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Martinez-Navarro E.M.,Molecular Genetics Laboratory | Rebollo J.,Medical Oncology | Gonzalez-Manzano R.,Molecular Genetics Laboratory | Sureda M.,Medical Oncology | And 5 more authors.
Clinical and Translational Oncology

Introduction Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. Material and methods Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. Results Activating mutations in the EGFR TK domain were found in 8 of 69 (11.6%) (7 deletions in exon 19 and one L858R mutation in exon 21). Seven of those mutations were found in adenocarcinoma and one mutation in bronchiolo-alveolar carcinoma; five of them in females (one smoker) and three of them in males (one smoker). All patients carrying activating mutations in the TK domain of EGFR were treated with TKIs. Ten patients not carrying an activating mutation in EGFR, who progressed after chemotherapy, were also treated with compassionate use of EGFR-specifi c TKIs (gefi tinib or erlotinib). An objective response (partial response) was observed in all patients carrying an activating mutation in EGFR that received TKIs. Median overall survival for these patients has not been reached, however mean survival has been estimated at 39.5 months (95% CI, 22-57). Conclusions As previously reported, EGFR TK mutational analysis was a predictive test for response to targeted therapy with EGFR TKIs. The early identifi cation of these patients consistently attains disease response and clearly improves outcomes. Source

Souto Bayarri M.,University of Santiago de Compostela | Garcia Tahoces P.,University of Santiago de Compostela | Masip Capdevila L.R.,University of Santiago de Compostela | Suarez Cuenca J.J.,University of Santiago de Compostela | And 2 more authors.

Objectives: The aim of this study was to compare a semiautomatic segmentation method to quantify the function of both ventricles in magnetic resonance imaging (MRI) with the manual tracing method. Material and methods: We examined 17 patients with diverse cardiovascular diseases on a 1.5 Tesla MRI unit (Magnetom Symphony Quantum; Siemens Medical Systems, Erlangen, Germany) using the following parameters: maximum gradient, 30 mT/m; and slew rate, 125 T/m/s. In all studies, we acquired images in cine mode in the short axis (SSFP, 6 mm slice thickness, from the base to the ventricular apex) with breath holding. To reduce the user interaction, we used only one image per patient to initiate the semiautomatic method. The semiautomatic method was based on a specifically designed algorithm of regional growth and border detection. We quantified the end-diastolic volume (EDV), end-systolic volume (ESV), and the ejection fraction (EF) for both ventricles in all patients. Results: No significant differences between the two segmentation techniques were found in the quantification of either ventricle (p > 0.05). The difference in the volumes, although nearly significant, are clinically irrelevant. The correlation for the estimation of left ventricular function was excellent (r > 0.9), and the correlation for the estimation of right ventricular function was good (r > 0.7). Conclusions: Our semiautomatic segmentation method enables the function of both ventricles to be quantified as accurately as the conventional method. © 2010 SERAM. Published by Elsevier España, S.L. All rights reserved. Source

Souto Bayarri M.,University of Santiago de Compostela | Masip Capdevila L.,University of Santiago de Compostela | Remuinan Pereira C.,University of Santiago de Compostela | Suarez-Cuenca J.J.,University of Santiago de Compostela | And 3 more authors.

Objective: To compare the methods of right ventricle segmentation in the short-axis and 4-chamber planes in cardiac magnetic resonance imaging and to correlate the findings with those of the tricuspid annular plane systolic excursion (TAPSE) method in echocardiography. Material and methods: We used a 1.5 T MRI scanner to study 26 patients with diverse cardiovascular diseases. In all MRI studies, we obtained cine-mode images from the base to the apex in both the short-axis and 4-chamber planes using steady-state free precession sequences and 6 mm thick slices. In all patients, we quantified the end-diastolic volume, end-systolic volume, and the ejection fraction of the right ventricle. On the same day as the cardiac magnetic resonance imaging study, 14 patients also underwent echocardiography with TAPSE calculation of right ventricular function. Results: No statistically significant differences were found in the volumes and function of the right ventricle calculated using the 2 segmentation methods. The correlation between the volume estimations by the two segmentation methods was excellent (r = 0,95); the correlation for the ejection fraction was slightly lower (r = 0,8). The correlation between the cardiac magnetic resonance imaging estimate of right ventricular ejection fraction and TAPSE was very low (r = 0,2, P <.01). Conclusion: Both ventricular segmentation methods quantify right ventricular function adequately. The correlation with the echocardiographic method is low. © 2012 SERAM. Source

Crujeiras A.B.,Cancer Epigenetics Laboratory | Crujeiras A.B.,Complejo Hospitalario Universitario Of Santiago Chus | Crujeiras A.B.,CIBER ISCIII | Diaz-Lagares A.,Cancer Epigenetics Laboratory | And 7 more authors.
Free Radical Research

Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer. © 2013 Informa UK, Ltd. Source

Han T.S.,Ashford and St Peters NHS Foundation Trust | Lee D.M.,University of Manchester | Lean M.E.J.,University of Glasgow | Finn J.D.,University of Manchester | And 14 more authors.
European Journal of Endocrinology

Background: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently.Objective: In this study, we examined the associations of socioeconomic status (SES) and lifestyle factors with BMI and waist circumference (WC) in middle-aged and elderly European men.Design and setting: A cross-sectional study of 3319 men aged 40-79 years recruited from eight European centres.Outcomes: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles.Results: The prevalence of BMI ≥30 kg/m2 or WC ≥102 cm rose linearly with age, except in the eighth decade when high BMI, but not high WC, declined. Among men aged 40-59 years, compared with non-smokers or most active men, centre and BMI-adjusted RRRs for having a WC between 94 and 101.9 cm increased by 1.6-fold in current smokers, 2.7-fold in least active men and maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC ≥102 cm, notably 8.4-fold greater in least active men who smoked. Compared with men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65 years group and by 1.3-fold in the 40-75 years group. These relationships were weaker among elderly men.Conclusion: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age. © 2015 European Society of Endocrinology Printed in Great Britain. Source

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