J Prados

University of Granada, Granata, Andalusia, Spain

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Publications (103)243.27 Total impact

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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with poor survival rates. Fast detection of PDAC appears to be the most relevant strategy to improve the long-term survival of patients.
    Digestive Diseases and Sciences 07/2014; · 2.26 Impact Factor
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    ABSTRACT: New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients.
    BMC Cancer 07/2014; 14(1):511. · 3.32 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer.
    Pancreas 06/2014; · 3.01 Impact Factor
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    ABSTRACT: The cancer stem cell (CSC) hypothesis on the origin of cancer has recently gained considerable support. CSCs are tumour cells with the capacity for self-renewal and differentiation that direct the origin and progression of the disease and may be responsible for relapse, metastasis and treatment failures. CSCs are identified and isolated by using membrane and cell activity markers; in the case of breast cancer CSCs (BCSCs), these are CD44(+) /CD24(low/-) and show aldehyde dehydrogenase activity, alongside their capacity to grow and form mammospheres. The presence of stem cell properties is associated with a worse outcome. Hence, these cells have important clinical implications, and elucidation of the mechanisms underlying their activity will allow the development of novel effective therapies and diagnostic instruments, improving the prognosis of these patients. Standard treatments are directed against the tumour mass and do not eliminate CSCs. There is therefore a need for specific anti-CSC therapies, and numerous authors are investigating new targets to this end, as reported in this review. It is also necessary for clinical trials to be undertaken to allow this new knowledge to be applied in the clinical setting. However, there have been few trials on anti-BSCSC therapies to date. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 04/2014; · 3.37 Impact Factor
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    ABSTRACT: This article describes the antitumor properties of a new family of merosesquiterpenes, which were synthesized by Diels-Alder cycloaddition of the labdane diene trans-communic acid, highly abundant in Cupressus sempervirens, or its methyl ester, with the appropriate dienophile. These compounds demonstrated potent cytotoxic activity in vitro against human breast, colon, and lung tumor cells. We highlight the elevated activity (IC50: 0.35 ± 0.10 μM) and specificity (TI: 9) of compound 13 against the MCF-7 line, which corresponds to the most prevalent breast cancer cell subtype, luminal A. It was found that compound 13 exerts its anti-tumor action by inducing oxidative stress, arresting the cell cycle in stages G0-G1, and activating apoptosis, which are all associated with low cyclin D1 regulation, pRb hypophosphorylation, increased expression of p27 and p53, and poly (ADP-ribose) polymerase (PARP) fractioning. Epithelial-mesenchymal transition, a phenomenon associated with metastasis promotion and a worsened prognosis also appeared to be inhibited by compound 13. In addition, it markedly reduced tumor development in immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells (luminal A subtype). According to these findings, this new family of compounds, especially compound 13, may be highly useful in the treatment of human breast cancer.
    European Journal of Medicinal Chemistry 03/2014; 79C:1-12. · 3.43 Impact Factor
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    ABSTRACT: Our aim was to evaluate the impact of anatomy as a multidisciplinary area and to identify trends in research by anatomists over time. Data from three main sources were analyzed: SCImago Journal & Country Rank (SJR), using the number of total documents as indicator; MEDLINE (PubMed) database (1898 through October 2012), using the keyword “anatomy” in the “affiliation” field; and the Journal Citation Report (JCR), gathering impact factor and quartile data. The number of publications by anatomists increased between 1898 and 1941, followed by a reduction until 1961 and then by a marked rise to reach 36,686 between 2002 and 2012. After 1941, anatomists began to publish in journals from JCR categories other than “Anatomy & Morphology”, especially after 1962. Between 2007 and 2012, only 22.23 % of articles by anatomists in JCR-indexed journals were in the “Anatomy & Morphology” area and 77.77 % in journals from other categories; 58 % of their articles were in journals in the first and second quartiles. The contribution of anatomists to scientific knowledge is high quality and considerably greater than indicated by the SJR database. This input is especially relevant in the Neurosciences, Cell Biology, and Biology categories. In addition, more than two-thirds of manuscripts by anatomists appear in JCR-ranked publications, and more than half in the top two quartiles of the impact factor ranking. Our results show that the scientific production of anatomists has improved the quantity and quality of multi-disciplinary scientific activity in different knowledge areas.
    Scientometrics 01/2014; 98(1). · 2.27 Impact Factor
  • European Journal of Medicinal Chemistry. 01/2014; 79:1–12.
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    ABSTRACT: Gastrointestinal cancers remain one of the main causes of death in developed countries. The main obstacles to combating these diseases are the limitations of current diagnostic techniques and the low stability, availability, and/or specificity of pharmacological treatment. In recent years, nanotechnology has revolutionized many fields of medicine, including oncology. The association of chemotherapeutic agents with nanoparticles offers improvement in the solubility and stability of antitumor agents, avoidance of drug degradation, and reductions in therapeutic dose and toxicity, increasing drug levels in tumor tissue and decreasing them in healthy tissue. The use of specific molecules that drive nanoparticles to the tumor tissue represents a major advance in therapeutic specificity. In addition, the use of nanotechnology in contrast agents has yielded improvements in the diagnosis and the follow-up of tumors. These nanotechnologies have all been applied in gastrointestinal cancer treatment, first in vitro, and subsequently in vivo, with promising results reported in some clinical trials. A large number of patents have been generated by nanotechnology research over recent years. The objective of this paper is to review patents on the clinical use of nanoparticles for gastrointestinal cancer diagnosis and therapy and to offer an overview of the impact of nanotechnology on the management of this disease.
    Recent patents on anti-cancer drug discovery. 05/2013;
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    ABSTRACT: Colorectal cancer is the third most common cancer in both men and women and has shown a progressive increase over the past 20 years. Current chemotherapy has major limitations, and a novel therapeutic approach is required. Given that neoplastic transformation of colon epithelial cells is a consequence of genetic and epigenetic alterations, RNA interference (RNAi) has been proposed as a new therapeutic strategy that offers important advantages over conventional treatments, with high specificity and potency and low toxicity. RNAi has been employed as an effective tool to study the function of genes, preventing their expression and leading to the development of new approaches to cancer treatment. In malignancies, including colon cancer, RNAi is being used for "silencing" genes that are deregulated by different processes such as gene amplification, mutation, or overexpression and may be the cause of oncogenesis. This strategy not only provides information on the involvement of certain genes in colon cancer, but also opens up a new perspective for its treatment. However, most studies have used adenovirus or lentivirus vectors to transport RNAi into tumor cells or tumors in animal models, because several technical obstacles must be overcome before RNAi can be used in the clinical setting. The aim of this study was to review current knowledge on the use of RNAi techniques in the treatment of colon cancer.
    BioDrugs 04/2013; · 2.12 Impact Factor
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    ABSTRACT: The number of patients with colorectal cancer, the third most frequently diagnosed malignancy in the world, has increased markedly over the past 20 years and will continue to increase in the future. Despite recent advances in chemotherapy, currently used anticancer molecules are unable to improve the prognosis of advanced or recurrent colorectal cancer, which remains incurable. The transport of classical drugs by nanoparticles has shown great promise in terms of improving drug distribution and bioavailability, increasing tissue half-life and concentrating anticancer molecules in the tumor mass, providing optimal drug delivery to tumor tissue, and minimizing drug toxicity, including those effects associated with pharmaceutical excipients. In addition, colon cancer targeting may be improved by incorporating ligands for tumor-specific surface receptors. Similarly, nanoparticles may interact with key drug-resistance molecules to prevent a reduction in intracellular drug levels drug. Recently published data have provided convincing pre-clinical evidence regarding the potential of active-targeted nanotherapeutics in colon cancer therapy, although, unfortunately, only a few of these therapies have translated into early-phase clinical trials. As nanotechnology promises to be a new strategy for improving the prognosis of colon cancer patients, it would be very useful to analyze recent progress in this field of research. This review discusses the current status of nanoparticle-mediated cancer-drug delivery, the challenges restricting its application, and the potential implications of its use in colon cancer therapy.
    Anti-cancer agents in medicinal chemistry 03/2013;
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    ABSTRACT: The present investigation aimed to develop magnetoliposome nanoparticles loaded with 5-fluorouracil by following a reproducible thin film hydration technique. The physicochemical characterization (including electron microscopy analysis, dynamic light scattering, infrared spectrometry, X-ray diffractometry, electrophoresis, and surface thermodynamics) suggested that superparamagnetic magnetite nuclei were successfully embedded into a multilamellar lipid vesicle. Magnetic responsiveness of these nanocomposites was quantitatively analyzed by determining the hysteresis cycle and qualitatively confirmed by microscopic visualizations. A high frequency alternating electromagnetic field was further used to define their heating properties. The absence of cytotoxicity in human colon fibroblast CCD-18 and in human colon carcinoma T-84 cell lines and excellent hemocompatibility of these core/shell particles were demonstrated. Additionally, 5-fluorouracil incorporation was investigated by two procedures: (i) entrapment into the nanoparticulate matrix and (ii) surface deposition onto already formed magnetoliposome particles. The former method reported greater drug loading values and a sustained release profile. Interestingly, 5-fluorouracil release was also triggered by the heating properties of the nanoparticles (hyperthermia-triggered drug release). Hence, we put forward that magnetoliposome particles hold important properties, that is, magnetically targeted delivery, hyperthermia inducing capability, high 5-fluorouracil loading capability, and hyperthermia-triggered burst drug release, suggestive of their potential for a combined antitumor therapy against colon cancer.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 02/2013; · 3.15 Impact Factor
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    ABSTRACT: Accessory (supernumerary) intrathoracic ribs are a very rare congenital disorder. Here, we present the first case of multiple supernumerary intrathoracic ribs in an adult, which are present consecutively between ribs 1 and 4 and without articulation with the vertebrae. Despite this, anatomical variation is usually silent and accidentally discovered; its knowledge can prevent confusion with other structures during imaging diagnostic techniques of thoracic pathologies.
    Anatomia Clinica 02/2013; 35(7). · 1.33 Impact Factor
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    ABSTRACT: Accessory (supernumerary) intrathoracic ribs are a very rare congenital disorder. Here, we present the first case of multiple supernumerary intrathoracic ribs in an adult, which are present consecutively between ribs 1 and 4 and without articulation with the vertebrae. Despite this, anatomical variation is usually silent and accidentally discovered; its knowledge can prevent confusion with other structures during imaging diagnostic techniques of thoracic pathologies.
    Anatomia Clinica 02/2013; 35(7). · 1.33 Impact Factor
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    ABSTRACT: We investigated the incorporation of gemcitabine into a colloidal carrier based on the biodegradable and biocompatible poly(D,L-lactide-co-glycolide) (PLGA) to optimize its anticancer activity. Two synthesis techniques (double emulsion/solvent evaporation, and Flow Focusing(®)) were compared in terms of particle geometry, electrophoretic properties (surface charge), gemcitabine vehiculization capabilities (drug loading and release), blood compatibility, and in vitro antitumor activity. To the best of our knowledge, the second formulation methodology (Flow Focusing(®)) has never been applied to the synthesis of gemcitabine-loaded PLGA particles. With the aim of achieving the finest (nano)formulation, experimental parameters associated to these preparation procedures were analyzed. The electrokinetics of the particles suggested that the chemotherapy agent was incorporated into the polymeric matrix. Blood compatibility was demonstrated in vitro. Flow Focusing(®) led to a more appropriate geometry, higher gemcitabine loading and a sustained release profile. In addition, the cytotoxicity of gemcitabine-loaded particles prepared by Flow Focusing(®) was tested in MCF-7 human breast adenocarcinoma cells, showing significantly greater antitumor activity compared to the free drug and to the gemcitabine-loaded particles synthesized by double emulsion/solvent evaporation. Thus, it has been identified the more adequate formulation conditions in the engineering of gemcitabine-loaded PLGA nanoparticles for the effective treatment of tumors.
    International Journal of Pharmaceutics 01/2013; · 3.99 Impact Factor
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    ABSTRACT: Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.
    BioMed research international. 01/2013; 2013:312656.
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    ABSTRACT: BACKGROUND: The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. METHODS: Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan--Meier method. RESULTS: The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients' survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. CONCLUSIONS: Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.
    Journal of Translational Medicine 12/2012; 10(1):250. · 3.99 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.
    International Journal of Molecular Sciences 12/2012; 13(12):16624-35. · 2.34 Impact Factor
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    ABSTRACT: PURPOSE: Multidrug resistance is one of the major obstacles to the successful treatment of non-small cell lung cancer (NSCLC). An ability to identify molecular markers of drug resistance in peripheral blood cells in order to better target treatment would therefore be extremely useful in selecting therapy protocols for patients. The aim of the present study was to evaluate whether expression of resistance genes (MDR1, MRP3 and LRP) can predict clinical outcome in NSCLC patients treated with paclitaxel and carboplatin. METHODS: Peripheral blood samples were obtained from lung cancer patients before and after chemotherapy and expression of the resistance gene in polymononuclear cells was detected by real-time reverse-transcription polymerase chain reaction. The results were correlated with treatment response and overall survival, which was calculated according to the Kaplan-Meier method. RESULTS: MDR1 expression levels in PMNs rose rapidly within 24 h post-administration of paclitaxel and carboplatin, whereas MRP and LRP expression levels remained unchanged. However, no significant correlation was observed between MDR1 expression and the patients' survival or treatment response. CONCLUSIONS: Modulation of MDR1 gene expression in PMNs after lung cancer treatment with paclitaxel and carboplatin cannot be used as a prognosis marker in these patients.
    Cancer Chemotherapy and Pharmacology 11/2012; · 2.80 Impact Factor
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    ABSTRACT: Cancer is the main cause of death in developing countries. Its development requires multiple steps in which the occurrence of certain events determines the state transition from a normal to a tumor cell. These events are related to the loss of mechanisms that control various biological processes, which results from the accumulation of genetic alterations, including mutations, chromosomal rearrangements, and variations in gene copy number, as well as from epigenetic alterations. In general, chemotherapeutic agents used for toxicity treatments have shown limited antitumor activity, with a high recurrence rate. This has prompted major research efforts to identify novel effective and selective anti-tumor compounds. In this article, we review recent patents that protect the antitumor properties of natural compounds and related molecules derived from plants, animals, or microorganisms. We consider their structure, mechanism of action, molecular targets and, in some cases, the clinical trial phase reached. We also report on various natural agents that appear to prevent cancer development.
    Recent patents on anti-cancer drug discovery. 11/2012;
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    ABSTRACT: Adult stem cells have an enormous potential for clinical use in regenerative medicine that avoids many of the drawbacks characteristic of embryonic stem cells and induced pluripotent stem cells. In this context, easily obtainable human adipose-derived stem cells offer an interesting option for future strategies in regenerative medicine. However, little is known about their repertoire of differentiation capacities, how closely they resemble the target primary tissues, and the potential safety issues associated with their use. DNA methylation is one of the most widely recognized epigenetic factors involved in cellular identity, prompting us to consider how the analyses of 27,578 CpG sites in the genome of these cells under different conditions reflect their different natural history. We show that human adipose-derived stem cells generate myogenic and osteogenic lineages that share much of the DNA methylation landscape characteristic of primary myocytes and osteocytes. Most important, adult stem cells and in vitro-generated myocytes and osteocytes display a significantly different DNA methylome from that observed in transformed cells from these tissue types, such as rhabdomyosarcoma and osteosarcoma. These results suggest that the plasticity of the DNA methylation patterns plays an important role in lineage commitment of adult stem cells and that it could be used for clinical purposes as a biomarker of efficient and safely differentiated cells.
    American Journal Of Pathology 09/2012; · 4.60 Impact Factor

Publication Stats

467 Citations
243.27 Total Impact Points

Institutions

  • 1992–2014
    • University of Granada
      • • Faculty of Medicine
      • • Department of Medicine
      • • Instituto de Biopatología y Medicina Regenerativa (IBIMER)
      Granata, Andalusia, Spain
  • 1995–2012
    • Universidad de Jaén
      • • Department of Health Sciences
      • • Department of Experimental Biology
      Jaén, Andalusia, Spain
  • 2011
    • Hospital Universitario Virgen de las Nieves
      Granata, Andalusia, Spain
  • 1995–2002
    • Universidad de Almería
      Unci, Andalusia, Spain