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Otolaryngol Head Neck Surg ; 151(3): 447-53, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24825873

RESUMO

OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: In vivo study. SETTING: Academic research laboratory. SUBJECTS AND METHODS: Mice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. For cytokine studies, mice were grouped into (1) no polymer, (2) plain polymer, (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week, (4) polymer containing parental dendritic cells, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21). RESULTS: The cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P < .01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P < .01). CONCLUSION: Herein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Citocinas/farmacologia , Implantes de Medicamento , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Polímeros/farmacologia , Análise de Variância , Animais , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C3H , Distribuição Aleatória , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
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