Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 374

Publication Record

Connections

Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A.
Sucre JMS, Vickers KC, Benjamin JT, Plosa EJ, Jetter CS, Cutrone A, Ransom M, Anderson Z, Sheng Q, Fensterheim BA, Ambalavanan N, Millis B, Lee E, Zijlstra A, Königshoff M, Blackwell TS, Guttentag SH
(2020) Am J Respir Crit Care Med 201: 1249-1262
MeSH Terms: Alveolar Epithelial Cells, Animals, Bronchopulmonary Dysplasia, Coculture Techniques, Fibroblasts, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Hyperoxia, In Situ Hybridization, Lung, Mesenchymal Stem Cells, Mice, Microscopy, Confocal, NF-kappa B, Nitriles, Organ Culture Techniques, Real-Time Polymerase Chain Reaction, Sulfones, Wnt-5a Protein
Show Abstract · Added February 6, 2020
Bronchopulmonary dysplasia (BPD) is a leading complication of preterm birth that affects infants born in the saccular stage of lung development at <32 weeks of gestation. Although the mechanisms driving BPD remain uncertain, exposure to hyperoxia is thought to contribute to disease pathogenesis. To determine the effects of hyperoxia on epithelial-mesenchymal interactions and to define the mediators of activated Wnt/β-catenin signaling after hyperoxia injury. Three hyperoxia models were used: A three-dimensional organotypic coculture using primary human lung cells, precision-cut lung slices (PCLS), and a murine hyperoxia model. Comparisons of normoxia- and hyperoxia-exposed samples were made by real-time quantitative PCR, RNA hybridization, quantitative confocal microscopy, and lung morphometry. Examination of an array of Wnt ligands in the three-dimensional organotypic coculture revealed increased mesenchymal expression of . Inhibition of Wnt5A abrogated the BPD transcriptomic phenotype induced by hyperoxia. In the PCLS model, Wnt5A inhibition improved alveolarization following hyperoxia exposure, and treatment with recombinant Wnt5a reproduced features of the BPD phenotype in PCLS cultured in normoxic conditions. Chemical inhibition of NF-κB with BAY11-7082 reduced expression in the PCLS hyperoxia model and mouse hyperoxia model, with improved alveolarization in the PCLS model. Increased mesenchymal Wnt5A during saccular-stage hyperoxia injury contributes to the impaired alveolarization and septal thickening observed in BPD. Precise targeting of Wnt5A may represent a potential therapeutic strategy for the treatment of BPD.
0 Communities
3 Members
0 Resources
20 MeSH Terms
Generating kinetic environments to study dynamic cellular processes in single cells.
Thiemicke A, Jashnsaz H, Li G, Neuert G
(2019) Sci Rep 9: 10129
MeSH Terms: Algorithms, Cell Line, Cell Shape, Equipment Design, Gene Expression Regulation, Humans, In Situ Hybridization, Fluorescence, Interrupted Time Series Analysis, Kinetics, Membrane Transport Proteins, Mitogen-Activated Protein Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Single Molecule Imaging, Single-Cell Analysis, Time-Lapse Imaging
Show Abstract · Added February 5, 2020
Cells of any organism are consistently exposed to changes over time in their environment. The kinetics by which these changes occur are critical for the cellular response and fate decision. It is therefore important to control the temporal changes of extracellular stimuli precisely to understand biological mechanisms in a quantitative manner. Most current cell culture and biochemical studies focus on instant changes in the environment and therefore neglect the importance of kinetic environments. To address these shortcomings, we developed two experimental methodologies to precisely control the environment of single cells. These methodologies are compatible with standard biochemistry, molecular, cell and quantitative biology assays. We demonstrate applicability by obtaining time series and time point measurements in both live and fixed cells. We demonstrate the feasibility of the methodology in yeast and mammalian cell culture in combination with widely used assays such as flow cytometry, time-lapse microscopy and single-molecule RNA Fluorescent in-situ Hybridization (smFISH). Our experimental methodologies are easy to implement in most laboratory settings and allows the study of kinetic environments in a wide range of assays and different cell culture conditions.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Multiplex RNA single molecule FISH of inducible mRNAs in single yeast cells.
Li G, Neuert G
(2019) Sci Data 6: 94
MeSH Terms: In Situ Hybridization, Fluorescence, Membrane Transport Proteins, RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Single-Cell Analysis
Show Abstract · Added February 5, 2020
Transcript levels powerfully influence cell behavior and phenotype and are carefully regulated at several steps. Recently developed single cell approaches such as RNA single molecule fluorescence in-situ hybridization (smFISH) have produced advances in our understanding of how these steps work within the cell. In comparison to single-cell sequencing, smFISH provides more accurate quantification of RNA levels. Additionally, transcript subcellular localization is directly visualized, enabling the analysis of transcription (initiation and elongation), RNA export and degradation. As part of our efforts to investigate how this type of analysis can generate improved models of gene expression, we used smFISH to quantify the kinetic expression of STL1 and CTT1 mRNAs in single Saccharomyces cerevisiae cells upon 0.2 and 0.4 M NaCl osmotic stress. In this Data Descriptor, we outline our procedure along with our data in the form of raw images and processed mRNA counts. We discuss how these data can be used to develop single cell modelling approaches, to study fundamental processes in transcription regulation and develop single cell image processing approaches.
0 Communities
1 Members
0 Resources
MeSH Terms
Analysis of Cardiac Chamber Development During Mouse Embryogenesis Using Whole Mount Epifluorescence.
Zhang Z, Nam YJ
(2019) J Vis Exp :
MeSH Terms: Animals, Embryo, Mammalian, Embryonic Development, Female, Fluorescence, Genotype, Heart, In Situ Hybridization, Male, Mice, Mice, Transgenic
Show Abstract · Added March 24, 2020
The goal of this protocol is to describe a method for the dissection of mouse embryos and visualization of embryonic mouse ventricular chambers during heart development using ventricular specific fluorescent reporter knock-in mice (MLC-2v-tdTomato mice). Heart development involves a linear heart tube formation, the heart tube looping, and four chamber septation. These complex processes are highly conserved in all vertebrates. The mouse embryonic heart has been widely used for heart developmental studies. However, due to their extremely small size, dissecting mouse embryonic hearts is technically challenging. In addition, visualization of cardiac chamber formation often needs in situ hybridization, beta-galactosidase staining using LacZ reporter mice, or immunostaining of sectioned embryonic hearts. Here, we describe how to dissect mouse embryonic hearts and directly visualize ventricular chamber formation of MLC-2v-tdTomato mice using whole mount epifluorescent microscopy. With this method, it is possible to directly examine heart tube formation and looping, and four chamber formation without further experimental manipulation of mouse embryos. Although the MLC-2v-tdTomato reporter knock-in mouse line is used in this protocol as an example, this protocol can be applied to other heart-specific fluorescent reporter transgenic mouse lines.
0 Communities
1 Members
0 Resources
MeSH Terms
Beyond the H&E: Advanced Technologies for in situ Tissue Biomarker Imaging.
Himmel LE, Hackett TA, Moore JL, Adams WR, Thomas G, Novitskaya T, Caprioli RM, Zijlstra A, Mahadevan-Jansen A, Boyd KL
(2018) ILAR J 59: 51-65
MeSH Terms: Animals, Biomarkers, Humans, Immunohistochemistry, In Situ Hybridization, Microscopy, Fluorescence, Quality Control, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Show Abstract · Added April 10, 2019
For decades, histopathology with routine hematoxylin and eosin staining has been and remains the gold standard for reaching a morphologic diagnosis in tissue samples from humans and veterinary species. However, within the past decade, there has been exponential growth in advanced techniques for in situ tissue biomarker imaging that bridge the divide between anatomic and molecular pathology. It is now possible to simultaneously observe localization and expression magnitude of multiple protein, nucleic acid, and molecular targets in tissue sections and apply machine learning to synthesize vast, image-derived datasets. As these technologies become more sophisticated and widely available, a team-science approach involving subspecialists with medical, engineering, and physics backgrounds is critical to upholding quality and validity in studies generating these data. The purpose of this manuscript is to detail the scientific premise, tools and training, quality control, and data collection and analysis considerations needed for the most prominent advanced imaging technologies currently applied in tissue sections: immunofluorescence, in situ hybridization, laser capture microdissection, matrix-assisted laser desorption ionization imaging mass spectrometry, and spectroscopic/optical methods. We conclude with a brief overview of future directions for ex vivo and in vivo imaging techniques.
© The Author(s) 2018. Published by Oxford University Press on behalf of the National Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.
0 Communities
3 Members
0 Resources
8 MeSH Terms
Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study.
Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, Sanborn RE, Whisenant JG, Du L, Neal JW, Gockerman JP, Dukart G, Harrow K, Liang C, Gibbons JJ, Holzhausen A, Lovly CM, Wakelee HA
(2018) Clin Cancer Res 24: 2771-2779
MeSH Terms: Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase, Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Lung Neoplasms, Male, Mice, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Staging, Piperazines, Prognosis, Protein Kinase Inhibitors, Pyridazines, Rats, Treatment Outcome, Young Adult
Show Abstract · Added September 10, 2020
Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). In dose escalation, ensartinib was administered at doses of 25 to 250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced -positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were eligible. Thirty-seven patients enrolled in dose escalation, and 60 enrolled in dose expansion. The most common treatment-related toxicities were rash (56%), nausea (36%), pruritus (28%), vomiting (26%), and fatigue (22%); 23% of patients experienced a treatment-related grade 3 to 4 toxicity (primarily rash and pruritus). The maximum tolerated dose was not reached, but the RP2D was chosen as 225 mg based on the frequency of rash observed at 250 mg without improvement in activity. Among the -positive efficacy evaluable patients treated at ≥200 mg, the response rate (RR) was 60%, and median progression-free survival (PFS) was 9.2 months. RR in ALK TKI-naïve patients was 80%, and median PFS was 26.2 months. In patients with prior crizotinib only, the RR was 69% and median PFS was 9.0 months. Responses were also observed in the central nervous system, with an intracranial RR of 64%. Ensartinib was active and generally well tolerated in patients with -positive NSCLC. .
©2018 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
MeSH Terms
Nup100 regulates replicative life span by mediating the nuclear export of specific tRNAs.
Lord CL, Ospovat O, Wente SR
(2017) RNA 23: 365-377
MeSH Terms: Active Transport, Cell Nucleus, Basic-Leucine Zipper Transcription Factors, Blotting, Northern, Cell Division, Cell Nucleus, Culture Media, Gene Expression Regulation, Fungal, In Situ Hybridization, Fluorescence, Karyopherins, Nuclear Pore, Nuclear Pore Complex Proteins, RNA, Fungal, RNA, Transfer, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors
Show Abstract · Added April 14, 2017
Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of We previously reported that deletion of the nonessential gene increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of Δ mutants. Protein levels of the transcription factor Gcn4 are increased when is deleted, and is required for the elevated life spans of Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of Δ and Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the life span.
© 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species.
Gelbard A, Katsantonis NG, Mizuta M, Newcomb D, Rotsinger J, Rousseau B, Daniero JJ, Edell ES, Ekbom DC, Kasperbauer JL, Hillel AT, Yang L, Garrett CG, Netterville JL, Wootten CT, Francis DO, Stratton C, Jenkins K, McGregor TL, Gaddy JA, Blackwell TS, Drake WP
(2017) Laryngoscope 127: 179-185
MeSH Terms: Case-Control Studies, Humans, Immunohistochemistry, In Situ Hybridization, Intubation, Intratracheal, Laryngostenosis, Microbiota, Microscopy, Electron, Mycobacterium, Phylogeny, Polymerase Chain Reaction, Tracheal Stenosis
Show Abstract · Added January 25, 2017
OBJECTIVES/HYPOTHESIS - Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.
METHODS - Utilizing 30 human iSGS, 20 intubation-related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger-sequencing techniques.
RESULTS - With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.
CONCLUSION - These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.
LEVEL OF EVIDENCE - NA Laryngoscope, 127:179-185, 2017.
© 2016 The American Laryngological, Rhinological and Otological Society, Inc.
1 Communities
3 Members
0 Resources
12 MeSH Terms
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer.
Mayer IA, Abramson VG, Formisano L, Balko JM, Estrada MV, Sanders ME, Juric D, Solit D, Berger MF, Won HH, Li Y, Cantley LC, Winer E, Arteaga CL
(2017) Clin Cancer Res 23: 26-34
MeSH Terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Aromatase Inhibitors, Biomarkers, Tumor, Breast Neoplasms, Cell Line, Tumor, DNA Mutational Analysis, Female, Humans, In Situ Hybridization, Fluorescence, Letrozole, Maximum Tolerated Dose, Middle Aged, Mutation, Neoplasm Metastasis, Neoplasm Staging, Nitriles, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Receptor, ErbB-2, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Estrogen, Thiazoles, Treatment Outcome, Triazoles
Show Abstract · Added April 6, 2017
PURPOSE - Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110α, has shown synergistic antitumor activity with endocrine therapy against ER/PIK3CA-mutated breast cancer cells. This phase Ib study evaluated alpelisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER breast cancer refractory to endocrine therapy.
EXPERIMENTAL DESIGN - Twenty-six patients received letrozole and alpelisib daily. Outcomes were assessed by standard solid-tumor phase I methods. Tumor blocks were collected for DNA extraction and next-generation sequencing.
RESULTS - Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER breast cancer are ongoing. Clin Cancer Res; 23(1); 26-34. ©2016 AACR.
©2016 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
26 MeSH Terms
MAGI-2 in prostate cancer: an immunohistochemical study.
Goldstein J, Borowsky AD, Goyal R, Roland JT, Arnold SA, Gellert LL, Clark PE, Hameed O, Giannico GA
(2016) Hum Pathol 52: 83-91
MeSH Terms: Adaptor Proteins, Signal Transducing, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Area Under Curve, Biomarkers, Tumor, Biopsy, Carrier Proteins, Guanylate Kinases, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Middle Aged, Neoplasm Grading, PTEN Phosphohydrolase, Predictive Value of Tests, Prostatic Hyperplasia, Prostatic Intraepithelial Neoplasia, Prostatic Neoplasms, ROC Curve, Tissue Array Analysis, Transcription Factors, Tumor Suppressor Proteins, Up-Regulation
Show Abstract · Added April 18, 2017
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) is a scaffolding protein that links cell adhesion molecules, receptors, and signaling molecules to the cytoskeleton and maintains the architecture of cell junctions. MAGI-2 gene rearrangements have recently been described in prostate cancer. We studied the immunohistochemical expression of MAGI-2 protein in prostate tissue. Seventy-eight radical prostatectomies were used to construct 3 tissue microarrays consisting of 512 cores, including benign tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma, Gleason patterns 3 to 5. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and double-stain MAGI-2/p63 was performed and analyzed by visual and image analysis, the latter as percent of analyzed area (%AREA), and mean optical density multiplied by %AREA (STAIN). By visual and image analysis, MAGI-2 was significantly higher in adenocarcinoma and HGPIN compared with benign (benign versus HGPIN P < .001; benign versus adenocarcinoma, P < .001). HGPIN and adenocarcinoma did not significantly differ by either modality. Using visual intensity to distinguish benign tissue and adenocarcinoma, a receiver operating curve yielded an area under the curve of 0.902. A STAIN threshold of 1470 yielded a sensitivity of 0.66 and specificity of 0.96. There was a significant correlation between PTEN and MAGI-2 staining for normal and benign prostatic hyperplasia, but this was lost in HGPIN and cancer. We conclude that MAGI-2 immunoreactivity is elevated in prostate cancer and HGPIN compared with normal tissue, and suggest that MAGI-2 may contribute to prostate carcinogenesis. This is the first report of MAGI-2 staining by immunohistochemistry in prostate cancer.
Copyright © 2016 Elsevier Inc. All rights reserved.
0 Communities
2 Members
0 Resources
26 MeSH Terms