Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations

Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therap...
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Gespeichert in:

Autor*in:	Zou, Jiale [verfasserIn] Wang, Shuang Chai, Ningli Yue, Hua Ye, Peng Guo, Peilin Li, Feng Wei, Bo Ma, Guanghui Wei, Wei Linghu, Enqiang

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Journal of nanobiotechnology - London : Biomed Central, 2003, 20(2022), 1 vom: 18. Mai
Übergeordnetes Werk:	volume:20 ; year:2022 ; number:1 ; day:18 ; month:05

Links:	Volltext

DOI / URN:	10.1186/s12951-022-01431-8

Katalog-ID:	SPR050721194

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520			\|a Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract
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allfields	10.1186/s12951-022-01431-8 doi (DE-627)SPR050721194 (SPR)s12951-022-01431-8-e DE-627 ger DE-627 rakwb eng Zou, Jiale verfasserin aut Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213 Wang, Shuang aut Chai, Ningli aut Yue, Hua aut Ye, Peng aut Guo, Peilin aut Li, Feng aut Wei, Bo aut Ma, Guanghui aut Wei, Wei aut Linghu, Enqiang aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 18. Mai (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:18 month:05 https://dx.doi.org/10.1186/s12951-022-01431-8 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_70 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_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 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 20 2022 1 18 05
spelling	10.1186/s12951-022-01431-8 doi (DE-627)SPR050721194 (SPR)s12951-022-01431-8-e DE-627 ger DE-627 rakwb eng Zou, Jiale verfasserin aut Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213 Wang, Shuang aut Chai, Ningli aut Yue, Hua aut Ye, Peng aut Guo, Peilin aut Li, Feng aut Wei, Bo aut Ma, Guanghui aut Wei, Wei aut Linghu, Enqiang aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 18. Mai (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:18 month:05 https://dx.doi.org/10.1186/s12951-022-01431-8 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_70 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_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 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 20 2022 1 18 05
allfields_unstemmed	10.1186/s12951-022-01431-8 doi (DE-627)SPR050721194 (SPR)s12951-022-01431-8-e DE-627 ger DE-627 rakwb eng Zou, Jiale verfasserin aut Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213 Wang, Shuang aut Chai, Ningli aut Yue, Hua aut Ye, Peng aut Guo, Peilin aut Li, Feng aut Wei, Bo aut Ma, Guanghui aut Wei, Wei aut Linghu, Enqiang aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 18. Mai (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:18 month:05 https://dx.doi.org/10.1186/s12951-022-01431-8 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_70 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_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 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 20 2022 1 18 05
allfieldsGer	10.1186/s12951-022-01431-8 doi (DE-627)SPR050721194 (SPR)s12951-022-01431-8-e DE-627 ger DE-627 rakwb eng Zou, Jiale verfasserin aut Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213 Wang, Shuang aut Chai, Ningli aut Yue, Hua aut Ye, Peng aut Guo, Peilin aut Li, Feng aut Wei, Bo aut Ma, Guanghui aut Wei, Wei aut Linghu, Enqiang aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 18. Mai (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:18 month:05 https://dx.doi.org/10.1186/s12951-022-01431-8 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_70 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_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 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 20 2022 1 18 05
allfieldsSound	10.1186/s12951-022-01431-8 doi (DE-627)SPR050721194 (SPR)s12951-022-01431-8-e DE-627 ger DE-627 rakwb eng Zou, Jiale verfasserin aut Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213 Wang, Shuang aut Chai, Ningli aut Yue, Hua aut Ye, Peng aut Guo, Peilin aut Li, Feng aut Wei, Bo aut Ma, Guanghui aut Wei, Wei aut Linghu, Enqiang aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 20(2022), 1 vom: 18. Mai (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:20 year:2022 number:1 day:18 month:05 https://dx.doi.org/10.1186/s12951-022-01431-8 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_70 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_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 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 20 2022 1 18 05
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source	Enthalten in Journal of nanobiotechnology 20(2022), 1 vom: 18. Mai volume:20 year:2022 number:1 day:18 month:05
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topic_facet	Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel
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author	Zou, Jiale
spellingShingle	Zou, Jiale misc Gastric cancer misc Patient-derived organoids misc Nanoformulation misc Albumin-bound paclitaxel misc Liposomal paclitaxel Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
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topic_title	Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations Gastric cancer (dpeaa)DE-He213 Patient-derived organoids (dpeaa)DE-He213 Nanoformulation (dpeaa)DE-He213 Albumin-bound paclitaxel (dpeaa)DE-He213 Liposomal paclitaxel (dpeaa)DE-He213
topic	misc Gastric cancer misc Patient-derived organoids misc Nanoformulation misc Albumin-bound paclitaxel misc Liposomal paclitaxel
topic_unstemmed	misc Gastric cancer misc Patient-derived organoids misc Nanoformulation misc Albumin-bound paclitaxel misc Liposomal paclitaxel
topic_browse	misc Gastric cancer misc Patient-derived organoids misc Nanoformulation misc Albumin-bound paclitaxel misc Liposomal paclitaxel
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title	Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
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title_full	Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
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author_browse	Zou, Jiale Wang, Shuang Chai, Ningli Yue, Hua Ye, Peng Guo, Peilin Li, Feng Wei, Bo Ma, Guanghui Wei, Wei Linghu, Enqiang
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title_sort	construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
title_auth	Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
abstract	Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract © The Author(s) 2022
abstractGer	Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract © The Author(s) 2022
abstract_unstemmed	Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract © The Author(s) 2022
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title_short	Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
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author2	Wang, Shuang Chai, Ningli Yue, Hua Ye, Peng Guo, Peilin Li, Feng Wei, Bo Ma, Guanghui Wei, Wei Linghu, Enqiang
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up_date	2024-07-03T17:21:33.409Z
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Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. 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Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations

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