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....
Ausführliche Beschreibung
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] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2018 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Cancer letters - Amsterdam [u.a.] : Elsevier Science, 1975, 433, Seite 232-241 |
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Übergeordnetes Werk: |
volume:433 ; pages:232-241 |
DOI / URN: |
10.1016/j.canlet.2018.07.009 |
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Katalog-ID: |
ELV000121827 |
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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 |
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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 |
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Enthalten in Cancer letters 433, Seite 232-241 volume:433 pages:232-241 |
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Enthalten in Cancer letters 433, Seite 232-241 volume:433 pages:232-241 |
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Adjuvant therapy Nexrutine Prostate cancer Radiotherapy RPS6KB1 TRAMP Natural products |
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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@@ |
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2018-01-01T00:00:00Z |
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Hussain, Suleman S. |
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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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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 |
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Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation |
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Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation |
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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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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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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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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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