ABSTRACT
OBJECTIVE: To evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of head and neck squamous cell carcinoma (HNSCC). DESIGN: In vivo study. SETTING: Academic research laboratory. Subjects and METHODS: C3H/HeJ mice and SCID/beige mice were randomized to receive implantation of no polymer, plain polymer, plain polymer with local cisplatin injection, or cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive 4 Gy of external beam radiation for 4 days or no radiation. Tumor size was measured until the mice were humanely killed. At necropsy, the tumors were excised and weighed. RESULTS: There was a significant reduction in tumor growth using this novel polymer platform. The cisplatin-secreting polymer effectively reduced human head and neck tumor growth in SCID mice by 17-fold and SCC VII/SF tumors in C3H/HeJ mice by more than 16-fold compared with the control, plain polymer, and plain polymer + intratumoral cisplatin injection groups (P = .01 for both). We also observed a statistically significant lower tumor weight in mice treated with cisplatin polymer and concomitant radiation compared with the radiation alone and control groups. CONCLUSIONS: We demonstrate the efficacy of a novel polymer platform in delivering cisplatin to a partially resected SCC in a murine model. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Drug Implants , Head and Neck Neoplasms/drug therapy , Animals , Biocompatible Materials , Caproates , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/pharmacology , Disease Models, Animal , Head and Neck Neoplasms/radiotherapy , Lactones , Mice , Mice, SCID , Polyesters , Polymers , Random AllocationSubject(s)
Adenoma/pathology , Cranial Nerve Neoplasms/pathology , Hypoglossal Nerve Diseases/pathology , Hypoglossal Nerve/pathology , Parathyroid Neoplasms/pathology , Adenoma/surgery , Adult , Cranial Nerve Neoplasms/surgery , Diagnosis, Differential , Humans , Hypoglossal Nerve Diseases/surgery , Magnetic Resonance Imaging , Male , Neoplasm Invasiveness , Parathyroid Neoplasms/surgery , Parathyroidectomy/methodsSubject(s)
Head and Neck Neoplasms/pathology , Hemangiosarcoma/diagnostic imaging , Hemangiosarcoma/secondary , Scalp , Skin Neoplasms/pathology , Aged , Female , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/therapy , Hemangiosarcoma/therapy , Humans , Radiography , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/therapyABSTRACT
OBJECTIVES: To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1. SETTING: An academic hospital laboratory. SUBJECTS AND METHODS: Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections. RESULTS: IL-1beta-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1beta exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverse relationship between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections. CONCLUSIONS: Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy.
