GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein e...
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Autor*in:	Verbeke, S. [verfasserIn] Perret, R. Chaire, V. Richard, E. Velasco, V. Giles, F. Cavalcante, L. Italiano, A.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Glycogen synthase kinase 3β Soft tissue sarcomas 9-ING-41

Anmerkung:	© The Author(s) 2021

Übergeordnetes Werk:	Enthalten in: Journal of hematology & oncology - London : Biomed Central, 2008, 14(2021), 1 vom: 02. Dez.
Übergeordnetes Werk:	volume:14 ; year:2021 ; number:1 ; day:02 ; month:12

Links:	Volltext

DOI / URN:	10.1186/s13045-021-01215-x

Katalog-ID:	SPR053767578

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allfields	10.1186/s13045-021-01215-x doi (DE-627)SPR053767578 (SPR)s13045-021-01215-x-e DE-627 ger DE-627 rakwb eng Verbeke, S. verfasserin aut GSK3-beta as a candidate therapeutic target in soft tissue sarcomas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213 Perret, R. aut Chaire, V. aut Richard, E. aut Velasco, V. aut Giles, F. aut Cavalcante, L. (orcid)0000-0002-9676-0789 aut Italiano, A. (orcid)0000-0002-8540-5351 aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 14(2021), 1 vom: 02. Dez. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:14 year:2021 number:1 day:02 month:12 https://dx.doi.org/10.1186/s13045-021-01215-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 14 2021 1 02 12
spelling	10.1186/s13045-021-01215-x doi (DE-627)SPR053767578 (SPR)s13045-021-01215-x-e DE-627 ger DE-627 rakwb eng Verbeke, S. verfasserin aut GSK3-beta as a candidate therapeutic target in soft tissue sarcomas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213 Perret, R. aut Chaire, V. aut Richard, E. aut Velasco, V. aut Giles, F. aut Cavalcante, L. (orcid)0000-0002-9676-0789 aut Italiano, A. (orcid)0000-0002-8540-5351 aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 14(2021), 1 vom: 02. Dez. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:14 year:2021 number:1 day:02 month:12 https://dx.doi.org/10.1186/s13045-021-01215-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 14 2021 1 02 12
allfields_unstemmed	10.1186/s13045-021-01215-x doi (DE-627)SPR053767578 (SPR)s13045-021-01215-x-e DE-627 ger DE-627 rakwb eng Verbeke, S. verfasserin aut GSK3-beta as a candidate therapeutic target in soft tissue sarcomas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213 Perret, R. aut Chaire, V. aut Richard, E. aut Velasco, V. aut Giles, F. aut Cavalcante, L. (orcid)0000-0002-9676-0789 aut Italiano, A. (orcid)0000-0002-8540-5351 aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 14(2021), 1 vom: 02. Dez. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:14 year:2021 number:1 day:02 month:12 https://dx.doi.org/10.1186/s13045-021-01215-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 14 2021 1 02 12
allfieldsGer	10.1186/s13045-021-01215-x doi (DE-627)SPR053767578 (SPR)s13045-021-01215-x-e DE-627 ger DE-627 rakwb eng Verbeke, S. verfasserin aut GSK3-beta as a candidate therapeutic target in soft tissue sarcomas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213 Perret, R. aut Chaire, V. aut Richard, E. aut Velasco, V. aut Giles, F. aut Cavalcante, L. (orcid)0000-0002-9676-0789 aut Italiano, A. (orcid)0000-0002-8540-5351 aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 14(2021), 1 vom: 02. Dez. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:14 year:2021 number:1 day:02 month:12 https://dx.doi.org/10.1186/s13045-021-01215-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 14 2021 1 02 12
allfieldsSound	10.1186/s13045-021-01215-x doi (DE-627)SPR053767578 (SPR)s13045-021-01215-x-e DE-627 ger DE-627 rakwb eng Verbeke, S. verfasserin aut GSK3-beta as a candidate therapeutic target in soft tissue sarcomas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213 Perret, R. aut Chaire, V. aut Richard, E. aut Velasco, V. aut Giles, F. aut Cavalcante, L. (orcid)0000-0002-9676-0789 aut Italiano, A. (orcid)0000-0002-8540-5351 aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 14(2021), 1 vom: 02. Dez. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:14 year:2021 number:1 day:02 month:12 https://dx.doi.org/10.1186/s13045-021-01215-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 14 2021 1 02 12
language	English
source	Enthalten in Journal of hematology & oncology 14(2021), 1 vom: 02. Dez. volume:14 year:2021 number:1 day:02 month:12
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topic_facet	Glycogen synthase kinase 3β Soft tissue sarcomas 9-ING-41
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authorswithroles_txt_mv	Verbeke, S. @@aut@@ Perret, R. @@aut@@ Chaire, V. @@aut@@ Richard, E. @@aut@@ Velasco, V. @@aut@@ Giles, F. @@aut@@ Cavalcante, L. @@aut@@ Italiano, A. @@aut@@
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spellingShingle	Verbeke, S. misc Glycogen synthase kinase 3β misc Soft tissue sarcomas misc 9-ING-41 GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
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topic_title	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas Glycogen synthase kinase 3β (dpeaa)DE-He213 Soft tissue sarcomas (dpeaa)DE-He213 9-ING-41 (dpeaa)DE-He213
topic	misc Glycogen synthase kinase 3β misc Soft tissue sarcomas misc 9-ING-41
topic_unstemmed	misc Glycogen synthase kinase 3β misc Soft tissue sarcomas misc 9-ING-41
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title	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
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title_full	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
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title_sort	gsk3-beta as a candidate therapeutic target in soft tissue sarcomas
title_auth	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
abstract	Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. © The Author(s) 2021
abstractGer	Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. © The Author(s) 2021
abstract_unstemmed	Abstract Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. © The Author(s) 2021
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title_short	GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
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GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

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