Aspirin and metformin exhibit antitumor activity in murine breast cancer
- Authors:
- Maoyuan Zhao
- Yuyi Wang
- Chi Du
- Yanyang Liu
- Nan Zhang
- Feng Luo
-
Affiliations: Department of Medical Oncology, Lung Cancer Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China - Published online on: January 4, 2018 https://doi.org/10.3892/or.2018.6190
- Pages: 1414-1422
This article is mentioned in:
Abstract
Berstein LM: Metformin in obesity, cancer and aging: Addressing controversies. Aging). 4:320–329. 2012. View Article : Google Scholar : PubMed/NCBI | |
Menendez JA, Oliveras-Ferraros C, Cufi S, Corominas-Faja B, Joven J, Martin-Castillo B and Vazquez-Martin A: Metformin is synthetically lethal with glucose withdrawal in cancer cells. Cell Cycle. 11:2782–2792. 2012. View Article : Google Scholar : PubMed/NCBI | |
Ma J, Guo Y, Chen S, Zhong C, Xue Y, Zhang Y, Lai X, Wei Y, Yu S, Zhang J and Liu W: Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma. BMC Cancer. 14:1722014. View Article : Google Scholar : PubMed/NCBI | |
Currie CJ, Poole CD and Gale EA: The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 52:1766–1777. 2009. View Article : Google Scholar : PubMed/NCBI | |
Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH and Huang YC: Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: A representative population prospective cohort study of 800,000 individuals. BMC Cancer. 11:202011. View Article : Google Scholar : PubMed/NCBI | |
Bodmer M, Becker C, Meier C, Jick SS and Meier CR: Use of antidiabetic agents and the risk of pancreatic cancer: A case-control analysis. Am J Gastroenterol. 107:620–626. 2012. View Article : Google Scholar : PubMed/NCBI | |
Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, et al: Metformin in early breast cancer: A prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat. 135:821–830. 2012. View Article : Google Scholar : PubMed/NCBI | |
Cazzaniga M, DeCensi A, Pruneri G, Puntoni M, Bottiglieri L, Varricchio C, Guerrieri-Gonzaga A, Gentilini OD, Pagani G, Dell'Orto P, et al: The effect of metformin on apoptosis in a breast cancer presurgical trial. Br J Cancer. 109:2792–2797. 2013. View Article : Google Scholar : PubMed/NCBI | |
Gronich N and Rennert G: Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol. 10:625–642. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zannella VE, Dal Pra A, Muaddi H, McKee TD, Stapleton S, Sykes J, Glicksman R, Chaib S, Zamiara P, Milosevic M, et al: Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response. Clin Cancer Res. 19:6741–6750. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ugurlucan M, Caglar IM, Caglar FN, Ziyade S, Karatepe O, Yildiz Y, Zencirci E, Ugurlucan FG, Arslan AH, Korkmaz S, et al: Aspirin: From a historical perspective. Recent Pat Cardiovasc Drug Discov. 7:71–76. 2012. View Article : Google Scholar : PubMed/NCBI | |
Half E, Tang XM, Gwyn K, Sahin A, Wathen K and Sinicrope FA: Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res. 62:1676–1681. 2002.PubMed/NCBI | |
Williams CS, Mann M and DuBois RN: The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 18:7908–7916. 1999. View Article : Google Scholar : PubMed/NCBI | |
Ulrich CM, Bigler J and Potter JD: Non-steroidal anti-inflammatory drugs for cancer prevention: Promise, perils and pharmacogenetics. Nat Rev Cancer. 6:130–140. 2006. View Article : Google Scholar : PubMed/NCBI | |
Fang L, Chang HM, Cheng JC, Leung PC and Sun YP: TGF-β1 induces COX-2 expression and PGE2 production in human granulosa cells through smad signaling pathways. J Clin Endocrinol Metab. 99:E1217–1226. 2014. View Article : Google Scholar : PubMed/NCBI | |
Adler AI, Shaw EJ, Stokes T and Ruiz F; Guideline Development Group, : Newer agents for blood glucose control in type 2 diabetes: Summary of NICE guidance. BMJ. 338:b16682009. View Article : Google Scholar : PubMed/NCBI | |
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R and Zinman B; American DiabetesAssociation, ; European Association for Study of Diabetes, : Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American diabetes association and the European association for the study of diabetes. Diabetes Care. 32:193–203. 2009. View Article : Google Scholar : PubMed/NCBI | |
Takahashi RU, Miyazaki H, Takeshita F, Yamamoto Y, Minoura K, Ono M, Kodaira M, Tamura K, Mori M and Ochiya T: Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1. Nat Commun. 6:73182015. View Article : Google Scholar : PubMed/NCBI | |
Bacci M, Giannoni E, Fearns A, Ribas R, Gao Q, Taddei ML, Pintus G, Dowsett M, Isacke CM, Martin LA, et al: miR-155 drives metabolic reprogramming of ER+ breast cancer cells following long-term estrogen deprivation and predicts clinical response to aromatase inhibitors. Cancer Res. 76:1615–1626. 2016. View Article : Google Scholar : PubMed/NCBI | |
Cabello P, Pineda B, Tormo E, Lluch A and Eroles P: The antitumor effect of metformin is mediated by miR-26a in breast cancer. Int J Mol Sci. 17:E12982016. View Article : Google Scholar : PubMed/NCBI | |
Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ and Wicha MS: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17:1253–1270. 2003. View Article : Google Scholar : PubMed/NCBI | |
Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, et al: Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 69:1302–1313. 2009. View Article : Google Scholar : PubMed/NCBI | |
Oliveras-Ferraros C, Cufi S, Vazquez-Martin A, Torres-Garcia VZ, Del Barco S, Martin-Castillo B and Menendez JA: Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: Induction of the tumor suppressor miRNA let-7a and suppression of the TGFβ-induced oncomiR miRNA-181a. Cell Cycle. 10:1144–1151. 2011. View Article : Google Scholar : PubMed/NCBI | |
Dowling RJ, Zakikhani M, Fantus IG, Pollak M and Sonenberg N: Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 67:10804–10812. 2007. View Article : Google Scholar : PubMed/NCBI | |
Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR and Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 142:1504–1515.e3. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yue W, Zheng X, Lin Y, Yang CS, Xu Q, Carpizo D, Huang H, DiPaola RS and Tan XL: Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2. Oncotarget. 6:21208–21224. 2015. View Article : Google Scholar : PubMed/NCBI | |
Blobe GC, Schiemann WP and Lodish HF: Role of transforming growth factor beta in human disease. N Engl J Med. 342:1350–1358. 2000. View Article : Google Scholar : PubMed/NCBI | |
Govinden R and Bhoola KD: Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther. 98:257–265. 2003. View Article : Google Scholar : PubMed/NCBI | |
Reddi AH: BMPs: From bone morphogenetic proteins to body morphogenetic proteins. Cytokine Growth Factor Rev. 16:249–250. 2005. View Article : Google Scholar : PubMed/NCBI | |
Joshi A and Cao D: TGF-beta signaling, tumor microenvironment and tumor progression: The butterfly effect. Front Biosci. 15:180–194. 2010. View Article : Google Scholar | |
Maurya VK, Jha RK, Kumar V, Joshi A, Chadchan S, Mohan JJ and Laloraya M: Transforming growth factor-beta 1 (TGF-B1) liberation from its latent complex during embryo implantation and its regulation by estradiol in mouse. Biol Reprod. 89:842013. View Article : Google Scholar : PubMed/NCBI | |
Dixon A and Maric C: 17beta-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-beta protein expression and signaling. Am J Physiol Renal Physiol. 293:F1678–F1690. 2007. View Article : Google Scholar : PubMed/NCBI | |
Ito I, Hanyu A, Wayama M, Goto N, Katsuno Y, Kawasaki S, Nakajima Y, Kajiro M, Komatsu Y, Fujimura A, et al: Estrogen inhibits transforming growth factor beta signaling by promoting Smad2/3 degradation. J Biol Chem. 285:14747–14755. 2010. View Article : Google Scholar : PubMed/NCBI | |
Li YC, Ding XS, Li HM, Zhang Y and Bao J: Role of G protein-coupled estrogen receptor 1 in modulating transforming growth factor-β stimulated mesangial cell extracellular matrix synthesis and migration. Mol Cell Endocrinol. 391:50–59. 2014. View Article : Google Scholar : PubMed/NCBI | |
Garijo R, Hernández-Alonso P, Rivas C, Diallo JS and Sanjuán R: Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells. PLoS One. 9:e1023652014. View Article : Google Scholar : PubMed/NCBI | |
Yerlikaya A, Okur E, Baykal AT, Acilan C, Boyaci I and Ulukaya E: A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line. J Proteomics. 113:315–325. 2015. View Article : Google Scholar : PubMed/NCBI | |
Saji S, Honma N, Hirose M, Hayashi S and Kuroi K: Translational cell study exploring the role of estrogen receptor beta expression as a predictive and/or prognostic factor in breast cancer patients. J Clin Oncol. 27:e221852009. | |
Wiggins AK, Kharotia S, Mason JK and Thompson LU: α-Linolenic acid reduces growth of both triple negative and luminal breast cancer cells in high and low estrogen environments. Nutr Cancer. 67:1001–1009. 2015. View Article : Google Scholar : PubMed/NCBI | |
O'Brien AJ, Villani LA, Broadfield LA, Houde VP, Galic S, Blandino G, Kemp BE, Tsakiridis T, Muti P and Steinberg GR: Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochem J. 469:177–187. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Du C, Zhao M, Li M, Zhang N, Liu Y, Wang J and Luo F: Treatment of colonic transplantation tumor-bearing mice with a high-dose aspirin in a short period of time. Int J Colorectal Dis. 31:1099–1100. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Jiang M, Li Z, Wang J, Du C, Yanyang L, Yu Y, Wang X, Zhang N, Zhao M, et al: Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors. Cell Biosci. 5:722015. View Article : Google Scholar : PubMed/NCBI | |
Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P, Jankowski J, La Vecchia C, Meyskens F, Senn HJ and Thun M: Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: An international consensus statement. Lancet Oncol. 10:501–507. 2009. View Article : Google Scholar : PubMed/NCBI | |
Zhao YS, Zhu S, Li XW, Wang F, Hu FL, Li DD, Zhang WC and Li X: Association between NSAIDs use and breast cancer risk: A systematic review and meta-analysis. Breast Cancer Res Treat. 117:141–150. 2009. View Article : Google Scholar : PubMed/NCBI | |
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP and Meade TW: Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials. Lancet. 377:31–41. 2011. View Article : Google Scholar : PubMed/NCBI | |
Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW and Mehta Z: Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 379:1591–1601. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chan AT, Arber N, Burn J, Chia WK, Elwood P, Hull MA, Logan RF, Rothwell PM, Schrör K and Baron JA: Aspirin in the chemoprevention of colorectal neoplasia: An overview. Cancer Prev Res. 5:164–178. 2012. View Article : Google Scholar | |
Algra AM and Rothwell PM: Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 13:518–527. 2012. View Article : Google Scholar : PubMed/NCBI | |
Sato A, Sunayama J, Okada M, Watanabe E, Seino S, Shibuya K, Suzuki K, Narita Y, Shibui S, Kayama T and Kitanaka C: Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK. Stem Cells Transl Med. 1:811–824. 2012. View Article : Google Scholar : PubMed/NCBI | |
Shank JJ, Yang K, Ghannam J, Cabrera L, Johnston CJ, Reynolds RK and Buckanovich RJ: Metformin targets ovarian cancer stem cells in vitro and in vivo. Gynecol Oncol. 127:390–397. 2012. View Article : Google Scholar : PubMed/NCBI | |
Lengyel E, Litchfield LM, Mitra AK, Nieman KM, Mukherjee A, Zhang Y, Johnson A, Bradaric M, Lee W and Romero IL: Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models. Am J Obstet Gynecol. 212:479.e471–479.e10. 2015. View Article : Google Scholar | |
Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA and Bae-Jump VL: Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy. Gynecol Oncol. 116:92–98. 2010. View Article : Google Scholar : PubMed/NCBI | |
Mitsuhashi A, Kiyokawa T, Sato Y and Shozu M: Effects of metformin on endometrial cancer cell growth in vivo: A preoperative prospective trial. Cancer. 120:2986–2995. 2014. View Article : Google Scholar : PubMed/NCBI | |
Sivalingam VN, Kitson S, McVey R, Roberts C, Pemberton P, Gilmour K, Ali S, Renehan AG, Kitchener HC and Crosbie EJ: Measuring the biological effect of presurgical metformin treatment in endometrial cancer. Br J Cancer. 114:281–289. 2016. View Article : Google Scholar : PubMed/NCBI | |
Bowker SL, Lin M, Eurich DT and Johnson JA: Time-varying risk for breast cancer following initiation of glucose-lowering therapy in women with type 2 diabetes: Exploring detection bias. Can J Diabetes. 41:204–210. 2017. View Article : Google Scholar : PubMed/NCBI | |
Rico M, Baglioni M, Bondarenko M, Laluce NC, Rozados V, André N, Carré M, Scharovsky OG and Menacho Márquez M: Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models. Oncotarget. 8:2874–2889. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gagnon B, Roseman M, Kasymjanova G, MacDonald N, Kreisman H and Small D: Protective effect of metformin in lung cancer patients. J Clin Oncol. 27:e220632009. | |
Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, Pond G, Wright J, Singh G and Tsakiridis T: Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer. 108:2021–2032. 2013. View Article : Google Scholar : PubMed/NCBI | |
Anisimov VN, Egormin PA, Piskunova TS, Popovich IG, Tyndyk ML, Yurova MN, Zabezhinski MA, Anikin IV, Karkach AS and Romanyukha AA: Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle. 9:188–197. 2010. View Article : Google Scholar : PubMed/NCBI | |
Bodmer M, Meier C, Krähenbühl S, Jick SS and Meier CR: Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 33:1304–1308. 2010. View Article : Google Scholar : PubMed/NCBI | |
Inman GJ: Switching TGFβ from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev. 21:93–99. 2011. View Article : Google Scholar : PubMed/NCBI | |
Meulmeester E and Ten Dijke P: The dynamic roles of TGF-β in cancer. J Pathol. 223:205–218. 2011. View Article : Google Scholar : PubMed/NCBI | |
Sheng H, Shao J, Hooton EB, Tsujii M, DuBois RN and Beauchamp RD: Cyclooxygenase-2 induction and transforming growth factor beta growth inhibition in rat intestinal epithelial cells. Cell Growth Differ. 8:463–470. 1997.PubMed/NCBI | |
Sheng H, Shao J, O'Mahony CA, Lamps L, Albo D, Isakson PC, Berger DH, DuBois RN and Beauchamp RD: Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2. Oncogene. 18:855–867. 1999. View Article : Google Scholar : PubMed/NCBI | |
Crew TE, Elder DJ and Paraskeva C: A cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug enhances the growth inhibitory effect of butyrate in colorectal carcinoma cells expressing COX-2 protein: Regulation of COX-2 by butyrate. Carcinogenesis. 21:69–77. 2000. View Article : Google Scholar : PubMed/NCBI | |
Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, Shen Q, Zhu Y and Zhang Y: Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovasc Res. 87:504–513. 2010. View Article : Google Scholar : PubMed/NCBI | |
Fan K, Wu K, Lin L, Ge P, Dai J, He X, Hu K and Zhang L: Metformin mitigates carbon tetrachloride-induced TGF-β1/Smad3 signaling and liver fibrosis in mice. Biomed Pharmacother. 90:421–426. 2017. View Article : Google Scholar : PubMed/NCBI | |
Cheng K and Hao M: Metformin inhibits TGF-β1-induced epithelial-to-mesenchymal transition via PKM2 relative-mTOR/p70s6k signaling pathway in cervical carcinoma cells. Int J Mol Sci. 17:E20002016. View Article : Google Scholar : PubMed/NCBI | |
Leonel C, Borin TF, de Carvalho Ferreira L, Moschetta MG, Bajgelman MC, Viloria-Petit AM and de Campos Zuccari DA: Inhibition of epithelial-mesenchymal transition and metastasis by combined TGFbeta knockdown and metformin treatment in a canine mammary cancer xenograft model. J Mammary Gland Biol Neoplasia. 22:27–41. 2017. View Article : Google Scholar : PubMed/NCBI | |
Marinello PC, da Silva TN, Panis C, Neves AF, Machado KL, Borges FH, Guarnier FA, Bernardes SS, de-Freitas-Junior JC, Morgado-Díaz JA, et al: Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction. Tumour Biol. 37:5337–5346. 2016. View Article : Google Scholar : PubMed/NCBI | |
Cortes P, Riser BL, Asano K, Rodríguez-Barbero A, Narins RG and Yee J: Effects of oral antihyperglycemic agents on extracellular matrix synthesis by mesangial cells. Kidney Int. 54:1985–1998. 1998. View Article : Google Scholar : PubMed/NCBI | |
Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S and Gustafsson JA: Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA. 93:pp. 5925–5930. 1996; View Article : Google Scholar : PubMed/NCBI | |
Schmierer B and Hill CS: TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 8:970–982. 2007. View Article : Google Scholar : PubMed/NCBI | |
Lönn P, Morén A, Raja E, Dahl M and Moustakas A: Regulating the stability of TGFbeta receptors and Smads. Cell Res. 19:21–35. 2009. View Article : Google Scholar : PubMed/NCBI | |
Luo K, Stroschein SL, Wang W, Chen D, Martens E, Zhou S and Zhou Q: The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev. 13:2196–2206. 1999. View Article : Google Scholar : PubMed/NCBI | |
Nomura T, Khan MM, Kaul SC, Dong HD, Wadhwa R, Colmenares C, Kohno I and Ishi S: Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev. 13:412–423. 1999. View Article : Google Scholar : PubMed/NCBI | |
Stroschein SL, Wang W, Zhou S, Zhou Q and Luo K: Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science. 286:771–774. 1999. View Article : Google Scholar : PubMed/NCBI | |
Heery DM, Kalkhoven E, Hoare S and Parker MG: A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature. 387:733–736. 1997. View Article : Google Scholar : PubMed/NCBI | |
Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK and Rosenfeld MG: The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 387:677–684. 1997. View Article : Google Scholar : PubMed/NCBI | |
Cheskis BJ, Greger JG, Nagpal S and Freedman LP: Signaling by estrogens. J Cell Physiol. 213:610–617. 2007. View Article : Google Scholar : PubMed/NCBI | |
Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, et al: NCCN guidelines insights breast cancer, Version 1.2016. J Natl Compr Canc Netw. 13:1475–1485. 2015. View Article : Google Scholar : PubMed/NCBI |