Institute Investigacion Marques Of Valdecilla Idival

Santander, Spain

Institute Investigacion Marques Of Valdecilla Idival

Santander, Spain
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Paz-Zulueta M.,University of Cantabria | Llorca J.,University of Cantabria | Llorca J.,Institute Investigacion Marques Of Valdecilla Idival | Llorca J.,CIBER ISCIII | And 2 more authors.
Journal of Immigrant and Minority Health | Year: 2015

This retrospective cohort study compares the utilization of prenatal care between African immigrant and native Spanish women. For 2007–2010, we identified 231 pregnant African immigrant women. The native-born population sample was obtained by simple random sampling in a 1:3 ratio. The Kessner Index (KI) and our Own Index (OI) were applied to rate prenatal care adequacy in three categories (adequate, intermediate, and inadequate). Odds ratios (ORs) were estimated using non-conditional logistic regression. Prenatal care was adequate according to the indexes (KI or OI) in 21.3 and 25.8 % of North Africans and in 22.5 and 30.4 % of sub-Saharan Africans. The ORs of inadequacy when adjusted for maternal age, social risk factors, and previous reproductive outcomes were 30.32 and 35.47 (KI or OI) in North and 64.43 and 67.93 in sub- Saharan Africans. These results suggest significant differences in obtaining adequate prenatal care between immigrant and native Spanish women. © 2014, Springer Science+Business Media New York.


Rodriguez-Del Rio E.,Institute Investigacion Marques Of Valdecilla Idival | Marradi M.,CIC Biomagune | Marradi M.,CIBER ISCIII | Calderon-Gonzalez R.,Institute Investigacion Marques Of Valdecilla Idival | And 6 more authors.
Vaccine | Year: 2015

In the search for an effective vaccine against the human pathogen, Listeria monocytogenes (Listeria), gold glyconanoparticles (GNP) loaded with a listeriolysin O peptide LLO91-99 (GNP-LLO) were used to immunise mice, initially using a dendritic cell (DC) vaccine approach, but subsequently using a standard parenteral immunisation approach. To enhance vaccine immunogenicity a novel polysaccharide adjuvant based on delta inulin (Advax™) was also co-formulated with the GNP vaccine. Confirming previous results, DC loaded in vitro with GNP-LLO provided better protection against listeriosis than DC loaded in vitro using free LLO peptide. The immunogenicity of GNP-LLO loaded DC vaccines was further increased by addition of Advax™ adjuvant. However, as DC vaccines are expensive and impracticable for prophylactic use, we next asked whether the same GNP-LLO antigen could be used to directly target DC in vivo. Immunisation of mice with GNP-LLO plus Advax™ adjuvant induced LLO-specific T-cell immunity and protection against Listeria challenge. Protection correlated with an increased frequency of splenic CD4+ and CD8+ T cells, NK cells and CD8α+ DC, and Th1 cytokine production (IL-12, IFN-γ, TNF-α, and MCP-1), post-challenge. Enhanced T-cell epitope recruitment post-challenge was seen in the groups that received Advax™ adjuvant. Immunisation with GNP-LLO91-99 plus Advax™ adjuvant provided equally robust Listeria protection as the best DC vaccine strategy but without the complexity and cost, making this a highly promising strategy for development of a prophylactic vaccine against listeriosis. © 2015 The Authors.


Garcia R.,University of Cantabria | Garcia R.,Institute Investigacion Marques Of Valdecilla Idival | Merino D.,Research Center Marques Of Valdecilla Idival | Gomez J.M.,Hospital Sierrallana | And 8 more authors.
Cellular Signalling | Year: 2016

The pathological remodeling heart shows an increase in left ventricular mass and an excess of extracellular matrix deposition that can over time cause heart failure. Transforming growth factor β (TGFβ) is the main cytokine controlling this process. The molecular chaperone heat shock protein 90 (Hsp90) has been shown to play a critical role in TGFβ signaling by stabilizing the TGFβ signaling cascade. We detected extracellular Hsp90 in complex with TGFβ receptor I (TGFβRI) in fibroblasts and determined a close proximity between both proteins suggesting a potential physical interaction between the two at the plasma membrane. This was supported by in silico studies predicting Hsp90 dimers and TGFβRI extracellular domain interaction. Both, Hsp90aa1 and Hsp90ab1 isoforms participate in TGFβRI complex. Extracellular Hsp90 inhibition lessened the yield of collagen production as well as the canonical TGFβ signaling cascade, and collagen protein synthesis was drastically reduced in Hsp90aa1 KO mice. These observations together with the significant increase in activity of Hsp90 at the plasma membrane pointed to a functional cooperative partnership between Hsp90 and TGFβRI in the fibrotic process. We propose that a surface population of Hsp90 extracellularly binds TGFβRI and this complex behaves as an active participant in collagen production in TGFβ-activated fibroblasts. We also offer an in vivo insight into the role of Hsp90 and its isoforms during cardiac remodeling in murine aortic banding model suffering from pathological cardiac remodeling and detect circulating Hsp90 overexpressed in remodeling mice. © 2016 Elsevier Inc.


PubMed | Institute Investigacion Marques Of Valdecilla Idival and Hospital Universitario Marques Of Valdecilla
Type: Journal Article | Journal: PloS one | Year: 2015

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal.


Stoll S.W.,University of Michigan | Stuart P.E.,University of Michigan | Lambert S.,University of Michigan | Gandarillas A.,Institute Investigacion Marques Of Valdecilla Idival | And 4 more authors.
Journal of Investigative Dermatology | Year: 2016

The epidermal growth factor receptor (EGFR) and its ligands are essential regulators of epithelial biology, which are often amplified in cancer cells. We have previously shown that shRNA-mediated silencing of one of these ligands, amphiregulin (AREG), results in keratinocyte growth arrest that cannot be rescued by soluble extracellular EGFR ligands. To further explore the functional importance of specific AREG domains, we stably transduced keratinocytes expressing tetracycline-inducible AREG-targeted shRNA with lentiviruses expressing silencing-proof, membrane-tethered AREG cytoplasmic and extracellular domains (AREG-CTD and AREG-ECD), as well as full-length AREG precursor (proAREG). Here we show that growth arrest of AREG-silenced keratinocytes occurs in G2/M and is significantly restored by proAREG and AREG-CTD but not by AREG-ECD. Moreover, the AREG-CTD was sufficient to normalize cell cycle distribution profiles and expression of mitosis-related genes. Our findings uncover an important role of the AREG-CTD in regulating cell division, which may be relevant to tumor resistance to EGFR-directed therapies. © 2015 The Authors


PubMed | CIC Biomagune, Institute Investigacion Marques Of Valdecilla Idival and Flinders University
Type: Journal Article | Journal: Vaccine | Year: 2015

In the search for an effective vaccine against the human pathogen, Listeria monocytogenes (Listeria), gold glyconanoparticles (GNP) loaded with a listeriolysin O peptide LLO91-99 (GNP-LLO) were used to immunise mice, initially using a dendritic cell (DC) vaccine approach, but subsequently using a standard parenteral immunisation approach. To enhance vaccine immunogenicity a novel polysaccharide adjuvant based on delta inulin (Advax) was also co-formulated with the GNP vaccine. Confirming previous results, DC loaded in vitro with GNP-LLO provided better protection against listeriosis than DC loaded in vitro using free LLO peptide. The immunogenicity of GNP-LLO loaded DC vaccines was further increased by addition of Advax adjuvant. However, as DC vaccines are expensive and impracticable for prophylactic use, we next asked whether the same GNP-LLO antigen could be used to directly target DC in vivo. Immunisation of mice with GNP-LLO plus Advax adjuvant induced LLO-specific T-cell immunity and protection against Listeria challenge. Protection correlated with an increased frequency of splenic CD4(+) and CD8(+) T cells, NK cells and CD8(+) DC, and Th1 cytokine production (IL-12, IFN-, TNF-, and MCP-1), post-challenge. Enhanced T-cell epitope recruitment post-challenge was seen in the groups that received Advax adjuvant. Immunisation with GNP-LLO91-99 plus Advax adjuvant provided equally robust Listeria protection as the best DC vaccine strategy but without the complexity and cost, making this a highly promising strategy for development of a prophylactic vaccine against listeriosis.


PubMed | University of Michigan and Institute Investigacion Marques Of Valdecilla Idival
Type: Journal Article | Journal: The Journal of investigative dermatology | Year: 2016

The epidermal growth factor receptor (EGFR) and its ligands are essential regulators of epithelial biology, which are often amplified in cancer cells. We have previously shown that shRNA-mediated silencing of one of these ligands, amphiregulin (AREG), results in keratinocyte growth arrest that cannot be rescued by soluble extracellular EGFR ligands. To further explore the functional importance of specific AREG domains, we stably transduced keratinocytes expressing tetracycline-inducible AREG-targeted shRNA with lentiviruses expressing silencing-proof, membrane-tethered AREG cytoplasmic and extracellular domains (AREG-CTD and AREG-ECD), as well as full-length AREG precursor (proAREG). Here we show that growth arrest of AREG-silenced keratinocytes occurs in G2/M and is significantly restored by proAREG and AREG-CTD but not by AREG-ECD. Moreover, the AREG-CTD was sufficient to normalize cell cycle distribution profiles and expression of mitosis-related genes. Our findings uncover animportant role of the AREG-CTD in regulating cell division, which may be relevant to tumor resistance to EGFR-directed therapies.


Calderon-Gonzalez R.,Institute Investigacion Marques Of Valdecilla Idival | Tobes R.,Information Technologies Research Group | Pareja E.,Information Technologies Research Group | Frande-Cabanes E.,Institute Investigacion Marques Of Valdecilla Idival | And 3 more authors.
Journal of Immunological Methods | Year: 2015

Dendritic cells loaded with antigenic peptides, because of their safety and robust immune stimulation, would be ideal for induction of immunity to protect against listeriosis. However, there is no currently accepted method to predict which peptides derived from the Listeria proteome might confer protection. While elution of peptides from MHC molecules after Listeria infection yields high-affinity immune-dominant epitopes, these individual epitopes did not reliably confer Listeria protection. Instead we applied bioinformatic predictions of MHC class I and II epitopes to generate antigenic peptides that were then formulated with Advax™, a novel polysaccharide particulate adjuvant able to enhance cross-presentation prior to being screened for their ability to induce protective T-cell responses. A combination of at least four intermediate strength MHC-I binding epitopes and one weak MHC-II binding epitope when expressed in a single peptide sequence and formulated with Advax adjuvant induced a potent T-cell response and high TNF-α and IL-12 production by dendritic cells resulting in robust listeriosis protection in susceptible mice. This T-cell vaccine approach might be useful for the design of vaccines to protect against listeriosis or other intracellular infections. © 2015.


PubMed | Information Technologies Research Group, Institute Investigacion Marques Of Valdecilla Idival and Flinders University
Type: | Journal: Journal of immunological methods | Year: 2015

Dendritic cells loaded with antigenic peptides, because of their safety and robust immune stimulation, would be ideal for induction of immunity to protect against listeriosis. However, there is no currently accepted method to predict which peptides derived from the Listeria proteome might confer protection. While elution of peptides from MHC molecules after Listeria infection yields high-affinity immune-dominant epitopes, these individual epitopes did not reliably confer Listeria protection. Instead we applied bioinformatic predictions of MHC class I and II epitopes to generate antigenic peptides that were then formulated with Advax, a novel polysaccharide particulate adjuvant able to enhance cross-presentation prior to being screened for their ability to induce protective T-cell responses. A combination of at least four intermediate strength MHC-I binding epitopes and one weak MHC-II binding epitope when expressed in a single peptide sequence and formulated with Advax adjuvant induced a potent T-cell response and high TNF- and IL-12 production by dendritic cells resulting in robust listeriosis protection in susceptible mice. This T-cell vaccine approach might be useful for the design of vaccines to protect against listeriosis or other intracellular infections.


PubMed | Institute Investigacion Marques Of Valdecilla Idival
Type: Journal Article | Journal: Molecular & cellular oncology | Year: 2016

The role of p53, the original guardian of the genome, in skin has remained elusive. We have explored p53 function in human epidermal cells and demonstrated the importance of a mitosis-differentiation checkpoint to suppress potentially precancerous cells. This model places epidermal endoreplication as an antioncogenic mechanism in the face of irreparable genetic alterations.

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