The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Branimir I. Sikic - One of the best experts on this subject based on the ideXlab platform.
-
cabazitaxel is more active than first generation taxanes in abcb1 cell lines due to its reduced affinity for p glycoprotein
Cancer Chemotherapy and Pharmacology, 2018Co-Authors: George E. Duran, Dorothee Semiond, Volker Derdau, Dietmar Weitz, Nicolas Philippe, Jorg Blankenstein, Jens Atzrodt, Diego A Gianolio, Sandrine Mace, Branimir I. SikicAbstract:The primary aim of this study was to determine cabazitaxel’s affinity for the ABCB1/P-glycoprotein (P-gp) transporter compared to first-generation taxanes. We determined the kinetics of drug accumulation and retention using [14C]-labeled taxanes in multidrug-resistant (MDR) cells. In addition, membrane-enriched fractions isolated from doxorubicin-selected MES-SA/Dx5 cells were used to determine sodium orthovanadate-sensitive ATPase stimulation after exposure to taxanes. Custom [3H]-azido-taxane analogues were synthesized for the photoaffinity labeling of P-gp. The maximum intracellular drug concentration was achieved faster with [14C]-cabazitaxel (5 min) than [14C]-docetaxel (15–30 min). MDR cells accumulated twice as much cabazitaxel than docetaxel, and these levels could be restored to parental levels in the presence of the P-gp inhibitor PSC-833 (Valspodar). Efflux in drug-free medium confirmed that MDR cells retained twice as much cabazitaxel than docetaxel. There was a strong association (r2 = 0.91) between the degree of taxane resistance conferred by P-gp expression and the accumulation differences observed with the two taxanes. One cell model expressing low levels of P-gp was not cross-resistant to cabazitaxel while demonstrating modest resistance to docetaxel. Furthermore, there was a 1.9 × reduction in sodium orthovanadate-sensitive ATPase stimulation resulting from treatment with cabazitaxel compared to docetaxel. We calculated a dissociation constant (Kd) value of 1.7 µM for [3H]-azido-docetaxel and ~ 7.5 µM for [3H]-azido-cabazitaxel resulting in a 4.4 × difference in P-gp labeling, and cold docetaxel was a more effective competitor than cabazitaxel. Our studies confirm that cabazitaxel is more active in ABCB1(+) cell models due to its reduced affinity for P-gp compared to docetaxel.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
mitoxantrone etoposide and cytarabine with or without Valspodar in patients with relapsed or refractory acute myeloid leukemia and high risk myelodysplastic syndrome a phase iii trial e2995
Journal of Clinical Oncology, 2004Co-Authors: Peter L Greenberg, Branimir I. Sikic, Sandra J Lee, Ranjana H Advani, Martin S Tallman, Louis Letendre, Kathleen Dugan, Bert L Lum, David L Chin, Gordon W DewaldAbstract:Purpose To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator Valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Patients and Methods A phase III randomized study was performed using Valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n = 66) versus MEC (n = 63) to treat patients with relapsed or refractory AML and high-risk MDS. Results For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P = not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased—35% versus 15% for the remaining patients (P = .018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the pati...
-
mitoxantrone etoposide and cytarabine with or without Valspodar in patients with relapsed or refractory acute myeloid leukemia and high risk myelodysplastic syndrome a phase iii trial e2995
Journal of Clinical Oncology, 2004Co-Authors: Peter L Greenberg, Branimir I. Sikic, Ranjana H Advani, Martin S Tallman, Louis Letendre, Kathleen Dugan, David L Chin, Gordon W Dewald, Elisabeth Paietta, John M BennettAbstract:Purpose To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator Valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Patients and Methods A phase III randomized study was performed using Valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n = 66) versus MEC (n = 63) to treat patients with relapsed or refractory AML and high-risk MDS. Results For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P = not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased—35% versus 15% for the remaining patients (P = .018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the pati...
George E. Duran - One of the best experts on this subject based on the ideXlab platform.
-
cabazitaxel is more active than first generation taxanes in abcb1 cell lines due to its reduced affinity for p glycoprotein
Cancer Chemotherapy and Pharmacology, 2018Co-Authors: George E. Duran, Dorothee Semiond, Volker Derdau, Dietmar Weitz, Nicolas Philippe, Jorg Blankenstein, Jens Atzrodt, Diego A Gianolio, Sandrine Mace, Branimir I. SikicAbstract:The primary aim of this study was to determine cabazitaxel’s affinity for the ABCB1/P-glycoprotein (P-gp) transporter compared to first-generation taxanes. We determined the kinetics of drug accumulation and retention using [14C]-labeled taxanes in multidrug-resistant (MDR) cells. In addition, membrane-enriched fractions isolated from doxorubicin-selected MES-SA/Dx5 cells were used to determine sodium orthovanadate-sensitive ATPase stimulation after exposure to taxanes. Custom [3H]-azido-taxane analogues were synthesized for the photoaffinity labeling of P-gp. The maximum intracellular drug concentration was achieved faster with [14C]-cabazitaxel (5 min) than [14C]-docetaxel (15–30 min). MDR cells accumulated twice as much cabazitaxel than docetaxel, and these levels could be restored to parental levels in the presence of the P-gp inhibitor PSC-833 (Valspodar). Efflux in drug-free medium confirmed that MDR cells retained twice as much cabazitaxel than docetaxel. There was a strong association (r2 = 0.91) between the degree of taxane resistance conferred by P-gp expression and the accumulation differences observed with the two taxanes. One cell model expressing low levels of P-gp was not cross-resistant to cabazitaxel while demonstrating modest resistance to docetaxel. Furthermore, there was a 1.9 × reduction in sodium orthovanadate-sensitive ATPase stimulation resulting from treatment with cabazitaxel compared to docetaxel. We calculated a dissociation constant (Kd) value of 1.7 µM for [3H]-azido-docetaxel and ~ 7.5 µM for [3H]-azido-cabazitaxel resulting in a 4.4 × difference in P-gp labeling, and cold docetaxel was a more effective competitor than cabazitaxel. Our studies confirm that cabazitaxel is more active in ABCB1(+) cell models due to its reduced affinity for P-gp compared to docetaxel.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
Modulation of resistance to idarubicin by the cyclosporin PSC 833 (Valspodar) in multidrug-resistant cells
2003Co-Authors: Norman J. Lacayo, George E. Duran, Branimir I. SikicAbstract:Idarubicin (IDA) is an anthracycline anticancer drug utilized in the treatment of acute leukemias. There are conflicting data published with regard to the cross-resistance of IDA in multidrug-resistant (MDR) cells expressing P-glycoprotein (P-gp). We evaluated the cytotoxicity and cellular accumulation of IDA in a panel of anthracycline-selected MDR cell lines. Leukemia K562/R7 cells and sarcoma MES-SA/Dx5 cells expressing high levels of the MDR1 (ABCB1) gene were resistant to IDA (42-fold and 150-fold, respectively). In both of these cell lines, resistance to IDA was equivalent to that for doxorubicin, the drug used to select for the MDR variants. The P-gp inhibitor PSC 833 (Valspodar) at 2 mM completely restored sensitivity to IDA. IDA accumulation was decreased 12-fold in MES-SA/ Dx5 cells vs parental cell line, and drug uptake was restored to control levels by PSC 833. Reduced intracellular IDA was correlated with P-gp content by flow cytometry. Experiments in NIH3T3 murine cells transfected with the human MDR1 gene substantiated the findings of cross-resistance to IDA and reversal of resistance by PSC 833. Our data indicate that IDA is a high-affinity substrate for P-gp
Yan C Wang - One of the best experts on this subject based on the ideXlab platform.
-
decreased levels of baseline and drug induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial to mesenchymal transition
British Journal of Cancer, 2017Co-Authors: Yan C Wang, Francois Moisan, Brian E FranciscoAbstract:ABCB1 expression is uncommon in ovarian cancers in the clinical setting so we investigated non-MDR mechanisms of resistance to taxanes. We established eight taxane-resistant variants from the human ovarian carcinoma cell lines A2780/1A9, ES-2, MES-OV and OVCAR-3 by selection with paclitaxel or docetaxel, with counter-selection by the transport inhibitor Valspodar. Non-MDR taxane resistance was associated with reduced intracellular taxane content compared to parental controls, and cross-resistance to other microtubule stabilising drugs. Collateral sensitivity to depolymerising agents (vinca alkaloids and colchicine) was observed with increased intracellular vinblastine. These variants exhibited marked decreases in basal tubulin polymer and in tubulin polymerisation in response to taxane exposure. TUBB3 content was increased in 6 of the 8 variants. We profiled gene expression of the parental lines and resistant variants, and identified a transcriptomic signature with two highly significant networks built around FN1 and CDKN1A that are associated with cell adhesion, cell-to-cell signalling, and cell cycle regulation. miR-200 family members miR-200b and miR-200c were downregulated in resistant cells, associated with epithelial to mesenchymal transition (EMT), with increased VIM, FN1, MMP2 and/or MMP9. These alterations may serve as biomarkers for predicting taxane effectiveness in ovarian cancer and should be considered as therapeutic targets.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
Rishil J Kathawala - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
Irving L Weissman - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
-
abstract 4001 the anti cd47 antibody hu5f9 g4 activates macrophages and inhibits ovarian cancer xenografts alone and in combination with chemotherapy or immunotherapy
Cancer Research, 2016Co-Authors: Rishil J Kathawala, George E. Duran, Yan C Wang, David C Mundy, Jenspeter Volkmer, Kevin S Kao, Aditi Bellary, Irving L Weissman, Branimir I. SikicAbstract:Macrophage activation by inhibition of CD47 signaling is a new therapeutic approach to cancers. Binding of CD47 to its receptor SIRPα on macrophages initiates a signal cascade that inhibits phagocytosis. Blocking CD47 from interaction with SIRPα by the CD47 antibody Hu5F9-G4 results in phagocytosis of cancer cells, and anticancer activity in xenografts of human cancers. We developed taxane resistant variants from human ovarian carcinoma (OC) cell lines (ES-2, MES-OV and OVCAR-3) by step-wise exposure to paclitaxel (Ptx) and the transport inhibitor Valspodar (6x resistance in ES-2/TP, 9x in MES-OV/TP, and 30x in OVCAR-3/TP). These 6 lines were transduced to establish stable luciferase expression for OC xenograft (OCX) imaging. All express CD47 by immunoblotting and flow cytometry, and all express calreticulin (CRT). CRT is a prophagocytic signal that promotes phagocytosis in the presence of CD47 blockade. CRT levels are lower in the Ptx-resistant variants (p Citation Format: Rishil J. Kathawala, David C. Mundy, George E. Duran, Jens-Peter Volkmer, Kevin S. Kao, Yan C. Wang, Aditi Bellary, Irving L. Weissman, Branimir I. Sikic. The anti-CD47 antibody Hu5F9-G4 activates macrophages and inhibits ovarian cancer xenografts, alone and in combination with chemotherapy or immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4001.
