{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:30:36Z","timestamp":1788921036132,"version":"build-2803163510"},"reference-count":116,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4]]},"abstract":"\n Context<\/jats:italic>\n .\u2014Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine\/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear.\n <\/jats:p>\n \n Objective<\/jats:italic>\n .\u2014To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma.\n <\/jats:p>\n \n Design<\/jats:italic>\n .\u2014Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of\n P<\/jats:italic>\n < .05, and Kaplan-Meier curves were constructed for survival analysis.\n <\/jats:p>\n \n Results<\/jats:italic>\n .\u2014Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (\n P<\/jats:italic>\n < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (\n P =<\/jats:italic>\n .02).\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n .\u2014Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0032-oa","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T16:29:13Z","timestamp":1364833753000},"page":"552-557","source":"Crossref","is-referenced-by-count":39,"title":["Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma"],"prefix":"10.5858","volume":"137","author":[{"given":"Pamela","family":"Leal","sequence":"first","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Sandoval","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Letelier","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Brebi","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Ili","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Tapia","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Roa","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, School of Medicine, CEGINBIOREN, University of La Frontera, Temuco, Chile (Drs Leal, Garc\u00eda, Brebi, Ili, Tapia, and Roa; Mses Sandoval and Letelier; the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr \u00c1lvarez); and the Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile (Drs Garc\u00eda and Roa)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"issue":"2","key":"i1543-2165-137-4-552-b01","series-title":"Am J Surg","first-page":"252","article-title":"Gallbladder cancer","volume":"196","author":"Gourgiotis\n S,","year":"2008","unstructured":"Gourgiotis\n S, \n \n Kocher\n HM, \n \n Solaini\n L, \n \n Yarollahi\n A, \n \n Tsiambas\n E, \n \n Salemis\n NS. \n \n Gallbladder cancer. Am J Surg. 2008;196(2):252\u2013264."},{"issue":"7","key":"i1543-2165-137-4-552-b02","series-title":"Int J Cancer","first-page":"1591","article-title":"Gallbladder cancer worldwide: geographical distribution and risk factors","volume":"118","author":"Randi\n G,","year":"2006","unstructured":"Randi\n G, \n \n Franceschi\n S, \n \n La Vecchia\n C. \n \n Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118(7):1591\u20131602."},{"issue":"6","key":"i1543-2165-137-4-552-b03","series-title":"CA Cancer J Clin","first-page":"349","article-title":"Epidemiology and molecular pathology of gallbladder cancer","volume":"51","author":"Lazcano-Ponce\n EC,","year":"2001","unstructured":"Lazcano-Ponce\n EC, \n \n Miquel\n JF, \n \n Munoz\n N, \n et al\n . Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51(6):349\u2013364."},{"issue":"2","key":"i1543-2165-137-4-552-b04","series-title":"Histopathology","first-page":"218","article-title":"Gallbladder cancer: a morphological and molecular update","volume":"55","author":"Goldin\n RD,","year":"2009","unstructured":"Goldin\n RD, \n \n Roa\n JC. \n \n Gallbladder cancer: a morphological and molecular update. Histopathology. 2009;55(2):218\u2013229."},{"key":"i1543-2165-137-4-552-b05","series-title":"Estadisticas de Salud","article-title":"Gobierno de Chile","author":"Ministerio de Salud, MINSAL.","year":"2009","unstructured":"Ministerio de Salud, MINSAL. \n \n Gobierno de Chile. Estadisticas de Salud. 2009."},{"issue":"1","key":"i1543-2165-137-4-552-b06","series-title":"Eur J Cancer Prev","first-page":"15","article-title":"Risk factors for gallbladder cancer: a reappraisal","volume":"12","author":"Pandey\n M.","year":"2003","unstructured":"Pandey\n M. \n \n Risk factors for gallbladder cancer: a reappraisal. Eur J Cancer Prev. 2003;12(1):15\u201324."},{"issue":"4","key":"i1543-2165-137-4-552-b07","series-title":"Eur J Cancer Prev","first-page":"269","article-title":"Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer","volume":"12","author":"Pandey\n M,","year":"2003","unstructured":"Pandey\n M, \n \n Shukla\n VK. \n \n Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. Eur J Cancer Prev. 2003;12(4):269\u2013272."},{"issue":"1","key":"i1543-2165-137-4-552-b08","series-title":"Gastroenterology","first-page":"232","article-title":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","volume":"111","author":"Roa\n I,","year":"1996","unstructured":"Roa\n I, \n \n Araya\n JC, \n \n Villaseca\n M, \n et al\n . Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression. Gastroenterology. 1996;111(1):232\u2013236."},{"issue":"2","key":"i1543-2165-137-4-552-b09","series-title":"Semin Surg Oncol","first-page":"145","article-title":"Gallbladder cancer","volume":"19","author":"Bartlett\n DL.","year":"2000","unstructured":"Bartlett\n DL. \n \n Gallbladder cancer. Semin Surg Oncol. 2000;19(2):145\u2013155."},{"issue":"1","key":"i1543-2165-137-4-552-b10","series-title":"Hum Pathol","first-page":"21","article-title":"Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas","volume":"30","year":"1999","unstructured":"Wistuba, II, Miquel JF, Gazdar AF, Albores-Saavedra J. Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas. Hum Pathol. 1999;30(1):21\u201325."},{"issue":"2","key":"i1543-2165-137-4-552-b11","series-title":"Oncologist","first-page":"168","article-title":"Current management of gallbladder carcinoma","volume":"15","author":"Zhu\n AX,","unstructured":"Zhu\n AX, \n \n Hong\n TS, \n \n Hezel\n AF, \n \n Kooby\n DA. \n \n Current management of gallbladder carcinoma. Oncologist.15(2):168\u2013181."},{"issue":"7","key":"i1543-2165-137-4-552-b12","series-title":"J Surg Oncol","first-page":"589","article-title":"Early gallbladder cancer: is further treatment necessary?","volume":"100","author":"de Aretxabala\n X,","year":"2009","unstructured":"de Aretxabala\n X, \n \n Roa\n I, \n \n Hepp\n J, \n et al\n . Early gallbladder cancer: is further treatment necessary?J Surg Oncol. 2009;100(7):589\u2013593."},{"issue":"4","key":"i1543-2165-137-4-552-b13","series-title":"Rev Med Chil","first-page":"387","article-title":"Morphological prognostic elements in gallbladder cancer [in Spanish]","volume":"130","author":"Roa\n I,","year":"2002","unstructured":"Roa\n I, \n \n de Aretxabala\n X, \n \n Araya\n JC, \n et al\n . Morphological prognostic elements in gallbladder cancer [in Spanish]. Rev Med Chil. 2002;130(4):387\u2013395."},{"issue":"6","key":"i1543-2165-137-4-552-b14","series-title":"Ann Surg","first-page":"893","article-title":"Gallbladder cancer: the role of laparoscopy and radical resection","volume":"245","author":"Shih\n SP,","year":"2007","unstructured":"Shih\n SP, \n \n Schulick\n RD, \n \n Cameron\n JL, \n et al\n . Gallbladder cancer: the role of laparoscopy and radical resection. Ann Surg. 2007;245(6):893\u2013901."},{"issue":"6","key":"i1543-2165-137-4-552-b15","series-title":"Eur J Surg","first-page":"419","article-title":"Curative resection in potentially resectable tumours of the gallbladder","volume":"163","author":"de Aretxabala\n XA,","year":"1997","unstructured":"de Aretxabala\n XA, \n \n Roa\n IS, \n \n Burgos\n LA, \n \n Araya\n JC, \n \n Villaseca\n MA, \n \n Silva\n JA. \n \n Curative resection in potentially resectable tumours of the gallbladder. Eur J Surg. 1997;163(6):419\u2013426."},{"issue":"6","key":"i1543-2165-137-4-552-b16","series-title":"World J Surg","first-page":"544","article-title":"Laparoscopic cholecystectomy: its effect on the prognosis of patients with gallbladder cancer","volume":"28","author":"de Aretxabala\n XA,","year":"2004","unstructured":"de Aretxabala\n XA, \n \n Roa\n IS, \n \n Mora\n JP, \n et al\n . Laparoscopic cholecystectomy: its effect on the prognosis of patients with gallbladder cancer. World J Surg. 2004;28(6):544\u2013547."},{"issue":"3","key":"i1543-2165-137-4-552-b17","series-title":"J Coll Physicians Surg Pak","first-page":"175","article-title":"Advanced carcinoma gallbladder","volume":"17","author":"Parvez\n T,","year":"2007","unstructured":"Parvez\n T, \n \n Parvez\n B, \n \n Alharbi\n TM. \n \n Advanced carcinoma gallbladder. J Coll Physicians Surg Pak. 2007;17(3):175\u2013179."},{"issue":"12","key":"i1543-2165-137-4-552-b18","series-title":"Presse Med","first-page":"1238","article-title":"Chemotherapy in gallbladder carcinoma [in French]","volume":"39","author":"Abahssain\n H,","year":"2010","unstructured":"Abahssain\n H, \n \n Afchain\n P, \n \n Melas\n N, \n et al\n . Chemotherapy in gallbladder carcinoma [in French]. Presse Med. 2010;39(12):1238\u20131245."},{"issue":"1","key":"i1543-2165-137-4-552-b19","series-title":"Rev Med Chil","first-page":"51","article-title":"Neoadjuvant chemoradiotherapy in gallbladder cancer [in Spanish]","volume":"132","author":"de Aretxabala\n X,","year":"2004","unstructured":"de Aretxabala\n X, \n \n Losada\n H, \n \n Mora\n J, \n et al\n . Neoadjuvant chemoradiotherapy in gallbladder cancer [in Spanish]. Rev Med Chil. 2004;132(1):51\u201357."},{"issue":"5","key":"i1543-2165-137-4-552-b20","series-title":"Ann Oncol","first-page":"807","article-title":"Chemotherapy with gemcitabine in patients with gall-bladder carcinoma","volume":"13","author":"Rudi\n J.","year":"2002","unstructured":"Rudi\n J. \n \n Chemotherapy with gemcitabine in patients with gall-bladder carcinoma. Ann Oncol. 2002;13(5):807."},{"issue":"1","key":"i1543-2165-137-4-552-b21","series-title":"Crit Rev Oncol Hematol","first-page":"44","article-title":"Biological characteristics of cancers in the gallbladder and biliary tract and targeted therapy","volume":"61","author":"Thomas\n MB.","year":"2007","unstructured":"Thomas\n MB. \n \n Biological characteristics of cancers in the gallbladder and biliary tract and targeted therapy. Crit Rev Oncol Hematol. 2007;61(1):44\u201351."},{"issue":"1","key":"i1543-2165-137-4-552-b22","series-title":"Curr Pharm Des","first-page":"34","article-title":"The PKB\/AKT pathway in cancer","volume":"16","author":"Carnero\n A.","year":"2010","unstructured":"Carnero\n A. \n \n The PKB\/AKT pathway in cancer. Curr Pharm Des. 2010;16(1):34\u201344."},{"issue":"5","key":"i1543-2165-137-4-552-b23","series-title":"Curr Cancer Drug Targets","first-page":"484","article-title":"The mTOR pathway: a new target in cancer therapy","volume":"10","author":"Ciuffreda\n L,","year":"2010","unstructured":"Ciuffreda\n L, \n \n Di Sanza\n C, \n \n Incani\n UC, \n \n Milella\n M. \n \n The mTOR pathway: a new target in cancer therapy. Curr Cancer Drug Targets. 2010;10(5):484\u2013495."},{"issue":"12","key":"i1543-2165-137-4-552-b24","series-title":"Carcinogenesis","first-page":"2047","article-title":"Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk","volume":"30","author":"Chen\n M,","year":"2009","unstructured":"Chen\n M, \n \n Cassidy\n A, \n \n Gu\n J, \n et al\n . Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk. Carcinogenesis. 2009;30(12):2047\u20132052."},{"issue":"7","key":"i1543-2165-137-4-552-b25","series-title":"BJU Int","first-page":"1009","article-title":"Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics","volume":"104","author":"Dai\n B,","year":"2009","unstructured":"Dai\n B, \n \n Kong\n YY, \n \n Ye\n DW, \n \n Ma\n CG, \n \n Zhou\n X, \n \n Yao\n XD. \n \n Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics. BJU Int. 2009;104(7):1009\u20131016."},{"issue":"3","key":"i1543-2165-137-4-552-b26","series-title":"J Neurooncol","first-page":"453","article-title":"Association between AKT\/mTOR signalling pathway and malignancy grade of human gliomas","volume":"103","author":"Li\n XY,","year":"2011","unstructured":"Li\n XY, \n \n Zhang\n LQ, \n \n Zhang\n XG, \n et al\n . Association between AKT\/mTOR signalling pathway and malignancy grade of human gliomas. J Neurooncol. 2011;103(3):453\u2013458."},{"issue":"7","key":"i1543-2165-137-4-552-b27","series-title":"Anticancer Agents Med Chem","first-page":"571","article-title":"Updates of mTOR inhibitors","volume":"10","author":"Zhou\n H,","year":"2010","unstructured":"Zhou\n H, \n \n Luo\n Y, \n \n Huang\n S. \n \n Updates of mTOR inhibitors. Anticancer Agents Med Chem. 2010;10(7):571\u2013581."},{"issue":"5","key":"i1543-2165-137-4-552-b28","series-title":"Clin Cancer Res","first-page":"1612","article-title":"mTOR inhibitor RAD001 (everolimus) has antiangiogenic\/vascular properties distinct from a VEGFR tyrosine kinase inhibitor","volume":"15","author":"Lane\n HA,","year":"2009","unstructured":"Lane\n HA, \n \n Wood\n JM, \n \n McSheehy\n PM, \n et al\n . mTOR inhibitor RAD001 (everolimus) has antiangiogenic\/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res. 2009;15(5):1612\u20131622."},{"issue":"6","key":"i1543-2165-137-4-552-b29","series-title":"Cancer Res","first-page":"2408","article-title":"RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer","volume":"67","author":"Mabuchi\n S,","year":"2007","unstructured":"Mabuchi\n S, \n \n Altomare\n DA, \n \n Connolly\n DC, \n et al\n . RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res. 2007;67(6):2408\u20132413."},{"issue":"17","key":"i1543-2165-137-4-552-b30","series-title":"Clin Cancer Res","first-page":"5404","article-title":"mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary","volume":"15","author":"Mabuchi\n S,","year":"2009","unstructured":"Mabuchi\n S, \n \n Kawase\n C, \n \n Altomare\n DA, \n et al\n . mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res. 2009;15(17):5404\u20135413."},{"issue":"6","key":"i1543-2165-137-4-552-b31","series-title":"Ann Surg Oncol","first-page":"1471","article-title":"The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM","volume":"17","author":"Edge\n SB,","year":"2010","unstructured":"Edge\n SB, \n \n Compton\n CC. \n \n The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471\u20131474."},{"key":"i1543-2165-137-4-552-b32","series-title":"J Exp Clin Cancer Res","first-page":"152","article-title":"The role of mTOR and phospho-p70S6K in pathogenesis and progression of gastric carcinomas: an immunohistochemical study on tissue microarray","volume":"28","author":"Xiao\n L,","year":"2009","unstructured":"Xiao\n L, \n \n Wang\n YC, \n \n Li\n WS, \n \n Du\n Y. \n \n The role of mTOR and phospho-p70S6K in pathogenesis and progression of gastric carcinomas: an immunohistochemical study on tissue microarray. J Exp Clin Cancer Res. 2009;28:152."},{"issue":"4 suppl 1","key":"i1543-2165-137-4-552-b33","series-title":"Cancer Biol Ther","first-page":"S169","article-title":"The molecular target of rapamycin (mTOR) as a therapeutic target against cancer","volume":"2","author":"Mita\n MM,","year":"2003","unstructured":"Mita\n MM, \n \n Mita\n A, \n \n Rowinsky\n EK. \n \n The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther. 2003;2(4 suppl 1):S169\u2013S177."},{"issue":"8","key":"i1543-2165-137-4-552-b34","series-title":"Cell Res","first-page":"666","article-title":"Expanding mTOR signaling","volume":"17","author":"Yang\n Q,","year":"2007","unstructured":"Yang\n Q, \n \n Guan\n KL. \n \n Expanding mTOR signaling. Cell Res. 2007;17(8):666\u2013681."},{"issue":"9","key":"i1543-2165-137-4-552-b35","series-title":"Nat Rev Cancer","first-page":"729","article-title":"mTOR and cancer: insights into a complex relationship","volume":"6","author":"Sabatini\n DM.","year":"2006","unstructured":"Sabatini\n DM. \n \n mTOR and cancer: insights into a complex relationship. Nat Rev Cancer. 2006;6(9):729\u2013734."},{"issue":"3","key":"i1543-2165-137-4-552-b36","series-title":"Nat Rev Cancer","first-page":"184","article-title":"Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis","volume":"6","author":"Cully\n M,","year":"2006","unstructured":"Cully\n M, \n \n You\n H, \n \n Levine\n AJ, \n \n Mak\n TW. \n \n Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6(3):184\u2013192."},{"issue":"7","key":"i1543-2165-137-4-552-b37","first-page":"1399","article-title":"Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. Cancer","volume":"117","author":"Baba\n Y,","year":"2011","unstructured":"Baba\n Y, \n \n Nosho\n K, \n \n Shima\n K, \n et al\n . Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. Cancer. 2011;117(7):1399\u20131408."},{"issue":"4","key":"i1543-2165-137-4-552-b38","series-title":"Diagn Mol Pathol","first-page":"200","article-title":"PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases","volume":"18","author":"Michelucci\n A,","year":"2009","unstructured":"Michelucci\n A, \n \n Di Cristofano\n C, \n \n Lami\n A, \n et al\n . PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases. Diagn Mol Pathol. 2009;18(4):200\u2013205."},{"issue":"2","key":"i1543-2165-137-4-552-b39","series-title":"J Clin Invest","first-page":"553","article-title":"An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice","volume":"122","author":"Kinross\n KM,","year":"2012","unstructured":"Kinross\n KM, \n \n Montgomery\n KG, \n \n Kleinschmidt\n M, \n et al\n . An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. J Clin Invest. 2012;122(2):553\u2013557."},{"issue":"6","key":"i1543-2165-137-4-552-b40","series-title":"Acta Neuropathol","first-page":"639","article-title":"PIK3CA mutations in glioblastoma multiforme","volume":"109","author":"Hartmann\n C,","year":"2005","unstructured":"Hartmann\n C, \n \n Bartels\n G, \n \n Gehlhaar\n C, \n \n Holtkamp\n N, \n \n von Deimling\n A. \n \n PIK3CA mutations in glioblastoma multiforme. Acta Neuropathol. 2005;109(6):639\u2013642."},{"issue":"3","key":"i1543-2165-137-4-552-b41","series-title":"Eur J Cancer","first-page":"443","article-title":"Oncogenic mutations in gastric cancer with microsatellite instability","volume":"47","author":"Corso\n G,","year":"2011","unstructured":"Corso\n G, \n \n Velho\n S, \n \n Paredes\n J, \n et al\n . Oncogenic mutations in gastric cancer with microsatellite instability. Eur J Cancer. 2011;47(3):443\u2013451."},{"issue":"2","key":"i1543-2165-137-4-552-b42","series-title":"Mol Cancer Ther","first-page":"485","article-title":"Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling","volume":"11","author":"Chaft\n JE,","year":"2012","unstructured":"Chaft\n JE, \n \n Arcila\n ME, \n \n Paik\n PK, \n et al\n . Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther. 2012;11(2):485\u2013491."},{"issue":"5","key":"i1543-2165-137-4-552-b43","series-title":"Genes Chromosomes Cancer","first-page":"363","article-title":"Rare PIK3CA hotspot mutations in carcinomas of the biliary tract","volume":"47","author":"Riener\n MO,","year":"2008","unstructured":"Riener\n MO, \n \n Bawohl\n M, \n \n Clavien\n PA, \n \n Jochum\n W. \n \n Rare PIK3CA hotspot mutations in carcinomas of the biliary tract. Genes Chromosomes Cancer. 2008;47(5):363\u2013367."},{"issue":"6","key":"i1543-2165-137-4-552-b44","series-title":"Curr Opin Cell Biol","first-page":"596","article-title":"Growing roles for the mTOR pathway","volume":"17","author":"Sarbassov\n DD,","year":"2005","unstructured":"Sarbassov\n DD, \n \n Ali\n SM, \n \n Sabatini\n DM. \n \n Growing roles for the mTOR pathway. Curr Opin Cell Biol. 2005;17(6):596\u2013603."},{"issue":"11","key":"i1543-2165-137-4-552-b45","series-title":"Expert Opin Investig Drugs","first-page":"1717","article-title":"mTOR inhibitors in the treatment of cancer","volume":"17","author":"Fasolo\n A,","year":"2008","unstructured":"Fasolo\n A, \n \n Sessa\n C. \n \n mTOR inhibitors in the treatment of cancer. Expert Opin Investig Drugs. 2008;17(11):1717\u20131734."},{"issue":"16","key":"i1543-2165-137-4-552-b46","series-title":"Clin Cancer Res","first-page":"4795","article-title":"Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma","volume":"13","author":"Herberger\n B,","year":"2007","unstructured":"Herberger\n B, \n \n Puhalla\n H, \n \n Lehnert\n M, \n et al\n . Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma. Clin Cancer Res. 2007;13(16):4795\u20134799."},{"issue":"2","key":"i1543-2165-137-4-552-b47","series-title":"Med Oncol","first-page":"255","article-title":"The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma","volume":"27","author":"Zhou\n L,","year":"2010","unstructured":"Zhou\n L, \n \n Huang\n Y, \n \n Li\n J, \n \n Wang\n Z. \n \n The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma. Med Oncol. 2010;27(2):255\u2013261."},{"issue":"3","key":"i1543-2165-137-4-552-b48","series-title":"Arch Pathol Lab Med","first-page":"386","article-title":"Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens","volume":"129","author":"Mukhopadhyay\n S,","year":"2005","unstructured":"Mukhopadhyay\n S, \n \n Landas\n SK. \n \n Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med. 2005;129(3):386\u2013390."},{"issue":"3","key":"i1543-2165-137-4-552-b49","series-title":"Ann Diagn Pathol","first-page":"147","article-title":"Histologic analysis of chronic inflammatory patterns in the gallbladder: diagnostic criteria for reporting cholecystitis","volume":"7","author":"Barcia\n JJ.","year":"2003","unstructured":"Barcia\n JJ. \n \n Histologic analysis of chronic inflammatory patterns in the gallbladder: diagnostic criteria for reporting cholecystitis. Ann Diagn Pathol. 2003;7(3):147\u2013153."},{"issue":"6","key":"i1543-2165-137-4-552-b50","series-title":"Cancer","first-page":"1878","article-title":"Metaplasia and precursor lesions of gallbladder carcinoma: frequency, distribution, and probability of detection in routine histologic samples","volume":"72","author":"Duarte\n I,","year":"1993","unstructured":"Duarte\n I, \n \n Llanos\n O, \n \n Domke\n H, \n \n Harz\n C, \n \n Valdivieso\n V. \n \n Metaplasia and precursor lesions of gallbladder carcinoma: frequency, distribution, and probability of detection in routine histologic samples. Cancer. 1993;72(6):1878\u20131884."},{"issue":"3","key":"i1543-2165-137-4-552-b51","series-title":"Ann Clin Lab Sci","first-page":"195","article-title":"Morphoproteomic profile of mTOR, Ras\/Raf kinase\/ERK, and NF-kappaB pathways in human gastric adenocarcinoma","volume":"38","author":"Feng\n W,","year":"2008","unstructured":"Feng\n W, \n \n Brown\n RE, \n \n Trung\n CD, \n et al\n . Morphoproteomic profile of mTOR, Ras\/Raf kinase\/ERK, and NF-kappaB pathways in human gastric adenocarcinoma. Ann Clin Lab Sci. 2008;38(3):195\u2013209."},{"issue":"3","key":"i1543-2165-137-4-552-b52","series-title":"Basic Appl Pathol","first-page":"78","article-title":"Frequent activation of mammalian target of rapamycin in primary lung adenocarcinoma and preinvasive lesion","volume":"4","author":"Kim\n Y,","year":"2011","unstructured":"Kim\n Y, \n \n Jeong\n H, \n \n Kim\n A, \n \n Kim\n HK, \n \n Shin\n BK. \n \n Frequent activation of mammalian target of rapamycin in primary lung adenocarcinoma and preinvasive lesion. Basic Appl Pathol. 2011;4(3):78\u201385."},{"issue":"12","key":"i1543-2165-137-4-552-b53","series-title":"Int J Cancer","first-page":"2904","article-title":"Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer","volume":"126","author":"An\n JY,","year":"2010","unstructured":"An\n JY, \n \n Kim\n KM, \n \n Choi\n MG, \n et al\n . Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer. Int J Cancer. 2010;126(12):2904\u20132913."},{"issue":"2","key":"i1543-2165-137-4-552-b54","series-title":"Rev Med Chil","first-page":"183","article-title":"Management of gallbladder cancer with invasion of the muscular layer [in Spanish]","volume":"132","author":"de Aretxabala\n X,","year":"2004","unstructured":"de Aretxabala\n X, \n \n Roa\n I, \n \n Mora\n J, \n et al\n . Management of gallbladder cancer with invasion of the muscular layer [in Spanish]. Rev Med Chil. 2004;132(2):183\u2013188."},{"issue":"12","key":"i1543-2165-137-4-552-b55","series-title":"Clin Cancer Res","first-page":"3094","article-title":"Inhibition of the PI3K pathway: hope we can believe in?","volume":"16","author":"van der Heijden\n MS,","year":"2010","unstructured":"van der Heijden\n MS, \n \n Bernards\n R. \n \n Inhibition of the PI3K pathway: hope we can believe in?\n Clin Cancer Res. 2010;16(12):3094\u20133099."},{"issue":"4","key":"i1543-2165-137-4-552-b56","series-title":"Curr Opin Pharmacol","first-page":"371","article-title":"Targeting mTOR signaling for cancer therapy","volume":"3","author":"Huang\n S,","year":"2003","unstructured":"Huang\n S, \n \n Houghton\n PJ. \n \n Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003;3(4):371\u2013377."},{"issue":"1\u20134","key":"i1543-2165-137-4-552-b57","series-title":"J Chem Biol","first-page":"27","article-title":"Rapamycin and mTOR kinase inhibitors","volume":"1","author":"Ballou\n LM,","year":"2008","unstructured":"Ballou\n LM, \n \n Lin\n RZ. \n \n Rapamycin and mTOR kinase inhibitors. J Chem Biol. 2008;1(1\u20134):27\u201336."},{"issue":"9","key":"i1543-2165-137-4-552-b58","series-title":"Clin Cancer Res","first-page":"2756","article-title":"A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies","volume":"14","author":"Rizzieri\n DA,","year":"2008","unstructured":"Rizzieri\n DA, \n \n Feldman\n E, \n \n Dipersio\n JF, \n et al\n . A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008;14(9):2756\u20132762."},{"issue":"2","key":"i1543-2165-137-4-552-b01","series-title":"Am J Surg","first-page":"252","article-title":"Gallbladder cancer","volume":"196","author":"Gourgiotis\n S,","year":"2008","unstructured":"Gourgiotis\n S, \n \n Kocher\n HM, \n \n Solaini\n L, \n \n Yarollahi\n A, \n \n Tsiambas\n E, \n \n Salemis\n NS. \n \n Gallbladder cancer. Am J Surg. 2008;196(2):252\u2013264."},{"issue":"7","key":"i1543-2165-137-4-552-b02","series-title":"Int J Cancer","first-page":"1591","article-title":"Gallbladder cancer worldwide: geographical distribution and risk factors","volume":"118","author":"Randi\n G,","year":"2006","unstructured":"Randi\n G, \n \n Franceschi\n S, \n \n La Vecchia\n C. \n \n Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118(7):1591\u20131602."},{"issue":"6","key":"i1543-2165-137-4-552-b03","series-title":"CA Cancer J Clin","first-page":"349","article-title":"Epidemiology and molecular pathology of gallbladder cancer","volume":"51","author":"Lazcano-Ponce\n EC,","year":"2001","unstructured":"Lazcano-Ponce\n EC, \n \n Miquel\n JF, \n \n Munoz\n N, \n et al\n . Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51(6):349\u2013364."},{"issue":"2","key":"i1543-2165-137-4-552-b04","series-title":"Histopathology","first-page":"218","article-title":"Gallbladder cancer: a morphological and molecular update","volume":"55","author":"Goldin\n RD,","year":"2009","unstructured":"Goldin\n RD, \n \n Roa\n JC. \n \n Gallbladder cancer: a morphological and molecular update. Histopathology. 2009;55(2):218\u2013229."},{"key":"i1543-2165-137-4-552-b05","series-title":"Estadisticas de Salud","article-title":"Gobierno de Chile","author":"Ministerio de Salud, MINSAL.","year":"2009","unstructured":"Ministerio de Salud, MINSAL. \n \n Gobierno de Chile. Estadisticas de Salud. 2009."},{"issue":"1","key":"i1543-2165-137-4-552-b06","series-title":"Eur J Cancer Prev","first-page":"15","article-title":"Risk factors for gallbladder cancer: a reappraisal","volume":"12","author":"Pandey\n M.","year":"2003","unstructured":"Pandey\n M. \n \n Risk factors for gallbladder cancer: a reappraisal. Eur J Cancer Prev. 2003;12(1):15\u201324."},{"issue":"4","key":"i1543-2165-137-4-552-b07","series-title":"Eur J Cancer Prev","first-page":"269","article-title":"Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer","volume":"12","author":"Pandey\n M,","year":"2003","unstructured":"Pandey\n M, \n \n Shukla\n VK. \n \n Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. Eur J Cancer Prev. 2003;12(4):269\u2013272."},{"issue":"1","key":"i1543-2165-137-4-552-b08","series-title":"Gastroenterology","first-page":"232","article-title":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","volume":"111","author":"Roa\n I,","year":"1996","unstructured":"Roa\n I, \n \n Araya\n JC, \n \n Villaseca\n M, \n et al\n . Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression. Gastroenterology. 1996;111(1):232\u2013236."},{"issue":"2","key":"i1543-2165-137-4-552-b09","series-title":"Semin Surg Oncol","first-page":"145","article-title":"Gallbladder cancer","volume":"19","author":"Bartlett\n DL.","year":"2000","unstructured":"Bartlett\n DL. \n \n Gallbladder cancer. Semin Surg Oncol. 2000;19(2):145\u2013155."},{"issue":"1","key":"i1543-2165-137-4-552-b10","series-title":"Hum Pathol","first-page":"21","article-title":"Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas","volume":"30","year":"1999","unstructured":"Wistuba, II, Miquel JF, Gazdar AF, Albores-Saavedra J. Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas. Hum Pathol. 1999;30(1):21\u201325."},{"issue":"2","key":"i1543-2165-137-4-552-b11","series-title":"Oncologist","first-page":"168","article-title":"Current management of gallbladder carcinoma","volume":"15","author":"Zhu\n AX,","unstructured":"Zhu\n AX, \n \n Hong\n TS, \n \n Hezel\n AF, \n \n Kooby\n DA. \n \n Current management of gallbladder carcinoma. Oncologist.15(2):168\u2013181."},{"issue":"7","key":"i1543-2165-137-4-552-b12","series-title":"J Surg Oncol","first-page":"589","article-title":"Early gallbladder cancer: is further treatment necessary?","volume":"100","author":"de Aretxabala\n X,","year":"2009","unstructured":"de Aretxabala\n X, \n \n Roa\n I, \n \n Hepp\n J, \n et al\n . Early gallbladder cancer: is further treatment necessary?J Surg Oncol. 2009;100(7):589\u2013593."},{"issue":"4","key":"i1543-2165-137-4-552-b13","series-title":"Rev Med Chil","first-page":"387","article-title":"Morphological prognostic elements in gallbladder cancer [in Spanish]","volume":"130","author":"Roa\n I,","year":"2002","unstructured":"Roa\n I, \n \n de Aretxabala\n X, \n \n Araya\n JC, \n et al\n . Morphological prognostic elements in gallbladder cancer [in Spanish]. Rev Med Chil. 2002;130(4):387\u2013395."},{"issue":"6","key":"i1543-2165-137-4-552-b14","series-title":"Ann Surg","first-page":"893","article-title":"Gallbladder cancer: the role of laparoscopy and radical resection","volume":"245","author":"Shih\n SP,","year":"2007","unstructured":"Shih\n SP, \n \n Schulick\n RD, \n \n Cameron\n JL, \n et al\n . Gallbladder cancer: the role of laparoscopy and radical resection. Ann Surg. 2007;245(6):893\u2013901."},{"issue":"6","key":"i1543-2165-137-4-552-b15","series-title":"Eur J Surg","first-page":"419","article-title":"Curative resection in potentially resectable tumours of the gallbladder","volume":"163","author":"de Aretxabala\n XA,","year":"1997","unstructured":"de Aretxabala\n XA, \n \n Roa\n IS, \n \n Burgos\n LA, \n \n Araya\n JC, \n \n Villaseca\n MA, \n \n Silva\n JA. \n \n Curative resection in potentially resectable tumours of the gallbladder. Eur J Surg. 1997;163(6):419\u2013426."},{"issue":"6","key":"i1543-2165-137-4-552-b16","series-title":"World J Surg","first-page":"544","article-title":"Laparoscopic cholecystectomy: its effect on the prognosis of patients with gallbladder cancer","volume":"28","author":"de Aretxabala\n XA,","year":"2004","unstructured":"de Aretxabala\n XA, \n \n Roa\n IS, \n \n Mora\n JP, \n et al\n . Laparoscopic cholecystectomy: its effect on the prognosis of patients with gallbladder cancer. World J Surg. 2004;28(6):544\u2013547."},{"issue":"3","key":"i1543-2165-137-4-552-b17","series-title":"J Coll Physicians Surg Pak","first-page":"175","article-title":"Advanced carcinoma gallbladder","volume":"17","author":"Parvez\n T,","year":"2007","unstructured":"Parvez\n T, \n \n Parvez\n B, \n \n Alharbi\n TM. \n \n Advanced carcinoma gallbladder. J Coll Physicians Surg Pak. 2007;17(3):175\u2013179."},{"issue":"12","key":"i1543-2165-137-4-552-b18","series-title":"Presse Med","first-page":"1238","article-title":"Chemotherapy in gallbladder carcinoma [in French]","volume":"39","author":"Abahssain\n H,","year":"2010","unstructured":"Abahssain\n H, \n \n Afchain\n P, \n \n Melas\n N, \n et al\n . Chemotherapy in gallbladder carcinoma [in French]. Presse Med. 2010;39(12):1238\u20131245."},{"issue":"1","key":"i1543-2165-137-4-552-b19","series-title":"Rev Med Chil","first-page":"51","article-title":"Neoadjuvant chemoradiotherapy in gallbladder cancer [in Spanish]","volume":"132","author":"de Aretxabala\n X,","year":"2004","unstructured":"de Aretxabala\n X, \n \n Losada\n H, \n \n Mora\n J, \n et al\n . Neoadjuvant chemoradiotherapy in gallbladder cancer [in Spanish]. Rev Med Chil. 2004;132(1):51\u201357."},{"issue":"5","key":"i1543-2165-137-4-552-b20","series-title":"Ann Oncol","first-page":"807","article-title":"Chemotherapy with gemcitabine in patients with gall-bladder carcinoma","volume":"13","author":"Rudi\n J.","year":"2002","unstructured":"Rudi\n J. \n \n Chemotherapy with gemcitabine in patients with gall-bladder carcinoma. Ann Oncol. 2002;13(5):807."},{"issue":"1","key":"i1543-2165-137-4-552-b21","series-title":"Crit Rev Oncol Hematol","first-page":"44","article-title":"Biological characteristics of cancers in the gallbladder and biliary tract and targeted therapy","volume":"61","author":"Thomas\n MB.","year":"2007","unstructured":"Thomas\n MB. \n \n Biological characteristics of cancers in the gallbladder and biliary tract and targeted therapy. Crit Rev Oncol Hematol. 2007;61(1):44\u201351."},{"issue":"1","key":"i1543-2165-137-4-552-b22","series-title":"Curr Pharm Des","first-page":"34","article-title":"The PKB\/AKT pathway in cancer","volume":"16","author":"Carnero\n A.","year":"2010","unstructured":"Carnero\n A. \n \n The PKB\/AKT pathway in cancer. Curr Pharm Des. 2010;16(1):34\u201344."},{"issue":"5","key":"i1543-2165-137-4-552-b23","series-title":"Curr Cancer Drug Targets","first-page":"484","article-title":"The mTOR pathway: a new target in cancer therapy","volume":"10","author":"Ciuffreda\n L,","year":"2010","unstructured":"Ciuffreda\n L, \n \n Di Sanza\n C, \n \n Incani\n UC, \n \n Milella\n M. \n \n The mTOR pathway: a new target in cancer therapy. Curr Cancer Drug Targets. 2010;10(5):484\u2013495."},{"issue":"12","key":"i1543-2165-137-4-552-b24","series-title":"Carcinogenesis","first-page":"2047","article-title":"Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk","volume":"30","author":"Chen\n M,","year":"2009","unstructured":"Chen\n M, \n \n Cassidy\n A, \n \n Gu\n J, \n et al\n . Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk. Carcinogenesis. 2009;30(12):2047\u20132052."},{"issue":"7","key":"i1543-2165-137-4-552-b25","series-title":"BJU Int","first-page":"1009","article-title":"Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics","volume":"104","author":"Dai\n B,","year":"2009","unstructured":"Dai\n B, \n \n Kong\n YY, \n \n Ye\n DW, \n \n Ma\n CG, \n \n Zhou\n X, \n \n Yao\n XD. \n \n Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics. BJU Int. 2009;104(7):1009\u20131016."},{"issue":"3","key":"i1543-2165-137-4-552-b26","series-title":"J Neurooncol","first-page":"453","article-title":"Association between AKT\/mTOR signalling pathway and malignancy grade of human gliomas","volume":"103","author":"Li\n XY,","year":"2011","unstructured":"Li\n XY, \n \n Zhang\n LQ, \n \n Zhang\n XG, \n et al\n . Association between AKT\/mTOR signalling pathway and malignancy grade of human gliomas. J Neurooncol. 2011;103(3):453\u2013458."},{"issue":"7","key":"i1543-2165-137-4-552-b27","series-title":"Anticancer Agents Med Chem","first-page":"571","article-title":"Updates of mTOR inhibitors","volume":"10","author":"Zhou\n H,","year":"2010","unstructured":"Zhou\n H, \n \n Luo\n Y, \n \n Huang\n S. \n \n Updates of mTOR inhibitors. Anticancer Agents Med Chem. 2010;10(7):571\u2013581."},{"issue":"5","key":"i1543-2165-137-4-552-b28","series-title":"Clin Cancer Res","first-page":"1612","article-title":"mTOR inhibitor RAD001 (everolimus) has antiangiogenic\/vascular properties distinct from a VEGFR tyrosine kinase inhibitor","volume":"15","author":"Lane\n HA,","year":"2009","unstructured":"Lane\n HA, \n \n Wood\n JM, \n \n McSheehy\n PM, \n et al\n . mTOR inhibitor RAD001 (everolimus) has antiangiogenic\/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res. 2009;15(5):1612\u20131622."},{"issue":"6","key":"i1543-2165-137-4-552-b29","series-title":"Cancer Res","first-page":"2408","article-title":"RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer","volume":"67","author":"Mabuchi\n S,","year":"2007","unstructured":"Mabuchi\n S, \n \n Altomare\n DA, \n \n Connolly\n DC, \n et al\n . RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res. 2007;67(6):2408\u20132413."},{"issue":"17","key":"i1543-2165-137-4-552-b30","series-title":"Clin Cancer Res","first-page":"5404","article-title":"mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary","volume":"15","author":"Mabuchi\n S,","year":"2009","unstructured":"Mabuchi\n S, \n \n Kawase\n C, \n \n Altomare\n DA, \n et al\n . mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res. 2009;15(17):5404\u20135413."},{"issue":"6","key":"i1543-2165-137-4-552-b31","series-title":"Ann Surg Oncol","first-page":"1471","article-title":"The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM","volume":"17","author":"Edge\n SB,","year":"2010","unstructured":"Edge\n SB, \n \n Compton\n CC. \n \n The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471\u20131474."},{"key":"i1543-2165-137-4-552-b32","series-title":"J Exp Clin Cancer Res","first-page":"152","article-title":"The role of mTOR and phospho-p70S6K in pathogenesis and progression of gastric carcinomas: an immunohistochemical study on tissue microarray","volume":"28","author":"Xiao\n L,","year":"2009","unstructured":"Xiao\n L, \n \n Wang\n YC, \n \n Li\n WS, \n \n Du\n Y. \n \n The role of mTOR and phospho-p70S6K in pathogenesis and progression of gastric carcinomas: an immunohistochemical study on tissue microarray. J Exp Clin Cancer Res. 2009;28:152."},{"issue":"4 suppl 1","key":"i1543-2165-137-4-552-b33","series-title":"Cancer Biol Ther","first-page":"S169","article-title":"The molecular target of rapamycin (mTOR) as a therapeutic target against cancer","volume":"2","author":"Mita\n MM,","year":"2003","unstructured":"Mita\n MM, \n \n Mita\n A, \n \n Rowinsky\n EK. \n \n The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther. 2003;2(4 suppl 1):S169\u2013S177."},{"issue":"8","key":"i1543-2165-137-4-552-b34","series-title":"Cell Res","first-page":"666","article-title":"Expanding mTOR signaling","volume":"17","author":"Yang\n Q,","year":"2007","unstructured":"Yang\n Q, \n \n Guan\n KL. \n \n Expanding mTOR signaling. Cell Res. 2007;17(8):666\u2013681."},{"issue":"9","key":"i1543-2165-137-4-552-b35","series-title":"Nat Rev Cancer","first-page":"729","article-title":"mTOR and cancer: insights into a complex relationship","volume":"6","author":"Sabatini\n DM.","year":"2006","unstructured":"Sabatini\n DM. \n \n mTOR and cancer: insights into a complex relationship. Nat Rev Cancer. 2006;6(9):729\u2013734."},{"issue":"3","key":"i1543-2165-137-4-552-b36","series-title":"Nat Rev Cancer","first-page":"184","article-title":"Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis","volume":"6","author":"Cully\n M,","year":"2006","unstructured":"Cully\n M, \n \n You\n H, \n \n Levine\n AJ, \n \n Mak\n TW. \n \n Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6(3):184\u2013192."},{"issue":"7","key":"i1543-2165-137-4-552-b37","first-page":"1399","article-title":"Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. Cancer","volume":"117","author":"Baba\n Y,","year":"2011","unstructured":"Baba\n Y, \n \n Nosho\n K, \n \n Shima\n K, \n et al\n . Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. Cancer. 2011;117(7):1399\u20131408."},{"issue":"4","key":"i1543-2165-137-4-552-b38","series-title":"Diagn Mol Pathol","first-page":"200","article-title":"PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases","volume":"18","author":"Michelucci\n A,","year":"2009","unstructured":"Michelucci\n A, \n \n Di Cristofano\n C, \n \n Lami\n A, \n et al\n . PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases. Diagn Mol Pathol. 2009;18(4):200\u2013205."},{"issue":"2","key":"i1543-2165-137-4-552-b39","series-title":"J Clin Invest","first-page":"553","article-title":"An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice","volume":"122","author":"Kinross\n KM,","year":"2012","unstructured":"Kinross\n KM, \n \n Montgomery\n KG, \n \n Kleinschmidt\n M, \n et al\n . An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. J Clin Invest. 2012;122(2):553\u2013557."},{"issue":"6","key":"i1543-2165-137-4-552-b40","series-title":"Acta Neuropathol","first-page":"639","article-title":"PIK3CA mutations in glioblastoma multiforme","volume":"109","author":"Hartmann\n C,","year":"2005","unstructured":"Hartmann\n C, \n \n Bartels\n G, \n \n Gehlhaar\n C, \n \n Holtkamp\n N, \n \n von Deimling\n A. \n \n PIK3CA mutations in glioblastoma multiforme. Acta Neuropathol. 2005;109(6):639\u2013642."},{"issue":"3","key":"i1543-2165-137-4-552-b41","series-title":"Eur J Cancer","first-page":"443","article-title":"Oncogenic mutations in gastric cancer with microsatellite instability","volume":"47","author":"Corso\n G,","year":"2011","unstructured":"Corso\n G, \n \n Velho\n S, \n \n Paredes\n J, \n et al\n . Oncogenic mutations in gastric cancer with microsatellite instability. Eur J Cancer. 2011;47(3):443\u2013451."},{"issue":"2","key":"i1543-2165-137-4-552-b42","series-title":"Mol Cancer Ther","first-page":"485","article-title":"Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling","volume":"11","author":"Chaft\n JE,","year":"2012","unstructured":"Chaft\n JE, \n \n Arcila\n ME, \n \n Paik\n PK, \n et al\n . Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther. 2012;11(2):485\u2013491."},{"issue":"5","key":"i1543-2165-137-4-552-b43","series-title":"Genes Chromosomes Cancer","first-page":"363","article-title":"Rare PIK3CA hotspot mutations in carcinomas of the biliary tract","volume":"47","author":"Riener\n MO,","year":"2008","unstructured":"Riener\n MO, \n \n Bawohl\n M, \n \n Clavien\n PA, \n \n Jochum\n W. \n \n Rare PIK3CA hotspot mutations in carcinomas of the biliary tract. Genes Chromosomes Cancer. 2008;47(5):363\u2013367."},{"issue":"6","key":"i1543-2165-137-4-552-b44","series-title":"Curr Opin Cell Biol","first-page":"596","article-title":"Growing roles for the mTOR pathway","volume":"17","author":"Sarbassov\n DD,","year":"2005","unstructured":"Sarbassov\n DD, \n \n Ali\n SM, \n \n Sabatini\n DM. \n \n Growing roles for the mTOR pathway. Curr Opin Cell Biol. 2005;17(6):596\u2013603."},{"issue":"11","key":"i1543-2165-137-4-552-b45","series-title":"Expert Opin Investig Drugs","first-page":"1717","article-title":"mTOR inhibitors in the treatment of cancer","volume":"17","author":"Fasolo\n A,","year":"2008","unstructured":"Fasolo\n A, \n \n Sessa\n C. \n \n mTOR inhibitors in the treatment of cancer. Expert Opin Investig Drugs. 2008;17(11):1717\u20131734."},{"issue":"16","key":"i1543-2165-137-4-552-b46","series-title":"Clin Cancer Res","first-page":"4795","article-title":"Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma","volume":"13","author":"Herberger\n B,","year":"2007","unstructured":"Herberger\n B, \n \n Puhalla\n H, \n \n Lehnert\n M, \n et al\n . Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma. Clin Cancer Res. 2007;13(16):4795\u20134799."},{"issue":"2","key":"i1543-2165-137-4-552-b47","series-title":"Med Oncol","first-page":"255","article-title":"The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma","volume":"27","author":"Zhou\n L,","year":"2010","unstructured":"Zhou\n L, \n \n Huang\n Y, \n \n Li\n J, \n \n Wang\n Z. \n \n The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma. Med Oncol. 2010;27(2):255\u2013261."},{"issue":"3","key":"i1543-2165-137-4-552-b48","series-title":"Arch Pathol Lab Med","first-page":"386","article-title":"Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens","volume":"129","author":"Mukhopadhyay\n S,","year":"2005","unstructured":"Mukhopadhyay\n S, \n \n Landas\n SK. \n \n Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med. 2005;129(3):386\u2013390."},{"issue":"3","key":"i1543-2165-137-4-552-b49","series-title":"Ann Diagn Pathol","first-page":"147","article-title":"Histologic analysis of chronic inflammatory patterns in the gallbladder: diagnostic criteria for reporting cholecystitis","volume":"7","author":"Barcia\n JJ.","year":"2003","unstructured":"Barcia\n JJ. \n \n Histologic analysis of chronic inflammatory patterns in the gallbladder: diagnostic criteria for reporting cholecystitis. Ann Diagn Pathol. 2003;7(3):147\u2013153."},{"issue":"6","key":"i1543-2165-137-4-552-b50","series-title":"Cancer","first-page":"1878","article-title":"Metaplasia and precursor lesions of gallbladder carcinoma: frequency, distribution, and probability of detection in routine histologic samples","volume":"72","author":"Duarte\n I,","year":"1993","unstructured":"Duarte\n I, \n \n Llanos\n O, \n \n Domke\n H, \n \n Harz\n C, \n \n Valdivieso\n V. \n \n Metaplasia and precursor lesions of gallbladder carcinoma: frequency, distribution, and probability of detection in routine histologic samples. Cancer. 1993;72(6):1878\u20131884."},{"issue":"3","key":"i1543-2165-137-4-552-b51","series-title":"Ann Clin Lab Sci","first-page":"195","article-title":"Morphoproteomic profile of mTOR, Ras\/Raf kinase\/ERK, and NF-kappaB pathways in human gastric adenocarcinoma","volume":"38","author":"Feng\n W,","year":"2008","unstructured":"Feng\n W, \n \n Brown\n RE, \n \n Trung\n CD, \n et al\n . Morphoproteomic profile of mTOR, Ras\/Raf kinase\/ERK, and NF-kappaB pathways in human gastric adenocarcinoma. Ann Clin Lab Sci. 2008;38(3):195\u2013209."},{"issue":"3","key":"i1543-2165-137-4-552-b52","series-title":"Basic Appl Pathol","first-page":"78","article-title":"Frequent activation of mammalian target of rapamycin in primary lung adenocarcinoma and preinvasive lesion","volume":"4","author":"Kim\n Y,","year":"2011","unstructured":"Kim\n Y, \n \n Jeong\n H, \n \n Kim\n A, \n \n Kim\n HK, \n \n Shin\n BK. \n \n Frequent activation of mammalian target of rapamycin in primary lung adenocarcinoma and preinvasive lesion. Basic Appl Pathol. 2011;4(3):78\u201385."},{"issue":"12","key":"i1543-2165-137-4-552-b53","series-title":"Int J Cancer","first-page":"2904","article-title":"Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer","volume":"126","author":"An\n JY,","year":"2010","unstructured":"An\n JY, \n \n Kim\n KM, \n \n Choi\n MG, \n et al\n . Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer. Int J Cancer. 2010;126(12):2904\u20132913."},{"issue":"2","key":"i1543-2165-137-4-552-b54","series-title":"Rev Med Chil","first-page":"183","article-title":"Management of gallbladder cancer with invasion of the muscular layer [in Spanish]","volume":"132","author":"de Aretxabala\n X,","year":"2004","unstructured":"de Aretxabala\n X, \n \n Roa\n I, \n \n Mora\n J, \n et al\n . Management of gallbladder cancer with invasion of the muscular layer [in Spanish]. Rev Med Chil. 2004;132(2):183\u2013188."},{"issue":"12","key":"i1543-2165-137-4-552-b55","series-title":"Clin Cancer Res","first-page":"3094","article-title":"Inhibition of the PI3K pathway: hope we can believe in?","volume":"16","author":"van der Heijden\n MS,","year":"2010","unstructured":"van der Heijden\n MS, \n \n Bernards\n R. \n \n Inhibition of the PI3K pathway: hope we can believe in?\n Clin Cancer Res. 2010;16(12):3094\u20133099."},{"issue":"4","key":"i1543-2165-137-4-552-b56","series-title":"Curr Opin Pharmacol","first-page":"371","article-title":"Targeting mTOR signaling for cancer therapy","volume":"3","author":"Huang\n S,","year":"2003","unstructured":"Huang\n S, \n \n Houghton\n PJ. \n \n Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003;3(4):371\u2013377."},{"issue":"1\u20134","key":"i1543-2165-137-4-552-b57","series-title":"J Chem Biol","first-page":"27","article-title":"Rapamycin and mTOR kinase inhibitors","volume":"1","author":"Ballou\n LM,","year":"2008","unstructured":"Ballou\n LM, \n \n Lin\n RZ. \n \n Rapamycin and mTOR kinase inhibitors. J Chem Biol. 2008;1(1\u20134):27\u201336."},{"issue":"9","key":"i1543-2165-137-4-552-b58","series-title":"Clin Cancer Res","first-page":"2756","article-title":"A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies","volume":"14","author":"Rizzieri\n DA,","year":"2008","unstructured":"Rizzieri\n DA, \n \n Feldman\n E, \n \n Dipersio\n JF, \n et al\n . A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008;14(9):2756\u20132762."}],"container-title":["Archives of Pathology & Laboratory Medicine"],"original-title":[],"link":[{"URL":"https:\/\/aplm.kglmeridian.com\/view\/journals\/arpa\/137\/4\/article-p552.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/aplm\/article-pdf\/137\/4\/552\/1611817\/arpa_2012-0032-oa.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aplm.kglmeridian.com\/downloadpdf\/journals\/arpa\/137\/4\/article-p552.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aplm.kglmeridian.com\/downloadpdf\/journals\/arpa\/137\/4\/article-p552.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:57:52Z","timestamp":1770771472000},"score":1,"resource":{"primary":{"URL":"https:\/\/aplm.kglmeridian.com\/view\/journals\/arpa\/137\/4\/article-p552.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":116,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.5858\/arpa.2012-0032-oa","relation":{},"ISSN":["0003-9985","1543-2165"],"issn-type":[{"value":"0003-9985","type":"print"},{"value":"1543-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4]]}}}