{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:33:30Z","timestamp":1780634010323,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIBERES 2018"],"award-info":[{"award-number":["CIBERES 2018"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 14\/00713 (FEDER)"],"award-info":[{"award-number":["FIS 14\/00713 (FEDER)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 18\/00075 (FEDER)"],"award-info":[{"award-number":["FIS 18\/00075 (FEDER)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"publisher","award":["SEPAR 2016"],"award-info":[{"award-number":["SEPAR 2016"]}],"id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-\u03baB and sirtuin-1) markers were analyzed (immunoblotting) in subcutaneous tumor of BALB\/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N = 9\/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. Conclusions: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.<\/jats:p>","DOI":"10.3390\/cancers11091301","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T03:22:36Z","timestamp":1567653756000},"page":"1301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events"],"prefix":"10.3390","volume":"11","author":[{"given":"Jun","family":"Tang","sequence":"first","affiliation":[{"name":"Pulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar<\/i>, Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona (UAB), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7793-773X","authenticated-orcid":false,"given":"Daniel","family":"Ramis-Cabrer","sequence":"additional","affiliation":[{"name":"Pulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar<\/i>, Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Health and Experimental Sciences Department (CEXS), <i>Pompeu Fabra<\/i> University (UPF), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-3942","authenticated-orcid":false,"given":"Xuejie","family":"Wang","sequence":"additional","affiliation":[{"name":"Pulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar<\/i>, Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona (UAB), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Pulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar<\/i>, Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"},{"name":"Health and Experimental Sciences Department (CEXS), <i>Pompeu Fabra<\/i> University (UPF), Biomedical Research Park (PRBB), C\/Dr. Aiguader, 88, E-08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"2","article-title":"Recommendations of the Spanish Society of Pneumology and Thoracic Surgery on the diagnosis and treatment of non-small-cell lung cancer","volume":"52","author":"Alvarez","year":"2016","journal-title":"Arch. Bronconeumol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/annonc\/mdx033","article-title":"European cancer mortality predictions for the year 2017, with focus on lung cancer","volume":"28","author":"Malvezzi","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.arbres.2017.03.018","article-title":"Spanish Guidelines for Management of Chronic Obstructive Pulmonary Disease (GesEPOC) 2017. Pharmacological Treatment of Stable Phase","volume":"53","author":"Miravitlles","year":"2017","journal-title":"Arch. Bronconeumol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.arbres.2017.02.001","article-title":"Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary","volume":"53","author":"Vogelmeier","year":"2017","journal-title":"Arch. Bronconeumol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.arbr.2016.02.020","article-title":"Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer","volume":"52","author":"Trueba","year":"2016","journal-title":"Arch. Bronconeumol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1164\/rccm.201508-1545CI","article-title":"Macrophages, Inflammation, and Lung Cancer","volume":"193","author":"Conway","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jtho.2016.09.137","article-title":"Systemic and Tumor Th1 and Th2 Inflammatory Profile and Macrophages in Lung Cancer: Influence of Underlying Chronic Respiratory Disease","volume":"12","author":"Curull","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1054\/bjoc.2001.1943","article-title":"Chronic immune activation and inflammation as the cause of malignancy","volume":"85","author":"Dalgleish","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1097\/JTO.0b013e3181f387e4","article-title":"The role of inflammation in the pathogenesis of non-small cell lung cancer","volume":"5","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.freeradbiomed.2013.08.006","article-title":"Oxidative stress and inflammation in the normal airways and blood of patients with lung cancer and COPD","volume":"65","author":"Barreiro","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5300","DOI":"10.2174\/1381612822666160623065523","article-title":"Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology","volume":"22","author":"Fermoselle","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2119\/molmed.2015.00199","article-title":"Redox Imbalance in Lung Cancer of Patients with Underlying Chronic Respiratory Conditions","volume":"22","author":"Aguilo","year":"2016","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E1122","DOI":"10.21037\/jtd.2016.09.54","article-title":"Relationships between chronic obstructive pulmonary disease and lung cancer: Biological insights","volume":"8","author":"Barreiro","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.canlet.2010.09.012","article-title":"Targeting apoptosis pathways in lung cancer","volume":"332","author":"Pore","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13148-017-0437-0","article-title":"Profile of epigenetic mechanisms in lung tumors of patients with underlying chronic respiratory conditions","volume":"10","author":"Curull","year":"2018","journal-title":"Clin. Epigenet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1126\/science.1203486","article-title":"Cancer immunoediting: Integrating immunity\u2019s roles in cancer suppression and promotion","volume":"331","author":"Schreiber","year":"2011","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/CJI.0b013e3182943549","article-title":"Long-lasting complete regression of established mouse tumors by counteracting Th2 inflammation","volume":"36","author":"Dai","year":"2013","journal-title":"J. Immunother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1158\/1078-0432.CCR-14-1339","article-title":"Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies","volume":"21","author":"Dai","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.1158\/0008-5472.CAN-16-0431","article-title":"The Emerging Role of B Cells in Tumor Immunity","volume":"76","author":"Tsou","year":"2016","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1158\/1078-0432.CCR-15-0263","article-title":"Boosting Cancer Immunotherapy with Anti-CD137 Antibody Therapy","volume":"21","author":"Yonezawa","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature21349","article-title":"Elements of cancer immunity and the cancer-immune set point","volume":"541","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: The cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"ref_24","first-page":"17","article-title":"Role of PD-1 in regulating T-cell immunity","volume":"350","author":"Jin","year":"2011","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/2326-6066.CIR-13-0013","article-title":"Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells","volume":"1","author":"Selby","year":"2013","journal-title":"Cancer Immunol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1756286418761697","DOI":"10.1177\/1756286418761697","article-title":"B cell-based therapies in CNS autoimmunity: Differentiating CD19 and CD20 as therapeutic targets","volume":"11","author":"Forsthuber","year":"2018","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/intimm\/dxu076","article-title":"Therapeutic use of anti-CTLA-4 antibodies","volume":"27","author":"Blank","year":"2015","journal-title":"Int. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000437178","article-title":"Immune Checkpoint Inhibitors","volume":"42","author":"Haanen","year":"2015","journal-title":"Prog. Tumor Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-3-319-53156-4_5","article-title":"Immunotherapy in NSCLC: A Promising and Revolutionary Weapon","volume":"995","author":"Rolfo","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.arbr.2017.10.019","article-title":"PD-L1 Expression in a Non-Small Cell Lung Cancer Specimen Obtained by EBUS-TBNA","volume":"54","author":"Pires","year":"2018","journal-title":"Arch. Bronconeumol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.arbres.2018.07.014","article-title":"Accurate Identification of Predictive Biomarkers of Response to Targeted Therapies in Lung Cancer with Next Generation Sequencing","volume":"55","author":"Moliner","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.arbres.2018.08.012","article-title":"Immunotherapy is Here to Stay: A New Treatment Paradigm in Lung Cancer","volume":"55","author":"Rocha","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.biochi.2015.11.030","article-title":"Reduced tumor burden through increased oxidative stress in lung adenocarcinoma cells of PARP-1 and PARP-2 knockout mice","volume":"121","author":"Yelamos","year":"2016","journal-title":"Biochimie"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cmet.2018.05.012","article-title":"Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-alpha-Dependent Intensification of Oxidative Stress and Tumor Cell Death","volume":"28","author":"Habtetsion","year":"2018","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/ni.3868","article-title":"Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor","volume":"18","author":"Maj","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/jcp.24611","article-title":"Pharmacological strategies in lung cancer-induced cachexia: Effects on muscle proteolysis, autophagy, structure, and weakness","volume":"229","author":"Fermoselle","year":"2014","journal-title":"J. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1016\/j.bbagen.2015.09.020","article-title":"MicroRNA expression and protein acetylation pattern in respiratory and limb muscles of Parp-1(\u2212\/\u2212) and Parp-2(\u2212\/\u2212) mice with lung cancer cachexia","volume":"1850","author":"Fermoselle","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1002\/jcp.25851","article-title":"Role of Parp Activity in Lung Cancer-induced Cachexia: Effects on Muscle Oxidative Stress, Proteolysis, Anabolic Markers and Phenotype","volume":"232","author":"Langohr","year":"2017","journal-title":"J. Cell Physiol."},{"key":"ref_39","first-page":"45","article-title":"Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer","volume":"2","author":"Diament","year":"1998","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/07357900500524322","article-title":"Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin","volume":"24","author":"Diament","year":"2006","journal-title":"Cancer Invest."},{"key":"ref_41","first-page":"639","article-title":"New murine cell line derived from a spontaneous lung tumor induces paraneoplastic syndromes","volume":"18","author":"Urtreger","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_42","first-page":"1415","article-title":"Short- and Long-Term Hindlimb Immobilization and Reloading: Profile of Epigenetic Events in Gastrocnemius","volume":"232","author":"Gea","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18041","DOI":"10.1002\/jcp.28437","article-title":"Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice","volume":"234","author":"Tang","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1158\/1078-0432.CCR-06-2872","article-title":"Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models","volume":"13","author":"Albert","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1105430","DOI":"10.1080\/2162402X.2015.1105430","article-title":"Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma","volume":"5","author":"Kryczek","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.cell.2016.04.009","article-title":"Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer","volume":"165","author":"Wang","year":"2016","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5438179","DOI":"10.1155\/2018\/5438179","article-title":"Anticancer Activity of Sulforaphane. The Epigenetic Mechanisms and the Nrf2 Signaling Pathway","volume":"2018","author":"Su","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3109\/07357907.2011.621916","article-title":"Inhibition of poly(ADP-ribose) polymerase (PARP) induces apoptosis in lung cancer cell lines","volume":"29","author":"Gangopadhyay","year":"2011","journal-title":"Cancer Invest."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3324\/haematol.2008.001933","article-title":"Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: Potential for therapy of myeloid leukemia and myelodysplastic syndromes","volume":"94","author":"Gaymes","year":"2009","journal-title":"Haematologica"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Karpel-Massler, G., Pareja, F., Aime, P., Shu, C., Chau, L., Westhoff, M.A., Halatsch, M.E., Crary, J.F., Canoll, P., and Siegelin, M.D. (2014). PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114583"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.molcel.2014.12.013","article-title":"Deacetylation of nuclear LC3 drives autophagy initiation under starvation","volume":"57","author":"Huang","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3389\/fimmu.2018.00526","article-title":"High-Mobility Group Nucleosome-Binding Protein 1 as Endogenous Ligand Induces Innate Immune Tolerance in a TLR4-Sirtuin-1 Dependent Manner in Human Blood Peripheral Mononuclear Cells","volume":"9","author":"Arts","year":"2018","journal-title":"Front. Immunol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/9\/1301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:41Z","timestamp":1760188601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/9\/1301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,4]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["cancers11091301"],"URL":"https:\/\/doi.org\/10.3390\/cancers11091301","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201906.0080.v1","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,4]]}}}