PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 21487929-1 2011 PURPOSE: To investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME). Cyclophosphamide 83-99 nuclear receptor subfamily 1 group I member 3 Homo sapiens 41-73 21487929-1 2011 PURPOSE: To investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME). Cyclophosphamide 83-99 nuclear receptor subfamily 1 group I member 3 Homo sapiens 75-78 21487929-1 2011 PURPOSE: To investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME). Cyclophosphamide 101-104 nuclear receptor subfamily 1 group I member 3 Homo sapiens 41-73 21487929-1 2011 PURPOSE: To investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME). Cyclophosphamide 101-104 nuclear receptor subfamily 1 group I member 3 Homo sapiens 75-78 21487929-3 2011 Activation of CAR, pregnane X receptor (PXR), and aryl hydrocarbon receptor by CPA and IFO was assessed in cell-based reporter assays in HepG2 cells and/or nuclear translocation assays in HPHs. Cyclophosphamide 79-82 nuclear receptor subfamily 1 group I member 3 Homo sapiens 14-17 21487929-4 2011 RESULTS: CYP2B6 reporter activity was significantly enhanced by CPA and IFO in HepG2 cells co-transfected with CYP2B6 reporter plasmid and a chemical-responsive human CAR variant (CAR1 + A) construct. Cyclophosphamide 64-67 nuclear receptor subfamily 1 group I member 3 Homo sapiens 167-170 21487929-4 2011 RESULTS: CYP2B6 reporter activity was significantly enhanced by CPA and IFO in HepG2 cells co-transfected with CYP2B6 reporter plasmid and a chemical-responsive human CAR variant (CAR1 + A) construct. Cyclophosphamide 64-67 nuclear receptor subfamily 1 group I member 3 Homo sapiens 180-184 21487929-6 2011 Notably, treatment of HPHs with CPA but not IFO resulted in significant nuclear accumulation of CAR, which represents the initial step of CAR activation. Cyclophosphamide 32-35 nuclear receptor subfamily 1 group I member 3 Homo sapiens 96-99 21487929-6 2011 Notably, treatment of HPHs with CPA but not IFO resulted in significant nuclear accumulation of CAR, which represents the initial step of CAR activation. Cyclophosphamide 32-35 nuclear receptor subfamily 1 group I member 3 Homo sapiens 138-141 21487929-8 2011 CONCLUSION: These results provide novel insights into the differential roles of CAR in the regulation of CPA- and IFO-induced DME expression and potential drug-drug interactions. Cyclophosphamide 105-108 nuclear receptor subfamily 1 group I member 3 Homo sapiens 80-83 29749441-4 2018 The second aim was to evaluate the abilities of fludarabine (FDR) and mafosfamide (MFA; a metabolite of cyclophosphamide) to induce apoptosis of CD19-CAR-T cells via the use of Annexin V/propidium iodide double staining. Cyclophosphamide 104-120 nuclear receptor subfamily 1 group I member 3 Homo sapiens 150-153 35579950-0 2022 Targeting CAR-Nrf2 improves cyclophosphamide bioactivation while reducing doxorubicin-induced cardiotoxicity in triple-negative breast cancer treatment. Cyclophosphamide 28-44 nuclear receptor subfamily 1 group I member 3 Homo sapiens 10-13 35579950-3 2022 CN06 enhances CAR-induced bioactivation of CPA (a prodrug) by provoking hepatic expression of CYP2B6, while repressing DOX-induced cytotoxicity in cardiomyocytes in vitro via stimulating Nrf2-antioxidant signaling. Cyclophosphamide 43-46 nuclear receptor subfamily 1 group I member 3 Homo sapiens 14-17 35579950-4 2022 Utilizing a multicellular co-culture model incorporating human primary hepatocytes, TNBC cells, and cardiomyocytes, we show that CN06 increased CPA/DOX-mediated TNBC cell death via CAR-dependent CYP2B6 induction and subsequent conversion of CPA to its active metabolite 4-hydroxy-CPA, while protecting against DOX-induced cardiotoxicity by selectively activating Nrf2-antioxidant signaling in cardiomyocytes but not in TNBC cells. Cyclophosphamide 144-147 nuclear receptor subfamily 1 group I member 3 Homo sapiens 181-184 35579950-4 2022 Utilizing a multicellular co-culture model incorporating human primary hepatocytes, TNBC cells, and cardiomyocytes, we show that CN06 increased CPA/DOX-mediated TNBC cell death via CAR-dependent CYP2B6 induction and subsequent conversion of CPA to its active metabolite 4-hydroxy-CPA, while protecting against DOX-induced cardiotoxicity by selectively activating Nrf2-antioxidant signaling in cardiomyocytes but not in TNBC cells. Cyclophosphamide 241-244 nuclear receptor subfamily 1 group I member 3 Homo sapiens 181-184 35579950-6 2022 Collectively, our findings identify CAR and Nrf2 as novel combined therapeutic targets whereby CN06 holds the potential to improve the efficacy:toxicity ratio of CPA/DOX-containing chemotherapy. Cyclophosphamide 162-165 nuclear receptor subfamily 1 group I member 3 Homo sapiens 36-39 31247375-0 2019 Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies. Cyclophosphamide 78-94 nuclear receptor subfamily 1 group I member 3 Homo sapiens 6-38 31247375-2 2019 As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Cyclophosphamide 14-17 nuclear receptor subfamily 1 group I member 3 Homo sapiens 114-146 26823489-1 2016 The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6, the enzyme predominantly responsible for the biotransformation of cyclophosphamide (CPA) to its pharmacologically active metabolite, 4-hydroxycyclophosphamide (4-OH-CPA). Cyclophosphamide 149-165 nuclear receptor subfamily 1 group I member 3 Homo sapiens 38-41 27605551-3 2016 Patients who received Cy/Flu lymphodepletion had increased CAR-T cell expansion and persistence, and higher response rates [50% complete remission (CR), 72% overall response rate (ORR)] than patients who received Cy-based lymphodepletion without Flu (8% CR, 50% ORR). Cyclophosphamide 22-24 nuclear receptor subfamily 1 group I member 3 Homo sapiens 59-62 26823489-1 2016 The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6, the enzyme predominantly responsible for the biotransformation of cyclophosphamide (CPA) to its pharmacologically active metabolite, 4-hydroxycyclophosphamide (4-OH-CPA). Cyclophosphamide 149-165 nuclear receptor subfamily 1 group I member 3 Homo sapiens 46-51 26823489-1 2016 The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6, the enzyme predominantly responsible for the biotransformation of cyclophosphamide (CPA) to its pharmacologically active metabolite, 4-hydroxycyclophosphamide (4-OH-CPA). Cyclophosphamide 167-170 nuclear receptor subfamily 1 group I member 3 Homo sapiens 38-41 26823489-1 2016 The constitutive androstane receptor (CAR and NR1i3) is a key regulator of CYP2B6, the enzyme predominantly responsible for the biotransformation of cyclophosphamide (CPA) to its pharmacologically active metabolite, 4-hydroxycyclophosphamide (4-OH-CPA). Cyclophosphamide 167-170 nuclear receptor subfamily 1 group I member 3 Homo sapiens 46-51 26823489-2 2016 Previous studies from our laboratory illustrated that CAR activation increases the formation of 4-OH-CPA; however, CPA is rarely used clinically outside of combination therapies. Cyclophosphamide 101-104 nuclear receptor subfamily 1 group I member 3 Homo sapiens 54-57 26823489-3 2016 Here, we hypothesize that including a selective human CAR activator with the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen can improve the efficacy without exacerbating off-target toxicity of this regimen in non-Hodgkin lymphoma treatment. Cyclophosphamide 83-99 nuclear receptor subfamily 1 group I member 3 Homo sapiens 54-57 23160467-2 2013 Given that the CYP2B6 gene is primarily regulated by the constitutive androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR can enhance systemic exposure of the pharmacologically active 4-hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based chemotherapy. Cyclophosphamide 244-247 nuclear receptor subfamily 1 group I member 3 Homo sapiens 57-89 23160467-0 2013 The constitutive androstane receptor is a novel therapeutic target facilitating cyclophosphamide-based treatment of hematopoietic malignancies. Cyclophosphamide 80-96 nuclear receptor subfamily 1 group I member 3 Homo sapiens 4-36 23160467-2 2013 Given that the CYP2B6 gene is primarily regulated by the constitutive androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR can enhance systemic exposure of the pharmacologically active 4-hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based chemotherapy. Cyclophosphamide 244-247 nuclear receptor subfamily 1 group I member 3 Homo sapiens 91-94 23160467-2 2013 Given that the CYP2B6 gene is primarily regulated by the constitutive androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR can enhance systemic exposure of the pharmacologically active 4-hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based chemotherapy. Cyclophosphamide 244-247 nuclear receptor subfamily 1 group I member 3 Homo sapiens 96-101 23160467-2 2013 Given that the CYP2B6 gene is primarily regulated by the constitutive androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR can enhance systemic exposure of the pharmacologically active 4-hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based chemotherapy. Cyclophosphamide 244-247 nuclear receptor subfamily 1 group I member 3 Homo sapiens 148-151 23160467-5 2013 Importantly, coadministration of CPA with a human CAR activator led to significantly enhanced cytotoxicity in leukemia cells by inducing the apoptosis pathways, without concomitant increase in the off-target hepatotoxicity. Cyclophosphamide 33-36 nuclear receptor subfamily 1 group I member 3 Homo sapiens 50-53 23160467-7 2013 Together, our findings offer proof of concept that CAR as a novel molecular target can facilitate CPA-based chemotherapy by selectively promoting its bioactivation. Cyclophosphamide 98-101 nuclear receptor subfamily 1 group I member 3 Homo sapiens 51-54