Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation

Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy....
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Autor*in:	Hussain, Suleman S. [verfasserIn] Huang, Shih-Bo [verfasserIn] Bedolla, Roble G. [verfasserIn] Rivas, Paul [verfasserIn] Basler, Joseph W. [verfasserIn] Swanson, Gregory P. [verfasserIn] Hui-Ming Huang, Tim [verfasserIn] Narayanasamy, Ganesh [verfasserIn] Papanikolaou, Nikos [verfasserIn] Miyamoto, Hiroshi [verfasserIn] Yeh, I-Tien [verfasserIn] Reddick, Robert L. [verfasserIn] Pollock, Brad H. [verfasserIn] Ghosh, Rita [verfasserIn] Kumar, Addanki P. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products

Übergeordnetes Werk:	Enthalten in: Cancer letters - Amsterdam [u.a.] : Elsevier Science, 1975, 433, Seite 232-241
Übergeordnetes Werk:	volume:433 ; pages:232-241

DOI / URN:	10.1016/j.canlet.2018.07.009

Katalog-ID:	ELV000121827

Internformat


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100	1		\|a Hussain, Suleman S. \|e verfasserin \|0 (orcid)0000-0003-1342-143X \|4 aut
245	1	0	\|a Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
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520			\|a Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.
650		4	\|a Adjuvant therapy
650		4	\|a Nexrutine
650		4	\|a Prostate cancer
650		4	\|a Radiotherapy
650		4	\|a RPS6KB1
650		4	\|a TRAMP
650		4	\|a Natural products
700	1		\|a Huang, Shih-Bo \|e verfasserin \|4 aut
700	1		\|a Bedolla, Roble G. \|e verfasserin \|4 aut
700	1		\|a Rivas, Paul \|e verfasserin \|4 aut
700	1		\|a Basler, Joseph W. \|e verfasserin \|4 aut
700	1		\|a Swanson, Gregory P. \|e verfasserin \|4 aut
700	1		\|a Hui-Ming Huang, Tim \|e verfasserin \|4 aut
700	1		\|a Narayanasamy, Ganesh \|e verfasserin \|4 aut
700	1		\|a Papanikolaou, Nikos \|e verfasserin \|4 aut
700	1		\|a Miyamoto, Hiroshi \|e verfasserin \|0 (orcid)0000-0001-7610-7769 \|4 aut
700	1		\|a Yeh, I-Tien \|e verfasserin \|4 aut
700	1		\|a Reddick, Robert L. \|e verfasserin \|4 aut
700	1		\|a Pollock, Brad H. \|e verfasserin \|4 aut
700	1		\|a Ghosh, Rita \|e verfasserin \|4 aut
700	1		\|a Kumar, Addanki P. \|e verfasserin \|0 (orcid)0000-0001-5596-6265 \|4 aut
773	0	8	\|i Enthalten in \|t Cancer letters \|d Amsterdam [u.a.] : Elsevier Science, 1975 \|g 433, Seite 232-241 \|h Online-Ressource \|w (DE-627)320434796 \|w (DE-600)2004212-7 \|w (DE-576)261677926 \|x 1872-7980 \|7 nnns
773	1	8	\|g volume:433 \|g pages:232-241
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912			\|a GBV_ILN_110
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912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
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912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
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912			\|a GBV_ILN_2025
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912			\|a GBV_ILN_2112
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912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
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936	b	k	\|a 44.81 \|j Onkologie
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publishDate	2018
allfields	10.1016/j.canlet.2018.07.009 doi (DE-627)ELV000121827 (ELSEVIER)S0304-3835(18)30458-0 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.81 bkl Hussain, Suleman S. verfasserin (orcid)0000-0003-1342-143X aut Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations. Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products Huang, Shih-Bo verfasserin aut Bedolla, Roble G. verfasserin aut Rivas, Paul verfasserin aut Basler, Joseph W. verfasserin aut Swanson, Gregory P. verfasserin aut Hui-Ming Huang, Tim verfasserin aut Narayanasamy, Ganesh verfasserin aut Papanikolaou, Nikos verfasserin aut Miyamoto, Hiroshi verfasserin (orcid)0000-0001-7610-7769 aut Yeh, I-Tien verfasserin aut Reddick, Robert L. verfasserin aut Pollock, Brad H. verfasserin aut Ghosh, Rita verfasserin aut Kumar, Addanki P. verfasserin (orcid)0000-0001-5596-6265 aut Enthalten in Cancer letters Amsterdam [u.a.] : Elsevier Science, 1975 433, Seite 232-241 Online-Ressource (DE-627)320434796 (DE-600)2004212-7 (DE-576)261677926 1872-7980 nnns volume:433 pages:232-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA 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_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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.81 Onkologie AR 433 232-241
spelling	10.1016/j.canlet.2018.07.009 doi (DE-627)ELV000121827 (ELSEVIER)S0304-3835(18)30458-0 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.81 bkl Hussain, Suleman S. verfasserin (orcid)0000-0003-1342-143X aut Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations. Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products Huang, Shih-Bo verfasserin aut Bedolla, Roble G. verfasserin aut Rivas, Paul verfasserin aut Basler, Joseph W. verfasserin aut Swanson, Gregory P. verfasserin aut Hui-Ming Huang, Tim verfasserin aut Narayanasamy, Ganesh verfasserin aut Papanikolaou, Nikos verfasserin aut Miyamoto, Hiroshi verfasserin (orcid)0000-0001-7610-7769 aut Yeh, I-Tien verfasserin aut Reddick, Robert L. verfasserin aut Pollock, Brad H. verfasserin aut Ghosh, Rita verfasserin aut Kumar, Addanki P. verfasserin (orcid)0000-0001-5596-6265 aut Enthalten in Cancer letters Amsterdam [u.a.] : Elsevier Science, 1975 433, Seite 232-241 Online-Ressource (DE-627)320434796 (DE-600)2004212-7 (DE-576)261677926 1872-7980 nnns volume:433 pages:232-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA 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_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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.81 Onkologie AR 433 232-241
allfields_unstemmed	10.1016/j.canlet.2018.07.009 doi (DE-627)ELV000121827 (ELSEVIER)S0304-3835(18)30458-0 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.81 bkl Hussain, Suleman S. verfasserin (orcid)0000-0003-1342-143X aut Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations. Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products Huang, Shih-Bo verfasserin aut Bedolla, Roble G. verfasserin aut Rivas, Paul verfasserin aut Basler, Joseph W. verfasserin aut Swanson, Gregory P. verfasserin aut Hui-Ming Huang, Tim verfasserin aut Narayanasamy, Ganesh verfasserin aut Papanikolaou, Nikos verfasserin aut Miyamoto, Hiroshi verfasserin (orcid)0000-0001-7610-7769 aut Yeh, I-Tien verfasserin aut Reddick, Robert L. verfasserin aut Pollock, Brad H. verfasserin aut Ghosh, Rita verfasserin aut Kumar, Addanki P. verfasserin (orcid)0000-0001-5596-6265 aut Enthalten in Cancer letters Amsterdam [u.a.] : Elsevier Science, 1975 433, Seite 232-241 Online-Ressource (DE-627)320434796 (DE-600)2004212-7 (DE-576)261677926 1872-7980 nnns volume:433 pages:232-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA 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_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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.81 Onkologie AR 433 232-241
allfieldsGer	10.1016/j.canlet.2018.07.009 doi (DE-627)ELV000121827 (ELSEVIER)S0304-3835(18)30458-0 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.81 bkl Hussain, Suleman S. verfasserin (orcid)0000-0003-1342-143X aut Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations. Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products Huang, Shih-Bo verfasserin aut Bedolla, Roble G. verfasserin aut Rivas, Paul verfasserin aut Basler, Joseph W. verfasserin aut Swanson, Gregory P. verfasserin aut Hui-Ming Huang, Tim verfasserin aut Narayanasamy, Ganesh verfasserin aut Papanikolaou, Nikos verfasserin aut Miyamoto, Hiroshi verfasserin (orcid)0000-0001-7610-7769 aut Yeh, I-Tien verfasserin aut Reddick, Robert L. verfasserin aut Pollock, Brad H. verfasserin aut Ghosh, Rita verfasserin aut Kumar, Addanki P. verfasserin (orcid)0000-0001-5596-6265 aut Enthalten in Cancer letters Amsterdam [u.a.] : Elsevier Science, 1975 433, Seite 232-241 Online-Ressource (DE-627)320434796 (DE-600)2004212-7 (DE-576)261677926 1872-7980 nnns volume:433 pages:232-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA 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_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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.81 Onkologie AR 433 232-241
allfieldsSound	10.1016/j.canlet.2018.07.009 doi (DE-627)ELV000121827 (ELSEVIER)S0304-3835(18)30458-0 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.81 bkl Hussain, Suleman S. verfasserin (orcid)0000-0003-1342-143X aut Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations. Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products Huang, Shih-Bo verfasserin aut Bedolla, Roble G. verfasserin aut Rivas, Paul verfasserin aut Basler, Joseph W. verfasserin aut Swanson, Gregory P. verfasserin aut Hui-Ming Huang, Tim verfasserin aut Narayanasamy, Ganesh verfasserin aut Papanikolaou, Nikos verfasserin aut Miyamoto, Hiroshi verfasserin (orcid)0000-0001-7610-7769 aut Yeh, I-Tien verfasserin aut Reddick, Robert L. verfasserin aut Pollock, Brad H. verfasserin aut Ghosh, Rita verfasserin aut Kumar, Addanki P. verfasserin (orcid)0000-0001-5596-6265 aut Enthalten in Cancer letters Amsterdam [u.a.] : Elsevier Science, 1975 433, Seite 232-241 Online-Ressource (DE-627)320434796 (DE-600)2004212-7 (DE-576)261677926 1872-7980 nnns volume:433 pages:232-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA 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_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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.81 Onkologie AR 433 232-241
language	English
source	Enthalten in Cancer letters 433, Seite 232-241 volume:433 pages:232-241
sourceStr	Enthalten in Cancer letters 433, Seite 232-241 volume:433 pages:232-241
format_phy_str_mv	Article
bklname	Onkologie
institution	findex.gbv.de
topic_facet	Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products
dewey-raw	570
isfreeaccess_bool	false
container_title	Cancer letters
authorswithroles_txt_mv	Hussain, Suleman S. @@aut@@ Huang, Shih-Bo @@aut@@ Bedolla, Roble G. @@aut@@ Rivas, Paul @@aut@@ Basler, Joseph W. @@aut@@ Swanson, Gregory P. @@aut@@ Hui-Ming Huang, Tim @@aut@@ Narayanasamy, Ganesh @@aut@@ Papanikolaou, Nikos @@aut@@ Miyamoto, Hiroshi @@aut@@ Yeh, I-Tien @@aut@@ Reddick, Robert L. @@aut@@ Pollock, Brad H. @@aut@@ Ghosh, Rita @@aut@@ Kumar, Addanki P. @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	320434796
dewey-sort	3570
id	ELV000121827
language_de	englisch
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author	Hussain, Suleman S.
spellingShingle	Hussain, Suleman S. ddc 570 fid BIODIV bkl 44.81 misc Adjuvant therapy misc Nexrutine misc Prostate cancer misc Radiotherapy misc RPS6KB1 misc TRAMP misc Natural products Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
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topic_title	570 DE-600 BIODIV DE-30 fid 44.81 bkl Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products
topic	ddc 570 fid BIODIV bkl 44.81 misc Adjuvant therapy misc Nexrutine misc Prostate cancer misc Radiotherapy misc RPS6KB1 misc TRAMP misc Natural products
topic_unstemmed	ddc 570 fid BIODIV bkl 44.81 misc Adjuvant therapy misc Nexrutine misc Prostate cancer misc Radiotherapy misc RPS6KB1 misc TRAMP misc Natural products
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title	Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
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title_full	Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
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author_browse	Hussain, Suleman S. Huang, Shih-Bo Bedolla, Roble G. Rivas, Paul Basler, Joseph W. Swanson, Gregory P. Hui-Ming Huang, Tim Narayanasamy, Ganesh Papanikolaou, Nikos Miyamoto, Hiroshi Yeh, I-Tien Reddick, Robert L. Pollock, Brad H. Ghosh, Rita Kumar, Addanki P.
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title_sort	suppression of ribosomal protein rps6kb1 by nexrutine increases sensitivity of prostate tumors to radiation
title_auth	Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
abstract	Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.
abstractGer	Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.
abstract_unstemmed	Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.
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title_short	Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
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author2	Huang, Shih-Bo Bedolla, Roble G. Rivas, Paul Basler, Joseph W. Swanson, Gregory P. Hui-Ming Huang, Tim Narayanasamy, Ganesh Papanikolaou, Nikos Miyamoto, Hiroshi Yeh, I-Tien Reddick, Robert L. Pollock, Brad H. Ghosh, Rita Kumar, Addanki P.
author2Str	Huang, Shih-Bo Bedolla, Roble G. Rivas, Paul Basler, Joseph W. Swanson, Gregory P. Hui-Ming Huang, Tim Narayanasamy, Ganesh Papanikolaou, Nikos Miyamoto, Hiroshi Yeh, I-Tien Reddick, Robert L. Pollock, Brad H. Ghosh, Rita Kumar, Addanki P.
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doi_str	10.1016/j.canlet.2018.07.009
up_date	2024-07-06T16:56:03.340Z
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Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. 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Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation

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