Activation of mammalian target of rapamycin pathway confers adverse outcome in nonsmall cell lung carcinoma

BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Cancer Ročník 117; číslo 16; s. 3763 - 3773
Hlavní autori:	Liu, Dan, Huang, Yi, Chen, Bojiang, Zeng, Jing, Guo, Na, Zhang, Shangfu, Liu, Lunxu, Xu, Hong, Mo, Xianming, Li, Weimin
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2011 Wiley-Blackwell
Predmet:	activated kinases Biological and medical sciences Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - mortality Female Humans Lung Neoplasms - metabolism Lung Neoplasms - mortality Male mammalian target of rapamycin pathway Medical sciences Middle Aged nonsmall cell lung carcinoma Phosphorylation Phosphotransferases - metabolism Pneumology Prognosis Protein Array Analysis protein expression profiles Signal Transduction TOR Serine-Threonine Kinases - metabolism Tumors Tumors of the respiratory system and mediastinum Lung disease Prognosis Enzyme Respiratory disease Transferases Lung cancer Malignant tumor Bronchopulmonary carcinoma Cancerology Kinase Mammalian target of rapamycin protein-expression profiles Bronchus disease Complication activated kinases mammalian target of rapamycin pathway nonsmall cell lung carcinoma Cancer
ISSN:	0008-543X, 1097-0142, 1097-0142
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of mTOR/phosphorylated (p‐)mTOR, phosphoinositide‐dependent kinase 1 (PDK1)/p‐PDK1, p‐Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p‐P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. RESULTS: Compared with normal lung tissues, the protein levels of mTOR/p‐mTOR, p‐Akt1 Ser473/Thr308, and P70S6K/p‐P70S6K were higher (all P < .05), whereas p‐PDK1 was lower (P < .05) in tumor tissues. p‐mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p‐mTOR, p‐PDK1, and p‐P70S6K (all P < .05). Subjects with coexpression of any 2 of p‐mTOR, p‐PDK1, p‐Akt1 Ser473, and p‐P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p‐mTOR/p‐P70S6K is an independent prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein‐expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Cancer 2011;. © 2011 American Cancer Society. This study provided the first clinical evidence that activated components of mammalian target of rapamycin pathway, not total protein, are predictors of poor prognosis in nonsmall cell lung carcinoma (NSCLC). Moreover, evaluating protein‐expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC.
AbstractList	BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of mTOR/phosphorylated (p‐)mTOR, phosphoinositide‐dependent kinase 1 (PDK1)/p‐PDK1, p‐Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p‐P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. RESULTS: Compared with normal lung tissues, the protein levels of mTOR/p‐mTOR, p‐Akt1 Ser473/Thr308, and P70S6K/p‐P70S6K were higher (all P < .05), whereas p‐PDK1 was lower (P < .05) in tumor tissues. p‐mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p‐mTOR, p‐PDK1, and p‐P70S6K (all P < .05). Subjects with coexpression of any 2 of p‐mTOR, p‐PDK1, p‐Akt1 Ser473, and p‐P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p‐mTOR/p‐P70S6K is an independent prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein‐expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Cancer 2011;. © 2011 American Cancer Society. This study provided the first clinical evidence that activated components of mammalian target of rapamycin pathway, not total protein, are predictors of poor prognosis in nonsmall cell lung carcinoma (NSCLC). Moreover, evaluating protein‐expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage. This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC).BACKGROUNDDysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC).The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis.METHODSThe protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis.Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage.RESULTSCompared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage.This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC.CONCLUSIONSThis study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC.
Author	Zeng, Jing Zhang, Shangfu Li, Weimin Guo, Na Xu, Hong Huang, Yi Mo, Xianming Liu, Lunxu Liu, Dan Chen, Bojiang
Author_xml	– sequence: 1 givenname: Dan surname: Liu fullname: Liu, Dan – sequence: 2 givenname: Yi surname: Huang fullname: Huang, Yi – sequence: 3 givenname: Bojiang surname: Chen fullname: Chen, Bojiang – sequence: 4 givenname: Jing surname: Zeng fullname: Zeng, Jing – sequence: 5 givenname: Na surname: Guo fullname: Guo, Na – sequence: 6 givenname: Shangfu surname: Zhang fullname: Zhang, Shangfu – sequence: 7 givenname: Lunxu surname: Liu fullname: Liu, Lunxu – sequence: 8 givenname: Hong surname: Xu fullname: Xu, Hong – sequence: 9 givenname: Xianming surname: Mo fullname: Mo, Xianming email: xmingmo@yahoo.com – sequence: 10 givenname: Weimin surname: Li fullname: Li, Weimin email: weimi003@yahoo.com
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24406662$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21387259$$D View this record in MEDLINE/PubMed
BookMark	eNp9kd1rFDEUxYNU7Lb64h8geRFBmJpkvpLHstQPKBaKgm_h7p2kRifJmsy07H9vprtFKMWX3CT8zuFyzgk5CjEYQl5zdsYZEx8wYDoTrWrVM7LiTPUV4404IivGmKzapv5xTE5y_lWevWjrF-RY8FqWq1qR3-c4uVuYXAw0WurBexgdBDpBujHT8pdgC36HLtAtTD_vYEcxBmtSpjDclmFonCeM3tCClNVycRgpmnKMc7ihCKmIo4eX5LmFMZtXh3lKvn-8-Lb-XF1effqyPr-ssOmYqmRfK7NRyBUqHJi0YExjeYsbsGh7rnoFrGeoOikkx4ZbLuRgsQQwMAG8PiXv9r7bFP_MJk_au7zsA8HEOWspS0isYwv55kDOG28GvU3OQ9rph3wK8PYAQEYYbYKALv_jmoZ1XScKx_YcpphzMlajm-5TnRK4UXOml6r0UpW-r6pI3j-SPLg-CfM9fOdGs_sPqddf19d7zV-1yKWL
CODEN	CANCAR
CitedBy_id	crossref_primary_10_1016_j_biocel_2014_12_018 crossref_primary_10_1111_1759_7714_12196 crossref_primary_10_1111_crj_12100 crossref_primary_10_1016_j_placenta_2017_03_013 crossref_primary_10_1371_journal_pone_0081451 crossref_primary_10_1177_0976500X221114003 crossref_primary_10_3892_ol_2012_938 crossref_primary_10_1002_cam4_5311 crossref_primary_10_3389_fonc_2019_00390 crossref_primary_10_1136_jclinpath_2012_201173 crossref_primary_10_1155_2018_4753507 crossref_primary_10_1038_onc_2011_295 crossref_primary_10_3892_or_2013_2512 crossref_primary_10_1016_j_yexcr_2014_04_012 crossref_primary_10_1007_s12032_011_0060_4 crossref_primary_10_1016_j_humpath_2016_12_012 crossref_primary_10_1038_onc_2014_428 crossref_primary_10_1371_journal_pone_0116771 crossref_primary_10_1038_leu_2013_226 crossref_primary_10_1007_s12274_021_3894_x crossref_primary_10_1097_MD_0000000000032340 crossref_primary_10_1177_1933719117734700 crossref_primary_10_1371_journal_pone_0091231 crossref_primary_10_1016_j_jvoice_2021_04_009 crossref_primary_10_1002_ijc_28788 crossref_primary_10_3390_molecules26195967 crossref_primary_10_3389_fcimb_2020_00258 crossref_primary_10_1016_j_canlet_2012_02_032 crossref_primary_10_1007_s12105_023_01576_4 crossref_primary_10_3892_ol_2017_6690 crossref_primary_10_1016_j_oooo_2013_01_022 crossref_primary_10_1186_1475_2867_13_53 crossref_primary_10_1016_j_humpath_2012_05_011 crossref_primary_10_1007_s13277_016_5332_3 crossref_primary_10_1371_journal_pone_0147185
Cites_doi	10.1634/theoncologist.12-8-1007 10.1016/j.lungcan.2006.09.026 10.1038/nrc1362 10.1158/1078-0432.CCR-09-0099 10.1634/theoncologist.2007-0171 10.1073/pnas.89.15.7282 10.1158/1078-0432.CCR-09-0986 10.1158/0008-5472.CAN-09-0164 10.1074/jbc.M507201200 10.1038/sj.bjc.6602646 10.1093/jjco/hyq047 10.1007/s00421-008-0786-7 10.3322/caac.20006 10.1016/S0960-9822(00)00441-3 10.1158/1078-0432.CCR-10-1601 10.1158/1078-0432.CCR-04-0941 10.4067/S0716-97602002000200022 10.1158/1078-0432.CCR-04-0112 10.1200/JCO.2005.02.4133 10.1097/JTO.0b013e3181ce6604 10.3816/CLC.2008.n.049 10.1074/jbc.M205141200 10.1182/blood-2009-09-220020 10.1038/sj.onc.1209888 10.1007/82_2010_43 10.1016/j.jamcollsurg.2009.12.008 10.1177/172460080802300101 10.1242/dmm.004671 10.1158/1078-0432.CCR-07-0717 10.1593/neo.04373 10.1126/stke.2001.66.pe1 10.1158/1078-0432.CCR-09-0234 10.4172/1948-5956.1000034 10.1016/j.ejphar.2008.06.028 10.1016/S0960-9822(99)80186-9 10.1074/jbc.M300376200 10.3816/CLC.2005.s.003 10.1002/jnr.22321 10.2146/ajhp100020 10.1158/1078-0432.CCR-06-1864 10.1016/j.lungcan.2005.10.003 10.1111/j.1464-410X.2008.07703.x
ContentType	Journal Article
Copyright	Copyright © 2011 American Cancer Society 2015 INIST-CNRS Copyright © 2011 American Cancer Society.
Copyright_xml	– notice: Copyright © 2011 American Cancer Society – notice: 2015 INIST-CNRS – notice: Copyright © 2011 American Cancer Society.
DBID	AAYXX CITATION IQODW CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1002/cncr.25959
DatabaseName	CrossRef Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE MEDLINE - Academic
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Medicine
EISSN	1097-0142
EndPage	3773
ExternalDocumentID	21387259 24406662 10_1002_cncr_25959 CNCR25959
Genre	article Research Support, Non-U.S. Gov't Journal Article
GroupedDBID	--- -~X .3N .GA .Y3 05W 0R~ 10A 1CY 1L6 1OC 29B 31~ 33P 3SF 3WU 4.4 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5GY 5VS 66C 6J9 6P2 6PF 702 7PT 8-0 8-1 8-3 8-4 8-5 85S 8UM 930 A01 A03 AAESR AAEVG AAHQN AAIPD AAMMB AAMNL AANLZ AAONW AAWTL AAXRX AAYCA AAZKR ABCQN ABCUV ABEML ABHFT ABIJN ABIVO ABJNI ABLJU ABOCM ABPPZ ABPVW ABQWH ABXGK ACAHQ ACCZN ACFBH ACGFO ACGFS ACGOF ACMXC ACNCT ACPOU ACPRK ACSCC ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN AEFGJ AEIGN AEIMD AENEX AEUYR AEYWJ AFBPY AFFPM AFGKR AFRAH AFWVQ AFZJQ AGNAY AGXDD AGYGG AHBTC AIACR AIAGR AIDQK AIDYY AITYG AIURR ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ATUGU AZBYB AZVAB BAFTC BAWUL BFHJK BHBCM BMXJE BROTX BRXPI BY8 C45 CS3 D-6 D-7 D-E D-F DCZOG DPXWK DR2 DRFUL DRMAN DRSTM E3Z EBS EJD EX3 F00 F01 F04 F5P FD6 FUBAC G-S G.N GNP GODZA GX1 H.X HBH HF~ HGLYW HHY HHZ HZ~ IH2 IX1 J0M JPC KBYEO KQQ KZ1 L7B LATKE LAW LC2 LC3 LH4 LITHE LMP LOXES LP6 LP7 LSO LUTES LW6 LYRES MEWTI MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM N04 N05 N9A NF~ NNB O66 O9- OIG OK1 OVD P2P P2W P2X P2Z P4B P4D Q.N Q11 QB0 QRW R.K ROL RX1 RYL SJN SUPJJ TEORI UDS UHB V2E V8K V9Y W8V W99 WBKPD WH7 WHWMO WIH WIJ WIK WIN WJL WOHZO WQJ WVDHM WXI WXSBR XG1 XPP XV2 Z0Y ZGI ZZTAW ~IA ~WT AAYXX CITATION O8X .GJ 3O- AAQOH AARRQ AFFNX AGHNM AI. C1A EMOBN H~9 IQODW J5H N4W NEJ OHT RSU VH1 WHG Y6R YQJ ZXP CGR CUY CVF ECM EIF NPM 7X8
ID	FETCH-LOGICAL-c4609-8739eb9c19c9cd08faee4f15cbafcf71979a070c968281c41f128dfc595d02a13
IEDL.DBID	WIN
ISICitedReferencesCount	41
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000293672700017&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	0008-543X 1097-0142
IngestDate	Sat Sep 27 19:06:32 EDT 2025 Mon Jul 21 06:04:22 EDT 2025 Mon Jul 21 09:15:13 EDT 2025 Sat Nov 29 07:13:08 EST 2025 Tue Nov 18 21:53:09 EST 2025 Tue Nov 11 03:13:04 EST 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	16
Keywords	Lung disease Prognosis Enzyme Respiratory disease Transferases Lung cancer Malignant tumor Bronchopulmonary carcinoma Cancerology Kinase Mammalian target of rapamycin protein-expression profiles Bronchus disease Complication activated kinases mammalian target of rapamycin pathway nonsmall cell lung carcinoma Cancer
Language	English
License	http://onlinelibrary.wiley.com/termsAndConditions#vor CC BY 4.0 Copyright © 2011 American Cancer Society.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c4609-8739eb9c19c9cd08faee4f15cbafcf71979a070c968281c41f128dfc595d02a13
Notes	We thank the patients and their families for participating in the study with patience and cooperation; Prof. Zhou Xing, McMaster University, for help with revision of the manuscript; and technicians in the Department of Pathology, West China Hospital, Sichuan University, who assisted us in collecting the tissue samples. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
OpenAccessLink	https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.25959
PMID	21387259
PQID	881090601
PQPubID	23479
PageCount	11
ParticipantIDs	proquest_miscellaneous_881090601 pubmed_primary_21387259 pascalfrancis_primary_24406662 crossref_citationtrail_10_1002_cncr_25959 crossref_primary_10_1002_cncr_25959 wiley_primary_10_1002_cncr_25959_CNCR25959
PublicationCentury	2000
PublicationDate	15 August 2011
PublicationDateYYYYMMDD	2011-08-15
PublicationDate_xml	– month: 08 year: 2011 text: 15 August 2011 day: 15
PublicationDecade	2010
PublicationPlace	Hoboken
PublicationPlace_xml	– name: Hoboken – name: Hoboken, NJ – name: United States
PublicationTitle	Cancer
PublicationTitleAlternate	Cancer
PublicationYear	2011
Publisher	Wiley Subscription Services, Inc., A Wiley Company Wiley-Blackwell
Publisher_xml	– name: Wiley Subscription Services, Inc., A Wiley Company – name: Wiley-Blackwell
References	2009; 69 2010; 16 2006; 51 2002; 35 2002; 277 2004; 4 2008; 9 2008; 13 2008; 104 2004 2008; 102 2002 2007; 55 2003; 278 2007; 12 2007; 13 2010; 40 1999; 9 2004; 10 2010; 67 2010; 88 2011; 346 2005; 280 2006; 24 2000; 10 2010; 115 2006; 25 2010; 210 2005; 7 1999; 11 2008; 23 2005; 10 2005; 92 2010; 3 2010; 2 2010; 5 1992; 89 2009; 16 2009; 59 2008; 591 2009; 15 2001; 2001 e_1_2_6_31_2 The Royal College of Radiologists Clinical Oncology Information Network (e_1_2_6_23_2) 1999; 11 e_1_2_6_30_2 International Union Against Cancer (e_1_2_6_22_2) 2002 Janus A (e_1_2_6_6_2) 2005; 10 e_1_2_6_18_2 e_1_2_6_19_2 e_1_2_6_12_2 e_1_2_6_35_2 e_1_2_6_13_2 e_1_2_6_34_2 e_1_2_6_10_2 e_1_2_6_33_2 e_1_2_6_11_2 e_1_2_6_32_2 e_1_2_6_16_2 e_1_2_6_39_2 e_1_2_6_17_2 e_1_2_6_38_2 e_1_2_6_14_2 e_1_2_6_37_2 e_1_2_6_15_2 e_1_2_6_36_2 e_1_2_6_42_2 e_1_2_6_20_2 e_1_2_6_41_2 e_1_2_6_40_2 e_1_2_6_8_2 e_1_2_6_7_2 e_1_2_6_9_2 e_1_2_6_29_2 e_1_2_6_4_2 e_1_2_6_3_2 Travis WD (e_1_2_6_21_2) 2004 e_1_2_6_5_2 e_1_2_6_24_2 e_1_2_6_47_2 e_1_2_6_2_2 e_1_2_6_28_2 e_1_2_6_43_2 e_1_2_6_27_2 e_1_2_6_44_2 e_1_2_6_26_2 e_1_2_6_45_2 e_1_2_6_25_2 e_1_2_6_46_2
References_xml	– volume: 40 start-page: 732 year: 2010 end-page: 738 article-title: A phase 1 clinical study of temsirolimus (CCI‐779) in Japanese patients with advanced solid tumors publication-title: Jpn J Clin Oncol – volume: 278 start-page: 28130 year: 2003 end-page: 28138 article-title: Mechanism of ribosomal p70S6 kinase activation by granulocyte macrophage colony‐stimulating factor in neutrophils: cooperation of a MEK‐related, THR421/SER424 kinase and a rapamycin‐sensitive, m‐TOR‐related THR389 kinase publication-title: J Biol Chem – volume: 2 start-page: 114 year: 2010 end-page: 119 article-title: MTA1 Aids the AKT pathway by inhibiting expression of a key regulator, PTEN publication-title: J Cancer Sci Ther. – volume: 13 start-page: 703s issue: 2 pt 2 year: 2007 end-page: 708s article-title: Protein expression profiles in renal cell carcinoma: staging, prognosis, and patient selection for clinical trials publication-title: Clin Cancer Res. – volume: 10 start-page: 439 year: 2000 end-page: 448 article-title: The role of 3‐phosphoinositide‐dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells publication-title: Curr Biol. – volume: 280 start-page: 33076 year: 2005 end-page: 33082 article-title: hVps34 is a nutrient‐regulated lipid kinase required for activation of p70 S6 kinase publication-title: J Biol Chem – volume: 13 start-page: 139 year: 2008 end-page: 147 article-title: The potential role of mTOR inhibitors in non‐small cell lung cancer publication-title: Oncologist – volume: 25 start-page: 6416 year: 2006 end-page: 6422 article-title: mTOR, translation initiation and cancer publication-title: Oncogene – volume: 12 start-page: 1007 year: 2007 end-page: 1018 article-title: The biology behind mTOR inhibition in sarcoma publication-title: Oncologist. – volume: 92 start-page: 2266 year: 2005 end-page: 2277 article-title: Synergistic growth inhibition by Iressa and rapamycin is modulated by VHL mutations in renal cell carcinoma publication-title: Br J Cancer – volume: 55 start-page: 115 year: 2007 end-page: 121 article-title: Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma publication-title: Lung Cancer – volume: 9 start-page: 393 year: 1999 end-page: 404 article-title: PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 publication-title: Curr Biol. – volume: 2001 start-page: pe1 year: 2001 article-title: PDK2: a complex tail in 1 Akt publication-title: Sci STKE – volume: 277 start-page: 39360 year: 2002 end-page: 39367 article-title: Regulation of kinase activity of 3‐phosphoinositide‐dependent protein kinase‐1 by binding to 14‐3‐3 publication-title: J Biol Chem – volume: 89 start-page: 7282 year: 1992 end-page: 7286 article-title: Activation of p70s6k is associated with phosphorylation of 4 clustered sites displaying Ser/Thr‐Pro motifs publication-title: Proc Natl Acad Sci U S A – volume: 11 start-page: S1 year: 1999 end-page: S53 article-title: Guidelines on the non‐surgical management of lung cancer publication-title: Clin Oncol (R Coll Radiol). – volume: 35 start-page: 305 year: 2002 end-page: 313 article-title: The S6 kinase signaling pathway in the control of development and growth publication-title: Biol Res – volume: 10 start-page: 8421 year: 2004 end-page: 8425 article-title: mTOR and P70 S6 kinase expression in primary liver neoplasms publication-title: Clin Cancer Res. – volume: 210 start-page: 767 year: 2010 end-page: 778 article-title: Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer publication-title: J Am Coll Surg. – volume: 16 start-page: 5692 year: 2010 end-page: 5702 article-title: Combination therapy targeting both tumor‐initiating and differentiated cell populations in prostate carcinoma publication-title: Clin Cancer Res – volume: 88 start-page: 1420 year: 2010 end-page: 1432 article-title: Intracellular calcium and calmodulin link brain‐derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis publication-title: J Neurosci Res. – volume: 346 start-page: 9 year: 2011 end-page: 29 article-title: PDK1: the major transducer of PI 3‐kinase actions publication-title: Curr Top Microbiol Immunol – volume: 115 start-page: 2127 year: 2010 end-page: 2135 article-title: Targeting the translational machinery as a novel treatment strategy for hematologic malignancies publication-title: Blood. – volume: 3 start-page: 705 year: 2010 end-page: 720 article-title: From man to mouse and back again: advances in defining tumor AKTivities in vivo publication-title: Dis Model Mech – volume: 10 start-page: 479 year: 2005 end-page: 498 article-title: The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted antitumour therapy publication-title: Cell Mol Biol Lett – volume: 9 start-page: 340 year: 2008 end-page: 345 article-title: The role of targeting mammalian target of rapamycin in lung cancer publication-title: Clin Lung Cancer – volume: 10 start-page: 6779 year: 2004 end-page: 6788 article-title: Activation of the Akt/mammalian target of rapamycin/4E‐BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers publication-title: Clin Cancer Res – volume: 13 start-page: s4628 issue: 15 pt 2 year: 2007 end-page: s4631 article-title: Rationale for a phase I trial of erlotinib and the mammalian target of rapamycin inhibitor everolimus (RAD001) for patients with relapsed non small cell lung cancer publication-title: Clin Cancer Res. – year: 2002 – volume: 7 start-page: S13 issue: suppl 1 year: 2005 end-page: S18 article-title: Current status of mammalian target of rapamycin inhibitors in lung cancer publication-title: Clin Lung Cancer. – volume: 104 start-page: 57 year: 2008 end-page: 65 article-title: Decrease in Akt/PKB signalling in human skeletal muscle by resistance exercise publication-title: Eur J Appl Physiol – volume: 5 start-page: 314 year: 2010 end-page: 319 article-title: Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non‐small cell lung cancer publication-title: J Thorac Oncol – year: 2004 – volume: 24 start-page: 306 year: 2006 end-page: 314 article-title: Evaluation of 2 phosphorylation sites improves the prognostic significance of Akt activation in non‐small‐cell lung cancer tumors publication-title: J Clin Oncol – volume: 51 start-page: 181 year: 2006 end-page: 191 article-title: Phosphorylated Akt overexpression and loss of PTEN expression in non‐small cell lung cancer confers poor prognosis publication-title: Lung Cancer. – volume: 102 start-page: 371 year: 2008 end-page: 382 article-title: Analysis of complex protein kinase B signalling pathways in human prostate cancer samples publication-title: BJU Int – volume: 16 start-page: 240 year: 2010 end-page: 248 article-title: Overexpression of phospho‐eIF4E is associated with survival through AKT pathway in non‐small cell lung cancer publication-title: Clin Cancer Res – volume: 59 start-page: 225 year: 2009 end-page: 249 article-title: Cancer statistics, 2009 publication-title: CA Cancer J Clin – volume: 69 start-page: 4059 year: 2009 end-page: 4066 article-title: Identification of potential driver genes in human liver carcinoma by genomewide screening publication-title: Cancer Res – volume: 23 start-page: 1 year: 2008 end-page: 9 article-title: The potential role of Akt phosphorylation in human cancers publication-title: Int J Biol Markers – volume: 7 start-page: 1 year: 2005 end-page: 6 article-title: Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small cell lung cancer and tumor‐associated stroma publication-title: Neoplasia – volume: 4 start-page: 335 year: 2004 end-page: 348 article-title: The TOR pathway: a target for cancer therapy publication-title: Nat Rev Cancer – volume: 16 start-page: 4 year: 2009 end-page: 10 article-title: The role of the Akt/mTOR pathway in tobacco carcinogen‐induced lung tumorigenesis publication-title: Clin Cancer Res. – volume: 67 start-page: 2095 year: 2010 end-page: 2106 article-title: Mammalian target of rapamycin: biological function and target for novel anticancer agents publication-title: Am J Health Syst Pharm – volume: 591 start-page: 124 year: 2008 end-page: 127 article-title: Inhibition of mTOR restores cisplatin sensitivity through down‐regulation of growth and anti‐apoptotic proteins publication-title: Eur J Pharmacol – volume: 15 start-page: 4157 year: 2009 end-page: 4164 article-title: High expression of mammalian target of rapamycin is associated with better outcome for patients with early stage lung adenocarcinoma publication-title: Clin Cancer Res – volume-title: TNM Classification of Malignant Tumors year: 2002 ident: e_1_2_6_22_2 – ident: e_1_2_6_20_2 doi: 10.1634/theoncologist.12-8-1007 – ident: e_1_2_6_41_2 doi: 10.1016/j.lungcan.2006.09.026 – ident: e_1_2_6_4_2 doi: 10.1038/nrc1362 – ident: e_1_2_6_30_2 doi: 10.1158/1078-0432.CCR-09-0099 – volume: 10 start-page: 479 year: 2005 ident: e_1_2_6_6_2 article-title: The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted antitumour therapy publication-title: Cell Mol Biol Lett – ident: e_1_2_6_32_2 doi: 10.1634/theoncologist.2007-0171 – ident: e_1_2_6_44_2 doi: 10.1073/pnas.89.15.7282 – ident: e_1_2_6_25_2 doi: 10.1158/1078-0432.CCR-09-0986 – ident: e_1_2_6_8_2 doi: 10.1158/0008-5472.CAN-09-0164 – ident: e_1_2_6_13_2 doi: 10.1074/jbc.M507201200 – volume: 11 start-page: S1 year: 1999 ident: e_1_2_6_23_2 article-title: Guidelines on the non‐surgical management of lung cancer publication-title: Clin Oncol (R Coll Radiol). – ident: e_1_2_6_42_2 doi: 10.1038/sj.bjc.6602646 – ident: e_1_2_6_17_2 doi: 10.1093/jjco/hyq047 – ident: e_1_2_6_14_2 doi: 10.1007/s00421-008-0786-7 – ident: e_1_2_6_2_2 doi: 10.3322/caac.20006 – ident: e_1_2_6_37_2 doi: 10.1016/S0960-9822(00)00441-3 – ident: e_1_2_6_27_2 doi: 10.1158/1078-0432.CCR-10-1601 – ident: e_1_2_6_26_2 doi: 10.1158/1078-0432.CCR-04-0941 – ident: e_1_2_6_45_2 doi: 10.4067/S0716-97602002000200022 – ident: e_1_2_6_3_2 doi: 10.1158/1078-0432.CCR-04-0112 – ident: e_1_2_6_39_2 doi: 10.1200/JCO.2005.02.4133 – ident: e_1_2_6_29_2 doi: 10.1097/JTO.0b013e3181ce6604 – ident: e_1_2_6_19_2 doi: 10.3816/CLC.2008.n.049 – ident: e_1_2_6_34_2 doi: 10.1074/jbc.M205141200 – ident: e_1_2_6_43_2 doi: 10.1182/blood-2009-09-220020 – ident: e_1_2_6_10_2 doi: 10.1038/sj.onc.1209888 – ident: e_1_2_6_33_2 doi: 10.1007/82_2010_43 – ident: e_1_2_6_28_2 doi: 10.1016/j.jamcollsurg.2009.12.008 – ident: e_1_2_6_38_2 doi: 10.1177/172460080802300101 – ident: e_1_2_6_9_2 doi: 10.1242/dmm.004671 – ident: e_1_2_6_16_2 doi: 10.1158/1078-0432.CCR-07-0717 – ident: e_1_2_6_31_2 doi: 10.1593/neo.04373 – ident: e_1_2_6_36_2 doi: 10.1126/stke.2001.66.pe1 – ident: e_1_2_6_18_2 doi: 10.1158/1078-0432.CCR-09-0234 – ident: e_1_2_6_40_2 doi: 10.4172/1948-5956.1000034 – ident: e_1_2_6_15_2 doi: 10.1016/j.ejphar.2008.06.028 – ident: e_1_2_6_35_2 doi: 10.1016/S0960-9822(99)80186-9 – ident: e_1_2_6_47_2 doi: 10.1074/jbc.M300376200 – ident: e_1_2_6_11_2 doi: 10.3816/CLC.2005.s.003 – ident: e_1_2_6_12_2 doi: 10.1002/jnr.22321 – ident: e_1_2_6_5_2 doi: 10.2146/ajhp100020 – ident: e_1_2_6_46_2 doi: 10.1158/1078-0432.CCR-06-1864 – volume-title: Pathology & Genetics: Tumours of the Lung, Pleura, Thymus and Heart year: 2004 ident: e_1_2_6_21_2 – ident: e_1_2_6_24_2 doi: 10.1016/j.lungcan.2005.10.003 – ident: e_1_2_6_7_2 doi: 10.1111/j.1464-410X.2008.07703.x
SSID	ssj0007253
Score	2.227201
Snippet	BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein... Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression...
SourceID	proquest pubmed pascalfrancis crossref wiley
SourceType	Aggregation Database Index Database Enrichment Source Publisher
StartPage	3763
SubjectTerms	activated kinases Biological and medical sciences Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - mortality Female Humans Lung Neoplasms - metabolism Lung Neoplasms - mortality Male mammalian target of rapamycin pathway Medical sciences Middle Aged nonsmall cell lung carcinoma Phosphorylation Phosphotransferases - metabolism Pneumology Prognosis Protein Array Analysis protein expression profiles Signal Transduction TOR Serine-Threonine Kinases - metabolism Tumors Tumors of the respiratory system and mediastinum
Title	Activation of mammalian target of rapamycin pathway confers adverse outcome in nonsmall cell lung carcinoma
URI	https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcncr.25959 https://www.ncbi.nlm.nih.gov/pubmed/21387259 https://www.proquest.com/docview/881090601
Volume	117
WOSCitedRecordID	wos000293672700017&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVWIB databaseName: Wiley Online Library Free Content customDbUrl: eissn: 1097-0142 dateEnd: 20241207 omitProxy: false ssIdentifier: ssj0007253 issn: 0008-543X databaseCode: WIN dateStart: 19960101 isFulltext: true titleUrlDefault: https://onlinelibrary.wiley.com providerName: Wiley-Blackwell – providerCode: PRVWIB databaseName: Wiley Online Library Full Collection 2020 customDbUrl: eissn: 1097-0142 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0007253 issn: 0008-543X databaseCode: DRFUL dateStart: 19960101 isFulltext: true titleUrlDefault: https://onlinelibrary.wiley.com providerName: Wiley-Blackwell
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3di9QwEB_OU0SQ81vX0yWgLwp717TpJoF7OVYXhXORw9N9K-k0AXHbPba7yv33TtKPZeEQDt9KmaRpZjKZycfvB_BWOhxLHSlKSwpKUKQsRori2JHIhXUyd3kaDsh-P5OzmZrP9dc9OOnuwjT4EP2Cmx8ZwV_7AW7y-ngLGooVro4oeE_97T0uuKcv-PF51rthGbcQlNSQVCTzHps0Pt4W3ZmN7l-amjrGNYwW14WcuxFsmIKmD_6v8Q_hoA092WljK49gz1aP4e6XdnP9Cfw6xY7rjC0dK01ZhkUQ1pwW9-88XXp5ReLMMxn_MVcMw43BmhlP7FxbttysqS2WkUhFBk01LJjfHGAL8ioMPXNRtSzNU7iYfvw2-TRquRhGKMaRJqeZaJtr5Bo1FpFyxlrheIq5cegk11Ib8h6ox5TCcRTc0cRXOKRfLKLY8OQZ7NNn7QtgSZoLlXgcQ2WEjjDXuUdpKwR9QFDANIB3nU4ybIHKPV_GImsgluPM914Wem8Ab3rZywae41qp4Y5qe1GKbXz-Fg-AdbrOaHj5bjGVXW7qTCl_cpWy1gE8b2xgW5gnioyMan8fVP2PBmST2eQ8PL28ifAh3OuWsHn6CvbXq419DXfw9_pnvRrCLTlXQ7j94Xx6cTYMxv8X7A4GIQ
linkProvider	Wiley-Blackwell
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3da9RAEB-0igrit_aq1gV9sXA2H5vL7mM5LC1eg0jVewubyS6Il1y53Fn63zuzyeU4KAXxLYTZzWZndnZmP34_gA-pw1GqA0VpSUkJSpqWQ0Vx7FAW0rq0cEXiD8j-mKRZpqZT_bU7m8N3YVp8iH7BjUeG99c8wHlB-nCDGoo1Lj5R9J7o23BHUqTBzA0_T7PeEadRB0JJTUlkPO3RSaPDTdmt-ejhhWmoa1zLaXFd0Lkdw_pJ6Pjxfzb_CTzqok9x1JrLU7hl62dw76zbX38Ov49wTXcm5k5Upqr8OohoD4zzO2ZMr65IXDCZ8aW5EugvDTbCMLdzY8V8taTGWEEiNdk01TATvD8gZuRYBDJ5UT2vzAv4fvz5fHwy7OgYhihHgSa_GWtbaAw1aiwD5Yy10oUJFsahS0OdakMOBPWIsrgQZeho7isd0i-WQWTC-CXs0GftLog4KaSKGcpQGakDLHTBQG2lpA9IipkG8HGtlBw7rHKmzJjlLcpylHPv5b73BvC-l71oETquldrf0m0vSuENp3DRAMRa2TmNMO4WU9v5qsmV4sOrlLgO4FVrBJvCYazIyqj2A6_rGxqQj7PxN_-09y_C7-D-yfnZJJ-cZl9ew4P1inaYvIGd5WJl38Jd_LP81Sz2ve3_BdaRB7c
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3ri9NAEB-0J8eB-D6tj3NBvyjUy2PT3f149CyKtRyHJ_0WNpNdEJu0NK1y_70zSZpSOATxWwiz79nZmX38fgBvlcehMoGmsCSnAEWpfKDJjx3ITDqvMp8l9QXZ7xM1nerZzFy0d3P4LUyDD9FtuPHMqO01T3C3zP3pDjUUS1x9IO89MbfhQDKLTA8Ozi_HV5POFKuohaGkyiQynnX4pNHpLvXeinR3aSvqHN-wWtzkdu57sfUyNL7_nw14APda_1OcNQrzEG658hEcfm1P2B_DzzPcEp6JhReFLYp6J0Q0V8b5H3OmF9ckLpjO-Le9Flg_G6yEZXbnyonFZk2VcYJEStJqymEu-IRAzMm0CGT6onJR2CdwNf74bfRp0BIyDFAOA0OWMzYuMxgaNJgH2lvnpA8TzKxHr0KjjCUTgmZIcVyIMvS0-uUeqYl5ENkwPoYeFeuegYiTTOqYwQy1lSbAzGQM1ZZLKkCS19SHd9tBSbFFK2fSjHna4CxHKfdeWvdeH950sssGo-NGqZO9se1EycHhIC7qg9gOdkpzjLvFlm6xqVKt-foqha59eNoowS5xGGvSMsr9fT3Wf6lAOpqOLuuv5_8i_BoOL87H6eTz9MsLONpuaYfJS-itVxv3Cu7gr_WPanXSKv8fg6QIYA
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Activation+of+mammalian+target+of+rapamycin+pathway+confers+adverse+outcome+in+nonsmall+cell+lung+carcinoma&rft.jtitle=Cancer&rft.au=Liu%2C+Dan&rft.au=Huang%2C+Yi&rft.au=Chen%2C+Bojiang&rft.au=Zeng%2C+Jing&rft.date=2011-08-15&rft.issn=0008-543X&rft.eissn=1097-0142&rft.volume=117&rft.issue=16&rft.spage=3763&rft.epage=3773&rft_id=info:doi/10.1002%2Fcncr.25959&rft.externalDBID=n%2Fa&rft.externalDocID=10_1002_cncr_25959
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0008-543X&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0008-543X&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0008-543X&client=summon