Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma
| Autor: | Athena Chalaris, Yahya Açil, Carola Heneweer, Nicolai Purcz, Olga Will, Sanjay Tiwari, Susann Boretius, Nureddin Ashammakhi, Holger Kalthoff, Larissa Purcz, Jörg Wiltfang, Claus-Christian Glüer, L. Nikkola |
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| Přispěvatelé: | Tampere University, Department of Electronics and Communications Engineering |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology NSAIDs Nanofibers Pharmaceutical Science 0302 clinical medicine International Journal of Nanomedicine Drug Discovery Polyglactin 910 Original Research Drug Implants biology Combination chemotherapy General Medicine oral squamous cell carcinoma Survival Rate 030220 oncology & carcinogenesis Carcinoma Squamous Cell Mouth Neoplasms medicine.drug drug releasing polymers medicine.medical_specialty Diclofenac mouse model Biophysics Urology Mice Nude Bioengineering Biomaterials 03 medical and health sciences Cell Line Tumor medicine Carcinoma Animals Humans Cyclooxygenase Inhibitors Survival rate Inflammation business.industry Organic Chemistry Head and neck cancer Cancer Neoplasms Experimental 217 Medical engineering medicine.disease tumor recurrence Xenograft Model Antitumor Assays Squamous carcinoma Drug Liberation stomatognathic diseases 030104 developmental biology biology.protein head and neck cancer Cyclooxygenase business |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s109199 |
| Popis: | Olga Maria Will,1,* Nicolai Purcz,2,* Athena Chalaris,3 Carola Heneweer,4,5 Susann Boretius,1 Larissa Purcz,2 Lila Nikkola,6 Nureddin Ashammakhi,6 Holger Kalthoff,7 Claus-Christian Glüer,1 Jörg Wiltfang,2 Yahya Açil,2 Sanjay Tiwari1 1Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC, 2Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein, 3Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, 4Clinic for Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, 5Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany; 6Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland; 7Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, Kiel, Germany *These authors contributed equally to this work Abstract: Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(d,l-lactide-co-glycolide) polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1) no treatment, 2) implanted scaffolds without diclofenac, 3) implanted scaffolds loaded with diclofenac, and 4) diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal determination of tumor recurrence. At the end of 7weeks following tumor resection, 33% of mice with diclofenac-loaded scaffolds had a recurrent tumor, in comparison to 90%–100% of the mice in the other three groups. At this time point, mice with diclofenac-releasing scaffolds showed 89% survival rate, while the other groups showed survival rates of 10%–25%. Immunohistochemical staining of recurrent tumors revealed a near 10-fold decrease in the proliferation marker Ki-67 in the tumors derived from mice with diclofenac-releasing scaffolds. In summary, the local application of diclofenac in an orthotopic mouse tumor resection model of oral cancer reduced tumor recurrence with significant improvement in survival over a 7-week study period following tumor resection. Local drug release of anti-inflammatory agents should be investigated as a therapeutic option in the prevention of tumor recurrence in oral squamous carcinoma. Keywords: tumor recurrence, oral squamous cell carcinoma, head and neck cancer, NSAIDs, drug releasing polymers, mouse model |
| Databáze: | OpenAIRE |
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