RESUMO
BACKGROUND: Based on its potent inhibition of dihydropyrimidine dehydrogenase (DPD), S-1 is expected to be more active than other flouropyrimidines against tumors with higher DPD activity, such as hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively investigated the efficacy of S-1 and platinum in HCC. Patients received S-1 (80 mg/m(2)/day on days 1-14) with either cisplatin (60 mg/m(2) on day 1) or oxaliplatin (130 mg/m(2) on day 1) every 3 weeks. The primary end point was overall response rate. RESULTS: Among the 21 HCC patients, 12 and 9 patients received S-1-based chemotherapy as a first-line and salvage treatment, respectively. Partial response was seen in 5 patients and stable disease in 6. The median time-to-progression was 4.0 months (95% confidence interval [CI], 2.4-5.6) and median overall survival was 14.0 months (95% CI, 6.7-21.3). Most patients were tolerable to chemotherapy and no grade 4 toxicity was observed. Tumors with lower DPD expression were more responsive to the therapy (response rate 60.0% in lower vs. 0.0% in higher DPD, p=0.045). CONCLUSION: S-1 and platinum combination chemotherapy shows favorable efficacy and tolerability in advanced HCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular/metabolismo , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estudos Retrospectivos , Tegafur/administração & dosagem , Tegafur/efeitos adversosRESUMO
The 70 kDa heat shock protein (Hsp70) plays a critical role in cell survival and thermotolerance in response to various stress stimuli. Two nearly identical genes, hsp70.1 and hsp70.3, in response to environmental stress, rapidly induce Hsp70. However, it remains unclear whether these two genes are differentially regulated by various stresses. To address the physiological role of the hsp70.1 and hsp70.3 genes in the stress response, we generated mice that specifically lack hsp70.1. In contrast to heat shock, which rapidly induced both hsp70.1 and hsp70.3 mRNA, osmotic stress selectively induced transcription of hsp70.1. In hsp70.1-deficient embryonic fibroblasts, osmotic stress markedly reduced cell viability. Furthermore, when osmotic stress was applied in vivo, hsp70.1-deficient mice exhibited increased apoptosis in the renal medulla. Taken together, our results demonstrate that differential expression of hsp70 genes contributes to the stress response and that the hsp70.1 gene plays a critical role in osmotolerance.
