Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma

Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pa...
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Autor*in:	Iwasaki, Takeshi [verfasserIn] Kohashi, Kenichi [verfasserIn] Toda, Yu [verfasserIn] Ishihara, Shin [verfasserIn] Yamada, Yuichi [verfasserIn] Oda, Yoshinao [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Soft tissue leiomyosarcoma Programmed death ligand 1 Indoleamine 2,3-dioxygenase 1 JAK–STAT pathway

Anmerkung:	© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Übergeordnetes Werk:	Enthalten in: Journal of cancer research and clinical oncology - Berlin : Springer, 1904, 147(2020), 5 vom: 20. Sept., Seite 1451-1463
Übergeordnetes Werk:	volume:147 ; year:2020 ; number:5 ; day:20 ; month:09 ; pages:1451-1463

Links:	Volltext

DOI / URN:	10.1007/s00432-020-03390-9

Katalog-ID:	SPR043696368

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520			\|a Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS.
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author_variant	t i ti k k kk y t yt s i si y y yy y o yo
matchkey_str	article:14321335:2020----::soitoopladd1xrsinihasaptwyciainno
hierarchy_sort_str	2020
bklnumber	44.81
publishDate	2020
allfields	10.1007/s00432-020-03390-9 doi (DE-627)SPR043696368 (SPR)s00432-020-03390-9-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl Iwasaki, Takeshi verfasserin aut Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213 Kohashi, Kenichi verfasserin aut Toda, Yu verfasserin aut Ishihara, Shin verfasserin aut Yamada, Yuichi verfasserin aut Oda, Yoshinao verfasserin aut Enthalten in Journal of cancer research and clinical oncology Berlin : Springer, 1904 147(2020), 5 vom: 20. Sept., Seite 1451-1463 (DE-627)253769515 (DE-600)1459285-X 1432-1335 nnns volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463 https://dx.doi.org/10.1007/s00432-020-03390-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 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_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 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_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE AR 147 2020 5 20 09 1451-1463
spelling	10.1007/s00432-020-03390-9 doi (DE-627)SPR043696368 (SPR)s00432-020-03390-9-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl Iwasaki, Takeshi verfasserin aut Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213 Kohashi, Kenichi verfasserin aut Toda, Yu verfasserin aut Ishihara, Shin verfasserin aut Yamada, Yuichi verfasserin aut Oda, Yoshinao verfasserin aut Enthalten in Journal of cancer research and clinical oncology Berlin : Springer, 1904 147(2020), 5 vom: 20. Sept., Seite 1451-1463 (DE-627)253769515 (DE-600)1459285-X 1432-1335 nnns volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463 https://dx.doi.org/10.1007/s00432-020-03390-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 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_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 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_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE AR 147 2020 5 20 09 1451-1463
allfields_unstemmed	10.1007/s00432-020-03390-9 doi (DE-627)SPR043696368 (SPR)s00432-020-03390-9-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl Iwasaki, Takeshi verfasserin aut Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213 Kohashi, Kenichi verfasserin aut Toda, Yu verfasserin aut Ishihara, Shin verfasserin aut Yamada, Yuichi verfasserin aut Oda, Yoshinao verfasserin aut Enthalten in Journal of cancer research and clinical oncology Berlin : Springer, 1904 147(2020), 5 vom: 20. Sept., Seite 1451-1463 (DE-627)253769515 (DE-600)1459285-X 1432-1335 nnns volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463 https://dx.doi.org/10.1007/s00432-020-03390-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 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_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 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_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE AR 147 2020 5 20 09 1451-1463
allfieldsGer	10.1007/s00432-020-03390-9 doi (DE-627)SPR043696368 (SPR)s00432-020-03390-9-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl Iwasaki, Takeshi verfasserin aut Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213 Kohashi, Kenichi verfasserin aut Toda, Yu verfasserin aut Ishihara, Shin verfasserin aut Yamada, Yuichi verfasserin aut Oda, Yoshinao verfasserin aut Enthalten in Journal of cancer research and clinical oncology Berlin : Springer, 1904 147(2020), 5 vom: 20. Sept., Seite 1451-1463 (DE-627)253769515 (DE-600)1459285-X 1432-1335 nnns volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463 https://dx.doi.org/10.1007/s00432-020-03390-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 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_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 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_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE AR 147 2020 5 20 09 1451-1463
allfieldsSound	10.1007/s00432-020-03390-9 doi (DE-627)SPR043696368 (SPR)s00432-020-03390-9-e DE-627 ger DE-627 rakwb eng 610 ASE 44.81 bkl Iwasaki, Takeshi verfasserin aut Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213 Kohashi, Kenichi verfasserin aut Toda, Yu verfasserin aut Ishihara, Shin verfasserin aut Yamada, Yuichi verfasserin aut Oda, Yoshinao verfasserin aut Enthalten in Journal of cancer research and clinical oncology Berlin : Springer, 1904 147(2020), 5 vom: 20. Sept., Seite 1451-1463 (DE-627)253769515 (DE-600)1459285-X 1432-1335 nnns volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463 https://dx.doi.org/10.1007/s00432-020-03390-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 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_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 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_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 ASE AR 147 2020 5 20 09 1451-1463
language	English
source	Enthalten in Journal of cancer research and clinical oncology 147(2020), 5 vom: 20. Sept., Seite 1451-1463 volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463
sourceStr	Enthalten in Journal of cancer research and clinical oncology 147(2020), 5 vom: 20. Sept., Seite 1451-1463 volume:147 year:2020 number:5 day:20 month:09 pages:1451-1463
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Soft tissue leiomyosarcoma Programmed death ligand 1 Indoleamine 2,3-dioxygenase 1 JAK–STAT pathway
dewey-raw	610
isfreeaccess_bool	false
container_title	Journal of cancer research and clinical oncology
authorswithroles_txt_mv	Iwasaki, Takeshi @@aut@@ Kohashi, Kenichi @@aut@@ Toda, Yu @@aut@@ Ishihara, Shin @@aut@@ Yamada, Yuichi @@aut@@ Oda, Yoshinao @@aut@@
publishDateDaySort_date	2020-09-20T00:00:00Z
hierarchy_top_id	253769515
dewey-sort	3610
id	SPR043696368
language_de	englisch
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In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). 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author	Iwasaki, Takeshi
spellingShingle	Iwasaki, Takeshi ddc 610 bkl 44.81 misc Soft tissue leiomyosarcoma misc Programmed death ligand 1 misc Indoleamine 2,3-dioxygenase 1 misc JAK–STAT pathway Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma
authorStr	Iwasaki, Takeshi
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topic_title	610 ASE 44.81 bkl Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma Soft tissue leiomyosarcoma (dpeaa)DE-He213 Programmed death ligand 1 (dpeaa)DE-He213 Indoleamine 2,3-dioxygenase 1 (dpeaa)DE-He213 JAK–STAT pathway (dpeaa)DE-He213
topic	ddc 610 bkl 44.81 misc Soft tissue leiomyosarcoma misc Programmed death ligand 1 misc Indoleamine 2,3-dioxygenase 1 misc JAK–STAT pathway
topic_unstemmed	ddc 610 bkl 44.81 misc Soft tissue leiomyosarcoma misc Programmed death ligand 1 misc Indoleamine 2,3-dioxygenase 1 misc JAK–STAT pathway
topic_browse	ddc 610 bkl 44.81 misc Soft tissue leiomyosarcoma misc Programmed death ligand 1 misc Indoleamine 2,3-dioxygenase 1 misc JAK–STAT pathway
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title	Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma
ctrlnum	(DE-627)SPR043696368 (SPR)s00432-020-03390-9-e
title_full	Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma
author_sort	Iwasaki, Takeshi
journal	Journal of cancer research and clinical oncology
journalStr	Journal of cancer research and clinical oncology
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author_browse	Iwasaki, Takeshi Kohashi, Kenichi Toda, Yu Ishihara, Shin Yamada, Yuichi Oda, Yoshinao
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author-letter	Iwasaki, Takeshi
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title_sort	association of pd-l1 and ido1 expression with jak–stat pathway activation in soft-tissue leiomyosarcoma
title_auth	Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma
abstract	Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. © Springer-Verlag GmbH Germany, part of Springer Nature 2020
abstractGer	Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. © Springer-Verlag GmbH Germany, part of Springer Nature 2020
abstract_unstemmed	Purpose Therapies targeting the immune checkpoint molecules programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) have been explored in various malignant tumours. In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. LMS cell line analysis revealed that IFN-γ supplementation induced IDO1 and PD-L1 expression; these effects were suppressed by JAK inhibition. Immunohistochemical analysis of the resected specimens revealed that TDO2 expression positively correlated with pJAK2 (P = 0.0490) and IDO1 expression (P < 0.0001). PD-L1-positive specimens tended to express pJAK2; however, the relationship did not reach statistical significance (P = 0.1477). Conclusion The results suggest the possible feasibility of the combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ–JAK–STAT pathway inhibition to treat soft tissue LMS. © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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container_issue	5
title_short	Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma
url	https://dx.doi.org/10.1007/s00432-020-03390-9
remote_bool	true
author2	Kohashi, Kenichi Toda, Yu Ishihara, Shin Yamada, Yuichi Oda, Yoshinao
author2Str	Kohashi, Kenichi Toda, Yu Ishihara, Shin Yamada, Yuichi Oda, Yoshinao
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doi_str	10.1007/s00432-020-03390-9
up_date	2024-07-03T20:17:37.582Z
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In this study, we examined the relationship between PDL-1, IDO1 and JAK2 expression and the roles of these signal pathways in soft tissue leiomyosarcoma (LMS). Methods The next-generation sequencing data of 53 patients with LMS were obtained from an online public database and were used to assess PD-L1, IDO1 and JAK2 gene amplification and mRNA expression. Then, we determined the relationship between JAK–STAT pathway activation and PD-L1 and IDO1 expression in a LMS cell line. In addition, immunohistochemical staining of 69 cases of LMS was performed for PD-L1, IDO1, TDO2 and phosphorylated JAK2 (pJAK2). Results Comprehensive gene expression analysis using microarray and RNA-Seq data revealed that PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression. Two of the 53 cases exhibited PD-L1 and JAK2 gene amplification; however, they were not related to their gene expression. 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Association of PD-L1 and IDO1 expression with JAK–STAT pathway activation in soft-tissue leiomyosarcoma

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