Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 248-252, 2003.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-356823
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect and metabolism of 5-fluorocytosine (5-FC) in human tongue squamous carcinoma cells after treatment with adenovirus-mediated cytosine deaminase (AdCMVCD)/5-FC system.</p><p><b>METHODS</b>Human tongue squamous carcinoma cells (Tca8113 cell line) and its xenografts in BALB/c nude mice were treated with AdCMVCD/5-FC system. The killing effect in vitro and bystander effect were detected by microculture tetrazolium (MTT) assay. Tumor inhibition effect and histopathological changes were observed in vivo. High-performance liquid chromatography (HPLC) was performed to determine the metabolism of 5-FC in vitro and in vivo.</p><p><b>RESULTS</b>AdCMVCD/5-FC system had strong killing effect and bystander effect on Tca8113 cells. Both condition media and cell extracts showed two peaks identified as 5-FC and 5-fluorouracil (5-FU) by HPLC and a time-dependent generation of 5-FU and concomitant time-dependent decreases of 5-FC. Compared to the control groups, mice treated with AdCMVCD/5-FC system demonstrated significant tumor regression (P < 0.001); the tumor doubling time prolonged and inhibition rate was 92.62%. There were substantial tumor necrotic areas and infiltrative lymphocytes around necrotic areas in the AdCMVCD/5-FC treated group under light microscope. There was a significantly low concentration of 5-FC and high concentration of 5-FU in tumor tissue, but only 5-FC was found in blood.</p><p><b>CONCLUSION</b>AdCMVCD/5-FC suicide gene system had significant in vitro and in vivo anti-tumor effect on human tongue squamous cell carcinoma due to convert 5-FC into 5-FU.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Terapêutica
/
Transplante Heterólogo
/
Neoplasias da Língua
/
Células Tumorais Cultivadas
/
Carcinoma de Células Escamosas
/
Terapia Genética
/
Adenoviridae
/
Citosina Desaminase
/
Usos Terapêuticos
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Chinese Medical Journal
Ano de publicação:
2003
Tipo de documento:
Artigo