A5043370759- Toxic Organic Pollutants Impact
- Effects and risks of endocrine disrupting chemicals
- Pharmacogenetics and Drug Metabolism
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Eicosanoids and Hypertension Pharmacology
- Sirtuins and Resveratrol in Medicine
- Colorectal Cancer Treatments and Studies
- Neuroscience and Neuropharmacology Research
- Liver physiology and pathology
- Chromosomal and Genetic Variations
- TGF-β signaling in diseases
- CRISPR and Genetic Engineering
- Neonatal Respiratory Health Research
- Peroxisome Proliferator-Activated Receptors
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Cancer, Stress, Anesthesia, and Immune Response
- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
Universidad de Extremadura
2015-2024
Centro Tecnológico Agroalimentario de Extremadura
2020-2021
Instituto de Investigación Biosanitaria de Granada
2020-2021
Centro de Implantología Cirugía Oral y Maxilofacial
2013-2015
Research Institute Hospital 12 de Octubre
2014
National Cancer Institute
1994-2012
Cancer Genetics (United States)
2012
China Medical University
2012
China Medical University Hospital
2012
China Medical University
2012
To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted ligand-binding domain alpha isoform mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for mutation lack expression mPPAR protein and yet are viable fertile exhibit no detectable gross phenotypic defects. Remarkably, these animals do not display proliferator pleiotropic response when challenged with classical proliferators, clofibrate Wy-14,643....
The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas homozygous for the were born dead and lacked lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium their pleural cavities. Furthermore, no thyroid gland but normal parathyroid. In addition, extensive defects found brain of mice,...
The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr -/- ) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half the mice died shortly after birth, whereas survivors reached maturity were fertile. Ahr showed decreased accumulation lymphocytes spleen lymph nodes, but not thymus. livers reduced size 50 percent bile duct fibrosis. also...
CYP2E1, a cytochrome P-450 that is well conserved across mammalian species, metabolizes ethanol and many low molecular weight toxins cancer suspect agents. The cyp2e1 gene was isolated, mouse line lacks expression of CYP2E1 generated by homologous recombination in embryonic stem cells. Animals deficient the enzyme were fertile, developed normally, exhibited no obvious phenotypic abnormalities, thus indicating has critical role development physiology absence external stimuli. When knockout...
Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria pediatric patients and increased risk of toxicity cancer receiving 5-fluorouracil (5-FU) treatment. The molecular basis for DPD a British family having patient that exhibited grade IV 10 d after 5-FU treatment was analyzed. A 165-bp deletion spanning complete exon the DPYD gene found some members pedigree low catalytic activity. Direct sequencing lymphocyte...
We have analyzed the possible role of aryl-hydrocarbon receptor (AHR) in aging process mice using a homozygous null mouse (Ahr-/-) line as model. studied 52 male and female Ahr-/- aged from 6-13 months. Forty-six percent died or were ill by 13 months age. developed age-related lesions several organs, some which apparent after only 9 Cardiovascular alterations included cardiomyopathy (100%) with hypertrophy focal fibrosis. Vascular mild fibrosis found portal areas liver (81%), vascular...
Mammalian cells harbor three highly homologous and widely expressed members of the ras family (H-ras, N-ras, K-ras), but it remains unclear whether they play specific or overlapping cellular roles. To gain insight into such functional roles, here we generated analyzed H-ras null mutant mice, which were then also bred with N-ras knockout animals to ascertain viability properties potential double mutations in both loci. Mating among heterozygous H-ras(+/-) mice produced H-ras(-/-) offspring a...
Furuya, Hirokazu; Fernandez-Salguero, Pedro; Gregory, Wendy; Taber, Heather; Steward, Annette; Gonzalez, Frank J.; Idle, Jeffrey R. Author Information
The aryl hydrocarbon receptor (AhR) mediates many of the biological effects 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and transcriptional activation genes encoding a number xenobiotic metabolizing enzymes. Prenatal exposure mice to TCDD causes severe alterations in embryo fetal development, including hydronephrosis cleft palate. However, mechanisms underlying these are unclear. In this work, teratogenicity AhR-null was evaluated determine if effect is mediated by AhR. Homozygous wild-type...
Abstract Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells different etiologies. We previously showed that RES alters cell cycle and induces apoptosis in MCF‐7 breast by interfering with estrogen receptor (ERaα)–dependent phosphoinositide 3‐kinase (PI3K) pathway. Here, we analyzed signaling downstream PI3K, to understand mechanisms RES‐induced apoptosis. Apoptotic death was mediated Bcl‐2 downregulation since overexpression this protein abolished...
Microsomal epoxide hydrolase (mEH) is a conserved enzyme that known to hydrolyze many drugs and carcinogens, few endogenous steroids bile acids. mEH-null mice were produced found be fertile have no phenotypic abnormalities thus indicating mEH not critical for reproduction physiological homeostasis. has also been implicated in participating the metabolic activation of polycyclic aromatic hydrocarbon carcinogens. Embryonic fibroblast derived from unable produce proximate carcinogenic...
Resveratrol is a polyphenol found at high concentrations in grapes and red wine with reported anticarcinogenic effects. We studied the molecular mechanism of resveratrol-induced apoptosis proliferation arrest prostate derived cells PZ-HPV-7 (nontumorigenic line), LNCaP (androgen-sensitive cancer PC-3 (androgen-insensitive line). Apoptosis cell cycle distribution were evaluated by flow cytometry MTT assay direct counting. Caspases, bax, bcl-2, cyclins, Cdks, p53, p21, p27 measured Western...
Background— Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (Per-Arnt-Sim homology domain) family known mediate toxic and carcinogenic effects of xenobiotics. Interestingly, AhR widely expressed in central nervous system, but its physiological pathological roles are still unclear. Methods Results— To define role stroke, we used middle cerebral artery occlusion mice oxygen-glucose deprivation rat cortical neurons. The results presented...
The contribution of environmental pollutants to liver fibrosis is an important and poorly explored issue. In vitro studies suggest that the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) other aryl hydrocarbon receptor (AhR) ligands induce several genes are known be upregulated during fibrosis. Our aim was determine whether exposure such can lead characterize mechanisms action. Mice were treated for 2, 14, or 42 days, once a week with 25 µg/kg TCDD. Gene protein expression, in vivo, as...
The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness implies a delay. We have recently described that sensitizes HCC cells to apoptosis. In this work, we explored six different liver tumor cell lines define phenotypic signature may predict lack patients. Results indicated show mesenchymal-like phenotype, resistance suppressor effects transforming growth factor beta...
Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss intestinal stem cells (ISCs). However, whether effect Notch is direct due to aberrant differentiation transit-amplifying into post-mitotic goblet unknown. To address this issue, we have generated composite tamoxifen-inducible intestine-specific genetic mouse models and analyzed expression markers. Importantly, found activation β-catenin partially rescues phenotype Rbpj deletion mutants, but not...