Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance
Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resis...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Harada, Kenji [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Anmerkung: |
© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 |
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| Übergeordnetes Werk: |
Enthalten in: Gastric Cancer - Springer-Verlag, 2002, 24(2021), 6 vom: 16. Juli, Seite 1264-1277 |
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| Übergeordnetes Werk: |
volume:24 ; year:2021 ; number:6 ; day:16 ; month:07 ; pages:1264-1277 |
| Links: |
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| DOI / URN: |
10.1007/s10120-021-01206-4 |
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SPR045255296 |
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| 100 | 1 | |a Harada, Kenji |e verfasserin |4 aut | |
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| 520 | |a Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. | ||
| 650 | 4 | |a Organoids |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Oxaliplatin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Gastric cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a MYOF |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Sakamoto, Naoya |0 (orcid)0000-0001-6273-0189 |4 aut | |
| 700 | 1 | |a Ukai, Shoichi |4 aut | |
| 700 | 1 | |a Yamamoto, Yusuke |4 aut | |
| 700 | 1 | |a Pham, Quoc Thang |4 aut | |
| 700 | 1 | |a Taniyama, Daiki |4 aut | |
| 700 | 1 | |a Honma, Ririno |4 aut | |
| 700 | 1 | |a Maruyama, Ryota |4 aut | |
| 700 | 1 | |a Takashima, Tsuyoshi |4 aut | |
| 700 | 1 | |a Ota, Hiroshi |4 aut | |
| 700 | 1 | |a Takemoto, Yuki |4 aut | |
| 700 | 1 | |a Tanabe, Kazuaki |4 aut | |
| 700 | 1 | |a Ohdan, Hideki |4 aut | |
| 700 | 1 | |a Yasui, Wataru |4 aut | |
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10.1007/s10120-021-01206-4 doi (DE-627)SPR045255296 (SPR)s10120-021-01206-4-e DE-627 ger DE-627 rakwb eng Harada, Kenji verfasserin aut Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. Organoids (dpeaa)DE-He213 Oxaliplatin (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 MYOF (dpeaa)DE-He213 Sakamoto, Naoya (orcid)0000-0001-6273-0189 aut Ukai, Shoichi aut Yamamoto, Yusuke aut Pham, Quoc Thang aut Taniyama, Daiki aut Honma, Ririno aut Maruyama, Ryota aut Takashima, Tsuyoshi aut Ota, Hiroshi aut Takemoto, Yuki aut Tanabe, Kazuaki aut Ohdan, Hideki aut Yasui, Wataru aut Enthalten in Gastric Cancer Springer-Verlag, 2002 24(2021), 6 vom: 16. Juli, Seite 1264-1277 (DE-627)SPR009286586 nnns volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 https://dx.doi.org/10.1007/s10120-021-01206-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA AR 24 2021 6 16 07 1264-1277 |
| spelling |
10.1007/s10120-021-01206-4 doi (DE-627)SPR045255296 (SPR)s10120-021-01206-4-e DE-627 ger DE-627 rakwb eng Harada, Kenji verfasserin aut Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. Organoids (dpeaa)DE-He213 Oxaliplatin (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 MYOF (dpeaa)DE-He213 Sakamoto, Naoya (orcid)0000-0001-6273-0189 aut Ukai, Shoichi aut Yamamoto, Yusuke aut Pham, Quoc Thang aut Taniyama, Daiki aut Honma, Ririno aut Maruyama, Ryota aut Takashima, Tsuyoshi aut Ota, Hiroshi aut Takemoto, Yuki aut Tanabe, Kazuaki aut Ohdan, Hideki aut Yasui, Wataru aut Enthalten in Gastric Cancer Springer-Verlag, 2002 24(2021), 6 vom: 16. Juli, Seite 1264-1277 (DE-627)SPR009286586 nnns volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 https://dx.doi.org/10.1007/s10120-021-01206-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA AR 24 2021 6 16 07 1264-1277 |
| allfields_unstemmed |
10.1007/s10120-021-01206-4 doi (DE-627)SPR045255296 (SPR)s10120-021-01206-4-e DE-627 ger DE-627 rakwb eng Harada, Kenji verfasserin aut Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. Organoids (dpeaa)DE-He213 Oxaliplatin (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 MYOF (dpeaa)DE-He213 Sakamoto, Naoya (orcid)0000-0001-6273-0189 aut Ukai, Shoichi aut Yamamoto, Yusuke aut Pham, Quoc Thang aut Taniyama, Daiki aut Honma, Ririno aut Maruyama, Ryota aut Takashima, Tsuyoshi aut Ota, Hiroshi aut Takemoto, Yuki aut Tanabe, Kazuaki aut Ohdan, Hideki aut Yasui, Wataru aut Enthalten in Gastric Cancer Springer-Verlag, 2002 24(2021), 6 vom: 16. Juli, Seite 1264-1277 (DE-627)SPR009286586 nnns volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 https://dx.doi.org/10.1007/s10120-021-01206-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA AR 24 2021 6 16 07 1264-1277 |
| allfieldsGer |
10.1007/s10120-021-01206-4 doi (DE-627)SPR045255296 (SPR)s10120-021-01206-4-e DE-627 ger DE-627 rakwb eng Harada, Kenji verfasserin aut Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. Organoids (dpeaa)DE-He213 Oxaliplatin (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 MYOF (dpeaa)DE-He213 Sakamoto, Naoya (orcid)0000-0001-6273-0189 aut Ukai, Shoichi aut Yamamoto, Yusuke aut Pham, Quoc Thang aut Taniyama, Daiki aut Honma, Ririno aut Maruyama, Ryota aut Takashima, Tsuyoshi aut Ota, Hiroshi aut Takemoto, Yuki aut Tanabe, Kazuaki aut Ohdan, Hideki aut Yasui, Wataru aut Enthalten in Gastric Cancer Springer-Verlag, 2002 24(2021), 6 vom: 16. Juli, Seite 1264-1277 (DE-627)SPR009286586 nnns volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 https://dx.doi.org/10.1007/s10120-021-01206-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA AR 24 2021 6 16 07 1264-1277 |
| allfieldsSound |
10.1007/s10120-021-01206-4 doi (DE-627)SPR045255296 (SPR)s10120-021-01206-4-e DE-627 ger DE-627 rakwb eng Harada, Kenji verfasserin aut Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. Organoids (dpeaa)DE-He213 Oxaliplatin (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 MYOF (dpeaa)DE-He213 Sakamoto, Naoya (orcid)0000-0001-6273-0189 aut Ukai, Shoichi aut Yamamoto, Yusuke aut Pham, Quoc Thang aut Taniyama, Daiki aut Honma, Ririno aut Maruyama, Ryota aut Takashima, Tsuyoshi aut Ota, Hiroshi aut Takemoto, Yuki aut Tanabe, Kazuaki aut Ohdan, Hideki aut Yasui, Wataru aut Enthalten in Gastric Cancer Springer-Verlag, 2002 24(2021), 6 vom: 16. Juli, Seite 1264-1277 (DE-627)SPR009286586 nnns volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 https://dx.doi.org/10.1007/s10120-021-01206-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA AR 24 2021 6 16 07 1264-1277 |
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Enthalten in Gastric Cancer 24(2021), 6 vom: 16. Juli, Seite 1264-1277 volume:24 year:2021 number:6 day:16 month:07 pages:1264-1277 |
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Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. 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Harada, Kenji Sakamoto, Naoya Ukai, Shoichi Yamamoto, Yusuke Pham, Quoc Thang Taniyama, Daiki Honma, Ririno Maruyama, Ryota Takashima, Tsuyoshi Ota, Hiroshi Takemoto, Yuki Tanabe, Kazuaki Ohdan, Hideki Yasui, Wataru |
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establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance |
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Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance |
| abstract |
Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 |
| abstractGer |
Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 |
| abstract_unstemmed |
Background The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. Methods In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. Results We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Conclusions Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases. © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2021 |
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Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance |
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Sakamoto, Naoya Ukai, Shoichi Yamamoto, Yusuke Pham, Quoc Thang Taniyama, Daiki Honma, Ririno Maruyama, Ryota Takashima, Tsuyoshi Ota, Hiroshi Takemoto, Yuki Tanabe, Kazuaki Ohdan, Hideki Yasui, Wataru |
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