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 impro...
Ausführliche Beschreibung
Autor*in: |
Jiale Zou [verfasserIn] Shuang Wang [verfasserIn] Ningli Chai [verfasserIn] Hua Yue [verfasserIn] Peng Ye [verfasserIn] Peilin Guo [verfasserIn] Feng Li [verfasserIn] Bo Wei [verfasserIn] Guanghui Ma [verfasserIn] Wei Wei [verfasserIn] Enqiang Linghu [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2022 |
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Übergeordnetes Werk: |
In: Journal of Nanobiotechnology - BMC, 2003, 20(2022), 1, Seite 16 |
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Übergeordnetes Werk: |
volume:20 ; year:2022 ; number:1 ; pages:16 |
Links: |
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DOI / URN: |
10.1186/s12951-022-01431-8 |
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Katalog-ID: |
DOAJ030178193 |
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520 | |a 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 | ||
650 | 4 | |a Gastric cancer | |
650 | 4 | |a Patient-derived organoids | |
650 | 4 | |a Nanoformulation | |
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650 | 4 | |a Liposomal paclitaxel | |
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700 | 0 | |a Enqiang Linghu |e verfasserin |4 aut | |
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10.1186/s12951-022-01431-8 doi (DE-627)DOAJ030178193 (DE-599)DOAJ41c37243fa3f4b6684db722255466994 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Jiale Zou 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 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 Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel Biotechnology Medical technology Shuang Wang verfasserin aut Ningli Chai verfasserin aut Hua Yue verfasserin aut Peng Ye verfasserin aut Peilin Guo verfasserin aut Feng Li verfasserin aut Bo Wei verfasserin aut Guanghui Ma verfasserin aut Wei Wei verfasserin aut Enqiang Linghu verfasserin aut In Journal of Nanobiotechnology BMC, 2003 20(2022), 1, Seite 16 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:20 year:2022 number:1 pages:16 https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/article/41c37243fa3f4b6684db722255466994 kostenfrei https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 |
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10.1186/s12951-022-01431-8 doi (DE-627)DOAJ030178193 (DE-599)DOAJ41c37243fa3f4b6684db722255466994 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Jiale Zou 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 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 Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel Biotechnology Medical technology Shuang Wang verfasserin aut Ningli Chai verfasserin aut Hua Yue verfasserin aut Peng Ye verfasserin aut Peilin Guo verfasserin aut Feng Li verfasserin aut Bo Wei verfasserin aut Guanghui Ma verfasserin aut Wei Wei verfasserin aut Enqiang Linghu verfasserin aut In Journal of Nanobiotechnology BMC, 2003 20(2022), 1, Seite 16 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:20 year:2022 number:1 pages:16 https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/article/41c37243fa3f4b6684db722255466994 kostenfrei https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 |
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10.1186/s12951-022-01431-8 doi (DE-627)DOAJ030178193 (DE-599)DOAJ41c37243fa3f4b6684db722255466994 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Jiale Zou 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 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 Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel Biotechnology Medical technology Shuang Wang verfasserin aut Ningli Chai verfasserin aut Hua Yue verfasserin aut Peng Ye verfasserin aut Peilin Guo verfasserin aut Feng Li verfasserin aut Bo Wei verfasserin aut Guanghui Ma verfasserin aut Wei Wei verfasserin aut Enqiang Linghu verfasserin aut In Journal of Nanobiotechnology BMC, 2003 20(2022), 1, Seite 16 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:20 year:2022 number:1 pages:16 https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/article/41c37243fa3f4b6684db722255466994 kostenfrei https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 |
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10.1186/s12951-022-01431-8 doi (DE-627)DOAJ030178193 (DE-599)DOAJ41c37243fa3f4b6684db722255466994 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Jiale Zou 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 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 Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel Biotechnology Medical technology Shuang Wang verfasserin aut Ningli Chai verfasserin aut Hua Yue verfasserin aut Peng Ye verfasserin aut Peilin Guo verfasserin aut Feng Li verfasserin aut Bo Wei verfasserin aut Guanghui Ma verfasserin aut Wei Wei verfasserin aut Enqiang Linghu verfasserin aut In Journal of Nanobiotechnology BMC, 2003 20(2022), 1, Seite 16 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:20 year:2022 number:1 pages:16 https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/article/41c37243fa3f4b6684db722255466994 kostenfrei https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 |
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10.1186/s12951-022-01431-8 doi (DE-627)DOAJ030178193 (DE-599)DOAJ41c37243fa3f4b6684db722255466994 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Jiale Zou 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 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 Gastric cancer Patient-derived organoids Nanoformulation Albumin-bound paclitaxel Liposomal paclitaxel Biotechnology Medical technology Shuang Wang verfasserin aut Ningli Chai verfasserin aut Hua Yue verfasserin aut Peng Ye verfasserin aut Peilin Guo verfasserin aut Feng Li verfasserin aut Bo Wei verfasserin aut Guanghui Ma verfasserin aut Wei Wei verfasserin aut Enqiang Linghu verfasserin aut In Journal of Nanobiotechnology BMC, 2003 20(2022), 1, Seite 16 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:20 year:2022 number:1 pages:16 https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/article/41c37243fa3f4b6684db722255466994 kostenfrei https://doi.org/10.1186/s12951-022-01431-8 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 16 |
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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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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 |
abstractGer |
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 |
abstract_unstemmed |
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 |
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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 |
url |
https://doi.org/10.1186/s12951-022-01431-8 https://doaj.org/article/41c37243fa3f4b6684db722255466994 https://doaj.org/toc/1477-3155 |
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Shuang Wang Ningli Chai Hua Yue Peng Ye Peilin Guo Feng Li Bo Wei Guanghui Ma Wei Wei Enqiang Linghu |
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Shuang Wang Ningli Chai Hua Yue Peng Ye Peilin Guo Feng Li Bo Wei Guanghui Ma Wei Wei Enqiang Linghu |
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up_date |
2024-07-03T13:27:35.747Z |
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