Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening

Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify a...
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Autor*in:	Nilubol, Naris [verfasserIn] Zhang, Lisa Shen, Min Zhang, Ya-Qin He, Mei Austin, Christopher P Kebebew, Electron

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Adrenocortical cancer High throughput drug screening Chemotherapy Drug repurposing Indication switching

Anmerkung:	© Nilubol et al.; licensee BioMed Central Ltd. 2012

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 10(2012), 1 vom: 21. Sept.
Übergeordnetes Werk:	volume:10 ; year:2012 ; number:1 ; day:21 ; month:09

Links:	Volltext

DOI / URN:	10.1186/1479-5876-10-198

Katalog-ID:	SPR028943457

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520			\|a Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC.
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allfields	10.1186/1479-5876-10-198 doi (DE-627)SPR028943457 (SPR)1479-5876-10-198-e DE-627 ger DE-627 rakwb eng Nilubol, Naris verfasserin aut Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nilubol et al.; licensee BioMed Central Ltd. 2012 Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213 Zhang, Lisa aut Shen, Min aut Zhang, Ya-Qin aut He, Mei aut Austin, Christopher P aut Kebebew, Electron aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 10(2012), 1 vom: 21. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:10 year:2012 number:1 day:21 month:09 https://dx.doi.org/10.1186/1479-5876-10-198 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2012 1 21 09
spelling	10.1186/1479-5876-10-198 doi (DE-627)SPR028943457 (SPR)1479-5876-10-198-e DE-627 ger DE-627 rakwb eng Nilubol, Naris verfasserin aut Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nilubol et al.; licensee BioMed Central Ltd. 2012 Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213 Zhang, Lisa aut Shen, Min aut Zhang, Ya-Qin aut He, Mei aut Austin, Christopher P aut Kebebew, Electron aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 10(2012), 1 vom: 21. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:10 year:2012 number:1 day:21 month:09 https://dx.doi.org/10.1186/1479-5876-10-198 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2012 1 21 09
allfields_unstemmed	10.1186/1479-5876-10-198 doi (DE-627)SPR028943457 (SPR)1479-5876-10-198-e DE-627 ger DE-627 rakwb eng Nilubol, Naris verfasserin aut Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nilubol et al.; licensee BioMed Central Ltd. 2012 Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213 Zhang, Lisa aut Shen, Min aut Zhang, Ya-Qin aut He, Mei aut Austin, Christopher P aut Kebebew, Electron aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 10(2012), 1 vom: 21. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:10 year:2012 number:1 day:21 month:09 https://dx.doi.org/10.1186/1479-5876-10-198 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2012 1 21 09
allfieldsGer	10.1186/1479-5876-10-198 doi (DE-627)SPR028943457 (SPR)1479-5876-10-198-e DE-627 ger DE-627 rakwb eng Nilubol, Naris verfasserin aut Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nilubol et al.; licensee BioMed Central Ltd. 2012 Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213 Zhang, Lisa aut Shen, Min aut Zhang, Ya-Qin aut He, Mei aut Austin, Christopher P aut Kebebew, Electron aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 10(2012), 1 vom: 21. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:10 year:2012 number:1 day:21 month:09 https://dx.doi.org/10.1186/1479-5876-10-198 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2012 1 21 09
allfieldsSound	10.1186/1479-5876-10-198 doi (DE-627)SPR028943457 (SPR)1479-5876-10-198-e DE-627 ger DE-627 rakwb eng Nilubol, Naris verfasserin aut Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nilubol et al.; licensee BioMed Central Ltd. 2012 Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213 Zhang, Lisa aut Shen, Min aut Zhang, Ya-Qin aut He, Mei aut Austin, Christopher P aut Kebebew, Electron aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 10(2012), 1 vom: 21. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:10 year:2012 number:1 day:21 month:09 https://dx.doi.org/10.1186/1479-5876-10-198 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2012 1 21 09
language	English
source	Enthalten in Journal of translational medicine 10(2012), 1 vom: 21. Sept. volume:10 year:2012 number:1 day:21 month:09
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All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. 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spellingShingle	Nilubol, Naris misc Adrenocortical cancer misc High throughput drug screening misc Chemotherapy misc Drug repurposing misc Indication switching Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
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topic_title	Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening Adrenocortical cancer (dpeaa)DE-He213 High throughput drug screening (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug repurposing (dpeaa)DE-He213 Indication switching (dpeaa)DE-He213
topic	misc Adrenocortical cancer misc High throughput drug screening misc Chemotherapy misc Drug repurposing misc Indication switching
topic_unstemmed	misc Adrenocortical cancer misc High throughput drug screening misc Chemotherapy misc Drug repurposing misc Indication switching
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title	Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
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title_full	Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
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title_sort	four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
title_auth	Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
abstract	Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. © Nilubol et al.; licensee BioMed Central Ltd. 2012
abstractGer	Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. © Nilubol et al.; licensee BioMed Central Ltd. 2012
abstract_unstemmed	Background Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC. © Nilubol et al.; licensee BioMed Central Ltd. 2012
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title_short	Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening
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The effective therapeutics for patients with advanced adrenocortical carcinoma(ACC) are greatly needed. The objective of this study was to identify and validate drugs with antineoplastic effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. Methods A quantitative high-throughput proliferation assay of 2,816 clinically approved drugs was performed in the NCI-H295R ACC cell line. We validated the antiproliferative effect of candidate compounds in NCI-H295R cells. Further validation was performed in 3-dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines. Results We identified 79 active compounds against ACC cells; 21 had an efficacy ≥60% and $ IC_{50} $ <1 μM. The top drug categories enriched were cardiotonic, antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate, pyrimethamine for validation. All had an antiproliferative effect in monolayer culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and ouabain inhibited growth of MCA in both cell lines at a low concentration (10 fold below $ IC_{50} $). Methotrexate inhibited growth and caused disintegration of MCA in both cell lines at concentrations well below the maximum serum level (10 to 100 fold of $ IC_{50} $). Pyrimethamine caused growth inhibition in both cell lines at 10 fold of $ IC_{50} $ concentration. Conclusions qHTS of previously approved compounds is an effective and efficient method to identify anticancer drugs for a rare cancer such as ACC. We have validated the antineoplastic effect of Bortezomib, ouabain, Methotrexate and pyrimethamine, which could be translated into clinical trials in patients with locally advanced and/or metastatic ACC.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Adrenocortical cancer</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">High throughput drug screening</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chemotherapy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Drug repurposing</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Indication switching</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhang, Lisa</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Shen, Min</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhang, Ya-Qin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">He, Mei</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Austin, Christopher P</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kebebew, Electron</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of translational medicine</subfield><subfield code="d">London : BioMed Central, 2003</subfield><subfield code="g">10(2012), 1 vom: 21. 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Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening

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