RESUMO
Certain polyunsaturated fatty acids can selectively kill tumor cell lines while causing little to no harm to normal cell lines. However, the mechanism of this cytotoxicity is only partially understood. Antioxidants such as vitamin E have been shown to be capable of completely blocking the cytotoxic response when administered concomitantly with the fatty acid. We report here that when vitamin E was added as late as 6 days following fatty acid treatment, at a time point when the process of cell death was well underway, any further development of cell death was blocked. This implies that the mechanism of fatty acid induced cytotoxicity does not involve a gradual compromising of the cell over the 5-7 day time course of cell death. Instead, the event triggering cell death is an oxidative phenomenon occurring over a short time span of minutes or hours, not days, and is completely blocked by vitamin E.
Assuntos
Antioxidantes/farmacologia , Vitamina E/farmacologia , Ácido gama-Linolênico/antagonistas & inibidores , Ácido gama-Linolênico/toxicidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Fluorescência , Humanos , Fatores de Tempo , Células Tumorais Cultivadas/efeitos dos fármacos , Vitamina E/farmacocinética , Ácido gama-Linolênico/farmacocinéticaRESUMO
BACKGROUND: Device selection has historically been supported by minimal comparative data. Since 1994, we have implanted 43 patients with the CardioWest Total Artificial Heart (CW), 23 with the Novacor Left Ventricular Assist System (N), and 26 with the Thoratec Ventricular Assist System (T). This experience provides a basis for our device selection criteria. METHODS: We reviewed retrospectively the results for survival, stroke, and infection in the CW, N, and T groups. Statistical methods included the Student's t-test, chi2 analysis, and Kaplan-Meier actuarial survival curves. RESULTS: The T group patients were younger and smaller sized than the CW or N group. The CW group had the highest mean central venous pressure (CVP) and lowest mean cardiac index. Survival to transplantation was 75% for CW, 57% for N, and 38% for T. Multiple organ failure postimplant caused most deaths in the CW and T groups. Right heart failure and stroke caused most N deaths. Linearized stroke rates (event/patient-month) were 0.03 for CW, 0.28 for N, and 0.08 for T. Serious infections were found in 20% of CW, 30% of N, and 8% of T patients, but linearized rates showed little difference and death from infection was rare. CONCLUSIONS: The N device should be used in "stable" patients with body surface area (BSA) greater than 1.7 m2 and with minimal right heart failure. Unstable patients with biventricular failure should receive a CW if the BSA is greater than 1.7 m2 or a T if they are smaller.
Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Artificial , Cuidados Pré-Operatórios , Adolescente , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Desenho de Prótese , Estudos RetrospectivosRESUMO
The mechanism by which tumour cells may be killed in vitro by exogenous polyunsaturated fatty acids may involve lipid peroxidation. Gamma-linolenic acid caused a dose and time-dependent reduction in ZR-75-1 cell growth. However, altering either the incubator temperature (35, 37 and 39 degrees C) or the oxygen content (16, 21 and 26%) had little effect on either the growth of cells in the presence of gamma-linolenic acid or on thiobarbiturate reactive material levels over a 7 day period. Thus, small changes in cell culture conditions do not affect 18:3n-6 cytotoxicity or markers of lipid peroxidation.
Assuntos
Neoplasias da Mama/terapia , Ácidos Linoleicos/farmacologia , Oxigênio/administração & dosagem , Temperatura , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Morte Celular , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fluorescência , Humanos , Ácido Linoleico , Peroxidação de Lipídeos , Tiobarbitúricos/metabolismo , Fatores de Tempo , Células Tumorais CultivadasRESUMO
We have investigated the nature of lipid peroxidation occurring in association with cancer-killing produced by gamma-linolenic acid (GLA) and iron (Fe) in cultured human breast cancer cells (ZR-75-1: ZR). UV-spectrophotometry, high performance liquid chromatography (HPLC) and gas chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) have been used to analyze lipid peroxides and their derivatives. Formation of conjugated dienes (CD), the conversion of triphenylphosphine (TPP) to its oxide (TPPO), and the simultaneous production of hydroxy polyunsaturated fatty acids (PUFA-OHs) from these corresponding PUFAs hydroperoxides (PUFA-OOHs) were analyzed in the total lipid extract of ZR cells and of normal human skin fibroblasts (CCD-41Sk:Sk). Fe enhanced the formation of both the CD and TPPO and increased the percentage of dead cells, while vitamin E inhibited these effects. Neither of these events was observed at any significant level in Sk cells. Identity of PUFA-OHs was confirmed by determining the regional positions of the hydroxyl group by GC-MS analysis of hydrogenated methyl ester tert-butyldimethylsilyl ether alcohol derivatives (Me-H2-PUFA-O-TBDMS). The regional isomers identified were 15-, 12- and 8-OH 20 carbon and 13-OH 18 carbon fatty acid derivatives. These results suggest that the increased formation of conjugated dienes and/or hydroperoxyl (or peroxyl) groups in PUFA molecules is relevant to the cancer cell-killing effect of GLA+Fe.