic strategy in this specific cardiomyopathy. Dexrazoxane 93-104 caveolin 1, caveolae protein Mus musculus 65-69 23798789-2 2012 Good chromatographic separation of dexrazoxane was achieved by using Kromasil C18 column. Dexrazoxane 35-46 Bardet-Biedl syndrome 9 Homo sapiens 78-81 22429609-12 2012 RESULTS: In vitro experiments showed a significantly higher MTT activity in cells treated with zoledronic acid together with dexrazoxane compared to the same cells treated with the bisphosphonate alone in t-test (HOB: p=0.0003; HGF: p below 0.0001) and one-way ANOVA. Dexrazoxane 125-136 hepatocyte growth factor Homo sapiens 228-231 23181280-10 2012 DOX binds and inactivates calsequestrin 2 expression so increased calsequestrin 2 expression in DOX:DEX-treated dams suggests some DEX compensation. Dexrazoxane 100-103 calsequestrin 2 Rattus norvegicus 26-41 23181280-10 2012 DOX binds and inactivates calsequestrin 2 expression so increased calsequestrin 2 expression in DOX:DEX-treated dams suggests some DEX compensation. Dexrazoxane 100-103 calsequestrin 2 Rattus norvegicus 66-81 22370326-5 2012 RESULTS: cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). Dexrazoxane 110-121 troponin T2, cardiac type Homo sapiens 9-13 22900064-8 2012 FILIP1L levels increase markedly through transcriptional mechanisms following treatment with doxorubicin and other TOP2 poisons, including etoposide and mitoxantrone, but not by the TOP2 catalytic inhibitors merbarone or dexrazoxane (ICRF187), or by UV irradiation. Dexrazoxane 234-241 filamin A interacting protein 1 like Homo sapiens 0-7 22447943-10 2012 Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Dexrazoxane 60-63 calsequestrin 2 Rattus norvegicus 0-15 20079798-6 2010 Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Dexrazoxane 38-49 topoisomerase (DNA) II alpha Mus musculus 142-147 21232037-5 2011 KEY RESULTS: Treatment with dexrazoxane induced HIF-1alpha and HIF-2alpha protein levels and transactivation capacity in H9c2 cells. Dexrazoxane 28-39 hypoxia inducible factor 1 subunit alpha Rattus norvegicus 48-58 21232037-5 2011 KEY RESULTS: Treatment with dexrazoxane induced HIF-1alpha and HIF-2alpha protein levels and transactivation capacity in H9c2 cells. Dexrazoxane 28-39 endothelial PAS domain protein 1 Rattus norvegicus 63-73 21232037-9 2011 Exposure to dexrazoxane increased the expression of the HIF-regulated, antiapoptotic proteins survivin, Mcl1 and haem oxygenase. Dexrazoxane 12-23 MCL1 apoptosis regulator, BCL2 family member Rattus norvegicus 104-108 20079798-6 2010 Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Dexrazoxane 173-184 topoisomerase (DNA) II alpha Mus musculus 142-147 19738618-0 2009 Induction of thrombospondin-1 partially mediates the anti-angiogenic activity of dexrazoxane. Dexrazoxane 81-92 thrombospondin 1 Homo sapiens 13-29 19841470-0 2010 Sublethal doses of an anti-erbB2 antibody leads to death by apoptosis in cardiomyocytes sensitized by low prosenescent doses of epirubicin: the protective role of dexrazoxane. Dexrazoxane 163-174 erb-b2 receptor tyrosine kinase 2 Rattus norvegicus 27-32 19738618-9 2009 Treatment of microvascular endothelial cells in vitro with subtoxic doses of dexrazoxane stimulated thrombospondin-1 (THBS-1) secretion. Dexrazoxane 77-88 thrombospondin 1 Homo sapiens 100-116 19738618-9 2009 Treatment of microvascular endothelial cells in vitro with subtoxic doses of dexrazoxane stimulated thrombospondin-1 (THBS-1) secretion. Dexrazoxane 77-88 thrombospondin 1 Homo sapiens 118-124 19738618-10 2009 Knockdown of THBS-1 with siRNA removed the angiogenesis inhibition effect of dexrazoxane, which is consistent with the anti-angiogenic and vascular normalising properties of the drug being principally mediated by THBS-1. Dexrazoxane 77-88 thrombospondin 1 Homo sapiens 13-19 19738618-11 2009 CONCLUSION: We show that dexrazoxane administered in small repeated doses is strongly anti-angiogenic and that this activity is mediated by induction of the anti-angiogenic THBS-1 in endothelial cells. Dexrazoxane 25-36 thrombospondin 1 Homo sapiens 173-179 17875725-7 2007 Furthermore, in addition to antagonizing Top2 cleavage complex formation, dexrazoxane also induced rapid degradation of Top2beta, which paralleled the reduction of doxorubicin-induced DNA damage. Dexrazoxane 74-85 topoisomerase (DNA) II beta Mus musculus 120-128 18379782-0 2009 Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Dexrazoxane 0-11 AKT serine/threonine kinase 1 Rattus norvegicus 81-84 18379782-0 2009 Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Dexrazoxane 0-11 Eph receptor B1 Rattus norvegicus 89-92 19417146-2 2009 The clinical application of dexrazoxane is limited, however, because its ability to inhibit topoisomerase IIalpha (TOP2A) is feared to adversely affect anthracycline chemotherapy, which involves TOP2A-mediated generation of DNA double-strand breaks (DSB). Dexrazoxane 28-39 DNA topoisomerase II alpha Homo sapiens 115-120 19417146-2 2009 The clinical application of dexrazoxane is limited, however, because its ability to inhibit topoisomerase IIalpha (TOP2A) is feared to adversely affect anthracycline chemotherapy, which involves TOP2A-mediated generation of DNA double-strand breaks (DSB). Dexrazoxane 28-39 DNA topoisomerase II alpha Homo sapiens 195-200 19417146-5 2009 Unexpectedly, dexrazoxane was found to cause TOP2A depletion, thereby reducing the doxorubicin-induced accumulation of DSB. Dexrazoxane 14-25 DNA topoisomerase II alpha Homo sapiens 45-50 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 36-47 DNA topoisomerase II alpha Homo sapiens 69-74 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 36-47 DNA topoisomerase II alpha Homo sapiens 89-94 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 36-47 DNA topoisomerase II alpha Homo sapiens 89-94 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 184-195 DNA topoisomerase II alpha Homo sapiens 69-74 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 184-195 DNA topoisomerase II alpha Homo sapiens 89-94 19417146-8 2009 In conclusion, both doxorubicin and dexrazoxane induce apoptosis via TOP2A-dependent and TOP2A-independent mechanisms, the latter compensating for the reduction in cell killing due to dexrazoxane-induced TOP2A depletion. Dexrazoxane 184-195 DNA topoisomerase II alpha Homo sapiens 89-94 18385176-6 2008 Crocidolite, dexrazoxane and hypoxia caused HIF-1alpha activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. Dexrazoxane 13-24 hypoxia inducible factor 1 subunit alpha Homo sapiens 44-54 18385176-6 2008 Crocidolite, dexrazoxane and hypoxia caused HIF-1alpha activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. Dexrazoxane 13-24 ATP binding cassette subfamily B member 1 Homo sapiens 67-70 18385176-8 2008 Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1alpha activity, through an iron-sensitive mechanism. Dexrazoxane 13-24 hypoxia inducible factor 1 subunit alpha Homo sapiens 119-150 17875725-5 2007 In the present study, we showed that dexrazoxane specifically abolished the DNA damage signal gamma-H2AX induced by doxorubicin, but not camptothecin or hydrogen peroxide, in H9C2 cardiomyocytes. Dexrazoxane 37-48 H2A.X variant histone Mus musculus 94-104 17875725-8 2007 Together, our results suggest that dexrazoxane antagonizes doxorubicin-induced DNA damage through its interference with Top2beta, which could implicate Top2beta in doxorubicin cardiotoxicity. Dexrazoxane 35-46 topoisomerase (DNA) II beta Mus musculus 120-128 17875725-8 2007 Together, our results suggest that dexrazoxane antagonizes doxorubicin-induced DNA damage through its interference with Top2beta, which could implicate Top2beta in doxorubicin cardiotoxicity. Dexrazoxane 35-46 topoisomerase (DNA) II beta Mus musculus 152-160 12433815-10 2002 Thus, dihydropyrimidinase and DHOase acting in succession on dexrazoxane and its metabolites to form ADR-925 provide a mechanism by which dexrazoxane is activated to exert its cardioprotective effects. Dexrazoxane 61-72 dihydropyrimidinase Homo sapiens 6-25 15764716-6 2005 Hepatocytes that contain both dihydropyrimidinase and dihydroorotase completely hydrolyzed dexrazoxane to ADR-925 and released it into the extracellular medium. Dexrazoxane 91-102 dihydropyrimidinase Rattus norvegicus 30-49 12433815-10 2002 Thus, dihydropyrimidinase and DHOase acting in succession on dexrazoxane and its metabolites to form ADR-925 provide a mechanism by which dexrazoxane is activated to exert its cardioprotective effects. Dexrazoxane 138-149 dihydropyrimidinase Homo sapiens 6-25 11430591-0 2001 Diminished molecular response to doxorubicin and loss of cardioprotective effect of dexrazoxane in Egr-1 deficient female mice. Dexrazoxane 84-95 early growth response 1 Mus musculus 99-104 11986942-7 2002 The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Dexrazoxane 132-135 annexin A5 Homo sapiens 83-92 11986942-8 2002 Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. Dexrazoxane 35-38 annexin A5 Homo sapiens 14-23 11986942-9 2002 This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. Dexrazoxane 132-135 annexin A5 Homo sapiens 93-102 11986942-9 2002 This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. Dexrazoxane 197-200 annexin A5 Homo sapiens 93-102 11794374-11 2001 Dexrazoxane alone had no effect on either Cs, k(s), or kRNA but raised plasma activities of alkaline phosphatase and aspartate aminotransferase. Dexrazoxane 0-11 glutamic-oxaloacetic transaminase 2 Rattus norvegicus 117-143 11794374-12 2001 Combined dexrazoxane + doxorubicin increased Cs and k(s) and decreased total plasma protein and increased plasma aspartate aminotransferase activities at 24 h. In conclusion, there is no evidence that acutely doxorubicin per se has measurable effects on hepatic protein synthesis in vivo in an acute period. Dexrazoxane 9-20 glutamic-oxaloacetic transaminase 2 Rattus norvegicus 113-139 11710630-0 2001 The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity. Dexrazoxane 84-95 troponin T2, cardiac type Rattus norvegicus 27-45 11286477-1 2001 Dexrazoxane combined with doxorubicin (+ 5-fluorouracil + cyclophosphamide - the FAC regime) leads to a significant decrease in doxorubicin cardiotoxicity and a significant increase in median survival time for patients with advanced breast cancer responsive to FAC. Dexrazoxane 0-11 FA complementation group C Homo sapiens 81-84 11410492-15 2001 These results suggest that dexrazoxane as a 96-h infusion can be safely administered with granulocyte-colony stimulating factor at doses that achieve plasma levels that have been demonstrated previously to inhibit topoisomerase II activity and to induce apoptosis in vitro. Dexrazoxane 27-38 colony stimulating factor 3 Homo sapiens 90-127 11286477-1 2001 Dexrazoxane combined with doxorubicin (+ 5-fluorouracil + cyclophosphamide - the FAC regime) leads to a significant decrease in doxorubicin cardiotoxicity and a significant increase in median survival time for patients with advanced breast cancer responsive to FAC. Dexrazoxane 0-11 FA complementation group C Homo sapiens 261-264 11286477-8 2001 In parallel, the expression of functional P-glycoprotein was delayed after concomitant addition of dexrazoxane to the selecting medium (P< 0.001). Dexrazoxane 99-110 ATP binding cassette subfamily B member 1 Homo sapiens 42-56 11286477-10 2001 These results suggest that dexrazoxane may delay the development of MDR1, thus allowing responders to the FAC regime to continue to respond. Dexrazoxane 27-38 ATP binding cassette subfamily B member 1 Homo sapiens 68-72 11286477-10 2001 These results suggest that dexrazoxane may delay the development of MDR1, thus allowing responders to the FAC regime to continue to respond. Dexrazoxane 27-38 FA complementation group C Homo sapiens 106-109 11179439-6 2001 Use of the Bcr-Abl tyrosine kinase inhibitor STI-571 resulted in a reduction in Bcl-xL levels and potentiation of dexrazoxane-induced apoptosis related to an earlier onset and more extensive cleavage of caspase-3. Dexrazoxane 114-125 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 11-18 11179439-6 2001 Use of the Bcr-Abl tyrosine kinase inhibitor STI-571 resulted in a reduction in Bcl-xL levels and potentiation of dexrazoxane-induced apoptosis related to an earlier onset and more extensive cleavage of caspase-3. Dexrazoxane 114-125 caspase 3 Homo sapiens 203-212 11179439-7 2001 These results indicated that dexrazoxane-induced apoptosis is associated with a caspase-3 activation/cleavage pathway. Dexrazoxane 29-40 caspase 3 Homo sapiens 80-89 10960060-2 2000 In this study, we examined the effect of dexrazoxane (ICRF-187), an iron chelator which prevents anthracycline cardiotoxicity, on RyR2 gene expression in rats treated chronically with daunorubicin. Dexrazoxane 41-52 ryanodine receptor 2 Rattus norvegicus 130-134 10960060-6 2000 Dexrazoxane pre-treatment (50 mg kg(-1); 1 h prior to each daunorubicin injection) prevented the decrease in RyR2/GAPDH mRNA ratio and histopathologic lesions in daunorubicin-treated rats. Dexrazoxane 0-11 ryanodine receptor 2 Rattus norvegicus 109-113 10960060-6 2000 Dexrazoxane pre-treatment (50 mg kg(-1); 1 h prior to each daunorubicin injection) prevented the decrease in RyR2/GAPDH mRNA ratio and histopathologic lesions in daunorubicin-treated rats. Dexrazoxane 0-11 glyceraldehyde-3-phosphate dehydrogenase Rattus norvegicus 114-119 10972478-3 2000 Dexrazoxane is also known to inhibit topoisomerase II, to prevent the inactivation of cytochrome c oxidase by Fe3+ -doxorubicin and to increase the levels of transferrin receptor (trf-rec) mRNA and cellular iron uptake. Dexrazoxane 0-11 transferrin receptor Homo sapiens 158-178 10487526-0 1999 Induction of apoptosis by dexrazoxane (ICRF-187) through caspases in the absence of c-jun expression and c-Jun NH2-terminal kinase 1 (JNK1) activation in VM-26-resistant CEM cells. Dexrazoxane 26-37 caspase 1 Homo sapiens 57-65 10412894-8 1999 Cardioxane fulfilled the bioequivalence criteria when compared with ICRF-187 reference formulation for all of the investigated parameters (AUC, t1/2beta, Vdss, Cl(tot), Cl(ren)). Dexrazoxane 0-10 interleukin 1 receptor like 1 Homo sapiens 144-152 10084428-0 1999 Cutaneous and subcutaneous necrosis following dexrazoxane-CHOP therapy. Dexrazoxane 46-57 DNA damage inducible transcript 3 Homo sapiens 58-62 9927611-6 1999 For instance, complex-stabilizing Topo II inhibitors such as etoposide, teniposide, and doxorubicin, which cause DNA damage, strongly induce FasL expression; by contrast, non-DNA-damaging catalytic Topo II inhibitors such as ICRF-187 and merbarone do not do this. Dexrazoxane 225-233 Fas ligand Homo sapiens 141-145 9768822-5 1998 Pharmacologic studies of single agent dexrazoxane (originally studied as an antineoplastic agent) demonstrates an alpha half-life of approximately 30 minutes and a beta half-life of 2 to 4 hours. Dexrazoxane 38-49 amyloid beta precursor protein Homo sapiens 162-168 9260868-0 1997 Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via activation of iron regulatory protein. Dexrazoxane 49-60 transferrin receptor Homo sapiens 14-34 9260868-0 1997 Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via activation of iron regulatory protein. Dexrazoxane 49-60 regenerating family member 1 alpha Homo sapiens 62-66 9260868-1 1997 Dexrazoxane (ICRF-187) has recently been demonstrated to reduce cardiac toxicity induced by chemotherapy with anthracyclines, although the reason for this phenomenon has remained obscure thus far. Dexrazoxane 0-11 regenerating family member 1 alpha Homo sapiens 13-17 9082586-0 1997 [The prevention of anthracycline-induced cardiomyopathy with a chelating agent (dexrazoxane = ICRF-187)]. Dexrazoxane 80-91 regenerating family member 1 alpha Homo sapiens 94-98 8285144-1 1993 The ability of the metal ion binding rings-opened hydrolysis product of the anthracycline cardioprotective agent ICRF-187 [dexrazoxane; (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] to remove iron from transferrin and ferritin, and copper from ceruloplasmin was examined. Dexrazoxane 123-134 transferrin Homo sapiens 203-214 8759037-2 1996 Compared with parental K562 cells, VP-16-resistant K/VP.5 cells were found to be 3.4-fold more sensitive to the effects of dexrazoxane (ICRF-187), a topoisomerase II inhibitor that does not stabilize topoisomerase II-DNA covalent complexes. Dexrazoxane 123-134 host cell factor C1 Homo sapiens 35-40 8759037-2 1996 Compared with parental K562 cells, VP-16-resistant K/VP.5 cells were found to be 3.4-fold more sensitive to the effects of dexrazoxane (ICRF-187), a topoisomerase II inhibitor that does not stabilize topoisomerase II-DNA covalent complexes. Dexrazoxane 123-134 regenerating family member 1 alpha Homo sapiens 136-140 7633562-0 1995 NADPH-cytochrome-P450 reductase promotes hydroxyl radical production by the iron complex of ADR-925, the hydrolysis product of ICRF-187 (dexrazoxane). Dexrazoxane 137-148 cytochrome p450 oxidoreductase Homo sapiens 0-31 7900413-4 1994 4-Chlorobenzenesulphonamide, which is a strong inhibitor of dihydropyrimidine amidohydrolase (DHPase), caused 82% inhibition of the loss of dexrazoxane from the hepatocyte suspension. Dexrazoxane 154-165 dihydropyrimidinase Rattus norvegicus 74-106 7900413-4 1994 4-Chlorobenzenesulphonamide, which is a strong inhibitor of dihydropyrimidine amidohydrolase (DHPase), caused 82% inhibition of the loss of dexrazoxane from the hepatocyte suspension. Dexrazoxane 154-165 dihydropyrimidinase Rattus norvegicus 108-114 7900413-9 1994 The ratios of the rates at which each of the one-ring open intermediates of dexrazoxane and levrazoxane were produced in the hepatocyte suspension are also consistent with DHPase being primarily responsible for the metabolism of dexrazoxane and levrazoxane. Dexrazoxane 76-87 dihydropyrimidinase Rattus norvegicus 172-178 7900413-9 1994 The ratios of the rates at which each of the one-ring open intermediates of dexrazoxane and levrazoxane were produced in the hepatocyte suspension are also consistent with DHPase being primarily responsible for the metabolism of dexrazoxane and levrazoxane. Dexrazoxane 229-240 dihydropyrimidinase Rattus norvegicus 172-178 7900413-11 1994 Thus, the DHPase-catalysed formation of the one-ring opened intermediates enhances the rate at which the presumably active metal-ion binding forms of dexrazoxane are produced in the hepatocyte. Dexrazoxane 150-161 dihydropyrimidinase Rattus norvegicus 10-16 8693714-3 1996 The latter include ICRF-187 bispiperazinedione (dexrazoxan) which is manufactured and supplied by CHIRON Cop. Dexrazoxane 48-58 caspase recruitment domain family member 16 Homo sapiens 105-108 8285144-1 1993 The ability of the metal ion binding rings-opened hydrolysis product of the anthracycline cardioprotective agent ICRF-187 [dexrazoxane; (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] to remove iron from transferrin and ferritin, and copper from ceruloplasmin was examined. Dexrazoxane 123-134 ceruloplasmin Homo sapiens 245-258 34551586-0 2021 Clinically Translatable Prevention of Anthracycline Cardiotoxicity by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation. Dexrazoxane 70-81 DNA topoisomerase II beta Homo sapiens 97-118 34551586-9 2021 DEX, but not ADR-925, inhibited and depleted TOP2B and prevented daunorubicin-induced genotoxic damage. Dexrazoxane 0-3 DNA topoisomerase II beta Homo sapiens 45-50 34551586-10 2021 TOP2B dependency of the cardioprotective effects was probed and supported by experiments with diastereomers of a new DEX derivative. Dexrazoxane 117-120 DNA topoisomerase II beta Homo sapiens 0-5 33406500-4 2021 Dexrazoxane suppressed radiation-induced myocardial apoptosis and significantly reversed changes in serum cardiac troponin I levels and histopathological characteristics six months post-radiation. Dexrazoxane 0-11 troponin I3, cardiac type Rattus norvegicus 106-124 34336950-14 2021 Therefore, DXZ has protective effects on ferroptosis and cardiomyopathy in rats through regulating HMGB1. Dexrazoxane 11-14 high mobility group box 1 Rattus norvegicus 99-104 33750129-2 2021 However, recent experimental evidence suggested that the inhibition and/or depletion of topoisomerase IIbeta (TOP2B) by dexrazoxane could be cardioprotective. Dexrazoxane 120-131 DNA topoisomerase II beta Homo sapiens 110-115 33750129-3 2021 Hence, we evaluated a series of dexrazoxane analogues and found that their cardioprotective activity strongly correlated with their interaction with TOP2B in cardiomyocytes, but was independent of their iron chelation ability. Dexrazoxane 32-43 DNA topoisomerase II beta Homo sapiens 149-154 33406500-7 2021 Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Dexrazoxane 170-181 inhibitor of nuclear factor kappa B kinase subunit epsilon Rattus norvegicus 37-42 33406500-7 2021 Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Dexrazoxane 170-181 mitogen-activated protein kinase kinase kinase 8 Rattus norvegicus 44-50 33406500-7 2021 Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Dexrazoxane 170-181 NFKB inhibitor alpha Rattus norvegicus 52-58 33406500-7 2021 Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Dexrazoxane 170-181 toll-like receptor 5 Rattus norvegicus 64-68 30517846-8 2019 Pretreatment of mice with DXZ significantly attenuated DOX-induced elevated levels of only NOTCH1 and vWF with mitigation of cardiotoxicity. Dexrazoxane 26-29 notch 1 Mus musculus 91-97 32992522-7 2020 We observed an increased succinate secretion in the extracellular fluid of DEX-exposed cardiomyocytes, a finding that led us to the hypothesis of a possible protective role of this agonist of the GPR91 receptor. Dexrazoxane 75-78 succinate receptor 1 Rattus norvegicus 196-201 31837803-8 2020 Forth, dexrazoxane attenuated doxorubicin-induced inflammation and necroptosis by the inhibition of p38MAPK/NF-kappaB pathways. Dexrazoxane 7-18 nuclear factor kappa B subunit 1 Homo sapiens 108-117 31773441-0 2020 The Role of Topoisomerase IIbeta in the Mechanisms of Action of the Doxorubicin Cardioprotective Agent Dexrazoxane. Dexrazoxane 103-114 DNA topoisomerase II beta Rattus norvegicus 12-32 31773441-5 2020 However, a competing hypothesis posits that dexrazoxane may be protective through its ability to inhibit and reduce topoisomerase IIbeta protein levels in the heart. Dexrazoxane 44-55 DNA topoisomerase II beta Rattus norvegicus 116-136 31773441-9 2020 Dexrazoxane treatment resulted in an almost complete reduction of topoisomerase IIbeta in the nucleus and a lesser reduction in the cytoplasm. Dexrazoxane 0-11 DNA topoisomerase II beta Rattus norvegicus 66-86 31773441-10 2020 The recovery of topoisomerase IIbeta levels after a pulse topoisomerase IIbeta inhibitory concentration of dexrazoxane occurred slowly, with partial recovery only occurring after 24 h. The ability of dexrazoxane to reduce doxorubicin-induced damage to myocytes was greatest when topoisomerase IIbeta levels were at their lowest. Dexrazoxane 107-118 DNA topoisomerase II beta Rattus norvegicus 58-78 31773441-10 2020 The recovery of topoisomerase IIbeta levels after a pulse topoisomerase IIbeta inhibitory concentration of dexrazoxane occurred slowly, with partial recovery only occurring after 24 h. The ability of dexrazoxane to reduce doxorubicin-induced damage to myocytes was greatest when topoisomerase IIbeta levels were at their lowest. Dexrazoxane 107-118 DNA topoisomerase II beta Rattus norvegicus 58-78 31773441-10 2020 The recovery of topoisomerase IIbeta levels after a pulse topoisomerase IIbeta inhibitory concentration of dexrazoxane occurred slowly, with partial recovery only occurring after 24 h. The ability of dexrazoxane to reduce doxorubicin-induced damage to myocytes was greatest when topoisomerase IIbeta levels were at their lowest. Dexrazoxane 200-211 DNA topoisomerase II beta Rattus norvegicus 16-36 31773441-10 2020 The recovery of topoisomerase IIbeta levels after a pulse topoisomerase IIbeta inhibitory concentration of dexrazoxane occurred slowly, with partial recovery only occurring after 24 h. The ability of dexrazoxane to reduce doxorubicin-induced damage to myocytes was greatest when topoisomerase IIbeta levels were at their lowest. Dexrazoxane 200-211 DNA topoisomerase II beta Rattus norvegicus 58-78 31773441-10 2020 The recovery of topoisomerase IIbeta levels after a pulse topoisomerase IIbeta inhibitory concentration of dexrazoxane occurred slowly, with partial recovery only occurring after 24 h. The ability of dexrazoxane to reduce doxorubicin-induced damage to myocytes was greatest when topoisomerase IIbeta levels were at their lowest. Dexrazoxane 200-211 DNA topoisomerase II beta Rattus norvegicus 58-78 32190669-14 2020 Taken together, dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade. Dexrazoxane 16-27 phosphatase and tensin homolog Mus musculus 160-164 32154027-3 2020 Here, we asked whether changes in hs-TnT and/or GLS can be detected in patients who were treated with continuous infusion of doxorubicin or pre-treated with dexrazoxane followed by bolus doxorubicin. Dexrazoxane 157-168 troponin T1, slow skeletal type Homo sapiens 37-40 32154027-14 2020 Conclusion: Elevation in hs-TnT levels were observed in more than 59% of patients who had received either continuous doxorubicin infusion or dexrazoxane pre-treatment before bolus doxorubicin. Dexrazoxane 141-152 troponin T1, slow skeletal type Homo sapiens 28-31 30517846-8 2019 Pretreatment of mice with DXZ significantly attenuated DOX-induced elevated levels of only NOTCH1 and vWF with mitigation of cardiotoxicity. Dexrazoxane 26-29 Von Willebrand factor Mus musculus 102-105 29078725-3 2018 Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Dexrazoxane 25-36 BCL2, apoptosis regulator Rattus norvegicus 64-69 30792806-1 2018 Following systematic scrutiny of the evidence in support of the hypothesis that the cardioprotective mechanism of action of dexrazoxane is mediated by a "depletion" or "downregulation" of Top2beta protein levels in heart tissue, the author concludes that this hypothesis is untenable. Dexrazoxane 124-135 DNA topoisomerase II beta Homo sapiens 188-196 29078725-3 2018 Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Dexrazoxane 25-36 BCL2 associated X, apoptosis regulator Rattus norvegicus 70-73 29078725-3 2018 Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Dexrazoxane 25-36 mitogen-activated protein kinase 8 Rattus norvegicus 111-114 29078725-3 2018 Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Dexrazoxane 25-36 caspase 3 Rattus norvegicus 119-128 27388042-9 2017 The doxorubicin cardioprotective agent dexrazoxane partially protected myocytes from doxorubicin plus bortezomib or carfilzomib treatment, in spite of the fact that bortezomib and carfilzomib inhibited the dexrazoxane-induced decreases in topoisomerase IIbeta protein levels in myocytes. Dexrazoxane 39-50 DNA topoisomerase II beta Rattus norvegicus 239-259 28941780-0 2017 Investigation of novel dexrazoxane analogue JR-311 shows significant cardioprotective effects through topoisomerase IIbeta but not its iron chelating metabolite. Dexrazoxane 23-34 DNA topoisomerase II beta Rattus norvegicus 102-122 28941780-5 2017 Although chemical instability is an obstacle for the development of JR-311, this study identified a novel dexrazoxane analogue with preserved pharmacodynamic properties, contributed to the investigation of structure-activity relationships and suggested that the cardioprotection of bis-dioxopiperazines is likely attributed to TOP2B activity of the parent compound rather than Fe chelation of their hydrolytic metabolites/degradation products. Dexrazoxane 106-117 DNA topoisomerase II beta Rattus norvegicus 327-332