Tumour cell lines HT-29 and FaDu produce proinflammatory cytokines and activate neutrophils in vitro: possible applications for neutrophil-based antitumour treatment.

There is evidence that polymorphonuclear neutrophils (PMNs) can exert severe antineoplastic effects. Cross-talk between tumour cells and endothelial cells (ECs) is necessary for the accumulation of PMN around a tumour. This work reports the ability of two PMN-sensitive, human, permanent cell lines-colorectal adenocarcinoma (HT-29) and pharyngeal squamous-cell carcinoma (FaDu) cells-to act as inflammatory foci. PMNs were cytotoxic to both lines, the adhesion of the PMNs to the tumour cells being important in this effect. The tumour cells released appreciable amounts of IL-8 and GROalpha, and induced the transmigration of PMN through human microvascular-EC monolayers. Conditioning media associated with both lines induced the adhesion of PMN and the surface expression of ICAM-1 in microvascular-EC. In addition, FaDu-conditioning-medium strongly induced the production of proinflammatory cytokines by microvascular-EC. These results support the idea that tumour cells might normally induce a potent acute inflammatory response, leading to their own destruction.

Position-dependent expression of GADD45alpha in rat brain tumours.

Although the complex and multifactorial process of tumour growth has been extensively studied for decades, our understanding of the fundamental relationship between tumour growth dynamics and genetic expression profile remains incomplete. Recent studies of tumour dynamics indicate that gene expression in solid tumours would depend on the distance from the centre of the tumour. Since tumour proliferative activity is mainly localised to its external zone, and taking into account that generation and expansion of genetic mutations depend on the number of cell divisions, important differences in gene expression between central and peripheral sections of the same tumour are to be expected. Here, we have studied variations in the genetic expression profile between peripheral and internal samples of the same brain tumour. We have carried out microarray analysis of mRNA expression, and found a differential profile of genetic expression between the two cell subsets. In particular, one major nuclear protein that regulates cell responses to DNA-damaging and stress signals, GADD45alpha, was expressed at much lower levels in the peripheral zone, as compared to tumour core samples. These differences in GADD45alpha mRNA transcription levels have been confirmed by quantitative analysis via real time PCR, and protein levels of GADD45alpha also exhibit the same pattern of differential expression. Our findings suggest that GADD45alpha might play a major role in the regulation of brain tumour invasive potential.

[Epidemiology of lipid profile of the Spanish elderly population: the EPICARDIAN study]. / Epidemiología del perfil lipídico de la población anciana española: el estudio EPICARDIAN.

BACKGROUND AND OBJECTIVE: The aim of this study was to describe the lipid profile, the levels of serum total cholesterol (TC), LDL cholesterol (C-LDL), HDL cholesterol (C-HDL) and triglyceride (TG), to compare these levels between geographical areas and to estimate the prevalence of dyslipidemia in elderly residents (65 years and older) from urban and rural areas of Spain. PATIENTS AND METHOD: Epidemiological, observational, multicentre study of Spanish elderly people residents (>or= 65 years old) of 3 communities in 3 Spanish regions: Arévalo (Avila) and Begonte (Lugo) as rural areas and Lista (Central Madrid) as urban area. Stratified randomized sample by age and sex from population census of each area. The participation rate was: 84.6%. At-home interviews (phase 1) (n = 4522): with determination of capillary blood cholesterol levels (Reflotron) and clinical visit (phase 2) (1/3 selected randomly, n = 1907): determination of serum TC levels (enzymatic colorimetric method CHOP-PAD), C-HDL, C-LDL (Friedewald equation) and TG (Trinder Method). RESULTS: Mean concentrations of TC was 230.3 (46.8) mg/dl. These levels decreased significantly with increasing age (p < 0.001), higher in women (p = 0.001); lower in Lugo (226.4 [49.7] mg/dl) than in Madrid (233.2 [42.3] mg/dl) and Arévalo (236.5 [43] mg/dl) (p = 0.002). Global prevalence of hypercholesterolemia by SEA simplified criteria was: 68.9% (95% confidence interval, 66.8-71). Mean concentrations of C-LDL was: 159.4 (37.9) mg/dl; C-HDL: 48.2 (15) mg/dl, and TG: 119.7 (63.85) mg/dl. 31% of cases were awarded about the hypercholesterolemia. Only 30% of them were under treatment with lipid lowering drugs; and 30% of the subjects showed CT concentrations < 200 mg/dl, with no differences by sex, age, study area or education level. Female sex, urban habitat and hypertension were the only variables independently associated to hypercholesterolemia in the logistic model. CONCLUSIONS: The prevalence of dyslipidemia is slightly higher to SEA estimation for the European elderly population (50%), greater in women and in younger groups. The awareness, treatment and control of hypercholesterolemia are low among the Spanish elderly population.

Fatty acid saturation of the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity.

BACKGROUND: The fatty acid content and saturation degree of the diet can modulate HDL composition and cholesterol efflux. OBJECTIVE: We studied the modifications in plasma lipoprotein particles and serum capacity to stimulate cholesterol efflux induced by different fatty acids. DESIGN: Seventeen women and 24 men followed in the same sequence 4 diets containing 35% of total energy as fat. The saturated fat diet contained 17% palm oil; the monounsaturated fat diet, 20.9% olive oil; the n-6 polyunsaturated fat diet, 12.5% sunflower oil; and the n-3 polyunsaturated fat diet, sunflower oil supplemented with 4-4.5 g fish oil/d. Each phase lasted 4-5 wk. RESULTS: In both sexes, apolipoprotein (apo) A-I concentrations were significantly lower with unsaturated fat diets than with the saturated fat diet, but concentrations of lipoproteins containing only apo A-I (Lp A-I) were lower only in the men. Concentrations of lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) were lower with both polyunsaturated fat diets in the women but significantly higher in the men. Lp E concentrations were significantly higher with the 2 polyunsaturated fat diets. Lp E non-B particle concentrations were not modified in the men but were significantly higher in the women in both polyunsaturated fat phases. Lp C-III concentrations were higher with the saturated fat diet only in the men. The serum samples taken after the n-3 polyunsaturated fat phase were the most efficient for extracting cellular cholesterol in both sexes. CONCLUSIONS: The monounsaturated and polyunsaturated fat diets were healthier, producing a better lipid profile. The n-3 polyunsaturated fat diet increased the capacity of serum to promote the efflux of cholesterol from cells in culture.

Expresión fenotípica de la Lp(a) en niños y adolescentes españoles / Phenotypic expressión of Lp(a) in Spanish children and adolescents

Fundamento: Conocer la distribución de los fenotipos de Lp(a) en una población infantojuvenil. Métodos: Se determinó el perfil lipoproteico, lipoproteína(a), apolipoproteínas y fenotipos de Lp(a) en 105 niños, seleccionados según sus concentraciones de colesterol. Resultados: Las concentraciones medias de Lp(a) eran significativamente mayores en el grupo con isoformas de bajo peso molecular respecto a los de alto peso molecular. La isoforma más frecuente fue S3. Conclusiones: Las concentraciones de Lp(a) se correlaccionaron inversamente con el peso molecular de las isoformas de Apo(a) (AU)

Background: To know the distribution of phenotypes Lp(a) in an young population. Methods: Lipoprotein levels, lipoprotein(a), apolipoproteins and the Lp(a) phenotypes were determinated in 105 children, selected according to their cholesterol concentrations. Results: The Lp(a) concentrations were significantly higher in group with low molecular weight respect to group with high molecular weight. The most frequent isoform was S3. Conclusions: The Lp(a) concentrations correlate inversely with the molecular weight of Apo(a) isoforms (AU)