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Métodos Terapêuticos e Terapias MTCI
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1.
Anticancer Res ; 33(9): 3871-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24023322

RESUMO

BACKGROUND: Hepatocellular carcinoma is generally diagnosed at advanced stages, for which only palliative treatments are possible by intra-arterial route or by targeted therapies. Among these treatments, metabolic radiotherapy using (90)-yttrium or (188)Re and sorafenib are two options adopted in monotherapy. MATERIALS AND METHODS: We address the question of a possible synergy arising from the combination of these two treatments. Two primary malignant hepatoma cell lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media containing increasing concentrations of sorafenib with/without (188)Re to assess the cellular toxicities of each treatment alone and in combination. The combination index method was used to look for synergy or additivity. RESULTS: A synergistic advantage of a treatment combining (188)Re and sorafenib is shown in vitro on hepatoma cell lines. CONCLUSION: This combined approach is promising and now needs to be confirmed by more complex in vitro models integrating the tumoral stroma, as well as by in vivo studies.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Radioisótopos/farmacologia , Rênio/farmacologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Terapia Combinada , Humanos , Técnicas In Vitro , Camundongos , Niacinamida/uso terapêutico , Sorafenibe
2.
Nucl Med Biol ; 37(7): 777-84, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20870152

RESUMO

INTRODUCTION: Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy. METHODS: The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of (99m)Tc-SSS-Lipiodol. RESULTS: The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 µM for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of (99m)Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57 ± 3.65% after treatment, as against 9.45 ± 4.44% without treatment (P<.05). CONCLUSIONS: Dexamethasone and tamoxifen fluidify the N1S1 cells membrane, leading to an increase in the tumoral uptake of Lipiodol. These drugs could be combined with chemo-Lipiodol-embolization or radiolabeled Lipiodol, with a view to improving the effectiveness of HCCs therapy.


Assuntos
Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/metabolismo , Dexametasona/farmacologia , Óleo Etiodado/farmacocinética , Neoplasias Hepáticas/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Tamoxifeno/farmacologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Espectroscopia de Ressonância de Spin Eletrônica , Injeções Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Ratos , Distribuição Tecidual , Células Tumorais Cultivadas
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