ABSTRACT
PURPOSE: Locally advanced non-small cell lung cancer (LA-NSCLC) is frequently treated with chemoradiotherapy (CRT). Despite the efforts, long-term outcomes are poor, and novel therapies have been introduced to improve results. Biomarkers are needed to detect early treatment failure and plan future follow-up and therapies. Our aim is to evaluate the role of dynamics of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced NSCLC treated with CRT. METHODS: We retrospectively reviewed patients diagnosed with LA-NSCLC receiving definitive CRT at our center from 2010 to 2015. Baseline and post-treatment NLR were collected from our center database. NLR was dichotomized (threshold = 4) and patients were divided into two groups based on the variation from baseline to post-treatment NLR. The prognostic role and association with response were examined with logistic regression and multivariate Cox regression model, respectively. RESULTS: Ninety-two patients were included. Our analysis shows that NLR after treatment is associated with response to treatment [OR in the multivariate analysis 4.94 (1.01-24.48); p value = 0.048]. Furthermore, NLR and ECOG are independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Specifically, PFS was 25.79 months for the good prognosis group and 12.09 for the poor prognosis group [HR 2.98 (CI 95% = 1.74-5.10), p < 0.001]; and OS was 42.94 months and 18.86 months, respectively [HR 2.81 (CI 95% = 1.62-4.90), p < 0.001]. CONCLUSION: Dynamics of NLR have a prognostic value in stage III NSCLC treated with definitive CRT. Pre- and post-CRT NLR should be evaluated in prospective clinical trials involving consolidation treatment with immunotherapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/blood , Lung Neoplasms/blood , Lymphocytes/cytology , Neutrophils/cytology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy , Female , Humans , Leukocyte Count , Logistic Models , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lymphocyte Count , Male , Middle Aged , Prognosis , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. METHODS/PATIENTS: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. RESULTS AND CONCLUSIONS: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.
Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , DNA Mismatch Repair/genetics , Female , Genes, ras , Humans , Male , Middle Aged , Molecular Diagnostic Techniques , Mutation , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Treatment OutcomeABSTRACT
Mammals along their early postnatal period develop a substantial amount of a very active brown adipose tissue (BAT). Through this work we explored the possibility that BAT may function as a long chain polyunsaturated fatty acids reservoir (LC-PUFA) during the rapid growth of brain structures. In new born rats 1, 6, 12 and 20 days old, we analyzed fatty acid percentage of triglycerides (TG) and phospholipid fractions, and the absolute amount of TG. In 6 day old rats we also evaluated the extend of further desaturation of 1-14C linoleic acid administered by intraperitoneal injection. Results demonstrated a drastic increase of TG concentration during experimental period (1,5; 40; 118; 120 mg/g wet weight) and LC-PUFA percentage was higher in [quot ]1 and 6[quot ] than [quot ]12 and 20[quot ] days old rats (16-17% vs 5%). Our results showed that BAT stored important amounts of LC-PUFA. On the other hand, 1-14C linoleic acid incorporation was higher in liver than BAT. In contrast, the desaturated products of 1-14C linoleic acid /1-14C linoleic acid ratio was greater in BAT than liver (>4). This could indicate that BAT synthesizes LC-PUFA in addition to store it. In summary we demonstrated than BAT is an important reservoir of LC-PUFA during postnatal brain growth.
Los mamíferos como el hombre y la rata, poseen durante su desarrollo postnatal temprano un tejido adiposo marrón (TAM) muy activo. En este trabajo se exploró la posibilidad de que el TAM funcione como un depósito de ácidos grasos poliinsaturados de cadena larga (AGPI-CL), durante el período de máximo crecimiento postnatal del cerebro de rata. En el TAM de ratas de 1, 6, 12 y 20 días de edad analizamos la concentración de triglicéridos (TG) y la composición de ácidos grasos en los TG y fosfolípidos (FL). Además, en ratas de 6 días de edad evaluamos la capacidad del TAM para desaturar 1- 14C ácido linoleico administrado por vía intraperitoneal. Los resultados mostraron un rápido incremento en la concentración de TG durante el período experimental (1,5; 40; 118; 120 mg /g de peso húmedo). El porcentaje de AGPI-CL fue mayor en las ratas de 1 y 6 días de edad que en las de 12 y 20 días (16-17% vs 5%). Por otra parte, la incorporación de 1-14C ácido linoleico fue más alta en el hígado que en el TAM, aunque la relación "productos desaturados de 1-14C ácido linoleico / 1-14C ácido linoleico" fue mayor en el TAM que en el hígado (>4), lo cual podría indicar que este tejido además de almacenar AGPI-CL los sintetiza. En resumen, nuestros resultados demuestran que el TAM es depósito importante de AGPICL durante el período de máximo desarrollo postnatal del cerebro.
Subject(s)
Animals , Female , Male , Rats , Linoleic Acid/administration & dosage , Liver/metabolism , Lipid Metabolism , Adipose Tissue, Brown/metabolism , Animals, Newborn , Linoleic Acid/pharmacokinetics , Chromatography, Gas , Brain/growth & development , Phospholipids/metabolism , Rats, Sprague-DawleyABSTRACT
La modificación oxidativa de las lipoproteínas de baja densidad (LDL) está asociada con el desarrollo de la aterosclerosis. El propósito del presente estudio es investigar cual de los ácidos grasos (AG) componentes de los fosfolípidos (FL) de las LDL y de las lipoproteínas de alta densidad (HDL) está relacionado con su susceptibilidad de oxidación (SO). Las LDL y HDL fueron aisladas del plasma de 13 voluntarios e incubadas con CuSO45uM por 3 h. a 37 ºC. El grado de oxidación fue medido por la producción de sustancias reactivas con el ácido tiobarbitúrico (TBARS) y correlacionado con la relación por ciento AG respecto por ciento ácido palmítico de los FL. Encontrándose en la LDL una correlación estadísticamente significativa (p<0,05) para el C22:6 y C20:4 y en la HDL para el C22:6 y C20:5. En conclusión la SO de las LDL y HDL está correlacionada con ácidos grasos poliinsaturados de sus FL.
Subject(s)
Humans , Male , Female , Arteriosclerosis , Biologic Oxidation , Fatty Acids , Lipoproteins, HDL , Lipoproteins, LDL , Phospholipids , Endocrinology , VenezuelaABSTRACT
A longitudinal principal components analysis was used to summarize trends or intraindividual changes in weight, height, blood pressure, serum cholesterol and triglycerides in 32 boys and 28 girls from the Caracas Longitudinal Study (1976-1982), who started follow-up at age 8. A first component was identified for each variable, it represents a measure of position across the whole age period, a "canalization pattern". This component accounted for most of the total variance. The second component represents an unidirectional change in relative position of the values of the variable, a "decanalization pattern", and a third pattern summarized deviations around a position level: "recanalization pattern". The results from the correlation analyses between the components indicate a positive and significant association between the identified trends. These patterns allow predictability of "high and low risk" factors of non-communicable chronic diseases.
Subject(s)
Blood Pressure/physiology , Body Height/physiology , Body Weight/physiology , Cholesterol/blood , Triglycerides/blood , Child , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Prospective Studies , Sex Distribution , Venezuela/epidemiologyABSTRACT
In the Caracas Longitudinal Study, the canalization of 24 girls that started follow-up at age 4, 43 at age 8, and 32 at age 12 in: height (H), weight (W), Body Mass Index (BMI), cholesterol (CHOL), triglycerides (TG) and glucose (GL), was studied using Schneiderman n Tracking Index (TI) and age to age correlations. TI presented a gradient H > W > BMI > CHOL and lower in TG and GL. TI of all variables diminished increased with age and in BMI and CHOL. Age to age correlations were significant at all ages in H, W. and BMI and higher in CHOL (p < 0.01) compared to TG and GL. The significant tracking of H, W, BMI and lipids, specially CHOL, is relevant in prevention of non-communicable chronic diseases.
Subject(s)
Blood Glucose/analysis , Body Height , Body Mass Index , Body Weight , Lipids/blood , Age Factors , Child , Child, Preschool , Chronic Disease , Female , Follow-Up Studies , Humans , Longitudinal Studies , Risk Factors , Social Class , Time Factors , VenezuelaABSTRACT
We address here the issue concerning the origin of essential long chain polyunsaturated fatty acids (LC-PUFA) needed for early postnatal brain development. Normal newborn rats 1, 5, 10 and 20 day-old were decapitated, immediately after, the livers were processed to obtain the microsomal fraction and its delta 6 fatty acid desaturase activity and fatty acid composition were determined. Samples of plasma, whole homogenized brain hemispheres and milk contained in the gastric cavity of the suckling rats, were analyzed to obtained their fatty acid composition. We fond that the rat neonate has a very low delta 6 desaturase activity in liver microsomes as compared with the adult. In contrast, there is a considerable quantity of DHA an AA in the milk, liver microsomes, plasma lipids and brain. In conclusion, we propose that brain DHA and AA cannot be derived substantially through liver synthesis, but through the availability of these preformed fatty acids in the milk. These fatty acids are concentrated in liver microsomes and then secreted into plasma lipid pool to reach finally to brain structures.
Subject(s)
Brain/growth & development , Fatty Acids, Essential/metabolism , Liver/metabolism , Animals , Arachidonic Acids/analysis , Arachidonic Acids/metabolism , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/metabolism , Fatty Acid Desaturases/metabolism , Fatty Acids/analysis , Female , Linoleoyl-CoA Desaturase , Liver/enzymology , Liver/physiology , Male , Microsomes, Liver/chemistry , Milk/chemistry , Phospholipids/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
In Venezuela a severe economic crisis beginning in 1983 provoked a progressive reduction of the quality and quantity of food consumed by the low socioeconomic strata of the population. In these strata, which represent > or = 80% of the Venezuelan population, we had seen a continuous increase in the prevalence of iron deficiency during that recent decade. As a result, in 1993 the Venezuela Government created the Special Commission for Enrichment of Foods. That same year a fortification program began in which precooked yellow and white maize and wheat flours were enriched with 20 and 50 mg Fe (as ferrous fumarate)/kg flour, respectively. The corn flour was also enriched with vitamin A, thiamine, riboflavin, and niacin, whereas the wheat flour was enriched with these same vitamins, except vitamin A. These two cereals represent 45% of the total energy consumed daily by the low socioeconomic strata of the population. A preliminary survey carried out in Caracas in 1994 in a population of 307 children aged 7, 11, and 15 y showed that the prevalence of iron deficiency determined by measuring the serum ferritin concentration and the prevalence of anemia were reduced from 37% and 19%, respectively, in 1992 to 15% and 10%, respectively in 1994.
Subject(s)
Anemia, Iron-Deficiency/epidemiology , Iron, Dietary/pharmacology , Adolescent , Adult , Anemia, Iron-Deficiency/drug therapy , Anemia, Iron-Deficiency/prevention & control , Child , Child, Preschool , Data Collection , Diet/standards , Female , Ferritins/blood , Flour/analysis , Food Analysis , Food-Processing Industry/methods , Food-Processing Industry/standards , Humans , Incidence , Infant , Iron, Dietary/analysis , Iron, Dietary/therapeutic use , Male , Middle Aged , Niacin/analysis , Niacin/pharmacology , Quality Control , Riboflavin/analysis , Riboflavin/pharmacology , Social Class , Thiamine/analysis , Thiamine/pharmacology , Triticum/chemistry , Venezuela/epidemiology , Vitamin A/analysis , Vitamin A/pharmacology , Zea mays/chemistryABSTRACT
Dietary experiments, performed in metabolic wards, gave rise to predictive regression equations relating changes of plasma cholesterol concentration to the intake of fatty acids of the diet. It has been established that polyunsaturated fatty acids diminish and most saturated fatty acids increase plasma cholesterol concentration. This information led to expect that dietary use of palm oil may induce an unfavorable plasma lipoprotein profile. This has not been the case as shown in various dietary experiments. The reasons for this discrepancy is discussed. The influence of palm oil enriched diets on prothrombotic variables show that platelets are not affected in their function during prolonged dietary intervention. It is important to continue research on the effects of palm oil based diet on plasma fibrinogen, factor VII. There is still discordant information in this field.
Subject(s)
Arteriosclerosis/etiology , Dietary Fats/pharmacology , Hypercholesterolemia/chemically induced , Plant Oils/pharmacology , Thrombosis/etiology , Adult , Animals , Arteriosclerosis/prevention & control , Child , Cholesterol/blood , Diet, Atherogenic , Dietary Fats/administration & dosage , Dietary Fats/adverse effects , Factor VII/analysis , Feeding Behavior , Female , Fibrinogen/analysis , Fish Oils/pharmacology , Humans , Linoleic Acid , Linoleic Acids/administration & dosage , Linoleic Acids/pharmacology , Lipoproteins/blood , Male , Palm Oil , Plant Oils/administration & dosage , Plant Oils/adverse effects , Plant Oils/chemistry , Platelet Aggregation/drug effects , Rabbits , Rural Population , Sunflower Oil , Thrombosis/prevention & control , Triglycerides/blood , Urban Population , VenezuelaABSTRACT
The object of this study was to evaluate the effect of increasing amounts of dietary fish oil on growth and hematological variables of the weanling male Sprague-Dawley rat. Animals were fed diets containing either fish oil (FO) or sesame oil (SO) at 5, 10 or 15% (w/w) for 31 d. Growth retardation and reduced food intake was noted in groups fed FO. Hemoglobin (Hb) concentration diminished when the dietary FO was above 5% (w/w). FO is a poor source of (n-6) fatty acids. We postulate that a partial deficiency in (n-6) polyenic family, is a consequence of the increasing amounts of FO in the diets, that may affect growth and erytropoiesis. In this report we show evidence supporting the hypothesis that diets enriched with fish oil can alter normal growth and induced hematological changes in the male weanling rat.
Subject(s)
Dietary Fats, Unsaturated/pharmacology , Eating/drug effects , Fish Oils/pharmacology , Growth/drug effects , Hemoglobins/analysis , Animals , Erythropoiesis/drug effects , Male , Rats , Rats, Sprague-Dawley , WeaningABSTRACT
The iron status of 3228 subjects from the nutrition survey Proyecto Venezuela was studied. The sample included children from 1 to 16 y of age grouped by age and sex. Values for three indicators of iron status were compared: hemoglobin concentration, serum ferritin concentration, and percentage saturation of serum transferrin. In all groups there was a strong overlap in the hemoglobin concentration distribution curves for non-iron-deficient and iron-deficient subjects classified as such according to the other two indexes. The prevalence of iron deficiency ranged from 35% in 1-3 y olds to 10% in adolescent males, the values being almost identical in the nonanemic group compared with the total population. In the different groups, 80-97% of the subjects with abnormal values of at least one of these two indexes were not anemic. The difficulties involved in establishing a state of iron deficiency according to these indexes are discussed.
Subject(s)
Anemia, Hypochromic/blood , Iron Deficiencies , Adolescent , Age Factors , Anemia, Hypochromic/epidemiology , Child , Child, Preschool , Female , Ferritins/blood , Hemoglobins/analysis , Humans , Infant , Male , Prevalence , Sex Factors , Transferrin/analysis , Venezuela/epidemiologyABSTRACT
Fats are important constituents of the human diet since on the one hand, they contribute to the caloric density of the diet, and on the other, they serve as vehicles of essential nutrients such as linoleic and alpha-linolenic acids, as well as fat-soluble vitamins. The existence of human populations subsisting on diets with values as low as 10% or more than 50% of the calories represented by fats, has been documented, demonstrating the great adaptability of man to a wide availability of this type of food. Nevertheless, extensive epidemiological and experimental research in relation to a frequent degenerative diseases of man, arteriosclerosis, have consistently demonstrated that the proportion of saturated fats in the diet has a positive correlation with the frequency of these alterations. Mortality and fat availability in Latin America is consistent with these results. In consequence, and taking into consideration the present level of fat availability in the Region, we propose that no more than 25% of the caloric requirement should be covered by fats. Additionally, this amount of fat should have equal proportions of saturated, monounsaturated and polyunsaturated fatty acids. Cholesterol, which is contained in animal fats, is not a necessary nutrient for humans, so that no minimum consumption needs to be established. Daily ingestion of cholesterol should be restrained to no more than 100 mg/1,000 calories. Introduction of new fatty foods for human consumption should be preceded by a thorough investigation of the metabolic consequences.
Subject(s)
Dietary Fats , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cholesterol, Dietary/administration & dosage , Cholesterol, Dietary/adverse effects , Dietary Fats/administration & dosage , Dietary Fats/adverse effects , Humans , Latin America/epidemiology , Nutritional Requirements , Thromboembolism/etiology , Vitamins/administration & dosageSubject(s)
Fatty Acids/analysis , Food Analysis , Animals , Chromatography, Gas , Egg Yolk/analysis , Female , Margarine/analysis , Meat/analysis , Meat Products/analysis , Oils/analysis , Poultry , Swine , VenezuelaSubject(s)
Coronary Disease/blood , Lipids/blood , Lipoproteins/blood , Adolescent , Adult , Age Factors , Blood Protein Electrophoresis , Female , Humans , Male , Middle Aged , Sex Factors , VenezuelaABSTRACT
Serum lipoproteins of pregnant and puerperal rats were studied by preparative and analytical ultracentrifugation. The concentration for the fraction with density less than 1.019 was markedly elevated in rats during the 3rd wk of gestation and in lactating rats. This fraction showed similar triglyceride fatty acid composition and immunoelectrophoretic behavior whether it was derived from pregnant or nonpregnant rats, and when partially delipidized, the lipoproteins from both groups showed similar immunoelectrophoretic characteristics and sedimentation rates. When lactation was interrupted during puerperium, serum lipoproteins returned to control levels; but in lactating rats, high levels of serum very low density lipoprotein persisted up to 3 wk post partum.