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Evidence","volume":"127","author":"JP Wisnivesky","year":"2005","journal-title":"Chest"},{"issue":"2","key":"ref3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/JTO.0b013e3181c6f035","article-title":"First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review","volume":"5","author":"J Goffin","year":"2010","journal-title":"J Thorac Oncol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0140-6736(13)62159-5","article-title":"Preoperative chemotherapy for non-small cell lung cancer: a systematic review and meta-analysis of individual participant data","volume":"383","year":"2014","journal-title":"Lancet"},{"issue":"131","key":"ref5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1183\/09059180.00008413","article-title":"First-line treatment of EGFR-mutated nonsmall cell lung cancer: critical review on study methodology","volume":"23","author":"M Sebastian","year":"2014","journal-title":"Eur Respir Rev"},{"issue":"6","key":"ref6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1177\/1758834011419002","article-title":"The potential for crizotinib in non-small cell lung cancer: a perspective review","volume":"3","author":"Y-J Bang","year":"2011","journal-title":"Ther Adv Med Oncol"},{"issue":"7467","key":"ref7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature12627","article-title":"Tumour heterogeneity in the clinic","volume":"501","author":"PL Bedard","year":"2013","journal-title":"Nature"},{"issue":"7","key":"ref8","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nbt.2940","article-title":"Assessing the clinical utility of cancer genomic and proteomic data across tumor types","volume":"32","author":"Y Yuan","year":"2014","journal-title":"Nat Biotechnol"},{"issue":"11","key":"ref9","first-page":"1764","article-title":"In silico radiation oncology: combining novel simulation algorithms with current visualization techniques","volume":"90","author":"GS Stamatakos","year":"2002","journal-title":"Proceedings of the IEEE: Special Issue on Bioinformatics: Advances and Chalenges"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtbi.2004.03.024","article-title":"A four dimensional in vivo model of tumour response to radiotherapy: parametric validation considering radiosensitivity, genetic profile and fractionation","volume":"230","author":"DD Dionysiou","year":"2004","journal-title":"J Theor Biol"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jtbi.2010.05.019","article-title":"An advanced discrete state\u2014discrete event multiscale simulation model of the response of a solid tumor to chemotherapy. Mimicking a clinical study","volume":"266","author":"GS Stamatakos","year":"2010","journal-title":"J Theor Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.mcm.2011.05.007","article-title":"Studying the growth kinetics of untreated clinical tumors by using an advanced discrete simulation model","volume":"54","author":"EA Kolokotroni","year":"2011","journal-title":"Math Comput Model"},{"issue":"3","key":"ref13","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1098\/rsfs.2010.0037","article-title":"Clinically driven design of multi-scale cancer models: the ContraCancrum project paradigm","volume":"1","author":"K Marias","year":"2011","journal-title":"Interface Focus"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"691513","DOI":"10.1117\/12.770356","article-title":"Automatic lesion tracking for a PET\/CT based computer aided cancer therapy monitoring system","author":"R Opfer","year":"2008","journal-title":"Proceedings of SPIE Medical Imaging"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1109\/TMI.2006.871547","article-title":"Morphological segmentation and partial volume analysis for volumetry of solid pulmonary lesions in thoracic CT scans","volume":"25","author":"JM Kuhnigk","year":"2006","journal-title":"IEEE Transactions on Medical Imaging"},{"key":"ref16","first-page":"651217","article-title":"A new general tumor segmentation framework based on radial basis function energy minimization with a validation study on LIDC lung nodules","author":"R Opfer","year":"2007","journal-title":"Proceedings of SPIE Medical Imaging"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"72600X","DOI":"10.1117\/12.811599","article-title":"Follow-up segmentation of lung tumors in PET and CT data","author":"R Opfer","year":"2009","journal-title":"Proceedings of SPIE Medical Imaging"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Pekar V, Kaus MR, Lorenz C, Lobregt S, Truyen R, Weese J. Shape model based adaptation of 3-D deformable meshes for segmentation of medical images. Proceedings of SPIE Medical Imaging. 2001: 281\u20139.","DOI":"10.1117\/12.430973"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.media.2004.06.015","article-title":"Automated segmentation of the left ventricle in cardiac MRI","volume":"8","author":"MR Kaus","year":"2004","journal-title":"Medical Image Analysis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF00547132","article-title":"A review of techniques for parameter sensitivity analysis of environmental models","volume":"32","author":"DM Hamby","year":"1994","journal-title":"Environ Monit Assess"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.ress.2005.11.017","article-title":"Survey of sampling-based methods for uncertainty and sensitivity analysis","volume":"91","author":"JC Helton","year":"2006","journal-title":"Reliab Eng Syst Saf"},{"key":"ref22","unstructured":"U.S. EPA. Risk Assessment Guidance for Superfund: Volume III\u2014Part A, Process for Conducting Probabilistic Risk Assessment. 2001. EPA 540-R-02-002 available in <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.epa.gov\/sites\/production\/files\/2015-09\/documents\/rags3adt_complete.pdf\" xlink:type=\"simple\">https:\/\/www.epa.gov\/sites\/production\/files\/2015-09\/documents\/rags3adt_complete.pdf<\/ext-link> (last visited on 1 July 2016)"},{"key":"ref23","article-title":"Basic Clinical Radiobiology","author":"GG Steel","year":"2002"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0007-0971(79)90002-0","article-title":"The natural history of lung cancer: a review based on rates of tumour growth","volume":"73","author":"DM Geddes","year":"1979","journal-title":"Br J Dis Chest"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1096-9098(199708)65:4<284::AID-JSO11>3.0.CO;2-2","article-title":"On the Growth Rates of Human Malignant Tumors: Implications for Medical Decision Making","volume":"65","author":"S Friberg","year":"1997","journal-title":"J Surg Oncol"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.crad.2007.07.011","article-title":"Lung lesion doubling times: values and variability based on method of volume determination","volume":"63","author":"LE Quint","year":"2008","journal-title":"Clin Radiol"},{"issue":"5","key":"ref27","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/resp.12311","article-title":"A retrospective study of volume doubling time in surgically resected non-small cell lung cancer","volume":"19","author":"JA Mackintosh","year":"2014","journal-title":"Respirology"},{"issue":"3","key":"ref28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.stem.2010.08.009","article-title":"Tumor-initiating cells are rare in many human tumors","volume":"7","author":"K Ishizawa","year":"2010","journal-title":"Cell Stem Cell"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0360-3016(98)00305-8","article-title":"The lifetime of hypoxic human tumor cells","volume":"42","author":"RE Durand","year":"1998","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"ref30","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1073\/pnas.0909390107","article-title":"Microenvironmental modulation of asymmetric cell division in human lung cancer cells","volume":"107","author":"SR Pine","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ref31","doi-asserted-by":"crossref","first-page":"e49752","DOI":"10.1371\/journal.pone.0049752","article-title":"Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells","volume":"7","author":"BJ Morrison","year":"2012","journal-title":"PLoS One"},{"issue":"4","key":"ref32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/bjc.1972.33","article-title":"Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics","volume":"26","author":"JF Kerr","year":"1972","journal-title":"Br J Cancer"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation","volume":"119","author":"Y Gavrieli","year":"1992","journal-title":"J Cell Biol"},{"issue":"5","key":"ref34","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/carcin\/11.5.847","article-title":"Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats","volume":"11","author":"W Bursch","year":"1990","journal-title":"Carcinogenesis"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1091\/mbc.E03-09-0668","article-title":"Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production","volume":"15","author":"G Brouckaert","year":"2004","journal-title":"Mol Biol Cell"},{"issue":"13","key":"ref36","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1242\/dev.02407","article-title":"Epithelial stem cells of the lung: privileged few or opportunities for many?","volume":"133","author":"EL Rawlins","year":"2006","journal-title":"Development"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"L231","DOI":"10.1152\/ajplung.90209.2008","article-title":"Ciliated epithelial cell lifespan in the mouse trachea and lung","volume":"295","author":"EL Rawlins","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref38","article-title":"Environmental Toxicants: Human Exposures and Their Health Effects","author":"Morton Lippmann","year":"2000"},{"key":"ref39","article-title":"Amazing Numbers in Biology","author":"R. Flindt","year":"2006"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.ress.2007.06.003","article-title":"Uncertainty and sensitivity analysis for models with correlated parameters","volume":"93","author":"Xu Ch","year":"2008","journal-title":"Reliability Engineering and System Safety"},{"key":"ref41","unstructured":"Protocol-SIOP-2001.pdf available in <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.skion.nl\/workspace\/uploads\/Protocol-SIOP-2001.pdf\" xlink:type=\"simple\">https:\/\/www.skion.nl\/workspace\/uploads\/Protocol-SIOP-2001.pdf<\/ext-link> (last visited on 1 July 2016)"},{"issue":"11","key":"ref42","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.compbiomed.2012.08.008","article-title":"Towards in silico oncology: adapting a four dimensional nephroblastoma treatment model to a clinical trial case based on multi-method sensitivity analysis","volume":"42","author":"ECh Georgiadi","year":"2012","journal-title":"Comput Biol Med"},{"key":"ref43","first-page":"339","article-title":"Multiscale cancer modeling","author":"NL Komarova","year":"2011"},{"issue":"9","key":"ref44","doi-asserted-by":"crossref","first-page":"e1003231","DOI":"10.1371\/journal.pcbi.1003231","article-title":"Predictive Modeling of In Vivo Response to Gemcitabine in Pancreatic Cancer","volume":"9","author":"JJ Lee","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1148\/radiol.2233011026","article-title":"Volumetric growth rate of stage I lung cancer prior to treatment: serial CT scanning","volume":"223","author":"HT Winer-Muram","year":"2002","journal-title":"Radiology"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1148\/radiology.212.2.r99au33561","article-title":"Small pulmonary nodules: evaluation with repeat CT\u2014preliminary experience","volume":"212","author":"DF Yankelevitz","year":"1999","journal-title":"Radiology"},{"issue":"3","key":"ref47","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.lungcan.2003.12.009","article-title":"Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer","volume":"44","author":"AP Meert","year":"2004","journal-title":"Lung Cancer"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0046-8177(97)90105-2","article-title":"Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung","volume":"28","author":"L Viberti","year":"1997","journal-title":"Hum Pathol"},{"issue":"12","key":"ref49","first-page":"4277","article-title":"The expression of Ki-67, but not proliferating cell nuclear antigen, predicts poor disease free survival in patients with adenocarcinoma of the lung","volume":"31","author":"S Oka","year":"2011","journal-title":"Anticancer Res"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1053\/ejso.1999.0781","article-title":"Cell production rates in human tissues and tumours and their significance. Part 1: an introduction to the techniques of measurement and their limitations","volume":"26","author":"DA Rew","year":"2000","journal-title":"Eur J Surg Oncol"},{"issue":"6","key":"ref51","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/cyto.990060618","article-title":"A method to measure the duration of DNA synthesis and the potential doubling time from a single sample","volume":"6","author":"AC Begg","year":"1985","journal-title":"Cytometry"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1471-2407-5-122","article-title":"A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample","volume":"5","author":"R Eidukevicius","year":"2005","journal-title":"BMC Cancer"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1242\/jcs.95.2.247","article-title":"The differentiation process of intestinal epithelial cells is associated with the appearance of statin, a non-proliferation-specific nuclear protein","volume":"95","author":"R Bissonnette","year":"1990","journal-title":"J Cell Sci"},{"key":"ref54","unstructured":"Kolokotroni E, Ouzounoglou E, Stanulla M, Dionysiou D and Stamatakos GS. In Silico Oncology: Developing and Clinically Adapting the Acute Lymphoblastic Leukemia (ALL) Oncosimulator by Exploiting Pathway Based Gene Expression Analysis in the Context of the ALL-BFM 2000 Clinical Study. In: Virtual Physiological Human Conference 2014 (VPH 2014): 2014 Sep 9\u201312; Trondheim, Norway."},{"key":"ref55","unstructured":"p-medicine (FP7-ICT-2009-6-270089) project deliverable D12.4: Report on the clinical adaptation and optimization of the Oncosimulator models. In silico studies. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/p-medicine.eu\/fileadmin\/p-medicine\/public_website\/downloads\/p-medicine_270089_D12-4_Report_on_clinical_adaptation_and_optimization_of_Oncosimulator_models_v4-0.pdf\" xlink:type=\"simple\">http:\/\/p-medicine.eu\/fileadmin\/p-medicine\/public_website\/downloads\/p-medicine_270089_D12-4_Report_on_clinical_adaptation_and_optimization_of_Oncosimulator_models_v4-0.pdf<\/ext-link>"},{"issue":"8\u20139","key":"ref56","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/PL00000762","article-title":"Molecular mechanisms involved in cisplatin cytotoxicity","volume":"57","author":"P Jordan","year":"2000","journal-title":"Cell Mol Life Sci"},{"issue":"47","key":"ref57","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1038\/sj.onc.1206933","article-title":"Cisplatin: mode of cytotoxic action and molecular basis of resistance","volume":"22","author":"Zahid H Siddik","year":"2003","journal-title":"Oncogene"},{"issue":"5","key":"ref58","first-page":"955","article-title":"Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer (Review)","volume":"12","author":"G Wang","year":"2004","journal-title":"Oncol Rep"},{"issue":"1","key":"ref59","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/bjc.1994.14","article-title":"The role of apoptosis in cell killing by cisplatin: a flow cytometric study","volume":"69","author":"MG Ormerod","year":"1994","journal-title":"Br J Cancer"},{"issue":"3","key":"ref60","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2174\/1568011053765967","article-title":"Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells: importance of apoptotic pathways","volume":"5","author":"Y Sedletska","year":"2005","journal-title":"Curr Med Chem Anticancer Agents"},{"issue":"1","key":"ref61","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3390\/cancers3011351","article-title":"Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects","volume":"3","author":"A-M Florea","year":"2011","journal-title":"Cancers"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"201367","DOI":"10.4061\/2010\/201367","article-title":"Cellular responses to Cisplatin-induced DNA damage","volume":"2010","author":"A Basu","year":"2010","journal-title":"J Nucleic Acids"},{"issue":"9","key":"ref63","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/jnci\/82.9.749","article-title":"Analysis of Events Associated With Cell Cycle Arrest at G2 Phase and Cell Death Induced by Cisplatin","volume":"82","author":"CM Sorenson","year":"1990","journal-title":"J Natl Cancer Inst"},{"issue":"9","key":"ref64","first-page":"983","article-title":"The Role of Cell Cycle Progression in Cisplatin-induced Apoptosis in Chinese Hamster Ovary Cells","volume":"5","author":"C Demarcq","year":"1994","journal-title":"Cell Growth Differ"},{"issue":"4","key":"ref65","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1124\/mol.59.4.657","article-title":"Is cisplatin-induced cell death always produced by apoptosis?","volume":"59","author":"VM Gonzalez","year":"2001","journal-title":"Mol Pharmacol"},{"issue":"3","key":"ref66","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/sj.cdd.4402286","article-title":"DNA damage induces two distinct modes of cell death in ovarian carcinomas","volume":"15","author":"H Vakifahmetoglu","year":"2008","journal-title":"Cell Death Differ"},{"key":"ref67","article-title":"The Chemotherapy Source Book","author":"MC Perry","year":"2001"},{"key":"ref68","article-title":"Basic and Clinical Pharmacology","author":"BG Katzung","year":"2001"},{"issue":"6","key":"ref69","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1023\/A:1009614703977","article-title":"Induction of apoptosis by gemcitabine in BG-1 human ovarian cancer cells compared with induction by staurosporine, paclitaxel and cisplatin","volume":"3","author":"L Cartee","year":"1998","journal-title":"Apoptosis"},{"issue":"5","key":"ref70","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S0959-8049(98)00425-0","article-title":"Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines","volume":"35","author":"C Tolis","year":"1999","journal-title":"Eur J Cancer"},{"issue":"3","key":"ref71","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/ijc.1351","article-title":"Cell cycle effects of gemcitabine","volume":"93","author":"P Cappella","year":"2001","journal-title":"Int J Cancer"},{"issue":"suppl 5","key":"ref72","doi-asserted-by":"crossref","first-page":"v7","DOI":"10.1093\/annonc\/mdj941","article-title":"Cellular pharmacology of gemcitabine","volume":"17","author":"E Mini","year":"2006","journal-title":"Ann Oncol"},{"issue":"3","key":"ref73","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF00685844","article-title":"Fludarabine- and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event","volume":"36","author":"P Huang","year":"1995","journal-title":"Cancer Chemother Pharmacol"},{"issue":"4","key":"ref74","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0360-3016(98)00105-9","article-title":"Radiosensitizing potential of gemcitabine (29,29-difluoro-29-deoxycytidine) within the cell cycle in vitro","volume":"41","author":"D Latz","year":"1998","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"8","key":"ref75","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1054\/bjoc.2000.1399","article-title":"Sequence dependent effect of paclitaxel on gemcitabine metabolism in relation to cell cycle and cytotoxicity in non-small-cell lung cancer cell lines","volume":"83","author":"JR Kroep","year":"2000","journal-title":"Br J Cancer"},{"issue":"8","key":"ref76","first-page":"2212","article-title":"Mechanism of inhibition of cell proliferation by Vinca alkaloids","volume":"51","author":"MA Jordan","year":"1991","journal-title":"Cancer Res"},{"issue":"4","key":"ref77","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"MA Jordan","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2174\/156800907783220480","article-title":"Microtubules in apoptosis induction: are they necessary?","volume":"7","author":"M-A Est\u00e8ve","year":"2007","journal-title":"Curr Cancer Drug Targets"},{"issue":"2","key":"ref79","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/ijc.2910460220","article-title":"Immunofluoresence study of the action of Navelbine, vincristine and vinblastine on mitotic and axonal microtubules","volume":"46","author":"S Binet","year":"1990","journal-title":"Int J Cancer"},{"issue":"1","key":"ref80","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1124\/mol.60.1.225","article-title":"Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine","volume":"60","author":"VK Ngan","year":"2001","journal-title":"Mol Pharmacol"},{"issue":"9","key":"ref81","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.bcp.2012.01.016","article-title":"Vinca alkaloids cause aberrant ROS-mediated JNK activation, Mcl-1 downregulation, DNA damage, mitochondrial dysfunction, and apoptosis in lung adenocarcinoma cells","volume":"83","author":"WH Chiu","year":"2012","journal-title":"Biochem Pharmacol"},{"issue":"9","key":"ref82","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.bcp.2009.06.025","article-title":"Transcriptional down-regulation of Bcl-2 by vinorelbine: identification of a novel binding site of p53 on Bcl-2 promoter","volume":"78","author":"V Bourgarel-Rey","year":"2009","journal-title":"Biochem Pharmacol"},{"issue":"Pt 4","key":"ref83","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1242\/jcs.091843","article-title":"The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively","volume":"125","author":"DM Klotz","year":"2012","journal-title":"J Cell Sci"},{"issue":"10","key":"ref84","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1158\/1535-7163.MCT-05-0130","article-title":"Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells","volume":"4","author":"DL Morse","year":"2005","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"ref85","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ccr.2005.06.011","article-title":"Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death","volume":"8","author":"BA Weaver","year":"2005","journal-title":"Cancer Cell"},{"issue":"5","key":"ref86","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0305-7372(03)00097-5","article-title":"Mode of action of docetaxel\u2014a basis for combination with novel anticancer agents","volume":"29","author":"RS Herbst","year":"2003","journal-title":"Cancer Treat Rev"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2121-7-6","article-title":"Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: a cytometric study","volume":"7","author":"F Fabbri","year":"2006","journal-title":"BMC Cell Biol"},{"issue":"7","key":"ref88","doi-asserted-by":"crossref","first-page":"780","DOI":"10.4161\/cc.6.7.4050","article-title":"Telling cells how to die: docetaxel therapy in cancer cell lines","volume":"6","author":"H Hern\u00e1ndez-Vargas","year":"2007","journal-title":"Cell Cycle"},{"issue":"3","key":"ref89","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s10549-009-0430-1","article-title":"Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses","volume":"120","author":"M Bayet-Robert","year":"2010","journal-title":"Breast Cancer Res Treat"},{"issue":"5","key":"ref90","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1023\/A:1025513106330","article-title":"Microtubules, microtubule-interfering agents and apoptosis","volume":"8","author":"F Mollinedo","year":"2003","journal-title":"Apoptosis"},{"issue":"5","key":"ref91","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.devcel.2004.09.002","article-title":"Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint","volume":"7","author":"CL Rieder","year":"2004","journal-title":"Dev Cell"},{"issue":"6","key":"ref92","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/bjc.1995.232","article-title":"S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells","volume":"71","author":"C Hennequin","year":"1995","journal-title":"Br J Cancer"},{"issue":"5","key":"ref93","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s002800050989","article-title":"The effect of antimicrotubule agents on signal transduction pathways of apoptosis: a review","volume":"44","author":"LG Wang","year":"1999","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"ref94","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/ijc.2910170110","article-title":"A continuous tumor-cell line from a human lung carcinoma Lieber with properties of type II alveolar epithelial cells","volume":"17","author":"M Lieber","year":"1976","journal-title":"Int J Cancer"},{"issue":"6","key":"ref95","first-page":"807","article-title":"Human lung cancer cell line (KSNY) producing colony-stimulating activity which affects both human and mouse marrow cells","volume":"70","author":"N Kimura","year":"1979","journal-title":"Gan"},{"issue":"8","key":"ref96","first-page":"3561","article-title":"Establishment and characterization of four new human non-small cell lung cancer cell lines","volume":"44","author":"PM Loh","year":"1984","journal-title":"Cancer Res"},{"issue":"9","key":"ref97","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/1097-0142(19841101)54:9<1757::AID-CNCR2820540902>3.0.CO;2-5","article-title":"Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies","volume":"54","author":"L Olsson","year":"1984","journal-title":"Cancer"},{"issue":"2","key":"ref98","first-page":"798","article-title":"Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium","volume":"46","author":"M Brower","year":"1986","journal-title":"Cancer Res"},{"issue":"2","key":"ref99","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1378\/chest.100.2.429","article-title":"Establishment and characterization of 20 human non-small cell lung cancer cell lines in a serum-free defined medium (ACL-4)","volume":"100","author":"N Masuda","year":"1991","journal-title":"Chest"},{"issue":"8","key":"ref100","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1002\/1097-0142(19920415)69:8<2064::AID-CNCR2820690811>3.0.CO;2-#","article-title":"Establishment and characterization of a panel of human lung cancer cell lines","volume":"69","author":"BG Campling","year":"1992","journal-title":"Cancer"},{"issue":"2","key":"ref101","first-page":"413","article-title":"Proto-oncogene and growth factor\/receptor expression in the establishment of primary human non-small cell lung carcinoma cell lines","volume":"142","author":"C Liu","year":"1993","journal-title":"Am J Pathol"},{"issue":"7","key":"ref102","first-page":"1666","article-title":"Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression","volume":"52","author":"G Giaccone","year":"1992","journal-title":"Cancer Res"},{"issue":"1","key":"ref103","first-page":"114","article-title":"Establishment and characterization of 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