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Trevino A.,University Hospital | Caballero E.,University of Barcelona | De Mendoza C.,University Hospital | Aguilera A.,Hospital Conxo CHUS | And 2 more authors.
AIDS Reviews

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain. Most persons infected with HIV-2 or HTLV-1 acknowledge epidemiological risk factors for contagion, such as originating from or living in endemic regions and/or having had sexual partners from those areas. However, risk factors could not be recognized in up to 20-25% of carriers in Spain. Thus, it seems worth keeping a high level of clinical suspicion in order to identify earlier these neglected human retroviral infections, since diagnostic procedures and antiviral treatment are specific for each of these agents. In this article we summarize the major contributions reported at the meeting of the Spanish Group for HIV-2/HTLV held in Madrid in December 2014. © Permanyer Publications 2015. Source

Martinez-Becerra P.,University of Salamanca | Vaquero J.,University of Salamanca | Romero M.R.,University of Salamanca | Romero M.R.,CIBER ISCIII | And 16 more authors.
Molecular Pharmaceutics

Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4064 resulted in reduced sensitivity to cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where FXR is expressed, exhibit marked refractoriness to pharmacological treatment. Here we have determined whether FXR is upregulated in hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma (HPB) and whether this is related with the expression of genes involved in mechanisms of chemoresistance. Using RT-QPCR and Taqman low density arrays we have analyzed biopsies from healthy livers or surgically removed tumors from naive patients and cell lines derived from HCC (SK-HEP-1, Alexander and Huh7), CGC (TFK1) and HPB (HepG2), before and after exposure to cisplatin at IC50 for 72 h. In liver tumors FXR expression was not enhanced but significantly decreased (healthy liver > HCC > HPB ≈ CGC). Except for CGC, this was not accompanied by changes in the proportions of FXR isoforms. Changes in 36 genes involved in drug uptake/efflux and metabolism, expression/function of molecular targets, and survival/apoptosis balance were found. Changes affecting SLC22A1, CYP2A1 and BIRC5 were shared by HCC, CGC and HPB. Similarity in gene expression profiles between cell lines and parent tumors was found. Pharmacological challenge with cisplatin induced changes that increased this resemblance. This was not dependent upon FXR expression. Thus, although FXR may play a role in inducing chemoresistance under certain circumstances, its upregulation does not seem to be involved in the multidrug resistance phenotype characteristic of HCC, CGC and HPB. © 2012 American Chemical Society. Source

Arruebo M.,University of Zaragoza | Arruebo M.,CIBER ISCIII | Vilaboa N.,CIBER ISCIII | Vilaboa N.,La Paz University Hospital Idi | And 2 more authors.
Expert Opinion on Drug Delivery

Importance of the field: Millions of people receive annually an internal device aimed to repair or reconstruct damaged bone, and different therapeutic moieties are administered during or after surgery generally using systemic routes. The local administration of those moieties using in situ drug-eluting devices emerges as an alternative to minimize undesired side effects in healthy tissues, optimize the amount of drug needed, and reduce the costs. Areas covered in this review: In vitro and in vivo published evidence regarding the performance of internally implantable drug-loaded biomedical devices for traumatology and orthopedic surgery are reviewed in this article, the problems that are encountered, and the main challenges in the development of a new generation of devices. What the reader will gain: An insight of past and current efforts to control the rate of drug release from devices, as well as the requirements that future developments may fulfill, such as responding 'on demand' after biological signaling or communicating the device with the exterior. Take home message: The main drawback for proper design of devices having improved capabilities mainly remains in the lack of understanding with regards to the complex regulation of physiopathological mechanisms and the thermodynamics at the interface between the implant surface and the surrounding tissue. The potential toxicity and risk versus benefits of any new drug-eluting device need to be evaluated carefully. © 2010 Informa UK Ltd. Source

Sanchez-Martinez R.,IMDEA Madrid Institute for Advanced Studies | Cruz-Gil S.,IMDEA Madrid Institute for Advanced Studies | de Cedron M.G.,IMDEA Madrid Institute for Advanced Studies | Alvarez-Fernandez M.,Cell Division and Cancer Group | And 11 more authors.

The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/ stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment. Source

Cejas P.,La Paz University Hospital Idi | Lopez-Gomez M.,Service of Medical Oncology | Aguayo C.,La Paz University Hospital Idi | Madero R.,La Paz University Hospital Idi | And 9 more authors.
Current Cancer Drug Targets

Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases. © 2012 Bentham Science Publishers. Source

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