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Peiro G.,University of Alicante | Ortiz-Martinez F.,University of Alicante | Gallardo A.,Clinica Girona | Perez-Balaguer A.,University of Alicante | And 8 more authors.
British Journal of Cancer | Year: 2014

Background:Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas.Methods:We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome.Results: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab.Conclusions:Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients. © 2014 Cancer Research UK. All rights reserved. Source

Navarro B.,Research Unit | Navarro B.,University of Castilla - La Mancha | Lopez-Torres J.,University of Castilla - La Mancha | Lopez-Torres J.,University Health Care Center Area of Albacete | And 3 more authors.
Geriatrics and Gerontology International | Year: 2013

Aim: The main objective of this study was the validation of a brief support instrument for the diagnosis of insomnia in older adults. Methods: An observational study was carried out for the evaluation of the Insomnia in the Elderly Scale using the psychiatric interview as the gold standard. Data was collected in a primary care setting in the city of Albacete, Spain. Participants were 926 non-institutionalized older adults aged ≥65 years. Results: Sleep characteristics, and the health and sociodemographic status of the participants were assessed. The Insomnia in the Elderly Scale is divided into two subscales for the evaluation of the Diagnostic and Statistical Manual of Mental Disorders, Fouth Edition criteriaA and B for insomnia. The area under the receiver operating characteristic curve for subscaleA was 0.868. The cut-off point to detect the presence of diagnostic criterionA for insomnia was a score of ≥3 (sensitivity: 86.4%; specificity: 69.5%). The area under the receiver operating characteristic curve for subscaleB was 0.832. The cut-off point to detect the presence of diagnostic criterionB was a score of ≥2 (sensitivity: 86.3%; specificity: 66.4%). Conclusions: The Insomnia in the Elderly Scale has appropriate psychometric properties. This scale compensates for the lack of validated instruments for use in the population aged 65 years or older. The fact that it is divided into two subscales to separately evaluate the insomnia criteria enables us to detect the presence of each of them. Finally, it has been validated in participants aged 65 years and older, which is the target population for this scale. Geriatr Gerontol Int 2013; 13: 646-653. © 2012 Japan Geriatrics Society. Source

Caminos E.,University of Castilla - La Mancha | Vaquero C.F.,University of Castilla - La Mancha | Garcia-Olmo D.C.,University General Hospital of Albacete
Histology and Histopathology | Year: 2014

Characterization of retinal cells, cell transplants and gene therapies may be helped by pre-labeled retinal cells, such as those transfected with vectors for green fluorescent protein expression. The aim of this study was to analyze retinal cells and optic nerve components from transgenic green mice (GM) with the ‘enhanced’ green fluorescent protein (EGFP) gene under the control of the CAG promoter (a chicken ?-actin promoter and a cytomegalovirus enhancer). The structural analysis and electroretinography recordings showed a normal, healthy retina. Surprisingly, EGFP expression was not ubiquitously located in the retina and optic nerve. Epithelial cells, photoreceptors and bipolar cells presented high green fluorescence levels. In contrast, horizontal cells, specific amacrine cells and ganglion cells exhibited a null EGFP expression level. The synaptic terminals of rod bipolar cells displayed a high green fluorescence level when animals were kept in the dark. Immature retinas exhibited different EGFP expression patterns to those noted in adults. Axons and glial cells in the optic nerve revealed a specific regional EGFP expression pattern, which correlated with the presence of myelin. These results suggest that EGFP expression might be related to the activity of both the CAG promoter and ?-actin in mature retinal neurons and oligodendrocytes. Moreover, EGFP expression might be regulated by light in both immature and adult animals. Since GM are used in numerous retina bioassays, it is essential to know the differential EGFP expression in order to select cells of interest for each study. © 2014, Histology and Histopathology. All rights reserved. Source

Solis Garcia del Pozo J.,Villarrobledo General Hospital | Lorente Ortuno S.,University General Hospital of Albacete | Navarro E.,University General Hospital of Albacete | Solera J.,University General Hospital of Albacete
PLoS Neglected Tropical Diseases | Year: 2014

The use of enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM antibodies antibrucella has become widespread in the diagnosis of human brucellosis. IgM anti-Brucella antibodies are indicative of acute infection. Between 2009–2013, 5307 patients were evaluated for serologic diagnosis at the Microbiology Laboratory of the Albacete General Hospital. A ELISA IgM-positive, IgG-negative anti-Brucella antibody serology pattern was detected in 17 of those patients. Epidemiology data, symptoms, laboratory data, treatment and outcome from these patients were reviewed. Sixteen patients presented with musculoskeletal pain, fatigue and/or fever and 1 was asymptomatic. Five patients received treatment with doxycycline combined with rifampin, gentamycin or streptomycin during 6–12 weeks, with no improvement. None of the 17 patients were finally diagnosed with brucellosis. Our results indicate that anti-Brucella IgM positive serology, per se, is not enough to diagnose acute brucellosis and other methods should be used for confirmation. Brucella serology data should be interpreted taking into account the patient's clinical history and epidemiological context. © 2014 Solís García del Pozo et al. Source

Martinez A.F.H.,University General Hospital of Albacete | Jimenez M.D.G.,University General Hospital of Albacete | Vicente A.G.,University of Castilla - La Mancha | Hidalgo J.L.-T.,Zone Health Center | And 4 more authors.
Revista Espanola de Medicina Nuclear e Imagen Molecular | Year: 2016

Objective: F-18 fluorodeoxyglucose integrated PET-CT scan is commonly used in the work-up of lung cancer to improve preoperative disease stage. The aim of the study was to analyze the ratio between SUVmax of N1 lymph nodes and primary lung cancer to establish prediction of mediastinal disease (N2) in patients operated on non-small cell lung cancer. Material and method: This is a retrospective study of a prospective database. Patients operated on non-small cell lung cancer (NSCLC) with N1 disease by PET-CT scan were included. None of them had previous induction treatment, but they underwent standard surgical resection plus systematic lymphadenectomy. Results: There were 51 patients with FDG-PET-CT scan N1 disease. 44 (86.3%) patients were male with a mean age of 64.1 ± 10.8 years. Type of resection: pneumonectomy = 4 (7.9%), lobectomy/bilobectomy = 44 (86.2%), segmentectomy = 3 (5.9%). Histology: adenocarcinoma = 26 (51.0%), squamous = 23 (45.1%), adenosquamous = 2 (3.9%). Lymph nodes after surgical resection: N0 = 21 (41.2%), N1 = 12 (23.5%), N2 = 18 (35.3%). Mean ratio of the SUVmax of N1 lymph node to the SUVmax of the primary lung tumor (SUVmax N1/T ratio) was 0.60 (range 0.08-2.80). ROC curve analysis to obtain the optimal cut-off value of SUVmax N1/T ratio to predict N2 disease was performed. At multivariate analysis, we found that a ratio of 0.46 or greater was an independent predictor factor of N2 mediastinal lymph node metastases with a sensitivity and specificity of 77.8% and 69.7%, respectively. Conclusions: SUVmax N1/T ratio in NSCLC patients correlates with mediastinal lymph node metastasis (N2 disease) after surgical resection. When SUVmax N1/T ratio on integrated PET-CT scan is equal or superior to 0.46, special attention should be paid on higher probability of N2 disease. © 2015 Elsevier España, S.L.U. and SEMNIM. Source

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