A5068655069- Cancer Cells and Metastasis
- NF-κB Signaling Pathways
- MicroRNA in disease regulation
- Melanoma and MAPK Pathways
- Cell death mechanisms and regulation
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
- Liver physiology and pathology
- RNA modifications and cancer
- Wnt/β-catenin signaling in development and cancer
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Growth Hormone and Insulin-like Growth Factors
- Renal and related cancers
- Cancer Mechanisms and Therapy
- Protein Tyrosine Phosphatases
- PI3K/AKT/mTOR signaling in cancer
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Cancer, Stress, Anesthesia, and Immune Response
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pharmaceutical industry and healthcare
- Journalism and Media Studies
European CanCer Organisation
2023
KU Leuven
2016-2021
Wellcome/MRC Cambridge Stem Cell Institute
2012-2016
University of Cambridge
2012-2016
Medical Research Council
2016
National Cancer Centre Japan
2007
Spanish National Cancer Research Centre
2006-2007
University of Massachusetts Chan Medical School
2003-2006
Howard Hughes Medical Institute
2003-2006
Universidad Complutense de Madrid
1991-2005
The p38 mitogen-activated protein kinase (MAPK) is activated in vitro by three different kinases: MKK3, MKK4, and MKK6. To examine the relative roles of these kinases mechanism MAP activation vivo, we examined effect disruption murine Mkk3, Mkk4 , Mkk6 genes on MAPK signaling pathway. We show that MKK3 MKK6are essential for tumor necrosis factor-stimulated activation. In contrast, ultraviolet radiation-stimulated was mediated Loss mutant cells associated with defects growth arrest increased...
The c-Jun NH 2 -terminal kinase (JNK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of JNK tumor necrosis factor (TNF)-stimulated using fibroblasts isolated from wild-type, Mkk4 -/- Mkk7 , Jnk1 Jnk2 mice. We demonstrate that can act suppress TNF-stimulated apoptosis. However, find also potentiate by increasing production reactive oxygen species (ROS). Together, these data indicate shift balance apoptosis necrosis. Increased...
The c-Jun NH2-terminal kinase (JNK) is activated by the cytokine tumor necrosis factor (TNF). This pathway implicated in regulation of AP-1-dependent gene expression TNF. To examine role JNK signaling pathway, we compared effects TNF on wild-type and Jnk1 −/− Jnk2 murine embryo fibroblasts. We show that required for normal AP-1 JNK-deficient cells exhibited decreased c-Jun, JunD, c-Fos, Fra1, Fra2; phosphorylation JunD; DNA binding activity. also defects AP-1-related transcription ATF2....
Mixed-lineage protein kinase 3 (MLK3) is a member of the mitogen-activated (MAP) group that has been implicated in multiple signaling cascades, including NF-kappaB pathway and extracellular signal-regulated kinase, c-Jun NH(2)-terminal (JNK), p38 MAP pathways. Here, we examined effect targeted disruption murine Mlk3 gene. Mlk3(-/-) mice were found to be viable healthy. Primary embryonic fibroblasts prepared from these exhibited no major defects. However, did find MLK3 deficiency caused...
Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. Here we report that stem cell marker Lgr6 becomes enriched in non-small (NSCLC) cells during malignant progression. Lgr6(+) NSCLC displayed self-renewal differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested defective repression miR-17-92 gene cluster was responsible for evolution selection outgrowth cells....
The cytokine tumor necrosis factor alpha (TNF-alpha) stimulates the NF-kappaB, SAPK/JNK, and p38 mitogen-activated protein (MAP) kinase pathways by recruiting RIP1 TRAF2 proteins to receptor 1 (TNFR1). Genetic studies have revealed that links TNFR1 IkappaB (IKK) complex, whereas couples SAPK/JNK cascade. In transfection studies, stimulate MAP activation, dominant-negative forms of inhibit TNF-alpha-induced activation. We found activation interleukin-6 (IL-6) production impaired in rip1(-/-)...
The c-Jun NH2-terminal kinase (JNK) has been implicated in the function of transforming growth factor beta (TGF-beta). To test role JNK, we examined effect compound disruption murine genes that encode ubiquitously expressed isoforms JNK (Jnk1 and Jnk2). We report JNK-deficient fibroblasts isolated from Jnk1-/- Jnk2-/- mice constitutively express TGF-beta1. Complementation studies demonstrate is a repressor Tgf-beta1 gene expression. This mechanism regulation TGF-beta1 expression by...
Abstract Epidermal growth factor (EGF) is a survival signal for transforming factor‐beta (TGF‐β)‐induced apoptosis in hepatocytes, phosphatidylinositol 3‐kinase (PI 3‐K) being involved this effect. Here, we analyze the possible cross talks between EGF and TGF‐β signals to understand how impairs early pro‐apoptotic events induced by TGF‐β. Data have indicated that neither SMAD nor c‐Jun NH 2 Terminal Kinase (JNK) activations are altered EGF, which clearly interferes with directly related...
Abstract The signals that regulate stem cell self-renewal and differentiation in the lung remain elusive. Lung cells undergo or lineage commitment to replenish tissue, depending on cross-talk with their environment. This environment, also known as niche, includes mesenchymal endothelial tissues. Here we define molecular mechanisms involved interaction between human Lgr6+ (LSCs) fibroblasts a functional microenvironment. We reveal central role for p38α MAPK establishing maintaining such...
Transforming growth factor β (TGF-β)-mediated apoptosis is one of the major death processes in liver. We have previously shown that epidermal (EGF) an important survival signal for TGF-β-induced fetal hepatocytes (Fabregat et al., FEBS Lett 1996;384:14-18). In this work we studied intracellular signaling implicated protective effect EGF. show here EGF activates p42 and p44 mitogen-activated protein kinases (MAPK). However, mitogen extracellular kinase (MEK) inhibitors do not block also...
Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive cancers. Chemotherapy remains mainstay for TNBC, platinum salts have been explored as a therapeutic alternative in neo-adjuvant metastatic settings. However, primary acquired resistance to chemotherapy general platinum-based regimens specifically strongly hampers TNBC management. In this study, we used...
Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, trade-offs patients willing make. IMI PREFER was a six-year European public-private partnership under Innovative Medicines Initiative that developed recommendations on use PPS in medical product decision-making, including regulatory evaluation This paper aims summarize...
The purpose of the present study is to detect by means MRI any structural changes in brain and their correlation with clinical history climbers who have ascended extremely high altitudes without supplementary oxygen. Clinical history, neurological examinations were obtained from a group 26 over 7000 m oxygen, results compared control (n = 21) healthy subjects. All studies carried out between days 36 months after return sea level. Significant neuropsychological disorders experienced all...
Abstract Tumor necrosis factor-α (TNFα) induces apoptosis and cell growth inhibition in primary rat fetal brown adipocytes. Here, we examine the role played by some members of mitogen-activated protein kinase (MAPK) superfamily. TNFα activates extracellular regulated kinase-1/2 (ERK1/2) p38MAPK. Inhibition p38MAPK either SB203580 or SB202190 highly reduces induced TNFα, whereas ERK potentiates it. Moreover, cotransfection an active MKK3 mutant apoptosis. also prevents TNFα-induced cycle...
// Neibla Priego 1,2,* , María Arechederra Celia Sequera 1,2 Paloma Bragado 3 Ana Vázquez-Carballo Álvaro Gutiérrez-Uzquiza 1,7 Víctor Martín-Granado 4 Juan José Ventura 5 Marcelo G. Kazanietz 6 Carmen Guerrero and Almudena Porras 1 Departamento de Bioquímica y Biología Molecular II, Facultad Farmacia, Universidad Complutense Madrid, Spain 2 Instituto Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS),...
We have previously found that transforming growth factor‐β (TGF‐β) induces an increase in radical oxygen species (ROS) production mediates its apoptotic effects fetal hepatocytes. In this paper we show TGF‐β activates p38 mitogen‐activated protein kinase (p38MAPK) and ROS may be responsible for activation. Activation of p38MAPK occurs late, coincident with the maximal ROS, it is inhibited by scavengers accentuated presence glutathione synthesis inhibitors. However, does not appear to...
Abstract Hepatic progenitor cells (HPCs) are small with a relative large oval nucleus and scanty cytoplasm situated in the canals of Hering that express markers (immature) hepatocytes cholangiocytes. HPCs present numbers alcoholic steatohepatitis (ASH), one leading causes chronic liver disease. To date, mechanisms responsible for proliferation differentiation human still poorly understood role ASH development is unknown. In this study, we aimed to characterise their interactions other...
<sec> <title>BACKGROUND</title> Breast cancer is one of the most frequent causes mortality among women’s population. Early diagnosis critical for successful treatment, but underscreening frequent. Novel screening methods that are more convenient, such as thermography, being developed. They could help a wider group screeners and they contribute to better compliance with thus decline in breast mortality. </sec> <title>OBJECTIVE</title> The study aims explore screeners’ preferences process,...