Navarra Institute for Health Research IdiSNA

Pamplona, Spain

Navarra Institute for Health Research IdiSNA

Pamplona, Spain

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PubMed | Hospital San Pedro, Institute Salud Carlos III, Navarra Institute for Health Research IdiSNA and Hospital Garcia Orcoyen
Type: | Journal: Infection | Year: 2016

In 2014, an autochthonous case of introduced malaria caused by Plasmodium vivax was identified in Spain. The strain that infected this patient was identical to that of a prior imported case from Pakistan. This is the first case where the source of infection could be identified since elimination in Spain.


PubMed | University of Pamplona and Navarra Institute for Health Research IdisNa
Type: Journal Article | Journal: Nutrients | Year: 2016

Obesity is defined as an abnormal or excessive fat accumulation that may impair health. Dual-energy X-ray absorptiometry (DEXA) has been suggested as the gold standard to define obesity, but because its use is complex and expensive, anthropometric measures such as body mass index (BMI) or the waist-to-height ratio (WtHr) have been used as alternatives. The aim of this study was to review the published literature and investigate the correlation of BMI and WtHr with body fat (BF) measured by DEXA in pediatric populations. References were sought in PubMed/Medline and Embase datasets. Five original articles, published between 2013 and 2015, were finally included in this review. Their sample size ranged from 83 to 5355, and the age of participants ranged from 4.9 to 19 years old. The most frequently reported association measurements were the coefficients of determination (R), followed by correlation coefficients and least-squares regression coefficients. BF measured by DEXA was strongly correlated with both BMI (R ranging from 0.32 to 0.91) and WtHr (R ranging from 0.49 to 0.73). Thus, either BMI or WtHr may be useful to define obesity when more sophisticated techniques are not available. Our systematic review of the available literature found that neither index demonstrated superiority in assessing obesity in children.


Berraondo P.,Navarra Institute for Health Research IDISNA | Berraondo P.,Center for Applied Medical Research | Minute L.,Navarra Institute for Health Research IDISNA | Minute L.,Center for Applied Medical Research | And 7 more authors.
Immunological Reviews | Year: 2016

Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors. Here, we review recent advances in the understanding of the role of cell populations and soluble components of the innate immune system in cancer, with a focus on complement, the adapter molecule Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


PubMed | Navarra Institute for Health Research IDISNA and Aduro Biotech
Type: Review | Journal: Immunological reviews | Year: 2016

Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors. Here, we review recent advances in the understanding of the role of cell populations and soluble components of the innate immune system in cancer, with a focus on complement, the adapter molecule Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells.


Solas M.,University of Navarra | Solas M.,Navarra Institute for Health Research IdISNA | Milagro F.I.,University of Navarra | Milagro F.I.,Institute Salud Carlos III | And 6 more authors.
Trends in Pharmacological Sciences | Year: 2016

Five pharmaceutical strategies are currently approved by the US FDA for the treatment of obesity: orlistat, lorcaserin, liraglutide, phentermine/topiramate, and bupropion/naltrexone. The most effective treatment seems to be the combined administration of phentermine/topiramate followed by lorcaserin and bupropion/naltrexone. In relation to the management of excessive weight, other aspects also need to be considered, including comorbidities accompanying obesity, drug interactions, and the risk of negative collateral effects, as well as individualized treatments based on the genetic make-up. This review aims to provide an overview of the approved anti-obesity drugs and newer molecules that could affect different targets in the central nervous system or peripheral tissues, the molecular mechanisms, emerging dietary treatments and phytogenic compounds, and pharmacogenetic/nutrigenetic approaches for personalized obesity management. © 2016 Elsevier Ltd.


PubMed | Mount Sinai School of Medicine, University of Navarra and Navarra Institute for Health Research IdiSNA
Type: Journal Article | Journal: Oncoimmunology | Year: 2016

Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon (IFN) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFN co-expressing in the liver a SR-B1 ligand and IFN by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFN signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFN enhancers while SR-B1 inhibitors dampen IFN activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFN and oncolytic viruses.


PubMed | Spanish National Institute of Health Carlos III, Ibsal Hospital Universitario Of Salamanca, University of Navarra and Navarra Institute for Health Research IdiSNA
Type: Journal Article | Journal: Journal of translational medicine | Year: 2016

Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial.A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 1010(6) or 10010(6) cultured autologous BM-MSCs, and followed up for 12months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12months (low-dose vs control group p=0.005 and high-dose vs control group p<0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12months (p<0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly.The single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 10010(6) cells are administered. These results pave the way for a future phase III clinical trial.gov identifier NCT02123368. N EudraCT: 2009-017624-72.


Interferon alpha (IFN) is a cytokine approved for the treatment of several types of cancer. However, the modest effect on overall survival and the high toxicity associated with the treatment has reduced the clinical use of this cytokine. In this study, we have developed a tumor model that reproduces this clinical setting. A high dose of an adeno-associated virus encoding IFN (AAV-IFN) was able to eradicate a liver metastases model of colon cancer but induced lethal pancytopenia. On the other hand, a safe dose of AAV-IFN was not able to eliminate the liver metastases of colon cancer. In this IFN-resistant tumor model, administration of an adeno-associated vector encoding apolipoprotein A-1 fused to IFN was able to fully eradicate the tumor in 43% of mice without toxicity. This antitumor effect was limited by suboptimal long-term CD8+ T cell activation and the expansion of T regulatory cells. In contrast, IFN upregulated suppressor molecules such as PD-1 and interleukin 10 on CD8+ T lymphocytes. In conclusion, we show that apolipoprotein A-1 fused to IFN is a novel antitumor drug that differs from IFN in the modulation of suppressor mechanisms of the immune response. These differential properties pave the way for rational combinations with other immunomodulatory drugs.


PubMed | University of Navarra and Navarra Institute for Health Research IdiSNA
Type: Journal Article | Journal: Oncotarget | Year: 2016

Blockade of PD-L1 with specific monoclonal antibodies (anti-PD-L1) represents a therapeutic strategy to increase the capability of the immune system to modulate the tumor immune-resistance. The relationship between anti-PD-L1 tumor exposition and anti-tumor effect represents a challenge that has been addressed in this work through the identification of certain biomarkers implicated in the antibodys mechanism of action, using a syngeneic melanoma mouse model. The development of an in-vitro/in-vivo platform has allowed us to investigate the PD-L1 behavior after its blockage with anti-PD-L1 at cellular level and in animals. In-vitro studies showed that the complex PD-L1/anti-PD-L1 was retained mainly at the cell surface. The antibody concentration and time exposure affected directly the recycling or ligand turnover. In-vivo studies showed that anti-PD-L1 was therapeutically active at all stage of the disease, with a rapid onset, a low but durable efficacy and non-relevant toxic effect. This efficacy measured as tumor shrinkage correlated with tumor-specific infiltrating lymphocytes (TILs), which increased as antibody tumor concentrations increased. Both, TILS and antibody concentrations followed similar kinetic patterns, justifying the observed anti-PD-L1 rapid onset. Interestingly, peripheral lymphocytes (PBLs) behave as infiltrating lymphocytes, suggesting that these PBLs might be considered as a possible biomarker for antibody activity.


PubMed | Navarra Institute for Health Research IdiSNA
Type: Journal Article | Journal: Cancer research | Year: 2016

The recent approval by the FDA of the combination of anti-CTLA4 and anti-PD-1 mAbs for the treatment of BRAF-unmutated unresectable or metastatic melanoma is a landmark for the development of cancer immunotherapy. On October 18 to 22, 2015, a symposium was held in Pamplona (Spain) to present and discuss the basic and clinical discoveries that have brought us to this milestone and to explore other targets and immunotherapy strategies aimed at attaining more efficacious oncology practice in the short term. Cancer Res; 76(10); 2863-7. 2016 AACR.

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