Centro Oncologico Of Galicia

A Coruña, Spain

Centro Oncologico Of Galicia

A Coruña, Spain
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Munteanu C.R.,University of La Coruña | Fernandez-Blanco E.,University of La Coruña | Seoane J.A.,University of La Coruña | Izquierdo-Novo P.,Centro Oncologico Of Galicia | And 4 more authors.
Current Pharmaceutical Design | Year: 2010

There is a need for the study of complex diseases due to their important impact on our society. One of the solutions involves the theoretical methods which are fast and efficient tools that can lead to the discovery of new active drugs specially designed for these diseases. The Quantitative Structure - Activity Relationship models (QSAR) and the complex network theory become important solutions for screening and designing efficient pharmaceuticals by coding the chemical information of the molecules into molecular descriptors. This review presents the most recent studies on drug discovery and design using QSAR of several complex diseases in the fields of Neurology, Cardiology and Oncology. © 2010 Bentham Science Publishers Ltd.

Alba E.,Hospital Universitario Virgen Of La Victoria | Albanell J.,Hospital Parc Of Salut Mar | De La Haba J.,Hospital Universitario Reina Sofia | Barnadas A.,Autonomous University of Barcelona | And 11 more authors.
British Journal of Cancer | Year: 2014

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.

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.
Andrologia | Year: 2011

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.

Rodriguez Martinez de Llano S.,Centro Oncologico Of Galicia | Jimenez-Vicioso A.,Complutense University of Madrid | Mahmood S.,Novartis | Carreras-Delgado J.L.,Hospital Clinico San Carlos
Revista Espanola de Medicina Nuclear | Year: 2010

We performed a retrospective study to evaluate the accuracy, diagnostic validity, and clinical impact of 18F-FDG PET in the management of recurrent and metastatic disease in patients with Renal Cell Carcinoma (RCC) from our database. 18F-FDG PET studies were identified from 58 patients that matched our criteria for inclusion in the study. Results were confirmed with histopathological findings, clinical follow-up time (at least 12 months), and/ or conventional imaging methods (CIM). A sensitivity of 80.56%, specificity 86.36%, diagnostic accuracy 58.7%, positive predictive value 90.63%, and a negative predictive value of 73.08% were observed. The clinical impact was high in 25 cases (43%) and we found no impact in only 10 studies (17.2%). We concluded that 18F-FDG PET was useful and had a high clinical impact in the management of recurrent and metastatic RCC. From our data, it seemed that a positive PET study was more helpful to the physician than a negative study. © 2009 Elsevier España, S.L. y SEMNIM.

Esteves S.C.,Referral Center for Male Reproduction | Gosalvez J.,Autonomous University of Madrid | Lopez-Fernandez C.,Autonomous University of Madrid | Nunez-Calonge R.,Tambre Clinic | And 4 more authors.
International Urology and Nephrology | Year: 2015

Purpose: Varicocele is a frequent cause of impaired testicular function that has been associated with increased levels of sperm DNA fragmentation (SDF). Sperm with degraded DNA (DDS), as observed using the sperm chromatin dispersion (SCD) test, represent a subpopulation of spermatozoa with extensive DNA and nuclear protein damage. The aim of this work was to determine the usefulness of sperm DNA degradation index (DDSi) as a novel noninvasive biomarker to identify infertile men with varicocele. Methods: A total of 593 semen samples obtained from men attending infertility clinics were analyzed for SDF and DDS with the SCD test. These samples were classified as: (1) fertile donors; (2) infertile patients with least two failed assisted reproduction cycles; (3) leukocytospermia; (4) Chlamydia trachomatis infection; (5) testicular cancer, and (6) infertile men with varicocele. The DDSi was obtained by determining the proportion of DDS in the whole sperm population presenting with fragmented DNA. The diagnostic accuracy of DDSi was evaluated by correlation coefficient and receiver operating characteristics analyses. Results: A positive correlation (r ≥ 0.52) was observed between the SDF and the frequency of degraded sperm in all patient groups. The sperm DNA degradation index (DDSi) was at least twice as higher in infertile men with varicocele (mean: 0.54) compared with other clinical conditions and fertile donors (means ranging from 0.02 to 0.21; P < 0.0001). A DDSi ≥ 0.33 identified patients with varicocele with 94 % accuracy. Conclusion: Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals with varicocele when examining sperm DNA damage during a routine semen analysis. This finding may alert practitioners and laboratories performing semen analysis that in the presence of an abnormal DDSi it is likely that a given patient has varicocele. It is therefore strongly recommended that such patients be referred to urologists in order to undergo a full andrological examination and be properly counseled. © 2015, Springer Science+Business Media Dordrecht.

Gosalvez J.,Autonomous University of Madrid | Rodriguez-Predreira M.,Complejo Hospitalario Universitario runa | Mosquera A.,Complejo Hospitalario Universitario runa | Lopez-Fernandez C.,Autonomous University of Madrid | And 4 more authors.
Andrologia | Year: 2014

Summary: Assessment of human sperm DNA fragmentation by the sperm chromatin dispersion (SCD) test is based on the detection of haloes of spreading DNA loops after sequential DNA denaturing and protamine removal. After the SCD test, sperm without DNA fragmentation show chromatin haloes emerging from the central nuclear core, while sperm containing fragmented DNA present small or no haloes. The nuclear degraded sperm are recognised as a differentiated category within the sperm with fragmented DNA, whose cores appear irregularly and/or faintly stained. This subpopulation is more prevalent in patients with varicocele. Protein staining with 2.7-dibrom-4-hydroxy-mercury-fluorescein demonstrated that degraded sperm intensely lose nuclear core proteins after the SCD processing. Moreover, degraded sperm are 65% more faintly labelled for DNA breaks after in situ nick translation (ISNT) on average, due to extensive DNA loss. A two-dimensional comet assay under sequential neutral and alkaline conditions demonstrated that degraded sperm contain both massive double- and single-strand DNA breaks. The degraded sperm appear as a subpopulation with stronger nuclear damage, affecting both DNA and protein fractions, possibly due to intense intratesticular oxidative stress, what could explain its higher proportion in patients with varicocele. © 2013 Blackwell Verlag GmbH.

Gamez-Pozo A.,Hospital Universitario La Paz | Anton-Aparicio L.M.,University of La Coruña | Bayona C.,Hospital General Yague | Borrega P.,Hospital Of San Pedro Of Alcantara | And 10 more authors.
Neoplasia (United States) | Year: 2012

Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood. samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting.© 2012 Neoplasia Press, Inc. All rights reserved.

Meseguer M.,University of Valencia | Santiso R.,Complejo Hospitalario Universitario runa | Santiso R.,Centro Oncologico Of Galicia | Garrido N.,University of Valencia | And 4 more authors.
Fertility and Sterility | Year: 2011

Objective: To quantify the effect of sperm DNA fragmentation (SDF) on reproductive outcome by evaluating the most statistically significant bias factors using logistic regression. Design: Prospective blind observational cohort study. Setting: University affiliated private IVF unit. Patient(s): Two hundred ten male partners of couples undergoing in vitro fertilization (IVF) or first intracytoplasmic sperm injection (ICSI) cycles with fresh or thawed sperm with the women's own or donated oocytes. Intervention(s): None. Main Outcome Measure(s): SDF determined before and after swim-up (n = 420), odds ratio calculated of the effect of an increase of one unit of SDF on pregnancy, and stratified regression analysis performed to evaluate the confusion effect of oocyte quality, sperm origin, and the fertilization procedure. Result(s): The effect of SDF on pregnancy was not affected by sperm origin (fresh or thawed) or fertilization procedure when measured both before and after swim-up. When oocytes from infertile patients were employed, SDF had a statistically significant negative impact on chance of pregnancy. For every 10% increase in SDF, the probability of not achieving pregnancy increased by 1.31. When donated oocytes were employed, SDF did not have a statistically significant effect. Conclusion(s): The effect of SDF on the probability of pregnancy can be calculated independent of the fertilization procedure or sperm origin. Oocyte quality conditions the extent of the negative impact of SDF on pregnancy; this can be overcome when good quality oocytes are employed. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

Mahmood S.,North Central Bronx Hospital | Mahmood S.,General Electric | Rodriguez Martinez De Llano S.,Centro Oncologico Of Galicia
Clinical Nuclear Medicine | Year: 2012

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.

Gomez-Veiga F.,Complejo Hospitalario Universitario runa | Marino A.,Centro Oncologico Of Galicia | Alvarez L.,Complejo Hospitalario Universitario runa | Rodriguez I.,Complejo Hospitalario Universitario runa | And 3 more authors.
BJU International | Year: 2012

Salvage therapeutic options following radical prostatectomy or radiotherapy for patients with local relapse of prostate cancer include radical prostatectomy, radiotherapy, brachytherapy or cryotherapy. Salvage radical prostatectomy following radiotherapy failure is associated with a 5-year PSA relapse-free rate of 30-40%. Biochemical relapse-free survival rates after salvage radiotherapy following radical prostatectomy failure range from 10% to 77% after a follow-up of 22-60 months. A number of studies have evaluated salvage brachytherapy for radiotherapy failure and 5-year biochemical disease-free survival (bDFS) rate results reported are of the order of 20-87%; one study reported a 10-year bDFS rate of 54%. Fewer studies in small numbers of patients and with shorter follow-up have been conducted on brachytherapy for radical prostatectomy failure and bDFS rates reported include 25.8% at a median of 29 months to 70% at a median of 20 months. The side-effects were as expected for brachytherapy. A newer initiative conducted in Spain in a larger series of 42 patients with failure following radical prostatectomy involves brachytherapy with RAPID Strand™ 125I seeds and real-time placement. The 5-year bDFS rate was 88.6% and cancer-specific survival was 97%; complication rates were low. Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection. © 2012 BJU INTERNATIONAL.

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