Javier Vaquero

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Verified

Javier verified their affiliation via an institutional email.

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• PhD
• Group Leader at Cancer Research Center

Hepatic stellate cells (HSCs) are the liver’s pericytes, and play key roles in liver homeostasis, regeneration, fibrosis and cancer. Upon injury, HSCs activate and are the main origin of myofibroblasts and cancer associated fibroblasts (CAFs) in liver fibrosis and cancer. Primary liver cancer has a grim prognosis, ranking as the 3rd leading cause o...

Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have delved into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocyte...

UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-derived exosomes to specific steps of the metastatic pr...

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro‐fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in h...

Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have deepened into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocy...

Chronic cholestatic damage is associated to both accumulation of cytotoxic levels of bile acids and expansion of adult hepatic progenitor cells (HPC) as part of the ductular reaction contributing to the regenerative response. Here, we report a bile acid-specific cytotoxic response in mouse HPC, which is partially impaired by EGF signaling. Addition...

The ectopic xenograft mouse model of cancer is a commonly employed tool for in vivo investigations, particularly for studying cell tumorigenicity and testing the efficacy and tolerability of systemic or local anti-cancer therapies. The model displays advantageous features with an easy-access to visualize and monitor tumor growth in real-time with a...

Background & Aims: Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of profibrotic factors are not well characterized. The Epidermal Growth Factor Receptor...

Background & Aims The class I‐ phosphatidylinositol‐3 kinases (PI3Ks) signalling is dysregulated in almost all human cancers whereas the isoform‐specific roles remain poorly investigated. We reported that the isoform δ (PI3Kδ) regulated epithelial cell polarity and plasticity and recent developments have heightened its role in hepatocellular carcin...

Background & Aims Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circ...

Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes...

The Epidermal Growth Factor Receptor (EGFR) has been targeted through the development of selective tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAb). These molecules have shown effectiveness in a subset of patients with specific genetic alterations (i.e. gain-of-function EGFR mutations or EGFR gene amplification) and have been appro...

Background and aims: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAFs). We aimed to define ZEB1 regulatory functions in malignant and...

Transforming Growth Factor-beta (TGF-β) superfamily members are essential for tissue homeostasis and consequently, dysregulation of their signaling pathways contributes to the development of human diseases. In the liver, TGF-β signaling participates in all the stages of disease progression from initial liver injury to hepatocellular carcinoma (HCC)...

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing 5 preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture...

Background & Aims Cholangiopathies are chronic liver diseases in which damaged cholangiocytes trigger a proinflammatory and profibrotic reaction. The nuclear vitamin D receptor (VDR) is highly expressed in cholangiocytes and exerts immune-regulatory functions in these cells. In the present study, we examined the protective function of VDR and other...

Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the b...

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing 5 preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture...

Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the b...

Physical oncology recognizes tissue stiffness mediated by activation of cancer-associated fibroblasts (CAF) and extracellular matrix (ECM) remodeling as an active modulator of tumorigenesis, treatment resistance and clinical outcome. Cholangiocarcinoma (CCA) is a highly aggressive and chemoresistant desmoplastic cancer enriched in CAF. CCA’s stroma...

Purpose of review: To give a state-of-art knowledge regarding cancer-associated fibroblasts (CAF) in cholangiocarcinoma (CCA) based both on direct evidence and studies on other desmoplastic cancers. High contingency of CAF characterizes CCA, a tumor with a biliary epithelial phenotype that can emerge anywhere in the biliary tree. Current treatment...

Two atmospheric pressure plasma jet devices - a plasma gun and a plasma Tesla jet - are compared in terms of safety and therapeutic efficiency to reduce the tumor volume progression of cholangiocarcinoma, i.e. a rare and very aggressive cancer emerging in biliary tree. For this, a three steps methodology is carried out. First, the two APPJ have bee...

Atmospheric pressure plasma jets (APPJ) are investigated as an efficient approach to induce antitumor effects of cancerous tissues without inducing any damage (e.g. dessication, burnings). For this, a two-steps methodology has been developed where first APPJ are calibrated and characterized on targets mimicking electrical properties of living organ...

Two atmospheric pressure plasma jet devices – a plasma gun and a plasma Tesla jet – are compared in terms of safety and therapeutic efficiency to reduce the tumor volume progression of cholangiocarcinoma, i.e. a rare and very aggressive cancer emerging in biliary tree. For this, a three steps methodology is carried out. First, the two APPJ have bee...

Cholangiocarcinoma (CCA) is a deadly disease. While surgery may attain cure in a minor fraction of cases, therapeutic options in either the adjuvant or advanced setting are limited. The possibility of advancing the efficacy of therapeutic approaches to CCA relies on understanding its molecular pathogenesis and developing rational therapies aimed at...

Purpose: Cholangiocarcinoma (CCA) is a desmoplastic tumor of the biliary tree in which epidermal growth factor receptor (EGFR) is overexpressed and contributes to cancer progression. Although EGFR has been envisaged as a target for therapy, treatment with tyrosine kinase inhibitors (TKI) such as erlotinib did not provide therapeutic benefit in pati...

Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expr...

Conclusion: different pro-inflammatory cytokines enhance the expression of miR-506 in biliary epithelial cells. MiR-506 induces PBC-like features in cholangiocytes and promotes immune activation, representing a potential therapeutic target for PBC patients. This article is protected by copyright. All rights reserved.

The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions including differentiation, proliferation, survival and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahep...

The transmission of cellular information requires fine and subtle regulation of proteins that need to interact in a coordinated and specific way to form efficient signaling networks. The spatial and temporal coordination relies on scaffold proteins. Thanks to protein interaction domains such as PDZ domains, scaffold proteins organize multiprotein c...

Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leadi...

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of...

Aims: Ezrin connects proteins from the plasma membrane to the subcortical cytoskeleton, and contributes to the epithelia integrity by interacting with the cell-cell adhesion molecule E-cadherin. In liver, ezrin is restricted to cholangiocytes where it regulates biliary secretory functions. During carcinogenesis, ezrin expression is impaired and as...

E-cadherin is a cell-to-cell adhesion molecule involved in epithelial cell behavior, tissue formation and cancer suppression. In the liver, E-cadherin is expressed by hepatocytes and biliary epithelial cells. However, the exact role of E-cadherin in hepatic pathophysiology remains largely unknown. Recently, specific loss of E-cadherin in liver epit...

The farnesoid X receptor (FXR) is a key sensor in bile acid homeostasis. Although four human FXR isoforms have been identified, the physiological role of this diversity is poorly understood. Here we investigated their subcellular localization, agonist sensitivity and response of target genes. Measurement of mRNA revealed that liver predominantly ex...

Unlabelled: Reduced drug uptake is an important mechanism of chemoresistance. Down-regulation of SLC22A1 encoding the organic cation transporter-1 (OCT1) may affect the response of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CGC) to sorafenib, a cationic drug. Here we investigated whether SLC22A1 variants may contribute to sorafenib che...

The success of pharmacological treatments in primary liver cancers is limited by the marked efficacy of mechanisms of chemoresistance already present in hepatocytes. The role of the nuclear receptor FXR is unclear. Although, in non-treated liver tumors, its expression is reduced, the refractoriness to anticancer drugs is high. Moreover, the treatme...

Treatment with glucocorticoids (GCs) may cause adverse effects, including cholestasis. The ability of dexamethasone, prednisolone and budesonide to affect the liver handling of bile acids (BA) has been investigated. In rats treated with GCs for 4 days, altered serum and bile BA levels, changed conjugation pattern, and delayed and decreased ability...

Several mechanisms are involved in the poor response of colorectal adenocarcinoma (CRAC) to pharmacological treatment. Since preliminary evidences have suggested that the enhanced expression of farnesoid X receptor (FXR) results in the stimulation of chemoresistance, we investigated whether FXR up-regulation is required for the expression of genes...

Export pumps often limit the usefulness of anticancer drugs. Here we investigated the effect of cisplatin on the expression of ABC proteins in human colon cancer cells. Short-term incubation of Caco-2 and LS174T cells with cisplatin resulted in up-regulation of several ABC pumps, in particular MRP2 and BCRP. In partially cisplatin-resistant cells (...

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 refracto...

ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly media...