{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:39:59Z","timestamp":1777275599006,"version":"3.51.4"},"reference-count":83,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/CVT\/00772\/2020"],"award-info":[{"award-number":["UIDB\/CVT\/00772\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) is a common and highly aggressive dog tumor known for its local invasiveness and metastatic potential. Understanding the molecular mechanisms driving the development and progression of OSCC is crucial for improving diagnostic and therapeutic strategies. Additionally, spontaneous oral squamous cell carcinomas in dogs are an excellent model for studying human counterparts. In this study, we aimed to investigate the significance of two key molecular components, Cox-2 and EGFR, in canine OSCC. We examined 34 tumor sections from various dog breeds to assess the immunoexpression of Cox-2 and EGFR. Our findings revealed that Cox-2 was highly expressed in 70.6% of cases, while EGFR overexpression was observed in 44.1%. Cox-2 overexpression showed association with histological grade of malignancy (HGM) (p = 0.006) and EGFR with vascular invasion (p = 0.006). COX-2 and EGFR concurrent expression was associated with HGM (p = 0.002), as well as with the presence of vascular invasion (p = 0.002). These data suggest that Cox-2 and EGFR could be promising biomarkers and potential therapeutic targets, opening avenues for developing novel treatment strategies for dogs affected by OSCC. Further studies are warranted to delve deeper into these findings and translate them into clinical practice.<\/jats:p>","DOI":"10.3390\/cimb46010031","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T05:23:30Z","timestamp":1704345810000},"page":"485-497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy"],"prefix":"10.3390","volume":"46","author":[{"given":"Rita","family":"Files","sequence":"first","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6130-8381","authenticated-orcid":false,"given":"Felisbina L.","family":"Queiroga","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Centre for the Study of Animal Science, CECA-ICETA, University of Porto, 4200-427 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-0926","authenticated-orcid":false,"given":"Filipe","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"given":"Leonor","family":"Delgado","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences\u2014CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Pathology Department, INNO Servi\u00e7os Especializados em Veterin\u00e1ria, 4710-503 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-4560","authenticated-orcid":false,"given":"Isabel","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-5374","authenticated-orcid":false,"given":"Justina","family":"Prada","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33290","DOI":"10.18632\/oncotarget.5396","article-title":"Simultaneous Targeting of 5-LOX-COX and EGFR Blocks Progression of Pancreatic Ductal Adenocarcinoma","volume":"6","author":"Rao","year":"2015","journal-title":"Oncotarget"},{"key":"ref_2","unstructured":"Dobson, J.M., and Lascelles, B.D.X. (2011). BSAVA Manual of Canine and Feline Oncology, British Small Animal Veterinary Association."},{"key":"ref_3","unstructured":"Munday, J.S., L\u00f6hr, C.V., and Kiupel, M. (2016). Tumors in Domestic Animals, Wiley."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1368-8375(02)00049-0","article-title":"Neck Disease and Distant Metastases","volume":"39","author":"Genden","year":"2003","journal-title":"Oral Oncol."},{"key":"ref_5","unstructured":"(2023, December 28). Squamous Cell Carcinomas in Dogs and Cats. Available online: https:\/\/www.embracepetinsurance.com\/health\/squamous-cell-carcinoma."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1439-0442.1987.tb00300.x","article-title":"Canine and Feline Oral-Pharyngeal Tumours","volume":"34","author":"Vos","year":"1987","journal-title":"J. Vet. Med. Ser. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103458","DOI":"10.1016\/j.critrevonc.2021.103458","article-title":"Oral Cancer in Non-Smoker Non-Drinker Patients. Could Comparative Pet Oncology Help to Understand Risk Factors and Pathogenesis?","volume":"166","author":"Grigolato","year":"2021","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Giuliano, A. (2021). Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma. Biology, 11.","DOI":"10.3390\/biology11010054"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.tvjl.2014.10.022","article-title":"Diagnostic Value of Cytological Analysis of Tumours and Tumour-like Lesions of the Oral Cavity in Dogs and Cats: A Prospective Study on 114 Cases","volume":"205","author":"Bonfanti","year":"2015","journal-title":"Vet. J."},{"key":"ref_10","first-page":"5026939","article-title":"Increased COX-2 Immunostaining in Urothelial Carcinoma of the Urinary Bladder Is Associated with Invasiveness and Poor Prognosis","volume":"2019","author":"Gomaa","year":"2019","journal-title":"Anal. Cell. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, S.H., Hsiao, S.Y., Chang, K.Y., and Chang, J.Y. (2021). New Insights into Oral Squamous Cell Carcinoma: From Clinical Aspects to Molecular Tumorigenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052252"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and Neck Squamous Cell Carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1939-1676.2003.tb02478.x","article-title":"Environmental and Lifestyle Risk Factors for Oral Squamous Cell Carcinoma in Domestic Cats","volume":"17","author":"Bertone","year":"2003","journal-title":"J. Vet. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1033704","DOI":"10.3389\/fonc.2022.1033704","article-title":"Canine Oral Squamous Cell Carcinoma as a Spontaneous, Translational Model for Radiation and Immunology Research","volume":"12","author":"Boss","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1002\/cncr.23100","article-title":"Response to Dual Blockade of Epidermal Growth Factor Receptor (EGFR) and Cycloxygenase-2 in Nonsmall Cell Lung Cancer May Be Dependent on the EGFR Mutational Status of the Tumor","volume":"110","author":"Gadgeel","year":"2007","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.21037\/tcr-20-3527","article-title":"Targeting COX-2 Potently Inhibits Proliferation of Cancer Cells in Vivo but Not in Vitro in Cutaneous Squamous Cell Carcinoma","volume":"10","author":"Gao","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.brainresrev.2004.12.024","article-title":"New Insights into COX-2 Biology and Inhibition","volume":"48","author":"Patrignani","year":"2005","journal-title":"Brain Res. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.canlet.2021.04.004","article-title":"Dual Blockade of EGFR and CDK4\/6 Delays Head and Neck Squamous Cell Carcinoma Progression by Inducing Metabolic Rewiring","volume":"510","author":"Chaudhary","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_19","first-page":"275","article-title":"SCC Highlights and Insights","volume":"1","author":"Yan","year":"2011","journal-title":"Am. J. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"557280","DOI":"10.3389\/fonc.2020.557280","article-title":"Interplay Between EGFR and the Platelet-Activating Factor\/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer","volume":"10","author":"Souza","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2478\/jvetres-2020-0018","article-title":"Cyclooxygenase-2 as a Biomarker with Diagnostic, Therapeutic, Prognostic, and Predictive Relevance in Small Animal Oncology","volume":"64","author":"Szweda","year":"2020","journal-title":"J. Vet. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.7150\/ijms.44439","article-title":"The Role of Cyclooxygenase-2 in Colorectal Cancer","volume":"17","author":"Sheng","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s12276-023-00977-3","article-title":"Comparative Oncology: Overcoming Human Cancer through Companion Animal Studies","volume":"55","author":"Oh","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.21037\/tcr.2020.03.52","article-title":"Overexpression of COX-2 and Clinicopathological Features of Gastric Cancer: A Meta-Analysis","volume":"9","author":"Hu","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"vii21","DOI":"10.1093\/annonc\/mdz413.077","article-title":"Overexpression of EGFR, COX2 and P53 in Oral Squamous Cell Carcinoma Patients of Pakistan and Correlation with Prognosis","volume":"30","author":"Ali","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13046-023-02618-z","article-title":"Silencing LCN2 Suppresses Oral Squamous Cell Carcinoma Progression by Reducing EGFR Signal Activation and Recycling","volume":"42","author":"Huang","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_27","first-page":"9010","article-title":"Relationship between Epidermal Growth Factor Receptor (EGFR) Mutation and Serum Cyclooxygenase-2 Level, and the Synergistic Effect of Celecoxib and Gefitinib on EGFR Expression in Non-Small Cell Lung Cancer Cells","volume":"8","author":"Li","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1111\/cas.15035","article-title":"Trametinib Overcomes KRAS-G12V\u2013Induced Osimertinib Resistance in a Leptomeningeal Carcinomatosis Model of EGFR-Mutant Lung Cancer","volume":"112","author":"Fukuda","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/jcp.10194","article-title":"Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs): Simple Drugs with a Complex Mechanism of Action?","volume":"194","author":"Normanno","year":"2003","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging Functions of the EGFR in Cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Head, K., Cullen, J.M., Dubielzig, R., Else, R., Misdorp, W., Patnaik, A.K., Tateyama, S., and Gaag, I. (2003). Histological Classification of Tumors of the Alimentary System of Domestic Animals, WHO. WHO Histological Classification of Tumors of Domestic Animal.","DOI":"10.1002\/9780470376928.ch8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1600-0722.1987.tb01836.x","article-title":"Review of the Literature and a Recommended System of Malignancy Grading in Oral Squamous Cell Carcinomas","volume":"95","author":"Anneroth","year":"1987","journal-title":"Eur. J. Oral Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Monteiro, A., Delgado, L., Monteiro, L., Pires, I., Prada, J., and Raposo, T. (2023). Immunohistochemical Expression of Tensin-4\/CTEN in Squamous Cell Carcinoma in Dogs. Vet. Sci., 10.","DOI":"10.3390\/vetsci10020086"},{"key":"ref_34","first-page":"2915","article-title":"Positive Interplay Between CD3+ T-Lymphocytes and Concurrent COX-2\/EGFR Expression in Canine Malignant Mammary Tumors","volume":"35","author":"Carvalho","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jcpa.2013.07.005","article-title":"Concurrent Expression of Cyclo-Oxygenase-2 and Epidermal Growth Factor Receptor in Canine Malignant Mammary Tumours","volume":"150","author":"Carvalho","year":"2014","journal-title":"J. Comp. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcpa.2011.09.007","article-title":"Evaluation of Cyclooxygenase-2 Expression in Canine Mast Cell Tumours","volume":"147","author":"Prada","year":"2012","journal-title":"J. Comp. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.humpath.2007.07.004","article-title":"Epidermal Growth Factor Receptor: A Novel Biomarker for Aggressive Head and Neck Cutaneous Squamous Cell Carcinoma","volume":"39","author":"Low","year":"2008","journal-title":"Hum. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41368-023-00249-w","article-title":"Oral Squamous Cell Carcinomas: State of the Field and Emerging Directions","volume":"15","author":"Tan","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.vetmic.2015.11.015","article-title":"Genomic Characterisation of Canine Papillomavirus Type 17, a Possible Rare Cause of Canine Oral Squamous Cell Carcinoma","volume":"182","author":"Munday","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e07073","DOI":"10.1590\/1678-5150-pvb-7073","article-title":"Lesions of the Oral Cavity of Dogs: 720 Cases","volume":"43","author":"Blume","year":"2023","journal-title":"Pesqui. Vet. Bras."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"iv74","DOI":"10.1093\/annonc\/mdi912","article-title":"Concurrent EGFr and Cox-2 Expression in Colorectal Cancer: Proliferation Impact and Tumour Spreading","volume":"16","author":"Ceccarelli","year":"2005","journal-title":"Ann. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1354\/vp.42-6-776","article-title":"Cyclooxygenase-2 Expression Is Associated with Histologic Tumor Type in Canine Mammary Carcinoma","volume":"42","author":"Heller","year":"2005","journal-title":"Vet. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.plefa.2003.10.002","article-title":"Expression of Cyclooxygenase-1 and 2 in Naturally-Occurring Canine Cancer","volume":"70","author":"Mohammed","year":"2004","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1177\/002215540104900707","article-title":"Expression of Cyclo-Oxygenase-2 in Naturally Occurring Squamous Cell Carcinomas in Dogs","volume":"49","author":"Sirois","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jcpa.2006.06.001","article-title":"COX-1 and COX-2 Expression in Feline Oral Squamous Cell Carcinoma","volume":"135","author":"Hayes","year":"2006","journal-title":"J. Comp. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nasry, W., Wang, H., Jones, K., Dirksen, W., Rosol, T., Rodriguez-Lecompte, J., and Martin, C. (2018). CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma. Vet. Sci., 5.","DOI":"10.3390\/vetsci5030072"},{"key":"ref_47","first-page":"506","article-title":"Inflammatory Mammary Carcinoma in 12 Dogs: Clinical Features, Cyclooxygenase-2 Expression, and Response to Piroxicam Treatment","volume":"50","author":"Souza","year":"2009","journal-title":"Can. Vet. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1177\/0300985810396517","article-title":"Cyclooxygenase-2 Expression Is Related with Localization, Proliferation, and Overall Survival in Canine Melanocytic Neoplasms","volume":"48","author":"Vilafranca","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1748-5827.2006.00094.x","article-title":"Cohort Study of COX-1 and COX-2 Expression in Canine Rectal and Bladder Tumours","volume":"47","author":"Knottenbelt","year":"2006","journal-title":"J. Small Anim. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1158\/1940-6207.CAPR-12-0358","article-title":"Molecular Imaging of Cyclooxygenase-2 in Canine Transitional Cell Carcinomas In Vitro and In Vivo","volume":"6","author":"Cekanova","year":"2013","journal-title":"Cancer Prev. Res."},{"key":"ref_51","first-page":"183","article-title":"Effects of the Cyclooxygenase Inhibitor, Piroxicam, in Combination with Chemotherapy on Tumor Response, Apoptosis, and Angiogenesis in a Canine Model of Human Invasive Urinary Bladder Cancer","volume":"2","author":"Mohammed","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_52","first-page":"343","article-title":"Prognostic Significance of Cyclooxygenase-2 in Laryngeal Squamous Cell Carcinoma","volume":"95","author":"Ranelletti","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ejso.2007.04.011","article-title":"Cyclooxygenase-2 Expression Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma","volume":"34","author":"Takatori","year":"2008","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_54","first-page":"E319","article-title":"Expression of Pro-Inflammatory Protein, iNOS, VEGF and COX-2 in Oral Squamous Cell Carcinoma (OSCC), Relationship with Angiogenesis and Their Clinico-Pathological Correlation","volume":"14","author":"Sappayatosok","year":"2009","journal-title":"Med. Oral Patol. Oral Y Cir. Bucal"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.4103\/0973-1482.138205","article-title":"Cyclo-Oxygenase-2 Expression in Oral Squamous Cell Carcinoma","volume":"10","author":"Seyedmajidi","year":"2014","journal-title":"J. Cancer Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"37191","DOI":"10.1074\/jbc.M405123200","article-title":"Epidermal Growth Factor Receptor Inhibition Promotes Desmosome Assembly and Strengthens Intercellular Adhesion in Squamous Cell Carcinoma Cells","volume":"279","author":"Lorch","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/modpathol.3800244","article-title":"COX-2 Expression Correlates with VEGF-C and Lymph Node Metastases in Patients with Head and Neck Squamous Cell Carcinoma","volume":"18","author":"Kyzas","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"633170","DOI":"10.3389\/fvets.2021.633170","article-title":"COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour","volume":"8","author":"Silveira","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.phrs.2012.02.003","article-title":"Non-Steroidal Anti-Inflammatory Drugs, Tumour Immunity and Immunotherapy","volume":"66","author":"Hussain","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/vco.12470","article-title":"The Selective Cyclooxygenase-2 Inhibitor Mavacoxib (Trocoxil) Exerts Anti-tumour Effects In Vitro Independent of Cyclooxygenase-2 Expression Levels","volume":"17","author":"Hurst","year":"2019","journal-title":"Vet. Comp. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pang, L.Y., Argyle, S.A., Kamida, A., Morrison, K.O., and Argyle, D.J. (2014). The Long-Acting COX-2 Inhibitor Mavacoxib (TrocoxilTM) Has Anti-Proliferative and pro-Apoptotic Effects on Canine Cancer Cell Lines and Cancer Stem Cells In Vitro. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0184-9"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/jvp.13042","article-title":"Selective Inhibition of Cyclooxygenase-2 by Enflicoxib, Its Enantiomers and Its Main Metabolites in Vitro in Canine Blood","volume":"45","author":"Menargues","year":"2022","journal-title":"Vet. Pharm. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"154082","DOI":"10.1016\/j.prp.2022.154082","article-title":"COX2 Effects on Endometrial Carcinomas Progression","volume":"238","author":"Lyndin","year":"2022","journal-title":"Pathol.\u2014Res. Pract."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"31270","DOI":"10.18632\/oncotarget.16116","article-title":"PGE2\/EP3\/SRC Signaling Induces EGFR Nuclear Translocation and Growth through EGFR Ligands Release in Lung Adenocarcinoma Cells","volume":"8","author":"Bazzani","year":"2017","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.ijom.2018.01.002","article-title":"EGFR Amplification and Expression in Oral Squamous Cell Carcinoma in Young Adults","volume":"47","author":"Costa","year":"2018","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_66","first-page":"73","article-title":"Epidermal Growth Factor Receptor (EGFR) Is Overexpressed in Both Dysplasia and Neoplastic Oral Diseases","volume":"13","author":"Badilla","year":"2022","journal-title":"Oral Maxillofac. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12957-018-1425-3","article-title":"Immunohistochemical Expression of Epidermal Growth Factor Receptor (EGFR) in South Asian Head and Neck Squamous Cell Carcinoma: Association with Various Risk Factors and Clinico-Pathologic and Prognostic Parameters","volume":"16","author":"Hashmi","year":"2018","journal-title":"World J. Surg. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1111\/bjd.14936","article-title":"Epidermal Growth Factor Receptor Expression Is Associated with Poor Outcome in Cutaneous Squamous Cell Carcinoma","volume":"176","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/vco.12174","article-title":"Quantification of Epidermal Growth Factor Receptor (EGFR) in Canine Mammary Tumours by ELISA Assay: Clinical and Prognostic Implications","volume":"15","author":"Queiroga","year":"2017","journal-title":"Vet. Comp. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/vco.12002","article-title":"EGFR Overexpression in Canine Primary Lung Cancer: Pathogenetic Implications and Impact on Survival","volume":"12","author":"Sabattini","year":"2014","journal-title":"Vet. Comp. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Abu-Humaidan, A.H.A., Ekblad, L., Wennerberg, J., and S\u00f8rensen, O.E. (2020). EGFR Modulates Complement Activation in Head and Neck Squamous Cell Carcinoma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6615-z"},{"key":"ref_72","first-page":"3847","article-title":"Tepoxalin a Dual 5-LOX-COX Inhibitor and Erlotinib an EGFR Inhibitor Halts Progression of Gastric Cancer in Tumor Xenograft Mice","volume":"10","author":"Lu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jcpa.2019.10.005","article-title":"Dysregulated Expression of Phosphorylated Epidermal Growth Factor Receptor and Phosphatase and Tensin Homologue in Canine Cutaneous Papillomas and Squamous Cell Carcinomas","volume":"174","author":"Massone","year":"2020","journal-title":"J. Comp. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"828608","DOI":"10.3389\/fendo.2022.828608","article-title":"Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_75","first-page":"2809","article-title":"A Novel Anti-EGFR Monoclonal Antibody (EMab-17) Exerts Antitumor Activity against Oral Squamous Cell Carcinomas via Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity","volume":"19","author":"Takei","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.annonc.2019.11.009","article-title":"Anti-EGFR plus Chemotherapy in Unselected Advanced Oesophageal Squamous Cell Carcinoma: Less POWERful than Expected","volume":"31","author":"Connell","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1040552","DOI":"10.3389\/fvets.2022.1040552","article-title":"Anti-EGFR Monoclonal Antibody Cetuximab Displays Potential Anti-Cancer Activities in Feline Oral Squamous Cell Carcinoma Cell Lines","volume":"9","author":"Altamura","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.cvsm.2019.04.005","article-title":"Targeted Therapies in Veterinary Oncology","volume":"49","author":"Londhe","year":"2019","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1158\/1535-7163.MCT-13-0288","article-title":"Generation of a Canine Anti-EGFR (ErbB-1) Antibody for Passive Immunotherapy in Dog Cancer Patients","volume":"13","author":"Singer","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.molimm.2012.01.002","article-title":"Comparative Oncology: ErbB-1 and ErbB-2 Homologues in Canine Cancer Are Susceptible to Cetuximab and Trastuzumab Targeting","volume":"50","author":"Singer","year":"2012","journal-title":"Mol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tvjl.2016.11.005","article-title":"Challenges and Opportunities for Monoclonal Antibody Therapy in Veterinary Oncology","volume":"218","author":"Raposo","year":"2016","journal-title":"Vet. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1111\/cas.14400","article-title":"Epidermal Growth Factor-Induced COX-2 Regulates Metastasis of Head and Neck Squamous Cell Carcinoma through Upregulation of Angiopoietin-like 4","volume":"111","author":"Chiang","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00404-017-4386-9","article-title":"Expressions and Clinical Significance of COX-2, VEGF-C, and EFGR in Endometrial Carcinoma","volume":"296","author":"Cai","year":"2017","journal-title":"Arch. Gynecol. Obstet."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/1\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:39:28Z","timestamp":1760103568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/1\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,4]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cimb46010031"],"URL":"https:\/\/doi.org\/10.3390\/cimb46010031","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,4]]}}}