Lourdes Gombau

Leitat Technological Center · BioInVitro Division

Gastric cancer (GC) is among the most common cancers worldwide. Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis induced by Helicobacter pylori (H. pylori) infection. This process is often described via a sequence of events known as Correas’s cascade, a stepwise progression from non-active gastritis,...

The human joint is a dynamically load-bearing structure that connects bones of the skeleton to one another. The most common type is the synovial joint which normally has to withstand complex, varied and often harsh loading regimes under conditions of sliding and rolling. Typical synovial joints have ends of opposing bones covered with a thin layer...

Nanogenotoxicity is a crucial endpoint in safety testing of nanomaterials as it addresses potential mutagenicity, which has implications for risks of both genetic disease and carcinogenesis. Within the NanoTEST project, we investigated the genotoxic potential of well-characterised nanoparticles (NPs): titanium dioxide (TiO2) NPs of nominal size 20...

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential...

Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding...

Engineered metal/mineral, lipid and biochemical macromolecule nanomaterials (NMs) have potential applications in food. Methodologies for the assessment of NM digestion and bioavailability in the gastrointestinal tract are nascent and require refinement. A working group was tasked by the International Life Sciences Institute NanoRelease Food Additiv...

No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay for detection of oxidative species. In the present research, nanomaterial interaction with DCFH-DA was studied...

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identif...

There are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by th...

The liver is the most important target for toxicity caused by drugs. This vulnerability is a consequence of the functional features of the liver and their role in the metabolic elimination of most drugs. Therefore, evaluation of potential hepatotoxicity represents a critical step in the development of new drugs. The liver is very active in metaboli...

The liver is the most important target for toxicity caused by drugs. This vulnerability is a consequence of the functional features of the liver and their role in the metabolic elimination of most drugs. Therefore, evaluation of potential hepatotoxicity represents a critical step in the development of new drugs. The liver is very active in metaboli...

Abstract. Nanoparticles (NPs) have unique, potentially beneficial properties, but their possible impact on human health is still not known. The area of nanomedicine brings humans into direct contact with NPs and it is essential for both public confidence and the nanotech companies that appropriate risk assessments are undertaken in relation to h...

The study of the ADME features of the huge number of new chemical entities (NCEs) produced mainly by combinatorial chemistry has become a bottleneck in the drug development process. In response the pharmaceutical industry is involved in the development of new medium/high-throughput screening capabilities. The aim of this paper is to review some of...

The extract of the fern Polypodium leucotomos (PL, Fernblock) is an oral photoprotectant with strong antioxidative properties. Recent studies to determine its chemical composition have shown 4-hydroxycinnamic acid (p-coumaric), 3 methoxy-4-hydroxycinnamic acid (ferulic), 3,4-dihydroxycinnamic acid (caffeic), 3-methoxy-4-hydroxybenzoic acid (vanilli...

Serine proteases are implicated in a variety of processes during neurogenesis, including cell migration, axon outgrowth, and synapse elimination. Tissue-type plasminogen activator and urokinase-type activator are expressed in the floor plate during embryonic development. F-spondin, a gene also expressed in the floor plate, encodes a secreted, extra...

Methylazoximethanol (MAM) acetate-induced cell death in the external granule cell layer of the developing cerebellum affects clusters of cells with morphological features of apoptosis. This is accompanied by selective induction of active caspase-3 expression and increased c-Jun/AP-1 (N) immunoreactivity in dying cells, as revealed with immunohistoc...

Botulinum neurotoxin type A (BoNT/A) inhibits neurotransmitter release by specific cleavage of SNAP-25, a synaptosome-associated protein also expressed in the ACTH secretory cell line AtT-20. Expression of light chain BoNT/A (L-BoNT/A) gene transfected into AtT-20 cells resulted in a cleaved form of SNAP-25 indistinguishable from that generated by...

Type 1 plasminogen activator inhibitor (PAI-1) is stored in the alpha granules of platelets from where it is released in a regulated manner. PAI-1 expressed in AtT-20 cells, a model cell system for regulated secretion, is also targeted to secretory granules from which it is released in response to stimulation by secretagogues, mimicking the behavio...

Because recent information suggests that the localized deposition of protease inhibitors is one mechanism by which cells regulate pericellular proteolysis during tissue invasion, the distribution of type 1 plasminogen activator inhibitor (PA1-1) associated with the invasive human glioma cell line U-251 was investigated. Direct and reverse fibrin zy...

Type 1 plasminogen activator inhibitor (PAI-1),is normally stored in the alpha granules of platelets. It has previously been demonstrated that PAI-1 expressed in AtT-20 cells is targeted for storage in secretory granules from which it is released in response to stimulation by the 8Br-cAMP secretagogue, mimicking the behaviour of PAI-1 in platelets....

To understand the processing of type 1 plasminogen activator inhibitor (PAI-1) into the storage granules of platelets, we utilized a eukaryotic expression vector (pRC/CMV) to transfer the human cDNA for PAI-1 into AtT-20 cells, a mouse pituitary cell line known to sort proteins in a regulated fashion. Immunofluorescence staining of PAI-1-transfecte...

Current information indicates that type 1 plasminogen activator inhibitor (PAI-1) released by platelets plays a key role in regulating the fibrinolytic system. Although PAI-1 was first detected in platelets in 1984, little is known about its origin (e.g., uptake from the plasma or synthesis in megakaryocytes) or the mechanisms that stabilize this r...