Notch1 phenotype and clinical stage progression in non-small cell lung cancer
Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an incre...
Ausführliche Beschreibung
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| Autor*in: |
Nguyen, Dat [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Anmerkung: |
© Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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| Übergeordnetes Werk: |
Enthalten in: Journal of hematology & oncology - London : Biomed Central, 2008, 8(2015), 1 vom: 06. Feb. |
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| Übergeordnetes Werk: |
volume:8 ; year:2015 ; number:1 ; day:06 ; month:02 |
| Links: |
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| DOI / URN: |
10.1186/s13045-014-0104-2 |
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| Katalog-ID: |
SPR029617243 |
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| 520 | |a Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. | ||
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| 650 | 4 | |a NSCLC |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Rubinstein, Larry |4 aut | |
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| 700 | 1 | |a Ivy, Percy |4 aut | |
| 700 | 1 | |a Doroshow, James H |4 aut | |
| 700 | 1 | |a Yang, Sherry X |4 aut | |
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10.1186/s13045-014-0104-2 doi (DE-627)SPR029617243 (SPR)s13045-014-0104-2-e DE-627 ger DE-627 rakwb eng Nguyen, Dat verfasserin aut Notch1 phenotype and clinical stage progression in non-small cell lung cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 Rubinstein, Larry aut Takebe, Naoko aut Miele, Lucio aut Tomaszewski, Joseph E aut Ivy, Percy aut Doroshow, James H aut Yang, Sherry X aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 8(2015), 1 vom: 06. Feb. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:8 year:2015 number:1 day:06 month:02 https://dx.doi.org/10.1186/s13045-014-0104-2 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2015 1 06 02 |
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10.1186/s13045-014-0104-2 doi (DE-627)SPR029617243 (SPR)s13045-014-0104-2-e DE-627 ger DE-627 rakwb eng Nguyen, Dat verfasserin aut Notch1 phenotype and clinical stage progression in non-small cell lung cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 Rubinstein, Larry aut Takebe, Naoko aut Miele, Lucio aut Tomaszewski, Joseph E aut Ivy, Percy aut Doroshow, James H aut Yang, Sherry X aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 8(2015), 1 vom: 06. Feb. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:8 year:2015 number:1 day:06 month:02 https://dx.doi.org/10.1186/s13045-014-0104-2 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2015 1 06 02 |
| allfields_unstemmed |
10.1186/s13045-014-0104-2 doi (DE-627)SPR029617243 (SPR)s13045-014-0104-2-e DE-627 ger DE-627 rakwb eng Nguyen, Dat verfasserin aut Notch1 phenotype and clinical stage progression in non-small cell lung cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 Rubinstein, Larry aut Takebe, Naoko aut Miele, Lucio aut Tomaszewski, Joseph E aut Ivy, Percy aut Doroshow, James H aut Yang, Sherry X aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 8(2015), 1 vom: 06. Feb. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:8 year:2015 number:1 day:06 month:02 https://dx.doi.org/10.1186/s13045-014-0104-2 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2015 1 06 02 |
| allfieldsGer |
10.1186/s13045-014-0104-2 doi (DE-627)SPR029617243 (SPR)s13045-014-0104-2-e DE-627 ger DE-627 rakwb eng Nguyen, Dat verfasserin aut Notch1 phenotype and clinical stage progression in non-small cell lung cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 Rubinstein, Larry aut Takebe, Naoko aut Miele, Lucio aut Tomaszewski, Joseph E aut Ivy, Percy aut Doroshow, James H aut Yang, Sherry X aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 8(2015), 1 vom: 06. Feb. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:8 year:2015 number:1 day:06 month:02 https://dx.doi.org/10.1186/s13045-014-0104-2 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2015 1 06 02 |
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10.1186/s13045-014-0104-2 doi (DE-627)SPR029617243 (SPR)s13045-014-0104-2-e DE-627 ger DE-627 rakwb eng Nguyen, Dat verfasserin aut Notch1 phenotype and clinical stage progression in non-small cell lung cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 Rubinstein, Larry aut Takebe, Naoko aut Miele, Lucio aut Tomaszewski, Joseph E aut Ivy, Percy aut Doroshow, James H aut Yang, Sherry X aut Enthalten in Journal of hematology & oncology London : Biomed Central, 2008 8(2015), 1 vom: 06. Feb. (DE-627)568914813 (DE-600)2429631-4 1756-8722 nnns volume:8 year:2015 number:1 day:06 month:02 https://dx.doi.org/10.1186/s13045-014-0104-2 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2015 1 06 02 |
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Notch1 phenotype and clinical stage progression in non-small cell lung cancer Lung cancer (dpeaa)DE-He213 N1-ICD (dpeaa)DE-He213 Notch1 (dpeaa)DE-He213 NSCLC (dpeaa)DE-He213 Stage (dpeaa)DE-He213 |
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notch1 phenotype and clinical stage progression in non-small cell lung cancer |
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Notch1 phenotype and clinical stage progression in non-small cell lung cancer |
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Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
| abstractGer |
Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
| abstract_unstemmed |
Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis. © Nguyen et al.; licensee Biomed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC. Methods Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided. Results Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells. Conclusions Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Lung cancer</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">N1-ICD</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Notch1</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">NSCLC</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Stage</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rubinstein, Larry</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Takebe, Naoko</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Miele, Lucio</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tomaszewski, Joseph E</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ivy, Percy</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Doroshow, James H</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Sherry X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of hematology & oncology</subfield><subfield code="d">London : Biomed Central, 2008</subfield><subfield code="g">8(2015), 1 vom: 06. 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