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A Coruña, Spain

Alba E.,Hospital Universitario Virgen Of La Victoria | Albanell J.,Hospital Parc de Salut Mar | De La Haba J.,Hospital Universitario Reina Sofia | Barnadas A.,Autonomous University of Barcelona | And 11 more authors.
British Journal of Cancer

Background:The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers.Methods:Patients with stages I-III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers.Results:We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups.Conclusion:EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR. © 2014 Cancer Research UK. Source

Mahmood S.,Jacobi Medical Center | Mahmood S.,General Electric | Rodriguez Martinez De Llano S.,Centro Oncologico Of Galicia
Clinical Nuclear Medicine

Dermatomyositis is an inflammatory myopathy that has an association with malignancy in adults. We present a patient who initially presented with adenopathy and progressive muscular weakness and was diagnosed with dermatomyositis and lung carcinoma on further investigation. Whole-body PET/CT scan revealed diffuse proximal muscle hypermetabolism representing the inflammatory nature of dermatomyositis, and an intensely FDG-avid primary right lower lung small cell lung carcinoma and metastatic thoracic lymphadenopathy. PET/CT imaging may offer an "all-in-one" procedure as an alternative to other diagnostic procedures, reducing the number of unnecessary investigations in patients presenting with paraneoplastic syndromes searching for underlying malignancy. © 2012 Lippincott Williams & Wilkins, Inc. Source

Fernandez J.L.,Complejo Hospitalario Universitario runa CHUAC | Fernandez J.L.,Centro Oncologico Of Galicia
Journal of Theoretical Biology

Two procedures for detection of Sister-Chromatid Exchanges (SCEs) in interphase cells within specific DNA sequence areas are delineated. Proliferating cells cultured with 5-bromodeoxyuridine (BrdU) for one cell cycle are subjected to cytokinesis-block to produce binucleated cells. Then, the BrdU-substituted DNA strands are removed as in the chromosome orientation-FISH (CO-FISH) procedure. In one case, the intact unsubstituted DNA strands may be hybridized with differentially labelled direct and reverse single-stranded DNA (ssDNA) probes from the target area. After formation of a SCE during the first cycle, specifically within the target area, three signals should be visualized in each nucleus of the binucleated cell. Two of them, of different color, must appear colocalized or adjacent simultaneously in both sister nuclei, corresponding to the SCE site, being accompanied by a signal from the other homologous locus showing a complementary color pattern in both sister nuclei. Other possibility is hybridizing two separated direct ssDNA probes flanking the target sequence area labelled with the same color and the two reverse complementary ssDNA probes labelled with other color. The presence of three signals with similar color and one of different color in each nucleus from the binucleated cell, following a complementary color pattern between both nuclei, would indicate the presence of a SCE within the DNA sequence area flanked by the DNA probes. The availability of complementary ssDNA probes specific for single locus should make the Interphase SCE-FISH a suitable procedure. © 2012 Elsevier Ltd. Source

Gosalvez J.,Autonomous University of Madrid | Nunez R.,Clinica Tambre | Fernandez J.L.,Complejo Hospitalario Universitario runa | Fernandez J.L.,Centro Oncologico Of Galicia | And 2 more authors.

The rate of increase of sperm DNA fragmentation (rsDF) in fresh and frozen-thawed and processed sperm samples after a density gradient for sperm selection was analysed after 0, 0.5, 1.5, 4.5, 6, 24, 48 and 72h of incubation at 37°C, in five donors with proven fertility. The results showed that: (i) sperm DNA fragmentation (sDF) at baseline in fresh samples (14.3±3.3) was lower than that obtained after freeze-thawing and selection (19.4±4.1), significant differences; (ii) After 6h of incubation the mean sDF in fresh samples (24.2±10.2) was significantly lower than that in frozen-thawed samples (45.3±7.1); (iii) Subsequently, the rsDF in fresh semen samples was 1.6% per h after 6h of incubation, while after thawing and selection the rsDF was 4.3% per h; The tendency to increase in sDF showed high R2 values (R2=0.90) for exponential functions in case of fresh samples, whereas R2 values for linear functions were higher after sperm selection (R2=0.97). These results indicate that differences in sperm DNA fragmentation dynamics before and after storage are an important issue that must be considered for storage of sperm to be used for artificial reproduction techniques. © 2011 Blackwell Verlag GmbH. Source

Perez-Rodriguez A.,Complexo Hospitalario Universitario runa | Loures E.,Complexo Hospitalario Universitario runa | Rodriguez-Trillo A.,Complexo Hospitalario Universitario runa | Costa-Pinto J.,Complexo Hospitalario Universitario runa | And 5 more authors.
Thrombosis Research

Congenital thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is associated with an inherited deficiency of ADAMTS13, a von Willebrand factor-cleaving protease. It is a rare, life-threatening disorder characterized by thrombocytopenia, hemolytic anemia, neurological symptoms, renal dysfunction, and fever resulting from formation of platelet thrombi within the microvasculature. Patients have initial episodes mainly during infancy or early childhood, and are conventionally treated with fresh frozen plasma. However, a more appropriate approach based on recombinant ADAMTS13 is slated to begin shortly. Mutations throughout the ADAMTS13 have been identified in congenital TTP patients. The prevalence of this entity is probably underestimated because it is often not suspected, the clinical course is usually heterogeneous and most of the symptoms are common to other diseases. The present review summarizes our current knowledge about Upshaw-Schulman syndrome. © 2014 Elsevier Ltd. All rights reserved. Source

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