{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:15:43Z","timestamp":1785413743115,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2023\/07\/X\/NZ7\/01746"],"award-info":[{"award-number":["2023\/07\/X\/NZ7\/01746"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2023\/07\/X\/NZ7\/01746"],"award-info":[{"award-number":["2023\/07\/X\/NZ7\/01746"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok","doi-asserted-by":"publisher","award":["SUB.B. 26. 547"],"award-info":[{"award-number":["SUB.B. 26. 547"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SUB.B. 26. 547"],"award-info":[{"award-number":["SUB.B. 26. 547"]}],"id":[{"id":"https:\/\/ror.org\/00y4ya841","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Papillary thyroid cancer (PTC) exhibits Warburg-type metabolic reprogramming with enhanced glycolysis and dependence on glucose-driven pathways. This study evaluated the effects of antihyperglycemic interventions on cytokine secretion, angiogenic signaling, metabolic activity, and proliferation in thyroid-derived cell models. Two PTC cell lines (MDA-T32 and SCC147) and a normal thyroid line (Nthy-ori) were analyzed for intracellular and extracellular cytokines, secretion efficiency (index), relative metabolic index (RMI), and marker of proliferation (Ki-67) expression following exposure to vandetanib (VDT), sodium\u2013glucose cotransporter 2 (SGLT2), or dipeptidyl peptidase (DPP) inhibitors. Baseline analysis revealed distinct cell line-specific profiles. Compared with Nthy-ori cells, MDA-T32 cells exhibited increased vascular endothelial growth factor (VEGF) concentrations in lysates and conditioned medium (p &lt; 0.001, q &lt; 0.001) with enhanced VEGF secretion efficiency (p = 0.002, q = 0.008), elevated intracellular fibroblast growth factor (FGF) (p &lt; 0.001, q &lt; 0.001) with reduced FGF secretion index (p = 0.004, q = 0.01), and lower interleukin 8 (IL-8) concentrations accompanied by increased IL-8 secretion efficiency (p = 0.006, q = 0.02). In contrast, SCC147 cells demonstrated reduced VEGF secretion (p &lt; 0.001, q &lt; 0.001), decreased intracellular IL-8 (p = 0.008, q = 0.02), reduced chemokines of the growth-regulated oncogene GRO\u03b2 family (GRO\u03b2) secretion (p = 0.01, q = 0.04), increased IL-8 secretion efficiency (p = 0.01, q = 0.03), and decreased GRO\u03b2 secretion efficiency (p = 0.008, q = 0.02). Nthy-ori cells displayed a balanced profile. Among the investigated interventions, VDT produced the most pronounced effects. In MDA-T32 cells, VDT significantly reduced VEGF levels (p &lt; 0.001, q &lt; 0.001) and increased IL-8 and GRO\u03b2 concentrations in conditioned medium (q &lt; 0.05), whereas no significant effects after FDR correction were observed in SCC147 or Nthy-ori cells. SGLT2 and DPP inhibitors produced only nominal effects (p &lt; 0.05), which did not remain significant after correction for multiple testing. VDT reduced RMI by approximately 50% in MDA-T32 cells while Ki-67 expression increased, whereas SCC147 cells remained largely unchanged. In Nthy-ori cells, SGLT2 inhibition increased RMI and decreased Ki-67 expression. These findings demonstrate marked heterogeneity among PTC cell lines and suggest that alterations in metabolic activity were not consistently accompanied by proportional changes in proliferative status under the experimental conditions used. VDT predominantly affected angiogenic and inflammatory signaling in MDA-T32 cells, whereas SGLT2 and DPP inhibition exerted limited measurable effects at clinically achievable concentrations.<\/jats:p>","DOI":"10.3390\/ijms27146131","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:22Z","timestamp":1783592182000},"page":"6131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Cytokine, Metabolic, and Proliferative Profiling Reveals Divergent Metabolic and Proliferative Responses in Papillary Thyroid Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-6928","authenticated-orcid":false,"given":"Angelika","family":"Buczy\u0144ska-Backiel","sequence":"first","affiliation":[{"name":"Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Redli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bia\u0142ystok, 15-276 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Zaj\u0105c","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ko\u015bciuszko","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Adamska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Siewko","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-4213","authenticated-orcid":false,"given":"Anna","family":"Pop\u0142awska-Kita","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-4978","authenticated-orcid":false,"given":"Adam Jacek","family":"Kr\u0119towski","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland"},{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2559852","DOI":"10.1001\/jamanetworkopen.2025.59852","article-title":"Overdiagnosis of Papillary Thyroid Cancer","volume":"9","author":"Francis","year":"2026","journal-title":"JAMA Netw. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26245","DOI":"10.1038\/s41598-025-10982-3","article-title":"Impact of Nitrosative Stress and Endothelial Damage on Angioinvasive Papillary Thyroid Cancer","volume":"15","author":"Adamska","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15316","DOI":"10.1038\/s41598-025-00255-4","article-title":"Preliminary Results Suggest the Potential of Evaluating Combined bFGF and TNF-\u03b2 Concentrations for Differentiating Papillary Thyroid Cancer from Benign Nodular Goiter","volume":"15","author":"Gacuta","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1007\/s12672-025-03533-9","article-title":"Mendelian Randomization Analysis Reveals Causal Roles of Inflammatory Cytokines in Thyroid Cancer Pathogenesis","volume":"16","author":"Liu","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5603\/fhc.108530","article-title":"Aggressiveness of Papillary Thyroid Carcinoma: A Comprehensive Analysis from Molecular Mechanisms to Clinical Applications","volume":"63","author":"Wang","year":"2025","journal-title":"Folia Histochem. ET Cytobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41598-025-29422-3","article-title":"Thioredoxin and Tetraspanin 30 (CD63) as Potential Biomarkers for Angioinvasion in Papillary Thyroid Cancer","volume":"16","author":"Sidorkiewicz","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13711","DOI":"10.1038\/s41598-023-40898-9","article-title":"Clinical Significance of Oxidative Stress Markers as Angioinvasion and Metastasis Indicators in Papillary Thyroid Cancer","volume":"13","author":"Sidorkiewicz","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.3892\/or.2015.3916","article-title":"Interleukin-8: A Potent Promoter of Human Lymphatic Endothelial Cell Growth in Gastric Cancer","volume":"33","author":"SHI","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/00005537-199905000-00002","article-title":"Role of Angiogenic Factors: Coexpression of Interleukin-8 and Vascular Endothelial Growth Factor in Patients with Head and Neck Squamous Carcinoma","volume":"109","author":"Eisma","year":"1999","journal-title":"Laryngoscope"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1097-0215(19970410)71:2<284::AID-IJC25>3.0.CO;2-G","article-title":"Expression and Functions of EGF, FGF and TGFbeta-Growth-Factor Family Members and Their Receptors in Invasive Human Transitional-Cell-Carcinoma Cells","volume":"71","author":"Houtsmuller","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1128\/JVI.76.22.11570-11583.2002","article-title":"Interleukin-8 and Growth-Regulated Oncogene Alpha Mediate Angiogenesis in Kaposi\u2019s Sarcoma","volume":"76","author":"Lane","year":"2002","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/1947601911423031","article-title":"Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis","volume":"2","author":"Shibuya","year":"2011","journal-title":"Genes. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41392-025-02249-0","article-title":"Vascular Endothelial Growth Factor Signaling in Health and Disease: From Molecular Mechanisms to Therapeutic Perspectives","volume":"10","author":"Lee","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and Tumor Progression: Signaling Pathways and Targeted Intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1080\/09553002.2019.1589653","article-title":"The Warburg Effect: Essential Part of Metabolic Reprogramming and Central Contributor to Cancer Progression","volume":"95","author":"Vaupel","year":"2019","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cassim, S., and Pouyssegur, J. (2019). Tumor Microenvironment: A Metabolic Player That Shapes the Immune Response. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010157"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"(2026, April 22). Enhancing Angioinvasion Assessment in Papillary Thyroid Cancer Via a Biomarker Panel Involving TAC, 8-OHdG, and Sortilin | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic. Available online: https:\/\/academic.oup.com\/jcem\/article\/109\/7\/1866\/7512030.","DOI":"10.1210\/clinem\/dgae007"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102483","DOI":"10.1016\/j.tranon.2025.102483","article-title":"Metformin as a Promising Therapeutic Agent for Papillary Thyroid Cancer: Mechanisms of Antitumor and pro-Apoptotic Activity","volume":"60","author":"Wincenciuk","year":"2025","journal-title":"Transl. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, Z., Huang, R., Wei, X., Yu, W., Min, Z., and Ye, M. (2020). The SIRT6-Autophagy-Warburg Effect Axis in Papillary Thyroid Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01265"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does It Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, Q., Huang, Z., Li, B., Nice, E.C., Huang, C., Wei, L., and Zou, B. (2022). Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies. Cancers, 14.","DOI":"10.3390\/cancers14194568"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Buczy\u0144ska, A., Sidorkiewicz, I., Kr\u0119towski, A.J., Zbucka-Kr\u0119towska, M., and Adamska, A. (2022). Metformin Intervention\u2014A Panacea for Cancer Treatment?. Cancers, 14.","DOI":"10.3390\/cancers14051336"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Buczy\u0144ska, A., Sidorkiewicz, I., Kr\u0119towski, A.J., and Adamska, A. (2024). Examining the Clinical Relevance of Metformin as an Antioxidant Intervention. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1330797"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Buczy\u0144ska, A., Ko\u015bciuszko, M., Kr\u0119towski, A.J., and Pop\u0142awska-Kita, A. (2024). Exploring the Clinical Utility of DPP-IV and SGLT2 Inhibitors in Papillary Thyroid Cancer: A Literature Review. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1323083"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cytogfr.2022.11.001","article-title":"Crosstalk between Glucose Metabolism, Lactate Production and Immune Response Modulation","volume":"68","author":"Ye","year":"2022","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.gendis.2022.10.006","article-title":"The Function and Mechanism of Lactate and Lactylation in Tumor Metabolism and Microenvironment","volume":"10","author":"Zhang","year":"2022","journal-title":"Genes. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.3892\/or.2016.5142","article-title":"Differential Glycolytic Profile and Warburg Effect in Papillary Thyroid Carcinoma Cell Lines","volume":"36","author":"Coelho","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1210\/jc.2017-00346","article-title":"Dipeptidyl Peptidase IV as a Prognostic Marker and Therapeutic Target in Papillary Thyroid Carcinoma","volume":"102","author":"Lee","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Buczy\u0144ska, A., Ko\u015bciuszko, M., Kr\u0119towski, A.J., and Pop\u0142awska-Kita, A. (2023). Exploring the Clinical Utility of Angioinvasion Markers in Papillary Thyroid Cancer: A Literature Review. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1261860"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107503","DOI":"10.1016\/j.pharmthera.2020.107503","article-title":"Dipeptidyl Peptidase 4 Inhibitors and Their Potential Immune Modulatory Functions","volume":"209","author":"Shao","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5181386","DOI":"10.1155\/2022\/5181386","article-title":"DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy","volume":"2022","author":"Gao","year":"2022","journal-title":"Int. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s40618-020-01455-7","article-title":"DPP4 Gene Silencing Inhibits Proliferation and Epithelial-Mesenchymal Transition of Papillary Thyroid Carcinoma Cells through Suppression of the MAPK Pathway","volume":"44","author":"Hu","year":"2021","journal-title":"J. Endocrinol. Invest."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113760","DOI":"10.1016\/j.intimp.2024.113760","article-title":"DPP4 Promotes an Immunoenhancing Tumor Microenvironment through Exhausted CD8+ T Cells with Activating IL13-IL13RA2 Axis in Papillary Thyroid Cancer","volume":"145","author":"Jing","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13044-025-00282-3","article-title":"Another Pleiotropic Effect of SGLT2 Inhibitors: Is It a New Frontier in Thyroid Function Regulation?","volume":"19","author":"Szklarz","year":"2026","journal-title":"Thyroid. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12935-022-02496-z","article-title":"SGLT2 Inhibition Restrains Thyroid Cancer Growth via G1\/S Phase Transition Arrest and Apoptosis Mediated by DNA Damage Response Signaling Pathways","volume":"22","author":"Wang","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"284","DOI":"10.14740\/jocmr2480w","article-title":"Signaling Pathways in Thyroid Cancer and Their Therapeutic Implications","volume":"8","author":"Jin","year":"2016","journal-title":"J. Clin. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ferrari, S.M., Fallahi, P., Galdiero, M.R., Ruffilli, I., Elia, G., Ragusa, F., Paparo, S.R., Patrizio, A., Mazzi, V., and Varricchi, G. (2019). Immune and Inflammatory Cells in Thyroid Cancer Microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184413"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108264","DOI":"10.1016\/j.celrep.2020.108264","article-title":"Activation of the CARD8 Inflammasome Requires a Disordered Region","volume":"33","author":"Chui","year":"2020","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.immuni.2021.04.024","article-title":"Dipeptidyl Peptidase 9 Sets a Threshold for CARD8 Inflammasome Formation by Sequestering Its Active C-Terminal Fragment","volume":"54","author":"Sharif","year":"2021","journal-title":"Immunity"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cui, C., Tian, X., Wei, L., Wang, Y., Wang, K., and Fu, R. (2022). New Insights into the Role of Dipeptidyl Peptidase 8 and Dipeptidyl Peptidase 9 and Their Inhibitors. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1002871"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Trejo-Solis, C., Silva-Adaya, D., Serrano-Garc\u00eda, N., Maga\u00f1a-Maldonado, R., Jimenez-Farfan, D., Ferreira-Guerrero, E., Cruz-Salgado, A., and Castillo-Rodriguez, R.A. (2023). Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417633"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s43018-023-00595-y","article-title":"Cancer Cell Plasticity during Tumor Progression, Metastasis and Response to Therapy","volume":"4","author":"Blanpain","year":"2023","journal-title":"Nat. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1007\/s40618-024-02351-0","article-title":"Sodium-Glucose Cotransporter 2 Inhibitors and Cancer: A Systematic Review and Meta-Analysis","volume":"47","author":"Xu","year":"2024","journal-title":"J. Endocrinol. Invest."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaat5933","DOI":"10.1126\/scitranslmed.aat5933","article-title":"Sodium-Glucose Transporter 2 Is a Diagnostic and Therapeutic Target for Early-Stage Lung Adenocarcinoma","volume":"10","author":"Scafoglio","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S276","DOI":"10.2337\/dc11-s229","article-title":"DPP-4 Inhibitors","volume":"34","author":"Dicker","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.2337\/db10-1707","article-title":"Dipeptidyl Peptidase 4 Is a Novel Adipokine Potentially Linking Obesity to the Metabolic Syndrome","volume":"60","author":"Lamers","year":"2011","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1210\/clinem\/dgae007","article-title":"Enhancing Angioinvasion Assessment in Papillary Thyroid Cancer Via a Biomarker Panel Involving TAC, 8-OHdG, and Sortilin","volume":"109","author":"Sidorkiewicz","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Owen, J.L., and Mohamadzadeh, M. (2013). Macrophages and Chemokines as Mediators of Angiogenesis. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00159"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1007\/s12672-025-03797-1","article-title":"Microenvironmental Regulation and Remodeling of Breast Cancer Angiogenesis: From Basic Mechanisms to Clinical Therapeutic Implications","volume":"16","author":"Zhou","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"GEINDREAU, M., BRUCHARD, M., and VEGRAN, F. (2022). Role of Cytokines and Chemokines in Angiogenesis in a Tumor Context. Cancers, 14.","DOI":"10.3390\/cancers14102446"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"853","DOI":"10.2741\/1579","article-title":"The Role of Interleukin-8 in Cancer Cells and Microenvironment Interaction","volume":"10","author":"Yuan","year":"2005","journal-title":"Front. Biosci."},{"key":"ref_55","first-page":"102347","article-title":"Emerging Hallmarks and the Rise of Complexities and Heterogeneity of Tumor","volume":"44","author":"Arora","year":"2025","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Belotti, D., Pinessi, D., and Taraboletti, G. (2021). Alternative Vascularization Mechanisms in Tumor Resistance to Therapy. Cancers, 13.","DOI":"10.3390\/cancers13081912"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S1470-2045(12)70335-2","article-title":"Vandetanib in Locally Advanced or Metastatic Differentiated Thyroid Cancer: A Randomised, Double-Blind, Phase 2 Trial","volume":"13","author":"Leboulleux","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8543","DOI":"10.2147\/OTT.S175578","article-title":"Vandetanib (ZD6474) Induces Antiangiogenesis through mTOR-HIF-1 Alpha-VEGF Signaling Axis in Breast Cancer Cells","volume":"11","author":"Li","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2147\/OTT.S17422","article-title":"Clinical Utility of Vandetanib in the Treatment of Patients with Advanced Medullary Thyroid Cancer","volume":"4","author":"Deshpande","year":"2011","journal-title":"Onco Targets Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nchembio.2229","article-title":"DPP8\/9 Inhibition Induces pro-Caspase-1-Dependent Monocyte and Macrophage Pyroptosis","volume":"13","author":"Okondo","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41419-020-02865-4","article-title":"DPP8\/9 Inhibitors Activate the CARD8 Inflammasome in Resting Lymphocytes","volume":"11","author":"Johnson","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_62","first-page":"101547","article-title":"Validation of an Algorithm for Selection of SGLT2 and DPP4 Inhibitor Therapies in People with Type 2 Diabetes across Major UK Ethnicity Groups: A Retrospective Cohort Study","volume":"61","author":"Young","year":"2025","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Koo, N., Lee, E.J., Chang, J.-E., Lee, K.-R., and Chae, Y.-J. (2025). Pharmacokinetic Landscape and Interaction Potential of SGLT2 Inhibitors: Bridging In Vitro Findings and Clinical Implications. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17121604"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12933-023-01914-4","article-title":"Comparison of SGLT2 Inhibitors with DPP-4 Inhibitors Combined with Metformin in Patients with Acute Myocardial Infarction and Diabetes Mellitus","volume":"22","author":"Lyu","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.2337\/db12-0052","article-title":"Why Do SGLT2 Inhibitors Inhibit Only 30\u201350% of Renal Glucose Reabsorption in Humans?","volume":"61","author":"Liu","year":"2012","journal-title":"Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1530\/eje.1.02221","article-title":"Plasma Dipeptidyl Peptidase-IV Activity in Patients with Type-2 Diabetes Mellitus Correlates Positively with HbAlc Levels, but Is Not Acutely Affected by Food Intake","volume":"155","author":"Ryskjaer","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/j.1463-1326.2009.01046.x","article-title":"Pharmacokinetics, Pharmacodynamics and Tolerability of Multiple Oral Doses of Linagliptin, a Dipeptidyl Peptidase-4 Inhibitor in Male Type 2 Diabetes Patients","volume":"11","author":"Heise","year":"2009","journal-title":"Diabetes Obes. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:18:38Z","timestamp":1783592318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":67,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146131"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146131","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}