RESUMO
BACKGROUND: Psoriasis is a chronic, immune-mediated and angiogenesis-dependent disease. Activated keratinocytes in psoriatic lesions produce pro-angiogenic cytokines, including vascular endothelial growth factor (VEGF), which binds to vascular endothelial growth factor receptor (VEGFR) and promotes cell proliferation and angiogenesis. Sorafenib (BAY 43-9006) is a molecular multikinase inhibitor of RAF kinase, platelet-derived growth factor (PDGF), VEGFR-1, -2, -3, platelet-derived growth factor receptor (PDGFR)-ß and c-Kit. This molecule inhibits tumor cell proliferation and angiogenesis and it is currently approved for the treatment of hepatocellular carcinoma (HCC). CASE REPORT: We present the complete remission of resistant psoriasis in a hepatitis C virus (HCV)-infected cirrhotic patient who was treated with sorafenib, for recurrent HCC. CONCLUSION: Several targeted therapies have demonstrated efficacy against psoriasis. More research and well-designed studies, both in novel drugs and those already marketed for other indications, are needed to determine their value as potential novel therapies for psoriasis.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Psoríase/tratamento farmacológico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Proliferação de Células/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/patologia , Hepatite C/virologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Niacinamida/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Psoríase/complicações , Psoríase/patologia , Psoríase/virologia , Indução de Remissão , Sorafenibe , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece. METHODS: Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ(2) test of independence. RESULTS: The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p=0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p<0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients. CONCLUSION: Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis.
