Garcia-Carbonero R.,University of Seville |
Garcia-Carbonero R.,Hospital Universitario Virgen del Rocio |
Carnero A.,University of Seville |
Paz-Ares L.,University of Seville |
Paz-Ares L.,Hospital Universitario Virgen del Rocio
The Lancet Oncology | Year: 2013
Heat shock protein 90 (HSP90) is a molecular chaperone that is crucial for the stability and function of many proteins essential for cell survival. Many oncogenes, including tyrosine kinases, transcription factors, and cell-cycle regulatory proteins, are client proteins of HSP90. Inhibition of HSP90 causes client protein degradation via the ubiquitin-proteasome pathway, and is a mechanism that might simultaneously downregulate several redundant pathways crucial for cell viability and tumour development. HSP90 inhibitors are currently being developed as anticancer agents, and have shown early promising results in molecularly defined subgroups of solid tumours (eg, ALK-rearranged non-small-cell lung cancer and HER2-amplified breast cancer) and some haematological malignancies (eg, multiple myeloma). Here, we review the current status of HSP90 inhibitors in clinical development, including geldanamycin derivatives, resorcinol derivatives, purine analogues, and other synthetic inhibitors. We also discuss novel strategies and future perspectives on how to optimise the therapeutic potential of this exciting new class of drugs. © 2013 Elsevier Ltd.
Remon J.,Hospital Of Mataro |
Corral J.,Hospital Universitario Virgen del Rocio |
Lianes P.,Hospital Of Mataro
Cancer Treatment Reviews | Year: 2015
Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. MPM incidence has been increasing in recent years and it is not expected to fall off in the next two decades. Prognosis of MPM patients is modest since the vast majority of patients are diagnosed at advanced stage and because platinum-based chemotherapy remains the cornerstone of treatment, with no standard second line treatment. Most current efforts to improve outcomes are based on a better understanding of the stromal compartment and deregulated pathways leading ultimately to the design of clinical trials based on novel therapeutic approaches such as immunotherapy or molecular-directed compounds. This review seeks to update the last clinical trials investigating novel agents in unresectable MPM. © 2014 Elsevier Ltd.
Cordero E.,Hospital Universitario Virgen Del Rocio |
Manuel O.,University of Lausanne
Current Opinion in Organ Transplantation | Year: 2012
PURPOSE OF REVIEW: We reviewed the most recent literature on solid-organ transplant (SOT) recipients regarding the clinical significance of influenza and the immunogenicity and safety of influenza vaccine in this population. RECENT FINDINGS: In SOT recipients, influenza is associated with significant graft dysfunction and even mortality. Early initiation of antiviral therapy is associated with a reduced risk for influenza-associated complications, mainly pneumonia. The main preventive strategy against influenza in SOT recipients remains the administration of yearly influenza vaccine. Although most studies have shown that influenza vaccination is safe after transplantation, impaired responses are expected in more immunosuppressed patients. A lower immunogenicity of influenza vaccine has been described in patients receiving mycophenolate and mammalian target of rapamycin inhibitors. The optimal timing of vaccination after transplant remains to be determined, although vaccination during the early posttransplant period appears to be safe. Novel vaccination strategies, such as intradermal vaccination or use of adjuvanted vaccines, have been evaluated in SOT recipients, with inconclusive results to date. SUMMARY: The administration of influenza vaccination is strongly recommended in SOT recipients and their relatives. Further research is needed for improving the immunogenicity of influenza vaccine in this population. Copyright © 2012 Lippincott Williams & Wilkins.
Martin-Garrido I.,Rochester College |
Martin-Garrido I.,Hospital Universitario Virgen Del Rocio |
Carmona E.M.,Rochester College |
Specks U.,Rochester College |
Limper A.H.,Rochester College
Chest | Year: 2013
Background: Pneumocystis pneumonia (PcP) is an opportunistic fungal infection. Although T-cell immunity is classically related to Pneumocystis defense, recent data support roles for B lymphocytes in the development of PcP in animals, and we have observed several cases of PcP in patients receiving rituximab. These observations prompted a systematic review of our experience to define the spectrum of clinical presentations in which PcP has occurred in the setting of rituximab therapy. Methods: Using a computer-based search, we reviewed the records of patients who received rituximab and developed PcP at Mayo Clinic Rochester over the years 1998 to 2011 to establish the underlying conditions, clinical course, possible risk factors, and potential association between this drug and the development of PcP. Results: Over this period, 30 patients developed PcP during treatment with rituximab. The underlying diseases included hematologic malignancies in 90% of cases. Glucocorticoids were used in 73% of these patients, under different chemotherapeutic regimens. Three patients (10%) developed PcP in the setting of rituximab without concomitant chemotherapy or significant glucocorticoid exposure. Of these 30 patients, 88% developed acute hypoxemic respiratory failure and 53% required ICU admission. The clinical course was fatal in 30%. Conclusion: PcP can occur in association with rituximab, with the majority of cases having also received cytotoxic chemotherapy or significant doses of glucocorticoids. The clinical course of cases of PcP in patients treated with rituximab can be quite fulminant, with significant mortality. Primary prophylaxis should be considered in patients at risk, and secondary prophylaxis provided unless immune reconstitution is well assured. © 2013 American College of Chest Physicians.
Ortiz Leyba C.,Hospital Universitario Virgen del Rocio
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral | Year: 2011
Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended.
Jimenez Jimenez F.J.,Hospital Universitario Virgen del Rocio
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral | Year: 2011
Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30-day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure.
Carnero A.,Hospital Universitario Virgen del Rocio |
Lleonart M.E.,Institute Of Recerca Hospital Vall Dhebron
Biological Reviews | Year: 2011
Cancer is controlled not only by genetic events but also by epigenetic events. The active acquisition of epigenetic changes is a poorly understood but very important process in mammalian development, differentiation, and disease. It is well established that epigenetic events are controlled by a specific subgroup of proteins, such as DNA methyltransferases, histone acetylases histone lysine methyltransferases or histone deacetylases, that influence methylation or acetylation patterns to modulate gene expression. We and others have identified S-adenosylhomocysteine hydrolase in a high-throughput genetic screen focused on discovering novel genes whose inhibition induces immortalisation of primary cells. Herein, we address the importance of genes involved in epigenetic mechanisms during senescence and how their effects might determine senescence bypass and immortalisation. The ways in which genes that regulate epigenetic mechanisms might modulate senescence/immortalisation and how these pathways could influence cancer development are explored. Overall, epigenetic modifications seem to play a major role in cancer, influencing tumour outcome by interfering with key senescence pathways. © 2010 The Authors. Biological Reviews © 2010 Cambridge Philosophical Society.
Carnero A.,Hospital Universitario Virgen del Rocio
Methods in molecular biology (Clifton, N.J.) | Year: 2013
Cellular senescence is a tumor suppression mechanism that evolved to limit duplication in somatic cells. Senescence is imposed by natural replicative boundaries or stress-induced signals, such as oncogenic transformation. Neoplastic cells can be forced to undergo senescence through genetic manipulations and epigenetic factors, including anticancer drugs, radiation, and differentiating agents. Senescent cells show distinct phenotypic and molecular characteristics, both in vitro or in vivo. These biomarkers might either cause or result from senescence induction, but could also be the byproducts of physiological changes in these non-replicating cells.
La Torre F.,University of Rome La Sapienza |
de la Portilla F.,Hospital Universitario Virgen del Rocio
Colorectal Disease | Year: 2013
Aim: Randomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long-term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12months after treatment. The objective of this study was to evaluate the long-term efficacy and safety of NASHA/Dx, assessed 24months after treatment. Method: This study was a 24-month follow-up assessment of patients treated with NASHA/Dx under open-label conditions. Data on FI episodes and quality of life measures were collected from diaries over the 28-day period immediately preceding the 24-month assessment. Adverse events were collected. Results: Eighty-three of 115 patients completed the 24-month follow-up assessment. At 24months, 62.7% of patients were considered responders and experienced a ≥50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P<0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence-free days increased from 14.6 at baseline to 21.7 at 24months (P<0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self-limited and resolved within 1month of the injection. Conclusion: NASHA/Dx is safe, effective and durable over a 24-month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI. © 2013 The Authors Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
De Alarcon A.,Hospital Universitario Virgen del Rocio
Current Infectious Disease Reports | Year: 2012
Q fever is an ubiquitous zoonosis caused by Coxiella burneti, an intracellular bacterium that can produce acute or chronic infections in humans. These forms are characterized by different evolution, serological profile and treatment that must be very long to achieve a cure in chronic forms. However, the serological profile for diagnosis and the real value of serology for predicting outcome are controversial, and management dilemmas for many patients with Q fever infection are continuously emerging. In this article, we describe in a comprehensive manner the different clinical presentations of the disease, making a critical overview of the evidence for serological predictions. We also take a broad view of new available diagnostic techniques and finally, we give recommendations for treatment. © Q fever is an ubiquitous zoonosis caused by Coxiella burneti, an intracellular bacterium that can produce acute or chronic infections in humans. These forms are characterized by different evolution, serological profile and treatment that must be very long to achieve a cure in chronic forms. However, the serological profile for diagnosis and the real value of serology for predicting outcome are controversial, and management dilemmas for many patients with Q fever infection are continuously emerging. In this article, we describe in a comprehensive manner the different clinical presentations of the disease, making a critical overview of the evidence for serological predictions. We also take a broad view of new available diagnostic techniques and finally, we give recommendations for treatment. © Springer Science+Business Media, LLC 2012.