p-mTOR在Ⅰ~Ⅲ期非小細胞肺癌組織中的表達及其與預后的關系_《中國呼吸與危重監護雜志》

作者：

劉紅兵 ,  宋勇 , 吳穎

南京大學醫學院臨床學院南京軍區南京總醫院呼吸科（江蘇南京 210002）;

關鍵詞：

磷酸化的哺乳動物雷帕霉素靶蛋白非小細胞肺癌預后

視頻：

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目的探討磷酸化的哺乳動物雷帕霉素靶蛋白(p-roTOR)在非小細胞肺癌(NSCLC) 中的表達及其對預后的預測價值。方法運用免疫組織化學EnVision法檢測59例NSCLC肺癌組織和10例非肺癌組織(3例肺結核和7例炎性假瘤)中p-mTOR蛋白的表達。結果 p-mTOR在肺良性疾病組均為陰性，在NSCLC組織中表達的陽性率為40.7％，顯著高于肺良性疾病組（χ2=6.237，P=0.013）；p-mTOR在NSCLC組織中的表達與性別、年齡和pTNM分期有關，而與其他臨床病理參數(腫瘤大小、病理類型和淋巴結轉移情況)無明顯相關性。Kaplan-Meire生存分析顯示， p-mTOR與生存期無明顯相關(Log rank檢驗P=0.055)。結論檢測p-mTOR有助于肺部良惡性疾病的鑒別，單獨p-mTOR不能作為判斷NSCLC預后的參考指標。

引用本文： 劉紅兵,宋勇,吳穎. p-mTOR在Ⅰ~Ⅲ期非小細胞肺癌組織中的表達及其與預后的關系. 中國呼吸與危重監護雜志, 2008, 08(5): 354-357. doi: 復制

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2.	Brown EJ，Albers MW，Shin TB，et al.A mammalian protein targeted by G1-arresting rapamycin-receptor complex.Nature，1994，369：756-758.
3.	Balsara BR，Pei J，Mitsuuchi Y，et al.Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.Carcinogenesis，2004，25：2053-2059.
4.	Herberger B，Puhalla H，Lehnert M，et al，Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.Clin Cancer Res，2007，13：4795-4799.
5.	Gera JF，Mellinghoff IK，Shi Y，et al.AKT activity determines sensitivity to mammalian target of rapamycin（mTOR） inhibitors by regulating cyclin D1 and c-myc expression.J Biol Chem，2004，279：2737-2746.
6.	Bjornsti MA，Houghton PJ.The TOR pathway：a target for cancer therapy.Nat Rev Cancer，2004，4：335-348.
7.	Nave BT，Ouwens M，Withers DJ，et al.Mammalian target of rapamycin is a direct target for protein kinase B：identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.Biochem J，1999，344：427-431.
8.	Sekulic A，Hudson CC，Homme JL，et al.A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.Cancer Res，2000，60：3504-3513.
9.	Scott PH，Lawrence JC Jr.Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3–L1 adipocytes.J Biol Chem，1998，273：34496-34501.
10.	Reynolds TH 4th，Bodine SC，Lawrence JC Jr.Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load.J Biol Chem，2002，277：17657-17662.
11.	Sahin F，Kannangai R，Adegbola O，et al.mTOR and P70 S6 Kinase Expression in Primary Liver Neoplasms.Clin Cancer Res，2004，10：8421-8425.
12.	Zhou X，Tan M，Stone Hawthorne V，et al.Activation of the Akt/Mammalian Target of Rapamycin/4E-BP1 Pathway by ErbB2 Overexpression Predicts Tumor Progression in Breast Cancers.Clin Cancer Res，2004，10：6779-6788.
13.	Faried LS，Faried A，Kanuma T，et al.Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.Oncol Rep，2006，16：57-63.
14.	Kremer CL，Klein RR，Mendelson J，et al.Expression of mTOR Signaling PathwayMarkers in Prostate Cancer Progression.Prostate，2006，66：1203-1212.
15.	Sieghart W，Fuereder T，Schmid K，et al.Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.Transplantation，2007，83：425-432.
16.	Atkins MB，Hidalgo M，Stadler WM，et al.Randomized phase II study of multiple dose levels of CCI-779，a novel mammalian target of rapamycin kinase inhibitor，in patients with advanced refractory renal cell carcinoma.J Clin Oncol，2004，22：909-918.
17.	Witzig TE，Geyer SM，Ghobrial I，et al.Phase II trial of single-agent temsirolimus（CCI-779） for relapsed mantle cell lymphoma.J Clin Oncol，2005，23：5347-5356.
18.	Galanis E，Buckner JC，Maurer MJ，et al.Phase II trial of temsirolimus（CCI-779） in recurrent glioblastoma multiforme：a North Central Cancer Treatment Group Study.J Clin On col，2005，23：5294-5304.
19.	Chan S，Scheulen ME，Johnston S，et al.Phase II study of temsirolimus（CCI-779），a novel inhibitor of mTOR，in heavily pretreated patients with locally advanced or metastatic breast cancer.J Clin Oncol，2005，23：5314-5322.

1. Sabatini DM，Erdjument-Bromage H，Lui M，et al.RAFT1：a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.Cell，1994，78：35-43.
2. Brown EJ，Albers MW，Shin TB，et al.A mammalian protein targeted by G1-arresting rapamycin-receptor complex.Nature，1994，369：756-758.
3. Balsara BR，Pei J，Mitsuuchi Y，et al.Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.Carcinogenesis，2004，25：2053-2059.
4. Herberger B，Puhalla H，Lehnert M，et al，Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.Clin Cancer Res，2007，13：4795-4799.
5. Gera JF，Mellinghoff IK，Shi Y，et al.AKT activity determines sensitivity to mammalian target of rapamycin（mTOR） inhibitors by regulating cyclin D1 and c-myc expression.J Biol Chem，2004，279：2737-2746.
6. Bjornsti MA，Houghton PJ.The TOR pathway：a target for cancer therapy.Nat Rev Cancer，2004，4：335-348.
7. Nave BT，Ouwens M，Withers DJ，et al.Mammalian target of rapamycin is a direct target for protein kinase B：identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.Biochem J，1999，344：427-431.
8. Sekulic A，Hudson CC，Homme JL，et al.A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.Cancer Res，2000，60：3504-3513.
9. Scott PH，Lawrence JC Jr.Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3–L1 adipocytes.J Biol Chem，1998，273：34496-34501.
10. Reynolds TH 4th，Bodine SC，Lawrence JC Jr.Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load.J Biol Chem，2002，277：17657-17662.
11. Sahin F，Kannangai R，Adegbola O，et al.mTOR and P70 S6 Kinase Expression in Primary Liver Neoplasms.Clin Cancer Res，2004，10：8421-8425.
12. Zhou X，Tan M，Stone Hawthorne V，et al.Activation of the Akt/Mammalian Target of Rapamycin/4E-BP1 Pathway by ErbB2 Overexpression Predicts Tumor Progression in Breast Cancers.Clin Cancer Res，2004，10：6779-6788.
13. Faried LS，Faried A，Kanuma T，et al.Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.Oncol Rep，2006，16：57-63.
14. Kremer CL，Klein RR，Mendelson J，et al.Expression of mTOR Signaling PathwayMarkers in Prostate Cancer Progression.Prostate，2006，66：1203-1212.
15. Sieghart W，Fuereder T，Schmid K，et al.Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.Transplantation，2007，83：425-432.
16. Atkins MB，Hidalgo M，Stadler WM，et al.Randomized phase II study of multiple dose levels of CCI-779，a novel mammalian target of rapamycin kinase inhibitor，in patients with advanced refractory renal cell carcinoma.J Clin Oncol，2004，22：909-918.
17. Witzig TE，Geyer SM，Ghobrial I，et al.Phase II trial of single-agent temsirolimus（CCI-779） for relapsed mantle cell lymphoma.J Clin Oncol，2005，23：5347-5356.
18. Galanis E，Buckner JC，Maurer MJ，et al.Phase II trial of temsirolimus（CCI-779） in recurrent glioblastoma multiforme：a North Central Cancer Treatment Group Study.J Clin On col，2005，23：5294-5304.
19. Chan S，Scheulen ME，Johnston S，et al.Phase II study of temsirolimus（CCI-779），a novel inhibitor of mTOR，in heavily pretreated patients with locally advanced or metastatic breast cancer.J Clin Oncol，2005，23：5314-5322.

《中國呼吸與危重監護雜志》

p-mTOR在Ⅰ~Ⅲ期非小細胞肺癌組織中的表達及其與預后的關系

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《中國呼吸與危重監護雜志》

p-mTOR在Ⅰ~Ⅲ期非小細胞肺癌組織中的表達及其與預后的關系

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