Diversos metales pueden ser biomarcadores precoces de cáncer de pulmón / Different metals can be early biomarkers for lung cancer x

FUNDAMENTO Y OBJETIVOS: el cáncer de pulmón (CP) es el que provoca mayor mortalidad, especialmente por su frecuente diagnóstico tardío, con menos posibilidades de curación. En el inicio del proceso carcinogénico, previo al diagnóstico clínico, los oligoelementos (metales o metaloides), desempeñan un papel importante al activar o inhibir las reacciones enzimáticas y las metaloproteínas. El objetivo de nuestro estudio es analizar la utilidad de diversos metales como biomarcadores (BM) precoces de CP, obtenidos en muestras de suero, orina, y lavado broncoalveolar (LBA)MATERIAL Y MÉTODOS: hemos analizado las concentraciones totales, incluyendo fracciones de alto y bajo peso molecular, de 11 metales en muestras de suero, orina y LBA de pacientes CP, controles sanos (CS) y pacientes con patología respiratoria no cáncer (NCP) empleando una técnica de análisis basada en un plasma de acoplamiento inductivo-espectrometría de masas (ICP-QQQ-MS). RESULTADOS: obtuvimos una clara discriminación entre los grupos en las tres muestras analizadas. Hemos obtenido metales sobreexpresados o reducidos en el CP que podrían utilizarse como BM. La concentración de vanadio (V) y cromo (Cr) en suero es claramente mayor en pacientes con CP. Hemos demostrado que varios metales (V, Cr y cobre), relacionados con procesos metabólicos alterados en CP como estrés oxidativo y homeostasis, y/o sus relaciones podrían ser buenos BM de CP. CONCLUSIONES: diversos metales, y sus relaciones y correlaciones, en la población estudiada diferencian claramente a los pacientes con cáncer de pulmón de los CS y NCP y parecen ser buenos biomarcadores en el diagnóstico precoz del cáncer de pulmón

BACKGROUND AND OBJECTIVES: Lung cancer (LC) has the highest mortality rate, especially due to its late diagnosis, with a lower chance of recovery. At the start of the carcinogenic process, before a clinical diagnosis, trace elements (metals or metalloids) play an important role by activating or inhibiting enzymatic reactions and metalloproteins. The objective of our study is to analyze the utility of different metals as early biomarkers (BM) for LC which are obtained in serum, urine and bronchoalveolar lavage (BAL) samples. MATERIAL AND METHODS: We analyzed the total concentrations, including fractions of high and low molecular weight, of 11 metals in serum, urine and BAL samples from patients with LC, healthy controls (HC) and patients with non-cancerous respiratory pathology (NCP) using an analysis technique based on inductively coupled plasma mass spectrometry (ICP-QQQ-MS).RESULTS: We obtained a clear discrimination between groups for the three samples analyzed. We obtained overexpressed or reduced metals in LC that could be used as BM. The concentration of vanadium (V) and chromium (Cr) in serum is clearly higher in patients with LC. We have shown that several metals (V, Cr and copper) related to the altered metabolic processes in LC such as oxidative stress and homeostasis and/or their connections could be good BM for LC. CONCLUSIONS: in the population studied, several metals and their connections and correlations were clearly differentiated in the patients with lung cancer compared to the HC and NCP groups and they appear to be good biomarkers for the early diagnosis of lung cancer

Perfiles metabolómicos de sujetos sanos y con cáncer de pulmón. Influencia de la carga tabáquica / The metabolomics of healthy subjects and those with lung cancer: the influence of smoking

INTRODUCCIÓN: la aplicación de técnicas metabolómicas presenta un gran potencial para la búsqueda de posibles biomarcadores de diagnóstico precoz en numerosas enfermedades. El empleo de procedimientos metabolómicos basados en espectrometría de masas permite estudiar las modificaciones metabólicas subyacentes al cáncer de pulmón (CP) y la influencia de la carga tabáquica (CT), medida en paquetes-año, en los correspondientes perfiles metabólicos. METODOLOGÍA: se estudió el suero de 9 controles sanos (no fumadores), 6 enfermos de CP con carga tabáquica moderada (CT 70). Se analizaron los metabolitos mediante técnicas de espectrometría de masas de alta resolución (DI-ESI-QTOFMS). Los perfiles metabólicos obtenidos se sometieron a análisis estadístico multivariante (PCA, PLS-DA). RESULTADOS: los tres grupos de estudio mostraron perfiles metabólicos claramente diferentes, lo que permitió identificar algunos posibles biomarcadores. Los niveles de glutatión se encontraron disminuidos en muestras de suero de pacientes con CP, mientras que se incrementó el contenido de distintos fosfolípidos de membrana (PL). La mayoría de estas anormalidades metabólicas se acentuó en pacientes con una CT elevada. CONCLUSIONES: el análisis metabolómico en muestras de suero permitió diferenciar claramente entre sujetos sanos y pacientes con CP. Así mismo, se identificaron posibles biomarcadores para el diagnóstico del CP (relacionados con rutas previamente conocidas en el proceso del cáncer). Además, estas alteraciones se vieron influenciadas por la carga tabáquica, confirmando la importancia del tabaquismo como factor de riesgo primario en el desarrollo del CP

By using high resolution metabolomics, we obtained the metabolomic profiles for patients who smoked and had lung cancer (LC) and a healthy, non-smoker control (HC) group; we assessed the influence of smoking on said profiles. The results show a clear discrimination between the metabolomic profiles of both groups studied; the metabolites causing said difference could be determined. Moreover, differences were encountered between the metabolomic profiles of heavy smokers with lung cancer compared to moderate smokers. INTRODUCTION: theapplicationof metabolomic techniques offers extensive potential to search for possible biomarkers in the early detection of several diseases. Using metabolomic procedures based on mass spectrometry allow us to study underlying metabolic changes in lung cancer and the influence of smoking, measured as packets/year, in the corresponding metabolic profiles. METHOD: the serum from 9 healthy control subjects (nonsmokers) was studied, as well as that of 6 patients with lung cancer who were moderate smokers (CT 70). The metabolites were analyzed using high resolution mass spectrometer techniques (DI-ESI-QTOF-MS). The metabolic profiles obtained were subject to multivariate statistical analysis (PCA, PLS-DA). RESULTS: the three groups studied showed clearly differentiated metabolic profiles, which facilitated the identification of certain biomarkers. Glutathione levels were found to be decreased in the sample from patients with lung cancer, while the content of various membrane phospholipids increased. Most of these metabolic abnormalities were heightened in patients who were heavy smokers. CONCLUSIONS: the metabolomics analysis in serum samples clearly differentiated healthy subjects from patients with lung cancer. Also, possible biomarkers were identified to diagnose lung cancer (linked to previously known routes in the cancer process. Moreover, these alterations were influenced by the amount smoked, thus confirming the importance of smoking as a primary risk factor in developing lung cáncer

Iberian ham typification by direct infusion electrospray and photospray ionization mass spectrometry fingerprinting.

RATIONALE: Iberian ham is a product of high commercial value whose quality mainly depends on breeding and feeding of pigs in an authorized way. Simple, fast, simple, reliable and high-throughput analytical methods are necessary to assure the quality of ham and for fraud prevention. Tandem mass spectrometry (MS/MS) is proposed as an advantageous alternative over other analytical techniques commonly used in this industry for product authentication. METHODS: The analytical approach is based on direct infusion electrospray mass spectrometry (ESI(+)-MS) of dichloromethane/methanol (60:40) extracts of ham intramuscular fat. Similarly, atmospheric pressure photoionization ionization mass spectrometry (APPI(+)-MS) was used with a flow injection analysis system for sample introduction with methanol/water (50%) as the mobile phase and toluene as the dopant. All experiments were performed on an API QSTAR® XL Hybrid system using both ESI and APPI sources. RESULTS: The ESI(+)-MS mass spectra present several clusters of peaks attributed to ammonium adducts [M + NH(4) (+) ] of lipid compounds (mono-, di- and triacylglycerols - MGs, DGs, TGs, and free fatty acids - FFAs), that can be identified by MS/MS spectra. On the other hand, the APPI(+)-MS spectra present [M + H(+) ] ions and reflect a higher fragmentation of the sample. Five different types of Iberian ham samples were successfully classified using partial least-squares discriminant analysis (PLS-DA) of data from these samples. CONCLUSIONS: The application of direct infusion tandem mass spectrometry to dichloromethane/methanol extracts from intramuscular fat ham allows the simple, fast and reliable fingerprinting typification of different Iberian ham samples from pigs with different diets. With the proposed method, sample handling is minimal and chromatographic separation is not necessary, which represents an evident advantage over other analytical procedures usually used for this purpose.

Doñana National Park survey using crayfish (Procambarus clarkii) as bioindicator: esterase inhibition and pollutant levels.

Utility of carboxylesterase and acetylcholinesterase inhibition as pesticide exposure biomarker was studied at Doñana National Park (SW Spain) in crayfish (Procambarus clarkii). Activities were measured in animals from reference sites or potentially exposed to pesticides, and their reactivation studied after dilution or 2-PAM treatment. Crayfish from affected sites had significantly less carboxylesterase and acetylcholinesterase activity than reference ones. No significant differences were found after dilution or 2-PAM treatment, showing that inhibition was irreversible. High pesticide levels were found in water and/or soil at rice growing sites, and lower levels at other affected places. High metal levels existed at rice growing sites and lower at other affected and at both reference sites. A combined effect on esterase inhibition of pesticides and metals is proposed. This field study suggest that the rice growing areas near Guadiamar stream are most polluted, followed by strawberry and citrics growing zones near Partido and Rocina streams. However, no correlation exist between the pesticide concentration at different sites and the extent of esterase inhibition, indicating that other factors could affect esterase response of animals from polluted sites.