A5011115344- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Glaucoma and retinal disorders
- Retinal Diseases and Treatments
- Thermal Regulation in Medicine
- Antimicrobial Peptides and Activities
- Neuroscience of respiration and sleep
- Neuroendocrine regulation and behavior
- RNA modifications and cancer
- Chemokine receptors and signaling
- Neonatal and fetal brain pathology
- Retinal Development and Disorders
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Retinopathy of Prematurity Studies
- Chemical Synthesis and Analysis
- RNA Research and Splicing
- Hormonal Regulation and Hypertension
- Pancreatic function and diabetes
- Inflammatory mediators and NSAID effects
National Institutes of Health
2000-2025
Center for Biomedical Research of La Rioja
2016-2025
Huntsman Cancer Institute
2025
University of Utah
1986-2025
Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno
2003-2024
Universidad de Navarra
2000-2023
Hospital Del Mar
1993-2023
Instituto Oncológico Dr. Rosell
2021
Universidad Independiente
2021
Gobierno de La Rioja
2021
HIF-1α is a normally labile proangiogenic transcription factor that stabilized and activated in hypoxia. Although the von Hippel Lindau (VHL) gene product, ubiquitin ligase responsible for regulating protein levels, efficiently targets rapid proteasome-dependent degradation under normoxia, resistant to destabilizing effects of VHL also associates with molecular chaperone Hsp90. To examine role Hsp90 function, we used renal carcinoma cell (RCC) lines lack functional express stable normoxia....
ABSTRACT The early progenitor cells to the pancreatic islets in mouse have been characterized so as re-examine their possible lineage relationships four islet cell types found mature islets. Insulin and glucagon were both first expressed at embryonic day 9.5, many co-expressed these two markers, shown by light electron microscopic analysis using double-label immunohistochemistry. Incubation of pancreas with 1% glutaraldehyde, a fixative commonly used microscopists, abolished this reactivity,...
Hypertension is a primary risk factor for cardiovascular diseases including myocardial infarction and stroke. Major determinants of blood pressure are vasodilatory factors such as nitric oxide (NO) released from the endothelium under influence fluid shear stress exerted by flowing blood. Several endothelial signaling processes mediating stress-induced formation release have been described. It is, however, still poorly understood how induces these responses. Here we show that mechanosensitive...
Insulin resistance is a hallmark of obesity-associated type 2 diabetes. Insulin’s actions go beyond metabolic cells and also involve blood vessels, where insulin increases capillary flow delivery nutrients. We show that adrenomedullin, whose plasma levels are increased in obese humans mice, inhibited signaling human endothelial through protein-tyrosine phosphatase 1B–mediated dephosphorylation the receptor. In mice lacking adrenomedullin receptor, insulin-induced nitric oxide–synthase...
Although adrenomedullin (AM) previously has been identified in human tumors, its role remained elusive. Analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed AM mRNA 18 of 20 normal tissues representing major organs, and 55 58 (95%) malignant cell lines. Western blot high performance liquid chromatography analysis showed immunoreactive species 18, 14, 6 kDa that are consistent with the precursor, intermediate product, active peptide, respectively. Immunohistochemistry...
Signal transduction pathways shared by different autocrine growth factors may provide an efficient approach to accomplish clinically significant control of lung cancer growth. In this study, we demonstrate that two activate 5-lipoxygenase action the arachidonic acid metabolic pathway in cell lines. Both increased production 5(S)-hydrooxyeicosa-6E,8Z,11Z,14Z-tetraeno ic (5-HETE), a major early product. Exogenously added 5-HETE stimulated vitro. Inhibition metabolism selective antagonists...
Adrenomedullin (AM) is an important regulatory peptide involved in both physiological and pathological states. We have previously demonstrated the existence of a specific AM-binding protein (AMBP-1) human plasma. In present study, we developed nonradioactive ligand blotting assay, which, together with high pressure liquid chromatography/SDS-polyacrylamide gel electrophoresis purification techniques, allowed us to isolate AMBP-1 homogeneity. The purified was identified as complement factor H....
Abstract Little is known about the molecular mechanisms that control adrenomedullin (AM) production in human cancers. We demonstrate here expression of AM mRNA a variety tumor cell lines highly induced time-dependent manner by reduced oxygen tension (1% O2) or exposure to hypoxia mimetics such as desferrioxamine mesylate (DFX) CoCl2. This seems be under hypoxia-inducible factor-1 (HIF-1) transcriptional regulation, since HIF-1α and HIF-1β knockout mouse had an ablated greatly induction....
Abstract Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show predilection to metastasize bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation bone resorption. IL-8 mRNA expression was surveyed in panel breast lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, ZR-75, adenocarcinoma cell line A549. higher with osteolytic potential vivo. Human increased by MDA-MET or A549 cell-conditioned medium, but not...
Many arachidonic acid metabolites function in growth signaling for epithelial cells, and we previously reported the expression of major enzymes human breast cancer cell lines. To evaluate role 5-lipoxygenase (5-LO) pathway on regulation, exposed cells to insulinlike factor-1 or transferrin, which increased levels 5-LO metabolite, 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic (5-HETE), by radioimmunoassay high-performance liquid chromatography. Addition 5-HETE resulted stimulation, whereas...
The aryl hydrocarbon receptor repressor (AHRR) is a bHLH/Per-ARNT-Sim transcription factor located in region of chromosome 5 (5p15.3) that has been proposed to contain one or more tumor suppressor genes. We report here consistent downregulation AHRR mRNA human malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary, demonstrate DNA hypermethylation as the regulatory mechanism gene silencing. Knockdown expression lung cancer cell line...
We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured cells as well microvascular possess immunoreactive NO dot MAb H210 H32 detect 1 ng 100 pg of purified synthase, respectively. Both are to the synthase do not cross-react with other known isoforms namely from brain, cytokine/endotoxin-induced macrophages, or vascular smooth muscle cells. Immunohistochemical studies demonstrated...
Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species, as demonstrated by immunocytochemistry. Electron microscopic studies with double immunogold showed colocalization AM and pancreatic polypeptide. A homogeneous expression receptor was found throughout islet using situ hybridization. Six insulin- producing cell lines have been analyzed reverse transcription-PCR both its receptor. Two experimental models used to study...
Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. In this report we present evidence, using reverse transcriptase-polymerase chain reaction, immunocytochemistry, and situ that AM synthesized by several cell populations the normal lung, tumor lines pulmonary origin, specimens. Among found expression columnar epithelium, some glands, neurons parasympathetic nervous system, endothelial cells, chondrocytes, alveolar macrophages, smooth...
Abstract Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on basis of their effects primed T cells and perhaps other system. Here we provide evidence that CD137 is selectively expressed surface tumor endothelial cells. Hypoxia upregulated murine Treatment tumor-bearing immunocompromised Rag−/− mice with agonist mAb did not elicit any measurable antiangiogenic effects. In contrast,...
The present study reports the developmental patterns of expression adrenomedullin (AM) in rat and mouse embryos. AM is a novel multifunctional peptide recently isolated from human pheochromocytoma, which has been shown to promote growth variety mammalian cell lines. We have applied several techniques investigate localization both its receptor throughout development. Immunocytochemical detection performed using different specific antibodies against gene-related pro-AM N-terminal 20 peptide....
The high frequency with which the novel tumor suppressor RASSF1A is inactivated by promoter methylation suggests that it plays a key role in development of many primary human tumors. Yet mechanism action remains unknown. We now show associates microtubules and this association essential for to mediate its growth inhibitory effects. Overexpression promotes formation stable microtubules, whereas dominant-negative fragment destabilizes microtubule networks. RASSF1 protein expressed as two main...
MMPs (matrix metalloproteinases) play a major role in the pathogenesis of hypertension by altering extracellular matrix during cardiovascular remodelling. In present study we show that MMP-2, but not MMP-9, cleaves vasodilator peptide AM (adrenomedullin). Addition AM-binding protein, complement factor H, prevents this cleavage, providing hitherto unknown mechanism action for binding protein. We identified signature cleavage fragments and found some them human urine, suggesting MMP-2...
The approval of histone deacetylase inhibitors for treatment lymphoma subtypes has positioned modifications as potential targets the development new classes anticancer drugs. Histones also undergo phosphorylation events, and Haspin is a protein kinase only known target which H3 at Thr3 residue (H3T3ph), necessary mitosis progression. Mitotic kinases can be blocked by small drugs several clinical trials are underway with these agents. As occurs Aurora inhibitors, might an optimal candidate...