RESUMO
AIM: To evaluate whether the results of chemosensitivity testing were associated with prognosis of colorectal cancer patients after adjuvant 5-fluorouracil (FU)/ leucovorin chemotherapy. PATIENTS AND METHODS: Eighty-nine patients who received 5-FU/leucovorin adjuvant chemotherapy for colorectal cancer were enrolled. Chemosensitivity tests were performed and tumor growth inhibition rate was calculated using the MTT (3-(4,5-dimethylthiazol-2-yl)02,5-diphenyl-2H tetrazolium bromide) assay. RESULTS: Fifty-one patients (57.3%) were sensitive to 5-FU according to the chemosensitivity test. After a median follow-up of 64 months, there was a significant difference between the 5-year disease-free survival rates of the chemo-sensitive and chemo-resistant groups. However, there was no significant difference in the overall 5-year survival between the chemo-sensitive and chemo-resistant groups. CONCLUSION: A positive 5-FU sensitivity test with in vitro histoculture drug response assay (HDRA) was associated with better disease-free survival. Chemosensitivity may be a prognostic factor for colorectal cancer patients undergoing adjuvant 5-FU/leucovorin chemotherapy.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Selenomethionine (SeMet) has been identified as a chemopreventive antioxidant to activate p53-mediated nucleotide excision repair. In this study, we examined whether p53-mediated base excision repair (BER) might be induced by SeMet. When methyl methanesulfonate, a BER-inducing agent, was treated in the cells, DNA damage was rapidly decreased in the presence of SeMet. In addition, our data showed that the removal of apurinic/apyrimidinic sites was significantly enhanced in the presence of SeMet. Furthermore, we observed that the expression of gadd45a, known to involve BER as one of the p53 downstream genes, was increased by SeMet in p53 wild-type RKO cells. Those results supported the proposal that BER activity might be dependent on wild-type p53 under the modulation of gadd45a expression in response to SeMet. We suggested that p53-dependent BER activity as a distinct mechanism of SeMet might play an important role to prevent cancer caused by various oxidative stresses.
Assuntos
Antioxidantes/farmacologia , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Selenometionina/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Dano ao DNA/genética , Reparo do DNA/genética , Expressão Gênica , Humanos , Metanossulfonato de Metila/efeitos adversos , Mutação , Proteínas Nucleares/genética , RNA Interferente Pequeno , Transfecção , Proteína Supressora de Tumor p53/genéticaRESUMO
The effects of Panax ginseng extracts on DNA damage, expression of cytochrome P450 (CYP) 1A1 and reproductive toxicity were evaluated in the testis of rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxinthe (TCDD). Fifty rats were divided into five groups according to treatment with 2,3,7,8-TCDD and P. ginseng extracts. Single cell gel electrophoresis assays were performed to evaluate DNA damage that occurred in the lymphocytes of rats. Histological changes in the seminiferous tubules of the testis were determined using Johnsen's scoring system and Real Time-PCR was performed to evaluate the mRNA expression of CYP1A1. Significant pathological effects were observed in the 2,3,7,8-TCDD treated rats including a reduced seminiferous tubular diameter, an increased number of damaged tubules (maturation arrest, eosinophilic degeneration and spermatid giant cells) and increased Johnsen's score. DNA damage and the expression of CYP1A1 mRNA were significantly increased in rat testes. There were no significant differences between the control and animals treated with P. ginseng extracts. However, a significantly decreased level of DNA damage, decreased CYP1A1 expression and reduced pathological effects were observed in the 2,3,7,8-TCDD with P. ginseng extracts treated groups when compared with the TCDD treated group. In summary, our study demonstrates that 2,3,7,8-TCDD induces the pathological and genotoxical damage in rat testes, while P. ginseng extract treatment exhibits a therapeutic capacity to reduce these effects via reduction of CYP1A1 mRNA.