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: 11 to 20 of 358

Publication Record

Connections

Biophysical Modeling of In Vivo Glioma Response After Whole-Brain Radiation Therapy in a Murine Model of Brain Cancer.
Hormuth DA, Weis JA, Barnes SL, Miga MI, Quaranta V, Yankeelov TE
(2018) Int J Radiat Oncol Biol Phys 100: 1270-1279
MeSH Terms: Animals, Brain Neoplasms, Cell Death, Cell Proliferation, Contrast Media, Cranial Irradiation, Diffusion Magnetic Resonance Imaging, Disease Models, Animal, Female, Glioma, Magnetic Resonance Imaging, Models, Biological, Radiation Dosage, Rats, Rats, Wistar, Treatment Outcome, Tumor Burden
Show Abstract · Added July 23, 2018
PURPOSE - To develop and investigate a set of biophysical models based on a mechanically coupled reaction-diffusion model of the spatiotemporal evolution of tumor growth after radiation therapy.
METHODS AND MATERIALS - Post-radiation therapy response is modeled using a cell death model (M), a reduced proliferation rate model (M), and cell death and reduced proliferation model (M). To evaluate each model, rats (n = 12) with C6 gliomas were imaged with diffusion-weighted magnetic resonance imaging (MRI) and contrast-enhanced MRI at 7 time points over 2 weeks. Rats received either 20 or 40 Gy between the third and fourth imaging time point. Diffusion-weighted MRI was used to estimate tumor cell number within enhancing regions in contrast-enhanced MRI data. Each model was fit to the spatiotemporal evolution of tumor cell number from time point 1 to time point 5 to estimate model parameters. The estimated model parameters were then used to predict tumor growth at the final 2 imaging time points. The model prediction was evaluated by calculating the error in tumor volume estimates, average surface distance, and voxel-based cell number.
RESULTS - For both the rats treated with either 20 or 40 Gy, significantly lower error in tumor volume, average surface distance, and voxel-based cell number was observed for the M and M models compared with the M model. The M model fit, however, had significantly lower sum squared error compared with the M and M models.
CONCLUSIONS - The results of this study indicate that for both doses, the M and M models result in accurate predictions of tumor growth, whereas the M model poorly describes response to radiation therapy.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Formulation and characterization of poly(propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles for pH-dependent membrane disruption and cytosolic delivery.
Fernando LP, Lewis JS, Evans BC, Duvall CL, Keselowsky BG
(2018) J Biomed Mater Res A 106: 1022-1033
MeSH Terms: Acrylic Resins, Animals, CHO Cells, Cell Death, Cell Membrane, Cricetinae, Cricetulus, Cytosol, Dendritic Cells, Endocytosis, Endosomes, Humans, Hydrogen-Ion Concentration, Mice, Inbred C57BL, Microspheres, Particle Size, Polylactic Acid-Polyglycolic Acid Copolymer, Proton Magnetic Resonance Spectroscopy
Show Abstract · Added March 14, 2018
Poly(lactic-co-glycolic acid) (PLGA) is widely used as a vehicle for delivery of pharmaceutically relevant payloads. PLGA is readily fabricated as a nano- or microparticle (MP) matrix to load both hydrophobic and hydrophilic small molecular drugs as well as biomacromolecules such as nucleic acids and proteins. However, targeting such payloads to the cell cytosol is often limited by MP entrapment and degradation within acidic endolysosomes. Poly(propylacrylic acid) (PPAA) is a polyelectrolyte polymer with the membrane disruptive capability triggered at low pH. PPAA has been previously formulated in various carrier configurations to enable cytosolic payload delivery, but requires sophisticated carrier design. Taking advantage of PPAA functionality, we have incorporated PPAA into PLGA MPs as a simple polymer mixture to enhance cytosolic delivery of PLGA-encapsulated payloads. Rhodamine loaded PLGA and PPAA/PLGA blend MPs were prepared by a modified nanoprecipitation method. Incorporation of PPAA into PLGA MPs had little to no effect on the size, shape, or loading efficiency, and evidenced no toxicity in Chinese hamster ovary epithelial cells. Notably, incorporation of PPAA into PLGA MPs enabled pH-dependent membrane disruption in a hemolysis assay, and a three-fold increased endosomal escape and cytosolic delivery in dendritic cells after 2 h of MP uptake. These results demonstrate that a simple PLGA/PPAA polymer blend is readily fabricated into composite MPs, enabling cytosolic delivery of an encapsulated payload. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1022-1033, 2018.
© 2017 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
18 MeSH Terms
CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC).
Trickey A, May MT, Schommers P, Tate J, Ingle SM, Guest JL, Gill MJ, Zangerle R, Saag M, Reiss P, Monforte AD, Johnson M, Lima VD, Sterling TR, Cavassini M, Wittkop L, Costagliola D, Sterne JAC, Antiretroviral Therapy Cohort Collaboration (ART-CC)
(2017) Clin Infect Dis 65: 959-966
MeSH Terms: Adolescent, Adult, Aged, Anti-HIV Agents, Biomarkers, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cause of Death, Europe, Female, HIV Infections, Humans, Lymphocyte Count, Male, Middle Aged, North America, Prognosis, Proportional Hazards Models, Viral Load, Young Adult
Show Abstract · Added March 14, 2018
Background - We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count.
Methods - We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines.
Results - During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality.
Conclusions - In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Quantitative Mass Spectrometry Analysis of PD-L1 Protein Expression, -glycosylation and Expression Stoichiometry with PD-1 and PD-L2 in Human Melanoma.
Morales-Betanzos CA, Lee H, Gonzalez Ericsson PI, Balko JM, Johnson DB, Zimmerman LJ, Liebler DC
(2017) Mol Cell Proteomics 16: 1705-1717
MeSH Terms: Acetylglucosamine, Adult, Aged, B7-H1 Antigen, Biopsy, Cohort Studies, Female, Glycosylation, Humans, Male, Mannose, Mass Spectrometry, Melanoma, Middle Aged, Polysaccharides, Programmed Cell Death 1 Ligand 2 Protein, Programmed Cell Death 1 Receptor, Protein Processing, Post-Translational, Skin Neoplasms, T-Lymphocytes
Show Abstract · Added March 14, 2018
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted MS platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from ∼0.03 to 1.5 fmol/microgram protein and the parallel reaction monitoring (PRM) data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody. PD-1 was measured at levels up to 20-fold lower than PD-L1, but the abundances were not significantly correlated (r = 0.062, = 0.264). PD-1 abundance was weakly correlated (r = 0.3057, = 0.009) with the fraction of lymphocytes and histiocytes in sections. PD-L2 was measured from 0.03 to 1.90 fmol/microgram protein and the ratio of PD-L2 to PD-L1 abundance ranged from 0.03 to 2.58. In 10 samples, PD-L2 was present at more than half the level of PD-L1, which suggests that PD-L2, a higher affinity PD-1 ligand, is sufficiently abundant to contribute to T-cell downregulation. We also identified five branched mannose and N-acetylglucosamine glycans at PD-L1 position N192 in all 22 samples. Extent of PD-L1 glycan modification varied by ∼10-fold and the melanoma with the highest PD-L1 protein abundance and most abundant glycan modification yielded a very low PD-L1 IHC estimate, thus suggesting that N-glycosylation may affect IHC measurement and PD-L1 function. Additional PRM analyses quantified immune checkpoint/co-regulator proteins LAG3, IDO1, TIM-3, VISTA, and CD40, which all displayed distinct expression independent of PD-1, PD-L1, and PD-L2. Targeted MS can provide a next-generation analysis platform to advance cancer immuno-therapeutic research and diagnostics.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Reactive Oxygen Species Shielding Hydrogel for the Delivery of Adherent and Nonadherent Therapeutic Cell Types.
Dollinger BR, Gupta MK, Martin JR, Duvall CL
(2017) Tissue Eng Part A 23: 1120-1131
MeSH Terms: Animals, Cell Adhesion, Cell Count, Cell Death, Cytoprotection, Humans, Hydrogels, Hydrogen Peroxide, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Polymers, Reactive Oxygen Species, Rheology
Show Abstract · Added March 14, 2018
Cell therapies suffer from poor survival post-transplant due to placement into hostile implant sites characterized by host immune response and innate production of high levels of reactive oxygen species (ROS). We hypothesized that cellular encapsulation within an injectable, antioxidant hydrogel would improve viability of cells exposed to high oxidative stress. To test this hypothesis, we applied a dual thermo- and ROS-responsive hydrogel comprising the ABC triblock polymer poly[(propylene sulfide)-block-(N,N-dimethyl acrylamide)-block-(N-isopropylacrylamide)] (PPS-b-PDMA-b-PNIPAAM, PDN). The PPS chemistry reacts irreversibly with ROS such as hydrogen peroxide (HO), imparting inherent antioxidant properties to the system. Here, PDN hydrogels were successfully integrated with type 1 collagen to form ROS-protective, composite hydrogels amenable to spreading and growth of adherent cell types such as mesenchymal stem cells (MSCs). It was also shown that, using a control hydrogel substituting nonreactive polycaprolactone in place of PPS, the ROS-reactive PPS chemistry is directly responsible for PDN hydrogel cytoprotection of both MSCs and insulin-producing β-cell pseudo-islets against HO toxicity. In sum, these results establish the potential of cytoprotective, thermogelling PDN biomaterials for injectable delivery of cell therapies.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Ventricular arrhythmias and sudden death in patients taking ibrutinib.
Lampson BL, Yu L, Glynn RJ, Barrientos JC, Jacobsen ED, Banerji V, Jones JA, Walewska R, Savage KJ, Michaud GF, Moslehi JJ, Brown JR
(2017) Blood 129: 2581-2584
MeSH Terms: Arrhythmias, Cardiac, Death, Sudden, Cardiac, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Pyrazoles, Pyrimidines
Added March 26, 2017
0 Communities
1 Members
0 Resources
8 MeSH Terms
Myocarditis with Immune Checkpoint Blockade.
Moslehi JJ, Johnson DB, Sosman JA
(2017) N Engl J Med 376: 292
MeSH Terms: B7-H1 Antigen, Humans, Myocarditis, Programmed Cell Death 1 Receptor
Added March 26, 2017
0 Communities
1 Members
0 Resources
4 MeSH Terms
PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Antitumor Immunity and Anti-PD1 Responses.
Sai J, Owens P, Novitskiy SV, Hawkins OE, Vilgelm AE, Yang J, Sobolik T, Lavender N, Johnson AC, McClain C, Ayers GD, Kelley MC, Sanders M, Mayer IA, Moses HL, Boothby M, Richmond A
(2017) Clin Cancer Res 23: 3371-3384
MeSH Terms: Aminopyridines, Animals, Cell Line, Tumor, Cell Proliferation, Class Ib Phosphatidylinositol 3-Kinase, Female, Humans, Immunity, Cellular, Mammary Neoplasms, Animal, Mice, Morpholines, Neoplasm Metastasis, Programmed Cell Death 1 Receptor, Protein Kinase Inhibitors, Signal Transduction, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays
Show Abstract · Added January 4, 2017
Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ in immune cell function, we sought to determine whether PI3K inhibition altered antitumor immunity. The effect of PI3K inhibition on tumor growth, metastasis, and antitumor immune response was characterized in mouse models utilizing orthotopic implants of 4T1 or PyMT mammary tumors into syngeneic or -null mice, and patient-derived breast cancer xenografts in humanized mice. Tumor-infiltrating leukocytes were characterized by IHC and FACS analysis in BKM120 (30 mg/kg, every day) or vehicle-treated mice and versus mice. On the basis of the finding that PI3K inhibition resulted in a more inflammatory tumor leukocyte infiltrate, the therapeutic efficacy of BKM120 (30 mg/kg, every day) and anti-PD1 (100 μg, twice weekly) was evaluated in PyMT tumor-bearing mice. Our findings show that PI3K activity facilitates tumor growth and surprisingly restrains tumor immune surveillance. These activities could be partially suppressed by BKM120 or by genetic deletion of in the host. The antitumor effect of loss in host, but not tumor, was partially reversed by CD8 T-cell depletion. Treatment with therapeutic doses of both BKM120 and antibody to PD-1 resulted in consistent inhibition of tumor growth compared with either agent alone. PI3K inhibition slows tumor growth, enhances antitumor immunity, and heightens susceptibility to immune checkpoint inhibitors. We propose that combining PI3K inhibition with anti-PD1 may be a viable therapeutic approach for triple-negative breast cancer. .
©2016 American Association for Cancer Research.
2 Communities
4 Members
0 Resources
17 MeSH Terms
NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury.
Nlandu-Khodo S, Dissard R, Hasler U, Schäfer M, Pircher H, Jansen-Durr P, Krause KH, Martin PY, de Seigneux S
(2016) Sci Rep 6: 38598
MeSH Terms: Animals, Apoptosis, Cell Death, Creatinine, Disease Models, Animal, Gene Expression, Gene Expression Regulation, Genetic Predisposition to Disease, Glutathione, Kelch-Like ECH-Associated Protein 1, Kidney Diseases, Kidney Tubules, Mice, Mice, Knockout, Mitochondria, NADPH Oxidase 4, NF-E2-Related Factor 2, Oxidation-Reduction, Proto-Oncogene Proteins c-bcl-2, Reperfusion Injury
Show Abstract · Added December 26, 2018
NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI. NOX4 KO mice displayed decreased renal function and more severe tubular apoptosis, decreased Bcl-2 expression and higher histologic damage scores compared to WT. Activation of NRF2 was decreased in NOX4 KO mice in response to IRI. This was related to decreased KEAP1 oxidation leading to decreased NRF2 stabilization. This resulted in decreased glutathione levels. In vitro silencing of NOX4 in cells showed an enhanced propensity to apoptosis, with reduced expression of NRF2, glutathione content and Bcl-2 expression, similar to cells derived from NOX4 KO mice. Overexpression of a constitutively active form of NRF2 (caNRF2) in NOX4 depleted cells rescued most of this phenotype in cultured cells, implying that NRF2 regulation by ROS issued from NOX4 may play an important role in its anti-apoptotic property.
0 Communities
1 Members
0 Resources
MeSH Terms
Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine.
Li B, Siuta M, Bright V, Koktysh D, Matlock BK, Dumas ME, Zhu M, Holt A, Stec D, Deng S, Savage PB, Joyce S, Pham W
(2016) Int J Nanomedicine 11: 6103-6121
MeSH Terms: Adjuvants, Immunologic, Administration, Intranasal, Animals, Cell Death, Cell Proliferation, Dendritic Cells, Galactosylceramides, Immunization, Injections, Intraperitoneal, Lactic Acid, Mice, Mice, Inbred C57BL, Microscopy, Atomic Force, Nanoparticles, Ovalbumin, Polyglycolic Acid, Polylactic Acid-Polyglycolic Acid Copolymer, T-Lymphocytes, Vaccines
Show Abstract · Added March 21, 2018
The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days. The in vivo immunization studies exhibited that the nanovaccine induced stronger and longer immune responses compared to its soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced more robust antigen-specific CD8 T cell response than intraperitoneal injection of nanovaccine.
0 Communities
1 Members
0 Resources
19 MeSH Terms