title: Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma.
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 7 weeks 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.
authors: Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC.
authors: Olga Maria
authors: OM
authors: Will
authors: Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein.
authors: Nicolai
authors: N
authors: Purcz
authors: Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel.
authors: Athena
authors: A
authors: Chalaris
authors: Clinic for Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel; Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany.
authors: Carola
authors: C
authors: Heneweer
authors: Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC.
authors: Susann
authors: S
authors: Boretius
authors: Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein.
authors: Larissa
authors: L
authors: Purcz
authors: Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland.
authors: Lila
authors: L
authors: Nikkola
authors: Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland.
authors: Nureddin
authors: N
authors: Ashammakhi
authors: Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, Kiel, Germany.
authors: Holger
authors: H
authors: Kalthoff
authors: Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC.
authors: Claus-Christian
authors: CC
authors: Glüer
authors: Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein.
authors: Jörg
authors: J
authors: Wiltfang
authors: Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein.
authors: Yahya
authors: Y
authors: Açil
authors: Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC.
authors: Sanjay
authors: S
authors: Tiwari
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004343:Drug Implants; D065546:Drug Liberation; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D057139:Nanofibers / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011098:Polyglactin 910 / Q000737:chemistry; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D016861:Cyclooxygenase Inhibitors; D004343:Drug Implants; D004008:Diclofenac; D011098:Polyglactin 910
keywords: NSAIDs; drug releasing polymers; head and neck cancer; mouse model; oral squamous cell carcinoma; tumor recurrence