A5082684040- Ovarian cancer diagnosis and treatment
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- PARP inhibition in cancer therapy
- Metabolism and Genetic Disorders
- Endometrial and Cervical Cancer Treatments
- BRCA gene mutations in cancer
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- Adipose Tissue and Metabolism
- Lung Cancer Research Studies
- Parkinson's Disease Mechanisms and Treatments
- Cancer Treatment and Pharmacology
- Genetics and Neurodevelopmental Disorders
- Lung Cancer Treatments and Mutations
- Neurological disorders and treatments
- Synthesis and Biological Activity
- Anesthesia and Neurotoxicity Research
- Renal cell carcinoma treatment
- Cancer therapeutics and mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Social Sciences and Policies
- ATP Synthase and ATPases Research
- Chemical Synthesis and Analysis
- Neuroscience and Neural Engineering
Duran i Reynals Hospital
2016-2025
Institut d'Investigació Biomédica de Bellvitge
2013-2025
Institut Català d'Oncologia
2015-2024
Centro de Biología Molecular Severo Ochoa
2014-2024
Universidad Autónoma de Madrid
2014-2024
Consejo Superior de Investigaciones Científicas
2008-2024
Hospital Universitario Fundación Jiménez Díaz
1995-2024
Institut Català d'Ornitologia
2010-2024
Spanish Ovarian Cancer Research Group
2014-2024
Universitat de Barcelona
2024
Neuronal respiration is controlled by ATP demand and Ca<sup>2+</sup> but the roles played each are unknown, as any signal also impacts on demand. can control mitochondrial function through Ca<sup>2+</sup>-regulated carriers, aspartate-glutamate ATP-Mg/Pi ARALAR/AGC1 SCaMC-3, respectively, or in matrix after transport uniporter. We have studied role of signaling regulation intact mouse cortical neurons basal conditions response to increased workload caused increases...
Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, involved the transport of aspartate from mitochondria to cytosol, transfer cytosolic reducing equivalents into as member malate-aspartate NADH shuttle. In present study, we describe characteristics aralar-deficient (Aralar-/-) mice, generated by gene-trap method, showing no aralar mRNA protein, detectable shuttle activity muscle mitochondria. Aralar-/- mice were...
Abstract The human neuroblastoma cells NB69 are a catecholamine‐rich cell line with pharmacological properties similar to dopamine neurons. This was used study the neurotoxicity of levodopa on catecholamine Levodopa, at 50 × 10 −6 M or higher concentrations, produced doseand time‐dependent reduction in number live cells, [ 3 H]thymidine uptake, levels protein and DNA, an enhancement quinone formation. is specific effect since it did not happen incubated equimolar concentrations leucine...
The glutamate–glutamine cycle faces a drain of glutamate by oxidation, which is balanced the anaplerotic synthesis and glutamine in astrocytes. De novo astrocytes requires an amino group whose origin unknown. deficiency Aralar/ AGC1, main mitochondrial carrier for aspartate–glutamate expressed brain, results drastic fall brain production but modest decrease levels, not due to decreases neuronal or synaptosomal content. In vivo 13 C nuclear magnetic resonance labeling with 2 acetate (1- C)...
Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant -refractory ovarian cancer who experienced failure after treatment two three therapy lines. Patients Methods were randomly assigned to receive either 300 mg intravenous infusion every 3 weeks an investigator’s choice of single-agent, nonplatinum,...
Abstract Background This trial investigated the hypothesis that treatment with trabectedin/PLD (TP) to extend platinum-free interval (TFIp) can improve overall survival (OS) in patients recurrent ovarian cancer (OC). Methods Patients OC (up two previous platinum-based lines), a TFIp of 6–12 months, were randomised receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results study enrolled 617 patients. median 8.3 months and 30.3%...
Aralar, the neuronal Ca(2+)-binding mitochondrial aspartate-glutamate carrier, has Ca(2+) binding domains facing extramitochondrial space and functions in malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity brain mitochondria is stimulated by with an S(0.5) of 324 nM. By employing primary cultures from control aralar-deficient mice NAD(P)H imaging two-photon excitation microscopy, lactate utilization involves a substantial transfer to but not neurons, agreement lack...
Glutamate excitotoxicity is caused by sustained activation of neuronal NMDA receptors causing a large Ca 2+ and Na + influx, poly(ADP ribose) polymerase-1 (PARP-1), delayed deregulation. Mitochondria undergo early changes in membrane potential during excitotoxicity, but their precise role these events still controversial. Using primary cortical neurons derived from mice, we show that exposure results rapid fall mitochondrial ATP deficient SCaMC-3/Slc25a23, -regulated ATP-Mg/Pi carrier. This...
Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In embryonic mouse cortical neurons using glucose as only fuel, activation NMDA elicits strong workload (ATP demand)-dependent on Na + and Ca 2+ entry, stimulates uptake, glycolysis, pyruvate lactate production, oxidative phosphorylation (OXPHOS) in -dependent way. We find that upregulation of levels, respiration, but not all depend Aralar/AGC1/Slc25a12,...
Abstract Background The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) non-BRCA homologous recombination repair (non-BRCA HRRm). Methods Patients were response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then gBRCAm testing...
LEVODOPA, a dopamine (DA) precursor administered to patients with Parkinson's disease (PD), produces at 25–200 × 10–6 M concentrations dose-dependent reduction of 3H-DA uptake in foetal rat midbrain cultures. Also, decrease the number viable cells and tyrosine hydroxylase (TH) positive neurones, plus disruption overall neuritic network are observed concurrently an elevation quinone levels culture medium. Ascorbic acid (AA), which abolished overproduction, partially prevented these effects....
A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen kahalalide F, cyclic depsipeptide isolated from marine mollusk Elysia rufescens, in adult patients with advanced solid tumors no standard treatment available.Patients received an i.v. infusion F once until disease progression or unacceptable toxicity. The starting dose was 266 microg/m(2), escalation proceeded based on worst toxicity found previous cohort.Thirty-eight were enrolled...
ARALAR/AGC1/Slc25a12, the aspartate-glutamate carrier from brain mitochondria, is regulatory step in malate-aspartate NADH shuttle, MAS. MAS used to oxidize cytosolic a process required maintain oxidative glucose utilization. The role of ARALAR was analyzed two paradigms glutamate-induced excitotoxicity cortical neurons: deprivation and acute glutamate stimulation. deficiency did not aggravate neuronal death vitro, although glutamate-stimulated respiration impaired. In contrast, presence...