Assuntos
Plaquetas , Epidermólise Bolhosa/terapia , Terapia com Luz de Baixa Intensidade , Cicatrização , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/genética , Feminino , Sangue Fetal , Géis , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mucosa Bucal , Dor/etiologia , Resultado do Tratamento , Adulto JovemAssuntos
Plaquetas , Epidermólise Bolhosa Distrófica/terapia , Sangue Fetal/citologia , Terapia com Luz de Baixa Intensidade , Doenças da Boca/terapia , Mucosa Bucal/efeitos da radiação , Adolescente , Adulto , Criança , Terapia Combinada , Epidermólise Bolhosa Distrófica/diagnóstico , Feminino , Géis , Humanos , Masculino , Doenças da Boca/diagnóstico , Mucosa Bucal/patologia , Projetos Piloto , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PUFA from fish oil appear to have anti-inflammatory and anti-oxidative effects and improve nutritional status in cancer patients. With this as background, the aim of the present study was to investigate the effect of EPA plus DHA on inflammatory condition, and oxidative and nutritional status in patients with lung cancer. In our multicentre, randomised, double-blind trial, thirty-three patients with a diagnosis of advanced inoperable non-small-cell lung cancer and undergoing chemotherapy were divided into two groups, receiving four capsules/d containing 510 mg of EPA and 340 mg of DHA, or 850 mg of placebo, for 66 d. At the start of chemotherapy (T0), after 8 d (T1), 22 d (T2) and 66 d (T3), biochemical (inflammatory and oxidative status parameters) and anthropometric parameters were measured in both groups. A significant increase of body weight in the n-3 group at T3 v. T0 was observed. Concerning inflammation, C-reactive protein and IL-6 levels differed significantly between the n-3 and placebo groups at T3, and progressively decreased during chemotherapy in the n-3 group, evidencing n-3 PUFA anti-inflammatory action. Concerning oxidative status, plasma reactive oxygen species levels increased in the placebo group v. the n-3 group at the later treatment times. Hydroxynonenal levels increased in the placebo group during the study, while they stabilised in the n-3 group. Our data confirm that the continual assumption of EPA plus DHA determined an anti-inflammatory and anti-oxidative action which could be considered a preliminary goal in anti-cachectic therapy.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Neoplasias Pulmonares/dietoterapia , Anti-Inflamatórios não Esteroides/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antioxidantes/efeitos adversos , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Masculino , Estresse Oxidativo , Pacientes Desistentes do Tratamento , Aumento de Peso , GencitabinaRESUMO
The introduction of paclitaxel into multimodal therapy for anaplastic thyroid carcinoma has failed to improve overall survival. Toxicity rules out the high doses required, especially in older patients. The search for strategies to enhance paclitaxel antineoplastic activity and reduce its side effects is thus advisable. The study aimed to determine whether the histone deacetylase (HDAC) inhibitor valproic acid (VPA) improves the anticancer action of paclitaxel and elucidate the mechanisms underlying the effects of combined treatment. We examined the effect of VPA on the sensitivity to paclitaxel of two anaplastic thyroid carcinoma cell lines (CAL-62 and ARO), and the ability of the drug to determine tubulin acetylation and enhance paclitaxel-induced acetylation. The addition of as little as 0.7 mM VPA to paclitaxel enhances both cytostatic and cytotoxic effects of paclitaxel alone. Increased apoptosis explains the enhancement of the cytotoxic effect. The mechanism underlying this effect is through inhibition of HDAC6 activity, which leads to tubulin hyperacetylation. The results suggest a mechanistic link between HDAC6 inhibition, tubulin acetylation, and the VPA-induced enhancement of paclitaxel effects, and provide the rationale for designing future combination therapies.