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1.
J Trace Elem Med Biol ; 68: 126808, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34126540

RESUMEN

AIMS: The aim of this study was to compare serum vanadium (V) concentrations between athletes of different sports modalities and people who did not practise physical exercise regularly. METHODS: One hundred and twenty-one subjects divided into a control group (CG; n = 37; 1.75 ± 0.03 m; 79.45 ± 10.20 kg; 24.72 ± 6.06 years) and an athletes' group (AG; n = 84; 1.77 ± 0.05 m; 66.34 ± 6.12 kg; 19.57 ± 1.95 years) participated in this research. AG were classified by sports modality: aerobic (AE; n = 26), anaerobic (ANA; n = 22); aerobic-anaerobic (AE-ANA; n = 36). Serum V concentrations were analysed by inductively coupled plasma mass spectrometry. RESULTS: AG showed higher V concentrations compared to CG (p < 0.01). AE obtained higher concentrations compared to ANA and AE-ANA (p < 0.05). CONCLUSIONS: Physical training could increase serum V levels. Specifically, aerobic sports modalities could increase serum V levels to a greater extent than other sports modalities.


Asunto(s)
Deportes , Vanadio , Atletas , Ejercicio Físico , Humanos
2.
Artículo en Inglés | MEDLINE | ID: mdl-33803383

RESUMEN

Several anthropometric and performance parameters related to aerobic metabolism are associated with performance in endurance runners and are modified according to the training performed. The objective of this study was to investigate the ergospirometric and body composition changes in endurance runners during a sports season in relation to their training. Twenty highly trained men endurance runners performed an incremental test until exhaustion (initial, and at 3, 6, and 9 months) on a treadmill to determine maximal oxygen consumption (VO2 max), second ventilatory threshold (VT2), and their associated running speeds. Skinfolds, perimeters, and weights were measured. No changes were obtained in VO2 max or VT2 during the study, although their associated running speeds increased (p < 0.05) after 3 months of the study. Decreases in fat mass (p < 0.05) and muscle mass (p < 0.05) were observed at the end of the season (9 months). Changes occurred in the different skinfolds according to the characteristics of the training performed during the season. In conclusion, vVO2 max and vVT2 increase with a greater volume of kilometres trained and can be adversely affected by loss of muscle mass.


Asunto(s)
Adaptación Fisiológica , Carrera , Atletas , Humanos , Masculino , Consumo de Oxígeno , Resistencia Física , Estaciones del Año
3.
Nutr. hosp ; 38(2): 374-382, mar.-abr. 2021. tab, graf
Artículo en Inglés | IBECS | ID: ibc-201882

RESUMEN

BACKGROUND: it is well known that moderate or vigorous physical exercise produces an increase in free radicals. AIM: the aims of this study were to observe changes in malondialdehyde and antioxidant vitamins after a maximum incremental test, and to relate malondialdehyde and antioxidant vitamin values to performance parameters. METHODS: eighty-four male athletes participated in this study. Participants performed a maximum incremental test until exhaustion on a treadmill. Malondialdehyde in plasma and antioxidant vitamins in plasma and erythrocytes were determined before and after the test. RESULTS: in plasma, there was a decrease in malondialdehyde after the test. In erythrocytes, results showed increases in vitamin C and decreases in vitamin E after the test. Maximal oxygen uptake values were associated positively with vitamin C and negatively with malondialdehyde levels before the test. On the other hand, maximal oxygen uptake, total test time, and total test distance were positively related to the malondialdehyde values obtained after the test. CONCLUSIONS: a maximum incremental test did not produce any changes in plasma vitamins in athletes. However, it increased the levels of vitamin C in erythrocytes and decreased malondialdehyde values in plasma and vitamin E in erythrocytes. The levels of malondialdehyde, vitamin C and vitamin E were related to performance parameters. These results may be linked to the adaptation of antioxidant systems due to regular training


INTRODUCCIÓN: es sabido que el ejercicio físico moderado o vigoroso produce un aumento de radicales libres. OBJETIVOS: los objetivos del estudio fueron: observar los cambios del malondialdehído y las vitaminas antioxidantes después de un test incremental máximo y relacionar los niveles de malondialdehído y vitaminas antioxidantes con parámetros de rendimiento. MÉTODOS: ochenta y cuatro atletas masculinos participaron en el estudio. Los participantes realizaron un test incremental hasta la extenuación en un tapiz rodante. El malondialdehído en plasma y las vitaminas antioxidantes en plasma y en eritrocitos se determinaron antes y después del test incremental. RESULTADOS: en el plasma hubo una disminución del malondialdehído después de la prueba incremental. En los eritrocitos, los resultados mostraron un aumento de la vitamina C y un descenso de la vitamina E después de la prueba. El consumo máximo de oxígeno se asoció positivamente con la vitamina C e inversamente con el malondialdehído antes del test. Por otro lado, el consumo máximo de oxígeno, el tiempo total del test y la distancia total durante el test se asociaron positivamente con los valores de malondialdehído obtenidos tras el test máximo. CONCLUSIÓN: un test incremental máximo hasta la extenuación no produjo cambios en las vitaminas antioxidantes del plasma. Sin embargo, sí aumentó los niveles de vitamina C en los eritrocitos y redujo los niveles de malondialdehído en el plasma y los de vitamina E en los eritrocitos. Los niveles de malondialdehído, vitamina C y vitamina E se relacionaron con los parámetros de rendimiento. Estos resultados podrían estar relacionados con la adaptación de los sistemas antioxidantes debido al entrenamiento regular


Asunto(s)
Humanos , Masculino , Adulto Joven , Adulto , Atletas , Malondialdehído/metabolismo , Antioxidantes/metabolismo , Eritrocitos/fisiología , Plasma/metabolismo , Radicales Libres/sangre , Suplementos Dietéticos , Malondialdehído/administración & dosificación , Antioxidantes/administración & dosificación , Ejercicio Físico/fisiología , Vitamina E/uso terapéutico , Antropometría , Evaluación Nutricional
5.
Artículo en Inglés | MEDLINE | ID: mdl-33348799

RESUMEN

Several essential trace minerals play an important role in the endocrine system; however, toxic trace minerals have a disruptive effect. The aim of this research was to determine basal concentrations and the possible correlations between trace minerals in plasma and several plasma hormones in runners. Sixty high-level male endurance runners (21 ± 3 years; 1.77 ± 0.05 m; 64.97 ± 7.36 kg) participated in the present study. Plasma hormones were analyzed using an enzyme-linked immunosorbent assay (ELISA) and plasma trace minerals were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). Correlations and simple linear regression were used to assess the association between trace minerals and hormones. Plasma testosterone concentrations were inversely correlated with manganese (r = -0.543; ß = -0.410; p < 0.01), selenium (r = -0.292; ß = -0.024; p < 0.05), vanadium (r = -0.406; ß = -1.278; p < 0.01), arsenic (r = -0.336; ß = -0.142; p < 0.05), and lead (r = -0.385; ß = -0.418; p < 0.01). Plasma luteinizing hormone (LH) levels were positively correlated with arsenic (r = 0.298; ß = 0.327; p < 0.05) and cesium (r = 0.305; ß = 2.272; p < 0.05), and negatively correlated with vanadium (r = -0.303; ß = -2.467; p < 0.05). Moreover, cortisol concentrations showed significant positive correlations with cadmium (r = 0.291; ß = 209.01; p < 0.05). Finally, insulin concentrations were inversely related to vanadium (r = -0.359; ß = -3.982; p < 0.05). In conclusion, endurance runners living in areas with high environmental levels of toxic minerals should check their concentrations of anabolic hormones.


Asunto(s)
Hormonas , Minerales , Oligoelementos , Arsénico/sangre , Cadmio/sangre , Ensayo de Inmunoadsorción Enzimática , Hormonas/sangre , Humanos , Masculino , Manganeso/sangre , Espectrometría de Masas , Minerales/sangre , Selenio/sangre , Oligoelementos/sangre
6.
Artículo en Inglés | MEDLINE | ID: mdl-32916939

RESUMEN

The aim of this study was to determine the possible correlations between essential and toxic trace elements of plasma with several anthropometric and body composition parameters and performance in endurance runners. Sixty-five high-level middle and long-distance runners (21 ± 3 years; 1.77 ± 0.05 m; 64.97 ± 7.36 kg; VO2 max. 67.55 ± 4.11 mL/min/kg) participated in the present study. Abdominal, subscapular, iliac crest, triceps, front thigh and medial calf skinfold thicknesses and an incremental test until exhaustion were recorded. Body, fat, muscle and bone mass were estimated. Plasma trace elements were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). Correlations and simple linear regression were used to assess the relationship between trace elements and several variables. Different skinfolds, fat mass, muscle mass and bone mass correlated positively and negatively with trace elements such as copper, manganese, selenium, vanadium, zinc, lithium, rubidium, strontium, arsenic, beryllium and lead. Lithium was related with performance. In conclusion, endurance training causes changes in the body concentrations of several trace elements that trigger modifications in body composition that may be interesting, if confirmed in the future, for the control of metabolic diseases such as obesity.


Asunto(s)
Carrera , Selenio , Oligoelementos , Composición Corporal , Humanos , Resistencia Física , Carrera/fisiología , Grosor de los Pliegues Cutáneos , Adulto Joven , Zinc
7.
Artículo en Inglés | MEDLINE | ID: mdl-32806586

RESUMEN

The aim of this study was to determine the possible changes in plasma of several hormones such as Luteinizing Hormone, Testosterone, Cortisol and Insulin in endurance runners during the sports season. Twenty-one high-level male endurance runners (22 ± 3.2 years, 1.77 ± 0.05 m) participated in the study. Basal plasma hormones were measured at four moments during the season (initial, 3, 6 and 9 months), and were analyzed using ELISA (enzyme-linked immunosorbent assay). Testosterone and Luteinizing Hormone (LH) suffered very significant decreases (p < 0.01) at 3 months compared with the beginning and an increase (p < 0.05) at 6 and 9 months compared with 3 months. Insulin level was significantly lower (p < 0.05) at 3, 6 and 9 months compared with the initial test. Insulin and cortisol were associated inversely (r = 0.363; ß = -0.577; p = 0.017) and positively (r = 0.202; ß = 0.310; p = 0.043), respectively, with the amount of km per week performed by the runners. There was a significant association between km covered at a higher intensity than the anaerobic threshold and I (r = 0.580; ß = -0.442; p = 0.000). Our findings indicate that testosterone, LH and insulin were more sensitive to changes in training volume and intensity than cortisol in high-level endurance runners. Basal testosterone and LH concentrations decrease in athletes who perform a high volume of aerobic km in situations of low energy availability.


Asunto(s)
Atletas , Resistencia Física , Adulto , Humanos , Hidrocortisona/metabolismo , Hormona Luteinizante/metabolismo , Masculino , Estaciones del Año , Testosterona/metabolismo , Adulto Joven
8.
J Int Soc Sports Nutr ; 15(1): 28, 2018 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-29898738

RESUMEN

BACKGROUND: The aim of the present study was to determine changes in the serum concentrations of trace elements Cobalt (Co), Molybdenum (Mo) and Zinc (Zn) among high-level sportsmen. METHODS: Eighty professional athletes of different metabolic modalities (aerobic, anaerobic and aerobic-anaerobic), were recruited before the beginning of their training seasons. Thirty-one sedentary participants of the same geographic area constituted the control group. Co, Mo and Zn analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: Serum concentration of Mo (p < 0.001) was higher among sportsmen compared to the control group values. Separated by modalities, the concentrations of Co in the aerobic-anaerobic athletes were lower (p < 0.01) than in the control group as well as than in the other athletes. The highest Mo concentration was found in anaerobic sportsmen (p < 0.001), followed by aerobic-anaerobic (p < 0.001) being both statistically higher in comparison with the control group. In relation to Zn, it was observed that aerobic-anaerobic (p < 0.001) and anaerobic (p < 0.001) sportsmen showed higher concentrations than the control participants. However, aerobic sportsmen showed lower concentrations (p < 0.01) than controls. CONCLUSION: This data manifest that long-term, daily physical training may induce variations in serum concentrations of several essential elements among sportsmen in comparison to untrained men and that these changes seems to be related to the sports modality practiced.


Asunto(s)
Cobalto/sangre , Molibdeno/sangre , Fenómenos Fisiológicos en la Nutrición Deportiva , Deportes/clasificación , Zinc/sangre , Adolescente , Atletas , Estudios de Casos y Controles , Humanos , Masculino , Conducta Sedentaria , Oligoelementos/sangre , Adulto Joven
9.
Biol Trace Elem Res ; 186(2): 361-369, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29623649

RESUMEN

The aim of the present study was to determine changes occurring in serum and urine concentrations of essential trace elements with proven essentiality (molybdenum, selenium, and zinc) as a result of performing an acute physical activity until exhaustion in middle- and long-distance runners who live in the same area of Extremadura (Spain). Twenty-one Spanish national middle- and long-distance runners and 26 sedentary students of a similar age were recruited for the study. Both groups ran on a treadmill until exhaustion, starting at a speed of 10 and 8 km/h, respectively, and increasing the speed at 1 km/h every 400 m, without modifying the slope, always within the recommended parameters. Serum and urine samples were obtained from all subjects before and after the tests. Analysis of trace metals was performed by inductively coupled plasma mass spectrometry (ICP-MS). Resting serum and urinary concentrations between groups were compared using the Student t test, and the Wilcoxon test was used to analyze the trends of changes before and after the effort. The results showed that molybdenum concentrations were significantly higher in athletes than in controls (p < 0.01). Selenium (p < 0.05) and zinc (p < 0.01) concentrations were significantly lower in athletes than in controls. When we compared the serum concentrations before and after the test in the controls, only in the case of selenium (p = 0.006), a significant increase was observed after the test. However, this signification disappears with the corrections for hematocrit. Athletes' serum concentrations of Se (p = 0.004) and Zn (p = 0.005) lowered at the end of the test. Also, the results showed that there were no statistical urinary concentration (expressed in µg/g creatinine) changes in Mo and Se. Zn urinary concentration increased at the end of exercise (p = 0.018), since an incremental exercise to exhaustion in middle- and long-distance elite athletes produces a decrease in Se and Zn serum concentrations but Zn urinary concentration increased. In conclusion, athletes show higher serum concentrations of molybdenum and lower serum concentrations of selenium and zinc than sedentary subjects. Additionally, a treadmill test until exhaustion provokes a decrease in serum concentration of selenium and zinc and a higher excretion of urinary zinc. Serum concentrations of Se and Zn should be carried out in order to avoid any possible deficit cases and to establish the optimal supplementation.


Asunto(s)
Atletas , Ejercicio Físico/fisiología , Fatiga Muscular/fisiología , Oligoelementos/sangre , Oligoelementos/orina , Adolescente , Adulto , Hematócrito , Hemoglobinas/metabolismo , Humanos , Masculino , Molibdeno/sangre , Molibdeno/orina , Carrera/fisiología , Selenio/sangre , Selenio/orina , Adulto Joven , Zinc/sangre , Zinc/orina
10.
Artículo en Inglés | MEDLINE | ID: mdl-29449792

RESUMEN

BACKGROUND: The aim of the present study was to determine changes in serum concentrations of trace elements Cooper (Cu), Chromiun (Cr), Manganesum (Mn), Nickel (Ni) and Selenium (Se) in high-level sportsmen. METHODS: Eighty professional athletes of different metabolic modalities, were recruited before the start of their training period. Thirty one sedentary participants of the same geographic area constituted the control group. Cu, Cr, Mn, Ni and Se analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: Higher concentrations of Cr (p < 0.001), Mn (p < 0.085), and Ni (p < 0.001) were found in sportsmen in comparison to controls, inversely, Se values were lower (p < 0.001) among sportsmen. When sportsmen were classified by metabolic modalities, it was found that aerobic-anaerobic group had higher (p < 0.01) Cu concentrations than controls and the other sportsmen. The highest Cr values were found in aerobic participants. For Mn, the major levels were found in aerobic and aerobic-anaerobic groups as well (p < 0.001). The lowest Se levels were found among anaerobic sportsmen (p < 0.001). CONCLUSION: This research showed that daily, continuum physical training induced alterations in serum essential minerals concentrations, as well as that these changes can be dependent of the exercise modality practiced.


Asunto(s)
Cromo/sangre , Cobre/sangre , Compuestos de Manganeso/sangre , Níquel/sangre , Selenio/sangre , Fenómenos Fisiológicos en la Nutrición Deportiva , Adolescente , Adulto , Antropometría , Atletas , Dieta , Ejercicio Físico , Humanos , Masculino , Espectrometría de Masas , Conducta Sedentaria , Deportes/clasificación , Adulto Joven
11.
J Sports Med Phys Fitness ; 58(12): 1713-1719, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29072036

RESUMEN

BACKGROUND: The main objective of this study was to observe any changes and possible adaptations produced in MDA and antioxidants vitamins on plasma and erythrocytes in endurance male athletes among an athletic season (12 months). METHODS: Twenty three long and middle distance male athletes participated in this study. Basal MDA on plasma and antioxidant vitamins in plasma and erythrocytes were measured at four moments along the season (0, 3, 6 and 9 months). Fatty acid concentrations in erythrocytes were obtained to determine lipid peroxidation indexes. RESULTS: In plasma, vitamin C suffered significant decreases at 3 and 6 months compared with the begin (P<0.01), and an increase at 9 months, compared with 3 months. On the other hand, vitamin A level was significantly lower at 9 months compared with the other periods (P<0.01 compared with 0 and 6 months; P<0.05 compared with 3 months). In erythrocytes, significant decreases were observed in vitamin E among the season at 6 months and an increase from 6 to 9 months (P<0.05). Vitamin A suffers a significant decrease in both for competitive periods, at 3 and 9 months, compared with the beginning of the season. The most of changes in lipid peroxidation indexes were produced along the firsts 3 months. CONCLUSIONS: 1) Physical training improves the antioxidant systems in order to reduce lipid peroxidation in trained athletes along the season; 2) PUFA/SFA ratios seem more reliable than MDA to observe oxidative stress.


Asunto(s)
Antioxidantes/análisis , Peroxidación de Lípido , Estrés Oxidativo , Fenómenos Fisiológicos en la Nutrición Deportiva , Vitaminas/sangre , Ácido Ascórbico/sangre , Atletas , Eritrocitos/química , Ejercicio Físico , Humanos , Masculino , Resistencia Física , Deportes , Vitamina A/sangre , Vitamina E/sangre
12.
J Int Soc Sports Nutr ; 14: 19, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28615997

RESUMEN

BACKGROUND: The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects and the possible influence that different energy sports training modalities can have on their concentration. METHODS: Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The results show higher concentrations in athletes on tin (p < 0.01), rubidium and antimony (p < 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (p < 0.001), followed by anaerobic group (p < 0.001). CONCLUSION: Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.


Asunto(s)
Ejercicio Físico , Oligoelementos/sangre , Adolescente , Adulto , Antropometría , Antimonio/sangre , Atletas , Boro/sangre , Estudios de Casos y Controles , Humanos , Litio/sangre , Masculino , Rubidio/sangre , España , Estroncio/sangre , Estaño/sangre , Adulto Joven
15.
Am J Pathol ; 177(2): 930-42, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20558579

RESUMEN

Polycomb proteins are known to be of great importance in human cancer pathogenesis. SUZ12 is a component of the Polycomb PRC2 complex that, along with EZH2, is involved in embryonic stem cell differentiation. EZH2 plays an essential role in many cancer types, but an equivalent involvement of SUZ12 has not been as thoroughly demonstrated. Here we show that SUZ12 is anomalously expressed in human primary tumors, especially in mantle cell lymphoma (MCL), pulmonary carcinomas and melanoma, and is associated with gene locus amplification in some cases. Using MCL as a model, functional and genomic studies demonstrate that SUZ12 loss compromises cell viability, increases apoptosis, and targets genes involved in central oncogenic pathways associated with MCL pathogenesis. Our results support the hypothesis that the abnormal expression of SUZ12 accounts for some of the unexplained features of MCL, such as abnormal DNA repair and increased resistance to apoptosis.


Asunto(s)
Proteínas Portadoras , Regulación Neoplásica de la Expresión Génica , Linfoma de Células del Manto , Proteínas Nucleares , Apoptosis , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Diferenciación Celular/genética , Línea Celular , Reparación del ADN , Perfilación de la Expresión Génica , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Proteínas de Neoplasias , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Complejo Represivo Polycomb 2 , Factores de Transcripción
16.
Blood ; 116(8): e12-7, 2010 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-20479282

RESUMEN

Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease. Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022). This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).


Asunto(s)
Biomarcadores de Tumor/genética , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Transducción de Señal/efectos de los fármacos , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Femenino , Perfilación de la Expresión Génica , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Adhesión en Parafina , ARN Mensajero/genética , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
17.
Blood ; 110(9): 3345-51, 2007 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-17634410

RESUMEN

Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response. We measured tumoral CYP3A and MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. To test whether the tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, their expression levels were compared with the clinical response and survival of the patients, finding that a high tumoral expression of CYP3A4 was significantly associated with a lower complete remission rate. This was further investigated with cell lines stably expressing CYP3A4 that exhibited an increased resistance to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored.


Asunto(s)
Antineoplásicos/uso terapéutico , Sistema Enzimático del Citocromo P-450/genética , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Cromosomas Humanos Par 7 , Citocromo P-450 CYP3A , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Etopósido/uso terapéutico , Duplicación de Gen , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Células Jurkat , Linfoma de Células T Periférico/mortalidad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Células Tumorales Cultivadas
18.
J Clin Oncol ; 25(22): 3321-9, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17577022

RESUMEN

PURPOSE: Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis. MATERIALS AND METHODS: We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray. RESULTS: We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68(+) cells. CONCLUSION: Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Ganglios Linfáticos/patología , Linfoma de Células T/genética , Linfoma de Células T/mortalidad , Humanos , Inmunohistoquímica , Linfoma de Células T/clasificación , Linfoma de Células T/patología , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estadísticas no Paramétricas , Análisis de Supervivencia
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