Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target
Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Nakamura, Yoshio [verfasserIn] Mizukami, Hayase [verfasserIn] Tanese, Keiji [verfasserIn] Fusumae, Takayuki [verfasserIn] Hirai, Ikuko [verfasserIn] Amagai, Masayuki [verfasserIn] Takamatsu, Reika [verfasserIn] Nakamura, Kohei [verfasserIn] Nishihara, Hiroshi [verfasserIn] Takimoto, Tetsuya [verfasserIn] Ueno, Masaru [verfasserIn] Saya, Hideyuki [verfasserIn] Funakoshi, Takeru [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: No title available - 112, Seite 23-30 |
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| Übergeordnetes Werk: |
volume:112 ; pages:23-30 |
| DOI / URN: |
10.1016/j.jdermsci.2023.08.005 |
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| Katalog-ID: |
ELV065651049 |
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| 100 | 1 | |a Nakamura, Yoshio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target |
| 264 | 1 | |c 2023 | |
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| 520 | |a Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. | ||
| 650 | 4 | |a Extramammary Paget’s disease | |
| 650 | 4 | |a Androgen | |
| 650 | 4 | |a Androgen receptor | |
| 650 | 4 | |a Organoid | |
| 650 | 4 | |a Darolutamide | |
| 700 | 1 | |a Mizukami, Hayase |e verfasserin |4 aut | |
| 700 | 1 | |a Tanese, Keiji |e verfasserin |4 aut | |
| 700 | 1 | |a Fusumae, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Hirai, Ikuko |e verfasserin |4 aut | |
| 700 | 1 | |a Amagai, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Takamatsu, Reika |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Nishihara, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Takimoto, Tetsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Ueno, Masaru |e verfasserin |4 aut | |
| 700 | 1 | |a Saya, Hideyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Funakoshi, Takeru |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t No title available |g 112, Seite 23-30 |w (DE-627)323606431 |x 0923-1811 |7 nnns |
| 773 | 1 | 8 | |g volume:112 |g pages:23-30 |
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2023 |
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2023 |
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10.1016/j.jdermsci.2023.08.005 doi (DE-627)ELV065651049 (ELSEVIER)S0923-1811(23)00182-2 DE-627 ger DE-627 rda eng Nakamura, Yoshio verfasserin aut Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide Mizukami, Hayase verfasserin aut Tanese, Keiji verfasserin aut Fusumae, Takayuki verfasserin aut Hirai, Ikuko verfasserin aut Amagai, Masayuki verfasserin aut Takamatsu, Reika verfasserin aut Nakamura, Kohei verfasserin aut Nishihara, Hiroshi verfasserin aut Takimoto, Tetsuya verfasserin aut Ueno, Masaru verfasserin aut Saya, Hideyuki verfasserin aut Funakoshi, Takeru verfasserin aut Enthalten in No title available 112, Seite 23-30 (DE-627)323606431 0923-1811 nnns volume:112 pages:23-30 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 112 23-30 |
| spelling |
10.1016/j.jdermsci.2023.08.005 doi (DE-627)ELV065651049 (ELSEVIER)S0923-1811(23)00182-2 DE-627 ger DE-627 rda eng Nakamura, Yoshio verfasserin aut Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide Mizukami, Hayase verfasserin aut Tanese, Keiji verfasserin aut Fusumae, Takayuki verfasserin aut Hirai, Ikuko verfasserin aut Amagai, Masayuki verfasserin aut Takamatsu, Reika verfasserin aut Nakamura, Kohei verfasserin aut Nishihara, Hiroshi verfasserin aut Takimoto, Tetsuya verfasserin aut Ueno, Masaru verfasserin aut Saya, Hideyuki verfasserin aut Funakoshi, Takeru verfasserin aut Enthalten in No title available 112, Seite 23-30 (DE-627)323606431 0923-1811 nnns volume:112 pages:23-30 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 112 23-30 |
| allfields_unstemmed |
10.1016/j.jdermsci.2023.08.005 doi (DE-627)ELV065651049 (ELSEVIER)S0923-1811(23)00182-2 DE-627 ger DE-627 rda eng Nakamura, Yoshio verfasserin aut Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide Mizukami, Hayase verfasserin aut Tanese, Keiji verfasserin aut Fusumae, Takayuki verfasserin aut Hirai, Ikuko verfasserin aut Amagai, Masayuki verfasserin aut Takamatsu, Reika verfasserin aut Nakamura, Kohei verfasserin aut Nishihara, Hiroshi verfasserin aut Takimoto, Tetsuya verfasserin aut Ueno, Masaru verfasserin aut Saya, Hideyuki verfasserin aut Funakoshi, Takeru verfasserin aut Enthalten in No title available 112, Seite 23-30 (DE-627)323606431 0923-1811 nnns volume:112 pages:23-30 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 112 23-30 |
| allfieldsGer |
10.1016/j.jdermsci.2023.08.005 doi (DE-627)ELV065651049 (ELSEVIER)S0923-1811(23)00182-2 DE-627 ger DE-627 rda eng Nakamura, Yoshio verfasserin aut Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide Mizukami, Hayase verfasserin aut Tanese, Keiji verfasserin aut Fusumae, Takayuki verfasserin aut Hirai, Ikuko verfasserin aut Amagai, Masayuki verfasserin aut Takamatsu, Reika verfasserin aut Nakamura, Kohei verfasserin aut Nishihara, Hiroshi verfasserin aut Takimoto, Tetsuya verfasserin aut Ueno, Masaru verfasserin aut Saya, Hideyuki verfasserin aut Funakoshi, Takeru verfasserin aut Enthalten in No title available 112, Seite 23-30 (DE-627)323606431 0923-1811 nnns volume:112 pages:23-30 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 112 23-30 |
| allfieldsSound |
10.1016/j.jdermsci.2023.08.005 doi (DE-627)ELV065651049 (ELSEVIER)S0923-1811(23)00182-2 DE-627 ger DE-627 rda eng Nakamura, Yoshio verfasserin aut Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide Mizukami, Hayase verfasserin aut Tanese, Keiji verfasserin aut Fusumae, Takayuki verfasserin aut Hirai, Ikuko verfasserin aut Amagai, Masayuki verfasserin aut Takamatsu, Reika verfasserin aut Nakamura, Kohei verfasserin aut Nishihara, Hiroshi verfasserin aut Takimoto, Tetsuya verfasserin aut Ueno, Masaru verfasserin aut Saya, Hideyuki verfasserin aut Funakoshi, Takeru verfasserin aut Enthalten in No title available 112, Seite 23-30 (DE-627)323606431 0923-1811 nnns volume:112 pages:23-30 GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 112 23-30 |
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Nakamura, Yoshio @@aut@@ Mizukami, Hayase @@aut@@ Tanese, Keiji @@aut@@ Fusumae, Takayuki @@aut@@ Hirai, Ikuko @@aut@@ Amagai, Masayuki @@aut@@ Takamatsu, Reika @@aut@@ Nakamura, Kohei @@aut@@ Nishihara, Hiroshi @@aut@@ Takimoto, Tetsuya @@aut@@ Ueno, Masaru @@aut@@ Saya, Hideyuki @@aut@@ Funakoshi, Takeru @@aut@@ |
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2023-01-01T00:00:00Z |
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The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. 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Nakamura, Yoshio |
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Nakamura, Yoshio misc Extramammary Paget’s disease misc Androgen misc Androgen receptor misc Organoid misc Darolutamide Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target |
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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target Extramammary Paget’s disease Androgen Androgen receptor Organoid Darolutamide |
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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target |
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Nakamura, Yoshio Mizukami, Hayase Tanese, Keiji Fusumae, Takayuki Hirai, Ikuko Amagai, Masayuki Takamatsu, Reika Nakamura, Kohei Nishihara, Hiroshi Takimoto, Tetsuya Ueno, Masaru Saya, Hideyuki Funakoshi, Takeru |
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role of androgen signaling in androgen receptor-positive extramammary paget's disease: establishment of organoids and their biological analysis as a novel therapeutic target |
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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target |
| abstract |
Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. |
| abstractGer |
Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. |
| abstract_unstemmed |
Background: Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that mainly affects the anogenital and axillary regions. Although its etiology has not been fully elucidated, there is evidence that androgen receptors (AR) are expressed in most cases of EMPD. However, the role of androgen signaling in the pathogenesis of EMPD remains unclear.Objective: To evaluate the role of androgen signaling in tumor growth of AR-positive EMPD.Methods: Patient-derived organoids were established and cultured from two AR-positive EMPD patients: one man and one woman. Cultured organoids were treated with androgen agonists and/or antagonists, then subjected to analysis of changes in organoid proliferation, as well as changes in androgen signaling pathway-specific genes.Results: Organoid cultures were established from each EMPD sample. These organoids were immunohistologically and genetically identical to the original tumor. For each organoid sample, viable cell number increased in response to androgen exposure. The mRNA level of Fkbp5, a known AR target gene, increased in a concentration-dependent manner in organoids exposed to the synthetic androgen R1881. Conversely, the AR inhibitor darolutamide suppressed the viable cell number in a concentration-dependent manner. The mRNA expression levels of MKI67 and Fkbp5 were also suppressed by darolutamide.Conclusion: Our results indicate that androgen signaling is a key pathway involved in the growth of AR-positive EMPD. Therefore, androgen signaling inhibition may be a novel treatment option for EMPD patients who require systemic therapy. |
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Role of androgen signaling in androgen receptor-positive extramammary Paget's disease: Establishment of organoids and their biological analysis as a novel therapeutic target |
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Mizukami, Hayase Tanese, Keiji Fusumae, Takayuki Hirai, Ikuko Amagai, Masayuki Takamatsu, Reika Nakamura, Kohei Nishihara, Hiroshi Takimoto, Tetsuya Ueno, Masaru Saya, Hideyuki Funakoshi, Takeru |
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| score |
7.4004107 |