{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T19:14:45Z","timestamp":1778354085565,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para Ci\u00eancia e Tecnologia","award":["PTDC\/MEC-CAR\/31626\/2017"],"award-info":[{"award-number":["PTDC\/MEC-CAR\/31626\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Doxorubicin (DOX) is commonly used in several chemotherapies to treat various cancers, but it is known to cause cardiotoxicity and cardiac symptoms. Autonomic dysfunction is thought to contribute to the cardiotoxic effects of DOX, but the specific dose required to disrupt homeostatic processes is still unclear and is influenced by numerous factors. This study aimed to investigate how the DOX dosage affects autonomic function and physiological parameters, to elucidate the neurocardiac mechanisms underlying the observed cardiovascular side effects. Wistar rats were treated with DOX for four weeks and divided into three dosing groups: DOX8 (2 mg\/kg\/week), DOX16 (4 mg\/kg\/week), and DOX20 (5 mg\/kg\/week). A control group received NaCl 0.9% saline (1 mL\/kg\/week). In an acute experiment, we recorded blood pressure (BP), electrocardiogram, heart rate (HR), and respiratory rate (RF). Baroreflex gain and chemoreflex sensitivity were calculated, and cardiac tissue was analyzed with picrosirius histochemistry to measure collagen content. Our results showed that the LF\/HF ratio, indicative of autonomic activity, was altered along with hypotension and bradycardia at a cumulative DOX dose threshold of 16 mg\/kg. We observed a positive correlation between DOX dose and BP, HR, urinary norepinephrine, LF\/HF ratio, and fibrotic heart area. Lower LF\/HF ratios were associated with high DOX doses, reflecting drug-induced impairment of autonomic control of HR. This study provides valuable insights into the dose-dependent effects of DOX on physiological parameters and the development of cardiovascular dysfunction. These findings are critical, which is important for optimizing the management and therapeutic strategies for patients undergoing DOX-based chemotherapy.<\/jats:p>","DOI":"10.3390\/biology12071031","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:47:03Z","timestamp":1690159623000},"page":"1031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Doxorubicin Dose-Dependent Impact on Physiological Balance\u2014A Holistic Approach in a Rat Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-8615","authenticated-orcid":false,"given":"Ana I.","family":"Afonso","sequence":"first","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-6372","authenticated-orcid":false,"given":"\u00c2ngela","family":"Amaro-Leal","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Egas Moniz School of Health and Science, 2829-511 Caparica, Portugal"}]},{"given":"Filipa","family":"Machado","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"given":"Isabel","family":"Rocha","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"given":"Vera","family":"Geraldes","sequence":"additional","affiliation":[{"name":"Cardiovascular Centre of the University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine of the University of Lisbon, 1649-028 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1056\/NEJM199809243391307","article-title":"Doxorubicin-Induced Cardiomyopathy","volume":"339","author":"Awan","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1056\/NEJM198107163050305","article-title":"The Antracycline Antineoplastic Drugs","volume":"305","author":"Young","year":"1981","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","article-title":"2016 ESC Position Paper on Cancer Treatments and Cardiovascular Toxicity Developed under the Auspices of the ESC Committee for Practice Guidelines","volume":"37","author":"Zamorano","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e187419242206271","DOI":"10.2174\/18741924-v16-e2206271","article-title":"Cardiovascular Dysautonomia in Patients with Breast Cancer","volume":"16","author":"Geraldes","year":"2022","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Norton, N., Weil, R.M., and Advani, P.P. (2021). Inter-individual Variation and Cardioprotection in Anthracycline-induced Heart Failure. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184079"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"710","DOI":"10.7326\/0003-4819-91-5-710","article-title":"Risk Factors for Doxorubicin-Lnduced Congestive Heart Failure","volume":"91","author":"Layard","year":"1979","journal-title":"Ann. Intern. Med."},{"key":"ref_7","first-page":"514","article-title":"Heart Rate Variability: A Noninvasive Electrocardiographic Method to Measure the Autonomic Nervous System","volume":"134","author":"Sztajzel","year":"2004","journal-title":"Swiss Med. Wkly."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.pcad.2013.07.003","article-title":"Heart Rate Variability in Risk Stratification of Cardiac Patients","volume":"56","author":"Huikuri","year":"2013","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart Rate Variability Standards of Measurement, Physiological Interpretation, and Clinical Use","volume":"17","author":"Camm","year":"1996","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Poto\u010dnik, N., Per\u0161e, M., Cerar, A., Injac, R., and Finderle, \u017d. (2017). Cardiac Autonomic Modulation Induced by Doxorubicin in a Rodent Model of Colorectal Cancer and the Influence of Fullerenol Pretreatment. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181632"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/FJC.0000000000000586","article-title":"Possible Ameliorative Effect of Ivabradine on the Autonomic and Left Ventricular Dysfunction Induced by Doxorubicin in Male Rats","volume":"72","author":"Sharabi","year":"2018","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1042\/cs1010601","article-title":"Neuroendocrine Changes during the Evolution of Doxorubicin-Induced Left Ventricular Dysfunction in Adult Lymphoma Patients","volume":"101","author":"Nousiainen","year":"2001","journal-title":"Clin. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1136\/hrt.81.4.419","article-title":"Early Detection of Anthracycline Induced Cardiotoxicity in Asymptomatic Patients with Normal Left Ventricular Systolic Function: Autonomic versus Echocardiographic Variables","volume":"81","author":"Tjeerdsma","year":"1999","journal-title":"Heart"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Moro, N., Dokshokova, L., Perumal Vanaja, I., Prando, V., Cnudde, S.J.A., Di Bona, A., Bariani, R., Schirone, L., Bauce, B., and Angelini, A. (2022). Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911098"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00520-002-0376-x","article-title":"Autonomic Nervous System Dysfunction in Advanced Cancer","volume":"10","author":"Walsh","year":"2002","journal-title":"Support. Care Cancer"},{"key":"ref_16","first-page":"228","article-title":"Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?","volume":"105","author":"Andrade","year":"2015","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/WNP.0000000000000210","article-title":"Prognostic Value of Heart Rate Variability in Patients with Cancer","volume":"32","author":"Guo","year":"2015","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103501","DOI":"10.1016\/j.amsu.2022.103501","article-title":"Doxorubicin Induced Immune Abnormalities and Inflammatory Responses via HMGB1, HIF1-\u03b1, and VEGF Pathway in Progressive of Cardiovascular Damage","volume":"76","author":"Syukri","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/nm.2919","article-title":"Identification of the Molecular Basis of Doxorubicin-Induced Cardiotoxicity","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"156848","DOI":"10.1155\/2014\/156848","article-title":"Osthole Attenuates Doxorubicin-Induced Apoptosis in PC12 Cells through Inhibition of Mitochondrial Dysfunction and ROS Production","volume":"2014","author":"Shokoohinia","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"951539","DOI":"10.1155\/2012\/951539","article-title":"Mitochondria Death\/Survival Signaling Pathways in Cardiotoxicity Induced by Anthracyclines and Anticancer-Targeted Therapies","volume":"2012","author":"Montaigne","year":"2012","journal-title":"Biochem. Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6534","DOI":"10.1111\/jcmm.15305","article-title":"Effects of Doxorubicin-Induced Cardiotoxicity on Cardiac Mitochondrial Dynamics and Mitochondrial Function: Insights for Future Interventions","volume":"24","author":"Osataphan","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"673340","DOI":"10.3389\/fonc.2021.673340","article-title":"Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights","volume":"11","author":"Du","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bosman, M., Kr\u00fcger, D.N., Favere, K., Wesley, C.D., Neutel, C.H.G., Van Asbroeck, B., Diebels, O.R., Faes, B., Schenk, T.J., and Martinet, W. (2021). Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312812"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/jat.2550050609","article-title":"Effects of Intravenous Infusion of Doxorubicin on Blood Chemistry, Blood Pressure and Heart Rate in Rabbits?","volume":"5","author":"Robison","year":"1985","journal-title":"J. Appl. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Agostinucci, K., Grant, M.K.O., Melaku, W., Nair, C., and Zordoky, B.N. (2023). Exposure to Doxorubicin Modulates the Cardiac Response to Isoproterenol in Male and Female Mice. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030391"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"670479","DOI":"10.3389\/fphar.2021.670479","article-title":"Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View from the Perspective of the Pathophysiologist and the Clinician","volume":"12","author":"Podyacheva","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/ilar.43.4.244","article-title":"Guidelines for the Design and Statistical Analysis of Experiments Using Laboratory Animals","volume":"43","author":"Festing","year":"2002","journal-title":"ILAR J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s12640-020-00162-8","article-title":"Persistent Effects on Cardiorespiratory and Nervous Systems Induced by Long-Term Lead Exposure: Results from a Longitudinal Study","volume":"37","author":"Shvachiy","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neuro.2016.04.016","article-title":"Lead Toxicity Promotes Autonomic Dysfunction with Increased Chemoreceptor Sensitivity","volume":"54","author":"Geraldes","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Shvachiy, L., Amaro-Leal, \u00c2., Outeiro, T.F., Rocha, I., and Geraldes, V. (2023). Intermittent Lead Exposure Induces Behavioral and Cardiovascular Alterations Associated with Neuroinflammation. Cells, 12.","DOI":"10.3390\/cells12050818"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Usui, H., and Nishida, Y. (2017). The Very Low-Frequency Band of Heart Rate Variability Represents the Slow Recovery Component after a Mental Stress Task. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182611"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jelectrocard.2005.08.001","article-title":"Spectral Analysis of Heart Rate Variability: Interchangeability between Autoregressive Analysis and Fast Fourier Transform","volume":"39","author":"Pichon","year":"2006","journal-title":"J. Electrocardiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tavares, C., Martins, C., Superior, I., Lisboa, T., Laranjo, P., and Rocha, S. (2011, January 1\u20134). Computational Tools for Assessing Cardiovascular Variability. Proceedings of the 1st Portuguese Biomedical Engineering Meeting, Lisbon, Portugal.","DOI":"10.1109\/ENBENG.2011.6026082"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF01002772","article-title":"Picrosirius Staining plus Polarization Microscopy, a Specific Method for Collagen Detection in Tissue Sections","volume":"11","author":"Junqueira","year":"1979","journal-title":"Histochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0005-8165(73)80016-2","article-title":"Polarization Microscopic Studies of Connective Tissue Stained with Picro Sirius Red F3BA","volume":"150","author":"Puchtler","year":"1973","journal-title":"Beitr\u00e4ge Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1155\/2010\/858356","article-title":"Rapid Quantification of Myocardial Fibrosis: A New Macro-Based Automated Analysis","volume":"33","author":"Hadi","year":"2010","journal-title":"Anal. Cell. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1113\/jphysiol.2003.050708","article-title":"Peripheral Chemoreflex and Baroreflex Interactions in Cardiovascular Regulation in Humans","volume":"552","author":"Halliwill","year":"2003","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1212\/01.wnl.0000335246.93495.92","article-title":"The Arterial Baroreflex Functional Organization and Involvement in Neurologic Disease","volume":"71","author":"Benarroch","year":"2008","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1161\/HYPERTENSIONAHA.106.076083","article-title":"Arterial Chemoreceptors and Sympathetic Nerve Activity: Implications for Hypertension and Heart Failure","volume":"50","author":"Schultz","year":"2007","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1088\/0967-3334\/36\/4\/727","article-title":"Heart Rate Dynamics in Doxorubicin-Induced Cardiomyopathy","volume":"36","author":"Glumac","year":"2015","journal-title":"Physiol. Meas."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.56808\/2985-1130.2577","article-title":"Changes in Electrophysiology, Heart Rate Variability and Proteinuria in Clinical Dogs Treated with Doxorubicin Chemotherapy","volume":"44","author":"Buranakarl","year":"2014","journal-title":"Thai J. Vet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.taap.2018.10.015","article-title":"Cardiovascular Variability and \u03b2-ARs Gene Expression at Two Stages of Doxorubicin\u2013Induced Cardiomyopathy","volume":"362","author":"Glumac","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.repc.2017.01.007","article-title":"Insights into the Background of Autonomic Medicine","volume":"36","author":"Laranjo","year":"2017","journal-title":"Rev. Port. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1023\/A:1009846123893","article-title":"Chemoreflex Function in Heart Failure","volume":"5","author":"Schultz","year":"2000","journal-title":"Heart Fail. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1152\/physrev.00039.2019","article-title":"Carotid Body Chemoreceptors: Physiology, Pathology, and Implications for Health and Disease","volume":"101","author":"Iturriaga","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12964-023-01077-5","article-title":"Role of Oxidative Stress and Inflammation-Related Signaling Pathways in Doxorubicin-Induced Cardiomyopathy","volume":"21","author":"Shi","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.yjmcc.2012.03.006","article-title":"Doxorubicin-Induced Cardiomyopathy: From Molecular Mechanisms to Therapeutic Strategies","volume":"52","author":"Octavia","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1021\/tx800002r","article-title":"Cardiotoxicity of Antitumor Drugs","volume":"21","author":"Menna","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1161\/CIRCRESAHA.115.303633","article-title":"Cardio-Oncology: An Update on Cardiotoxicity of Cancer-Related Treatment","volume":"118","author":"Lenneman","year":"2016","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.pharep.2019.02.013","article-title":"Time Course of Cardiomyopathy Induced by Doxorubicin in Rats","volume":"71","author":"Carvalho","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.metabol.2015.10.013","article-title":"Wnt Signaling Pathway in Cardiac Fibrosis: New Insights and Directions","volume":"65","author":"Tao","year":"2016","journal-title":"Metabolism"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100575","DOI":"10.1016\/j.cophys.2022.100575","article-title":"Cardiac Fibrosis in Oncologic Therapies","volume":"29","author":"Packard","year":"2022","journal-title":"Curr. Opin. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.phrs.2017.03.016","article-title":"Doxorubicin Targets Multiple Players: A New View of an Old Problem","volume":"127","author":"Cappetta","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1573403X14666180111145207","article-title":"Oxidative Stress and Cardiac Remodeling: An Updated Edge","volume":"14","author":"Guillory","year":"2018","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/labinvest.3700669","article-title":"Pathobiology of Transforming Growth Factor \u03b2 in Cancer, Fibrosis and Immunologic Disease, and Therapeutic Considerations","volume":"87","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1015976430790","article-title":"Doxorubicin-Induced Apoptosis: Implications in Cardiotoxicity","volume":"234","author":"Kalyanaraman","year":"2002","journal-title":"Mol. Cell. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1385\/CT:1:3:181","article-title":"Oxidative Stress and Diabetic Cardiomyopathy Oxidative Stress and Diabetic Cardiomyopathy A Brief Review","volume":"1","author":"Kang","year":"2001","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2165\/00003088-200948030-00001","article-title":"Sex Differences in Pharmacokinetics and Pharmacodynamics","volume":"48","author":"Soldin","year":"2009","journal-title":"Clin. Pharmacokinet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00280-018-3683-8","article-title":"Gender Differences in Doxorubicin Pharmacology for Subjects with Chemosensitive Cancers of Young Adulthood","volume":"82","author":"Liu","year":"2018","journal-title":"Cancer Chemother. Pharmacol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/7\/1031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:16:56Z","timestamp":1760127416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/7\/1031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,22]]},"references-count":60,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["biology12071031"],"URL":"https:\/\/doi.org\/10.3390\/biology12071031","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,22]]}}}