A5019609592- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- Photoreceptor and optogenetics research
- melanin and skin pigmentation
- Skin Protection and Aging
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Retinoids in leukemia and cellular processes
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Genetic Syndromes and Imprinting
- Mass Spectrometry Techniques and Applications
- vaccines and immunoinformatics approaches
- Mast cells and histamine
- Biochemical Analysis and Sensing Techniques
- Metabolomics and Mass Spectrometry Studies
- Slime Mold and Myxomycetes Research
- Plant and Biological Electrophysiology Studies
- Cancer-related Molecular Pathways
- Protein Structure and Dynamics
- Receptor Mechanisms and Signaling
University of the Basque Country
2016-2025
BioCruces Health research Institute
2015-2024
Hospital de Cruces
2015-2023
Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by show drug can potentially activate distinct intrinsic signaling pathways depending culture conditions. Serum-deprived conditions enhance cytotoxic effect terfenadine and caspase-4 -2 are upstream caspase-9. Moreover, although increase ROS levels,...
Melanoma is the main cause of death among skin cancers and its incidence worldwide has been experiencing an appalling increase. However, traditional treatments lack effectiveness in advanced or metastatic patients. Immunotherapy, meanwhile, shown to be effective treatment option, but rate responding remains far from ideal. Here we have developed a personalized neoantigen peptide-based cancer vaccine by encapsulating patient derived melanoma neoantigens polyethylenimine (PEI)-functionalised...
Activated HSCs play a major role in tissue repair, extracellular matrix regulation, immune response, and inflammation. However, their contributions to the hepatic tumor microenvironment are underexplored need be clarified. In vitro, we analyzed responses of freshly isolated LSECs cell supernatants secretome-driven activation both primary types. For vivo HSC depletion, transgenic mice expressing herpes simplex virus-thymidine kinase (HSV-Tk) gene driven by mouse glial fibrillary acidic...
Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study a 3-year follow-up was performed different stages disease were considered. Mean values sIL-2R significantly higher than normal controls all correlated The...
Sepsis is a life-threatening illness with challenging diagnosis. Current serum biomarkers are not sensitive enough for With the aim of finding proteins associated sepsis, protein profile was compared between patients and healthy donors classical inflammatory were analyzed in both groups. Serum profiles characterized by two-dimensional electrophoresis (2DE). Identification carried out mass spectrophotometry their validation performed Enzyme-Linked-ImmunoSorbent Assay (ELISA) cohort 85 67...
Associative memory is the main type of learning by which complex organisms endowed with evolved nervous systems respond efficiently to certain environmental stimuli. It has been found in different multicellular species, from cephalopods humans, but never individual cells. Here we describe a motility pattern consistent associative conditioned behavior microorganism Amoeba proteus. We use controlled direct-current electric field as stimulus, and specific chemotactic peptide unconditioned...
This study set out to assess the performance of an artificial intelligence (AI) algorithm based on clinical data and dermatoscopic imaging for early diagnosis melanoma, its capacity define metastatic progression melanoma through serological histopathological biomarkers, enabling dermatologists make more informed decisions about patient management. Integrated analysis demographic data, images skin lesions, serum markers were analyzed in a group 196 patients with melanoma. The interleukins...
The observed correlation between ultraviolet light incidence and skin color, together with the geographical apportionment of reflectance among human populations, suggests an adaptive value for pigmentation skin. We have used Affymetrix U133a v2.0 gene expression microarrays to investigate profiles a total 9 melanocyte cell lines (5 from lightly pigmented donors 4 darkly donors) plus their respective unirradiated controls. In order reveal signatures selection in loci bearing on humans, we...
Bexarotene is the first synthetic retinoid X receptor-selective (rexinoid) approved for treatment of cutaneous T-cell lymphoma (CTCL). However, little known about signalling pathways by which it exerts its anticarcinogenic effect.To characterize effects bexarotene in CTCL cell lines and elucidate underlying molecular antineoplastic effect.The Hut-78, HH MJ were used. Cell viability was assessed with XTT assay. The self-renewal potential cells after studied methylcellulose clonogenic Flow...
The execution phase of apoptosis is characterized by extensive blebbing the plasma membrane, which usually results in secondary lysis vitro. To analyse permeability cellular membranes during this process, we induced human melanoma A375 cells that had been transfected with fluorescently tagged proteins were targeted to different subcellular locations.The dual treatment resveratrol and butyrate produced a synergistic induction blocking phases cell cycle. Changes nuclear envelope nucleoli...
Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was identify possible sex differences in phenotype as well melanoma association case-control population Spanish origin.Five hundred ninety-nine females (316 cases 283 controls) 458 males (234 224 were analysed. We genotyped 363 polymorphisms (single nucleotide...
Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although important proportion stage I–II patients may still develop metastasis during follow‐up. The aim this work was discover serum biomarkers in diagnosed with primary that identify those at high risk developing the follow‐up period. Proteomic and mass spectrophotometry analysis performed on obtained from who developed first years after surgery for tumors compared remained disease‐free more than...
4-(Hydroxyphenyl)retinamide (4-HPR) is a synthetic retinoid with strong apoptotic effect towards different cancer cell lines in vitro, and it currently tested clinical trials. Increases of reactive oxygen species (ROS) modulation endogenous sphingolipid levels are well-described events observed upon 4-HPR treatment, but there still lack understanding their relationship contribution to death. LC-MS analysis sphingolipids revealed that human leukemia CCRF-CEM Jurkat cells, induced...
Recent epidemiological studies indicate that the antidiabetic drug metformin has chemosensitizing and chemopreventive effects against carcinogenesis. Here, we demonstrate exerts varying degrees of antitumor activity human leukemia cells, as reflected by differences in growth inhibition, apoptosis, alterations to metabolic enzymes. In metformin-sensitive autophagy was not induced but rather it blocked proliferation means arresting cells S G2/M phases which associated with downregulation...
Imaging mass spectrometry (IMS) is becoming an essential technique in lipidomics. Still, many questions remain open, precluding it from achieving its full potential. Among them, identification of species directly the tissue paramount importance. However, not easy task, due to abundance and variety lipid species, their numerous fragmentation pathways, formation a significant number adducts, both with matrix cations present tissue. Here, we explore pathways 17 classes, demonstrating that...
Metastasis development represents an important threat for melanoma patients, even when diagnosed at early stages and upon removal of the primary tumor. In this scenario, determination prognostic biomarkers would be great interest. Serum contains information about general status organism therefore a valuable source biomarkers. Thus, we aimed to define serological that could used along with clinical histopathological features disease predict metastatic events on early‐stage population...
The capacity to learn new efficient systemic behavior is a fundamental issue of contemporary biology. We have recently observed, in preliminary analysis, the emergence conditioned some individual amoebae cells. In these experiments, cells were able acquire migratory patterns and remember them for long periods their cellular cycle, forgetting later on. Here, following similar conceptual framework Pavlov's we exhaustively studied migration trajectories more than 2000 belonging three different...
In our previous works, we have demonstrated that terfenadine (TEF) induces DNA damage and apoptosis in human melanoma cell lines. this present work, studied the effect of histamine on viability A375 cells cell-signalling pathways through which TEF may induce its apoptotic effect. We found exogenous stimulates proliferation a dose- time-dependent manner. Moreover, TEF-induced seems to occur via other cellular independent histamine-signalling system since co-treatment with did not protect from...
We aimed to study the selective pressures interacting on SLC45A2 investigate interplay between selection and susceptibility disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques North of Spain) by resequencing whole coding region intron 5 34 most least pigmented individuals according reflectance distribution, observed that polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In...
The imprinted U2af1-rs1 gene on mouse chromosome 11 is expressed exclusively from the paternal allele. We found that resides in a chromosomal domain displays marked differences chromatin conformation and DNA methylation between parental chromosomes. Chromatin was assayed brain liver, fetuses, embryonic stem cells by sensitivity to nucleases nuclei. In all these tissues, unmethylated sensitive DNase-I andMspI has two hypersensitive sites 5′-untranslated region. differentiated cells, which...
We have previously reported that, in leukemia cells, the cytotoxicity of anticancer agent N-(4-hydroxyphenyl)retinamide (4-HPR) is mediated by mitochondria-derived reactive oxygen species (ROS) and cardiolipin peroxidation. Here, we analyzed at greater depth 4-HPR-triggered molecular events, demonstrating that 4-HPR induces an early (15 min) increase ceramide levels sphingomyelin hydrolysis later (from 1 h) de novo synthesis. Using specific inhibitors both pathways, demonstrate accumulation...
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated pigmentation tanning response to may be associated with susceptibility MM. In this study, 363 SNPs 65 gene regions belonging pathway have been successfully genotyped using a SNP array. Five hundred ninety MM cases 507 controls were analyzed discovery phase I. Ten candidate based on p-value threshold 0.01 identified. Two them, rs35414 (SLC45A2) rs2069398...
Programmed cell death and especially apoptotic death, occurs under physiological conditions is also desirable pathological circumstances. However, the more we learn about cellular signaling cascades, less plausible it becomes to find restricted well-limited pathways. In this context, an extensive description of pathway-connections necessary in order point out main regulatory molecules as well select most appropriate therapeutic targets. On other hand, irregularities programmed pathways often...