Ontology highlight
ABSTRACT:
PROVIDER: PRJNA556308 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000-2016
2020-03-26 | GSE147493 | GEO
Project description:Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.
Yoon DJ1, Chen KY1, Lopes AM1, Pan AA1, Shiloach J2, Mason AB3, Kamei DT4.
Author information
1
Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, USA.
2
Biotechnology Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD 20892, USA.
3
Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA.
4
Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, USA. Electronic address: kamei@seas.ucla.edu.
Abstract
The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole-cell kinetic models can be useful in cancer therapeutic design.
Copyright © 2017 Elsevier Ltd. All rights reserved.
2020-01-09 | MODEL1912160006 | BioModels
Project description:Qionger He1, Erica D Arroyo2, Samuel N Smukowski3, Jian Xu, Claire Piochon1, Jeffrey N Savas3, Carlos Portera-Cailliau2 and Anis Contractor1,4*
1Department of Physiology & 3Department of Neurology, Northwestern University Feinberg School of Medicine; 2Departments of Neurology and Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 & 4Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL 60611
| MSV000081526 | MassIVE
Project description:We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with the gestational age (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.
2021-04-27 | GSE168788 | GEO
Project description:Exome sequencing of (MXL) Mexican Ancestry in Los Angeles, California HapMap population
| PRJNA59811 | ENA
Project description:Hornyhead turbot (Pleuronichthys verticalis) captured near sewage outfalls are used as sentinel fish for monitoring exposure to industrial and agricultural chemicals of ~20 million people living in coastal southern California. Although analyses of hormones in blood and organ morphology and histology in fish are useful for assessing exposure, there is a need for quantitative and sensitive molecular measurements, as many contaminants produce subtle effects. A novel multispecies microarray and qRT-PCR were used to investigate endocrine disruption in turbot captured near sewage outfalls in San Diego, Orange County and Los Angeles California. Analysis of expression of genes involved in hormone [e.g. estrogen, androgen, thyroid] responses and xenobiotic metabolism in turbot livers was correlated with phenotypic end points.
2013-12-10 | E-MEXP-3852 | biostudies-arrayexpress
Project description:Comparison of transcript abundance estimates derived from DBS vs saliva vs gold standard peripheral blood mononuclear cell (PBMC) samples. Gene expression profiling was conducted using parallel collection and assay of venipuncture blood samples (PBMC), DBS samples, and saliva. Data come from 58 community dwelling adults recruited from the Los Angeles metropolitan area. Analyzed data include basic demographic characteristics (age, sex, race/ethnicity) and body mass index (BMI) as well as RNA indicators of major leukocyte subset prevalence (i.e., estimated abundance of mRNA for CD3, CD4, CD8, CD19, FCGR3A/CD16, NCAM1/CD56, and CD14; all provided here as log2-transformed values of normalized gene expression data). Categorial variables were coded 0=no/absent and 1=yes/present.
2016-07-27 | E-GEOD-79269 | biostudies-arrayexpress
Project description:We present metaproteome data from maize rhizosphere from sodic soil. Isolation of proteome from maize rhizosphere collected from Experimental Farm, ICAR-IISS, Mau, India was done with the standardized protocol at our laboratory and metaproteome analysis was done with the standardized pipepline. In total 696 proteins with different functions representing 245 genus and 395 species were identified. The proteome data provides direct evidence on the biological processes in soil ecosystem and is the first reported reference data from maize rhizosphere.
2019-10-08 | PXD014519 | Pride