A5087406461- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Sphingolipid Metabolism and Signaling
- Lymphoma Diagnosis and Treatment
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Circular RNAs in diseases
- Natural product bioactivities and synthesis
- Pharmacological Receptor Mechanisms and Effects
- Cholesterol and Lipid Metabolism
- Cellular transport and secretion
- Gastrointestinal Tumor Research and Treatment
- Wnt/β-catenin signaling in development and cancer
- Lipid Membrane Structure and Behavior
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Cancer-related molecular mechanisms research
- Neuroscience and Neuropharmacology Research
- Chronic Myeloid Leukemia Treatments
- Protein Kinase Regulation and GTPase Signaling
- Fatty Acid Research and Health
- Molecular Biology Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Adipose Tissue and Metabolism
- Plant biochemistry and biosynthesis
Research Institute of Health Sciences
2012-2023
Universitat de les Illes Balears
2014-2023
Health Research Institute of the Balearic Islands
2007-2023
Institut Català d'Oncologia
2016-2023
Duran i Reynals Hospital
2023
Institut d'Investigació Biomédica de Bellvitge
2023
Instituto de Salud Carlos III
2014-2016
University of Duisburg-Essen
2007
Fundació Universitat-Empresa de les Illes Balears
2006
Instituto de la Grasa
2003-2004
Purpose Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both was hypothesized to be advantageous safe on the basis preclinical evidence a previous phase I trial, respectively. aim this study compare clinical outcome plus doxorubicin with as first-line treatment advanced STS patients. Patients Methods In open-label randomized II main end point progression-free survival (PFS). Trabectedin 1.1 mg/m 2 3-hour infusion 60 experimental arm 75...
Sphingosine-1-phosphate (SPP) produced from sphingosine by kinase has recently been reported to act as intracellular second messenger for a number of plasma membrane receptors. In the present study, we investigated whether kinase/SPP pathway is involved in cellular signaling Gi protein-coupled formyl peptide receptor myeloid differentiated human leukemia (HL-60) cells. Receptor activation resulted rapid and transient production SPP kinase, which was abolished after pertussis toxin treatment....
We have recently reported that lipid structure regulates the interaction with membranes, recruitment to and distribution membrane domains of heterotrimeric Gαβγ proteins, Gα subunits, Gβγ dimers (<i>J Biol Chem</i><b>279:</b>36540–36545, 2004). Here, we demonstrate modulation not only determines G protein localization but also function proteins related signaling proteins. In this context, antitumor drug daunorubicin (daunomycin) oleic acid changed inhibited activity in biological membranes....
Most drugs currently used for human therapy interact with proteins, altering their activity to modulate the pathological cell physiology. In contrast, 2-hydroxy-9-<i>cis</i>-octadecenoic acid (Minerval) was designed modify lipid organization of membrane. Its structure deduced following guidelines mechanism action previously proposed by us certain antitumor drugs. The antiproliferative Minerval supports above-mentioned hypothesis. This molecule augments propensity membrane lipids organize...
Introduction: Soft tissue sarcomas (STS) are a group of rare malignancies with limited treatment options and persistent lack effective therapies. Despite the heterogeneous nature STS, canonical WNT/β-catenin signalling pathway has been associated sarcomagenesis, also initiation progression other cancers. Methods: Eight patient-derived primary cultures representing different STS histological subtypes were characterized by immunohisto(cyto)chemistry, activation, Next-Generation Sequencing...
In this study, we quantified the levels of lipids and signaling proteins in erythrocyte membranes from elderly normotensive hypertensive subjects. subjects, cholesterol/phospholipid ratio increased significantly membranes, owing to reduction phospholipid concomitant with a rise cholesterol. addition, differences were also found amount fatty acids both cholesterol esters. Erythrocyte subjects contained higher monounsaturated lower polyunsaturated acids. On other hand, such as G protein kinase...
The concentration of the astrocytic marker, glial fibrillary acidic protein (GFAP) was quantitated by immunoblotting (western blotting) in rat brain after treatment with various imidazoline drugs and other agents. Chronic (7 days) but not acute (1 day) drugs, cirazoline mg kg −1 , i.p.) idazoxan (10 i.p.), structurally related α 2 ‐adrenoceptor antagonists, RX821002 (2‐methoxy idazoxan) efaroxan markedly increased (45%) GFAP immunoreactivity cerebral cortex. yohimbine a non‐imidazoline...
Contribution of sphingosine kinase (SPK)‐catalyzed production sphingosine‐1‐phosphate (SPP), in comparison to phospholipase C (PLC), Ca 2+ signalling by epidermal growth factor (EGF) was studied two HEK‐293 cell clones (HEK2 and HEK3), expressing functional EGF receptors exhibiting release stored intracellular SPP. In HEK3 cells, increased [Ca ] i stimulated both, SPK PLC. increase, but not PLC stimulation, strongly reduced inhibition. HEK2 similarly PLC, did increase or stimulate SPK,...
The therapeutic effect of doxorubicin (DXR) in the treatment soft tissue sarcomas (STS) is limited by its toxicity and development multidrug resistance (MDR), latter mainly induced high expression efflux pumps (e.g., P-glycoprotein [P-gp]). Therefore, search for alternative therapies, which sensitize these tumors to chemotherapy while maintaining a low profile, rational approach. We assessed efficacy molecular mechanisms involved antiproliferative effects tyrosine kinase inhibitors,...
Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed explore the feasibility of nilotinib as coadjuvant by inhibiting MRP-1/P-gp efflux activity. The I part study is presented here.Patients and Methods: 400 mg/12 hours administered fixed dose from day 1 6, on 5 each cycle. Three escalation levels for at 60, 65, 75 mg/m2 were planned. Cycles repeated every 3 weeks a total 4 cycles. Eligible...
The red blood cell distribution width (RDW) is a parameter available from an automated count, which measures the degree of heterogeneity erythrocyte volume and increases in inflammatory conditions. prognostic role RDW has been described different types cancers. Hodgkin lymphoma (HL) hematological malignancy, known to have proinflammatory background. We aim study HL. retrospectively analyzed 264 patients with HL two hospitals Balearic Islands between 1990 2018. Higher levels were...
Recent studies have shown that diets rich in monounsaturated fatty acids (MUFAs) from olive oil, a natural source of oleic acid, beneficial effects on blood pressure (BP) hypertensive patients. With this mind, we investigated whether synthetic derivative the MUFA 2-hydroxyoleic acid (2-OHOA), was capable regulating BP Sprague-Dawley rats. Intraperitoneal and oral administration 2-OHOA to rats induced significant sustained decreases time-dependent manner. Without affecting heart rate,...
The binding of [ 3 H]‐idazoxan in the presence 10 −6 m (−)‐adrenaline was used to quantitate I 2 imidazoline‐preferring receptors rat brain and liver after chronic treatment with various irreversible reversible monoamine oxidase (MAO) inhibitors. Chronic (7–14 days) MAO inhibitors, phenelzine (1–20 mg kg −1 , i.p.), isocarboxazid (10 clorgyline (3 i.p.) tranylcypromine markedly decreased (21–71%) density liver. In contrast, (7 MAO‐A moclobemide (1 or chlordimeform MAO‐B inhibitor Ro 16–6491...
We studied the interactions of hypotensive drug, 2-hydroxyoleic acid (2OHOA), with model membranes using techniques DSC, 31P NMR and X-ray diffraction. demonstrate that 2OHOA alters thermotropic behaviour 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE), thereby promoting formation hexagonal phases (H(II)), despite stabilizing lamellar phase (Lalpha). The lattice parameters non-lamellar structures were not altered by presence 2OHOA. molecular bases underlying alterations in membrane...
Olive oil consumption leads to high monounsaturated fatty acid intake, especially oleic acid, and has been associated with a reduced risk of hypertension. However, the molecular mechanisms contribution its different components lower blood pressure (BP) require further evaluation. Here, we examined whether synthetic, non-beta-oxidation-metabolizable derivative 2-hydroxyoleic (2-OHOA), can normalize BP in adult spontaneously hypertensive rats (SHRs) antihypertensive action involves...
MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Selected sarcoma subtypes are being treated with Trabectedin in second line, which promotes DNA damage and p53-dependent apoptosis. The aim this study was to evaluate improvement response inhibitors soft tissue sarcomas. antitumor effects Trabectedin, Nutlin-3A RG7112 as single agents or combination were examined vitro. significantly synergized MDM2-amplified liposarcoma cells, representing promising new therapeutic...