{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:23:34Z","timestamp":1775150614158,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"CHAIR in On-co-Innovation","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Drug combination and drug repurposing are two strategies that allow to find novel oncological therapies, in a faster and more economical process. In our previous studies, we developed a novel model of drug combination using antineoplastic and different repurposed drugs. We demonstrated the combinations of doxorubicin (DOX) + artesunate, DOX + chloroquine, paclitaxel (PTX) + fluoxetine, PTX + fluphenazine, and PTX + benztropine induce significant cytotoxicity in Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Furthermore, it was found that 5-FU + thioridazine and 5-fluorouracil (5-FU) + sertraline can synergistically induce a reduction in the viability of human colorectal adenocarcinoma cell line (HT-29). In this study, we aim to (1) evaluate the biosafety profile of these drug combinations for non-tumoral cells and (2) determine their mechanism of action in cancer cells. To do so, human fetal lung fibroblast cells (MRC-5) fibroblast cells were incubated for 48 h with all drugs, alone and in combination in concentrations of 0.25, 0.5, 1, 2, and 4 times their half-maximal inhibitory concentration (IC50). Cell morphology and viability were evaluated. Next, we designed and constructed a cell microarray to perform immunohistochemistry studies for the evaluation of palmitoyl-protein thioesterase 1 (PPT1), Ki67, cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), and nuclear factor-kappa-B (NF-kB) p65 expression. We demonstrate that these combinations are cytotoxic for cancer cells and safe for non-tumoral cells at lower concentrations. Furthermore, it is also demonstrated that PPT1 may have an important role in the mechanism of action of these combinations, as demonstrated by their ability to decrease PPT1 expression. These results support the use of antimalarial and central nervous system (CNS) drugs in combination regimens with chemotherapeutic agents; nevertheless, additional studies are recommended to further explore their complete mechanisms of action.<\/jats:p>","DOI":"10.3390\/biom12101490","type":"journal-article","created":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T21:10:10Z","timestamp":1665954610000},"page":"1490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-5042","authenticated-orcid":false,"given":"Diana","family":"Duarte","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-5778","authenticated-orcid":false,"given":"Mariana","family":"Nunes","sequence":"additional","affiliation":[{"name":"Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S), University of Porto\/Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-2226","authenticated-orcid":false,"given":"Sara","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S), University of Porto\/Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Toxicology Research Unit (TOXRUN), University Institute of Health Sciences, Polytechnic and University Cooperative (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer Statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.2147\/IJN.S257700","article-title":"Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer","volume":"15","author":"Tayebi","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41698-019-0084-3","article-title":"Resistance to Paclitaxel Is Associated with a Variant of the Gene BCL2 in Multiple Tumor Types","volume":"3","author":"Zilberberg","year":"2019","journal-title":"Npj Precis. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/FPC.0b013e32833ffb56","article-title":"Doxorubicin Pathways","volume":"21","author":"Thorn","year":"2011","journal-title":"Pharmacogenet. Genom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"172784","DOI":"10.1016\/j.ejphar.2019.172784","article-title":"Old Wine in New Bottles: Drug Repurposing in Oncology","volume":"866","author":"Antoszczak","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.addr.2015.10.022","article-title":"Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems","volume":"98","author":"Hu","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1248\/cpb.c17-00261","article-title":"Synergistic Activity of an Antimetabolite Drug and Tyrosine Kinase Inhibitors against Breast Cancer Cells","volume":"65","author":"Wu","year":"2017","journal-title":"Chem. Pharm. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Miskimins, W.K., Ahn, H.J., Kim, J.Y., Ryu, S., Jung, Y.-S., and Choi, J.Y. (2014). Synergistic Anti-Cancer Effect of Phenformin and Oxamate. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085576"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1111\/bph.13045","article-title":"Synergistic Anti-Tumour Effects of Tetrandrine and Chloroquine Combination Therapy in Human Cancer: A Potential Antagonistic Role for P21","volume":"172","author":"Mei","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12380","DOI":"10.1111\/jpi.12380","article-title":"Melatonin Synergizes the Chemotherapeutic Effect of 5-Fluorouracil in Colon Cancer by Suppressing PI3K\/AKT and NF-\u039aB\/INOS Signaling Pathways","volume":"62","author":"Gao","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e50036","DOI":"10.7554\/eLife.50036","article-title":"A Curative Combination Cancer Therapy Achieves High Fractional Cell Killing through Low Cross-Resistance and Drug Additivity","volume":"8","author":"Palmer","year":"2019","journal-title":"Elife"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Duarte, D., Cardoso, A., and Vale, N. (2021). Synergistic Growth Inhibition of HT-29 Colon and MCF-7 Breast Cancer Cells with Simultaneous and Sequential Combinations of Antineoplastics and CNS Drugs. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147408"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Duarte, D., and Vale, N. (2020). New Trends for Antimalarial Drugs: Synergism between Antineoplastics and Antimalarials on Breast Cancer Cells. Biomolecules, 10.","DOI":"10.3390\/biom10121623"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Duarte, D., R\u00eama, A., Amorim, I., and Vale, N. (2022). Drug Combinations: A New Strategy to Extend Drug Repurposing and Epithelial-Mesenchymal Transition in Breast and Colon Cancer Cells. Biomolecules, 12.","DOI":"10.3390\/biom12020190"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Magalh\u00e3es, A.C., Ricardo, S., Moreira, A.C., Nunes, M., Tavares, M., Pinto, R.J., Gomes, M.S., and Pereira, L. (2022). InfectionCMA: A Cell MicroArray Approach for Efficient Biomarker Screening in In Vitro Infection Assays. Pathogens, 11.","DOI":"10.3390\/pathogens11030313"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1158\/2159-8290.CD-18-0706","article-title":"PPT1 Promotes Tumor Growth and Is the Molecular Target of Chloroquine Derivatives in Cancer","volume":"9","author":"Rebecca","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.2174\/1389200222666211118114057","article-title":"How Antimalarials and Antineoplastic Drugs Can Interact in Combination Therapies: A Perspective on the Role of PPT1 Enzyme","volume":"22","author":"Duarte","year":"2021","journal-title":"Curr. Drug Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2147\/JIR.S140188","article-title":"Mechanisms of NF-KB P65 and Strategies for Therapeutic Manipulation","volume":"11","author":"Giridharan","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137","DOI":"10.18773\/austprescr.2014.050","article-title":"P-Glycoprotein and Its Role in Drug-Drug Interactions","volume":"37","author":"Finch","year":"2014","journal-title":"Aust. Prescr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1517\/17425255.2.3.351","article-title":"Structure and Function of the MRP2 (ABCC2) Protein and Its Role in Drug Disposition","volume":"2","author":"Jedlitschky","year":"2006","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3892\/mmr.2014.2914","article-title":"Ki67 Is a Promising Molecular Target in the Diagnosis of Cancer (Review)","volume":"11","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, L., Liang, C., Li, F., Guan, D., Wu, X., Fu, X., Lu, A., and Zhang, G. (2017). PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102111"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bjp.2015.02.009","article-title":"Cytotoxicity Screening of Essential Oils in Cancer Cell Lines","volume":"25","author":"Alves","year":"2015","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mellado, M., Soto, M., Madrid, A., Montenegro, I., Jara-Guti\u00e9rrez, C., Villena, J., Werner, E., Godoy, P., and Aguilar, L.F. (2019). In Vitro Antioxidant and Antiproliferative Effect of the Extracts of Ephedra Chilensis K Presl Aerial Parts. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2462-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.3389\/fonc.2021.752127","article-title":"Generation of Two Paclitaxel-Resistant High-Grade Serous Carcinoma Cell Lines With Increased Expression of P-Glycoprotein","volume":"11","author":"Nunes","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1159\/000185488","article-title":"Cell Growth Inhibition, G2\/M Cell Cycle Arrest, and Apoptosis Induced by Chloroquine in Human Breast Cancer Cell Line Bcap-37","volume":"22","author":"Jiang","year":"2008","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7369","DOI":"10.1039\/C7RA10997K","article-title":"Epigallocatechin Gallate-Zinc Oxide Co-Crystalline Nanoparticles as an Anticancer Drug That Is Non-Toxic to Normal Cells","volume":"8","author":"Samutprasert","year":"2018","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.3389\/fendo.2021.687244","article-title":"The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1083\/jcb.123.3.513","article-title":"The Cell Proliferation-Associated Antigen of Antibody Ki-67: A Very Large, Ubiquitous Nuclear Protein with Numerous Repeated Elements, Representing a New Kind of Cell Cycle-Maintaining Proteins","volume":"123","author":"Schluter","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"463","DOI":"10.5732\/cjc.011.10111","article-title":"PARP Inhibitors: Its Role in Treatment of Cancer","volume":"30","author":"Chen","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.2147\/OTT.S161109","article-title":"Role of the NF\u03baB-Signaling Pathway in Cancer","volume":"11","author":"Xia","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102337","DOI":"10.1016\/j.isci.2021.102337","article-title":"The Converging Roles of Batten Disease Proteins in Neurodegeneration and Cancer","volume":"24","author":"Yap","year":"2021","journal-title":"Iscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100054","DOI":"10.1016\/j.crphar.2021.100054","article-title":"Exploring New Horizons in Overcoming P-Glycoprotein-Mediated Multidrug-Resistant Breast Cancer via Nanoscale Drug Delivery Platforms","volume":"2","author":"Famta","year":"2021","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1177\/38.9.1974900","article-title":"Expression of the Multidrug Resistance Gene Product (P-Glycoprotein) in Human Normal and Tumor Tissues","volume":"38","author":"Boccia","year":"1990","journal-title":"J. Histochem. Cytochem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Karthika, C., Sureshkumar, R., Zehravi, M., Akter, R., Ali, F., Ramproshad, S., Mondal, B., Tagde, P., Ahmed, Z., and Khan, F.S. (2022). Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein. Life, 12.","DOI":"10.3390\/life12060897"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.semcancer.2020.06.014","article-title":"Phytochemicals in Cancer Cell Chemosensitization: Current Knowledge and Future Perspectives","volume":"80","author":"Khatoon","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Turner, A.P., Alam, C., and Bendayan, R. (2020). Efflux Transporters in Cancer Resistance: Molecular and Functional Characterization of P-Glycoprotein. Drug Efflux Pumps in Cancer Resistance Pathways: From Molecular Recognition and Characterization to Possible Inhibition Strategies in Chemotherapy, Academic Press.","DOI":"10.1016\/B978-0-12-816434-1.00001-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1021\/acs.jafc.8b04104","article-title":"Targeting Tumor Metabolism with Plant-Derived Natural Products: Emerging Trends in Cancer Therapy","volume":"66","author":"Guerra","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.drup.2020.100715","article-title":"Tumor Microenvironment and Epithelial Mesenchymal Transition as Targets to Overcome Tumor Multidrug Resistance","volume":"53","author":"Erin","year":"2020","journal-title":"Drug Resist. Updates"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1208\/s12248-015-9757-1","article-title":"Multidrug Resistance Proteins (MRPs) and Cancer Therapy","volume":"17","author":"Zhang","year":"2015","journal-title":"AAPS J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cbi.2014.10.009","article-title":"The Role of the Efflux Carriers Abcg2 and Abcc2 for the Hepatobiliary Elimination of Benzo[a]Pyrene and Its Metabolites in Mice","volume":"224","author":"Kranz","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3109\/08880018.2013.870625","article-title":"Association of -24CT, 1249GA, and 3972CT ABCC2 Gene Polymorphisms with Methotrexate Serum Levels and Toxic Side Effects in Children with Acute Lymphoblastic Leukemia","volume":"31","author":"Sharifi","year":"2014","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/sj.bjc.6606071","article-title":"Role of Multidrug Resistance Protein 2 (MRP2) in Chemoresistance and Clinical Outcome in Oesophageal Squamous Cell Carcinoma","volume":"104","author":"Yamasaki","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/ijc.21013","article-title":"MRP2 (ABCC2) Transports Taxanes and Confers Paclitaxel Resistance and Both Processes Are Stimulated by Probenecid","volume":"116","author":"Huisman","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guo, B., Tam, A., Santi, S.A., and Parissenti, A.M. (2016). Role of Autophagy and Lysosomal Drug Sequestration in Acquired Resistance to Doxorubicin in MCF-7 Cells. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2790-3"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000448802","article-title":"Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells","volume":"62","author":"Li","year":"2017","journal-title":"Chemotherapy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"C1630","DOI":"10.1152\/ajpcell.1998.275.6.C1630","article-title":"Taxol Inhibits Endosomal-Lysosomal Membrane Trafficking at Two Distinct Steps in CV-1 Cells","volume":"275","author":"Sonee","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41401-020-0445-z","article-title":"Enhanced Lysosomal Function Is Critical for Paclitaxel Resistance in Cancer Cells: Reversed by Artesunate","volume":"42","author":"Li","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13046-017-0662-6","article-title":"5-FU Resistant EMT-like Pancreatic Cancer Cells Are Hypersensitive to Photochemical Internalization of the Novel Endoglin-Targeting Immunotoxin CD105-Saporin","volume":"36","author":"Lund","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:05Z","timestamp":1760144105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,16]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101490"],"URL":"https:\/\/doi.org\/10.3390\/biom12101490","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,16]]}}}