A5033465424- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- RNA modifications and cancer
- Renal and related cancers
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Brain Metastases and Treatment
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Circular RNAs in diseases
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Molecular Biology Techniques and Applications
- FOXO transcription factor regulation
- Prostate Cancer Treatment and Research
- Radiomics and Machine Learning in Medical Imaging
- Pluripotent Stem Cells Research
- Cancer Mechanisms and Therapy
- Lung Cancer Research Studies
- Chromatin Remodeling and Cancer
University of Nebraska Medical Center
2017-2025
Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) its mutant EGFRvIII are amplified in ~ 60% 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation tyrosine kinase receptor, cMET, regulates CSC maintenance promote recurrence. Here, we evaluated the...
Bone metastases occur in patients with advanced-stage prostate cancer (PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates microenvironment, increases deformities, drives tumor growth bone. However, molecular mechanisms of PCa-mediated modulation are complex remain poorly defined. Here, we evaluated differentiation factor-15 (GDF15) function using vivo preclinical PCa-bone metastasis mouse models an vitro cell coculture system. Our...
Purpose: MUC16, a tumor biomarker and cell surface-associated mucin, is overexpressed in various cancers; however, its role lung cancer pathogenesis unknown. Here, we have explored the mechanistic of MUC16 cancer.Experimental Design: To identify functional stable knockdown was carried cells with two different shRNAs. Clinical significance evaluated patient tissues using IHC. We generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate preclinical MUC16.Results: (P = 0.03) as...
A pro-oxidant enzyme, NADPH oxidase 4 (Nox4) has been reported to be a critical downstream effector of TGFβ-induced myofibroblast transformation during fibrosis. While there are small number studies suggesting an oncogenic role Nox4 derived from activated fibroblasts, direct evidence linking this the tumor-supporting CAF phenotype and mechanisms involved lacking, particularly in breast cancer.
Docetaxel plays an indispensable role in the management of advanced prostate cancer. However, more than half patients do not respond to docetaxel, and those good responders frequently experience significant cumulative toxicity, which limits its dose duration intensity. Hence, a second agent that could increase initial efficacy docetaxel maintain tolerability at biologically effective doses may improve outcomes for patients.We determined phosphodiesterase 5 (PDE5) expression levels human...
Abstract Purpose: Breast cancer (BC) brain metastasis (BrM) remains a significant clinical problem. Mucins have been implicated in metastasis; however, if they are also involved BCBrM unknown. We queried BrM patient databases and found Mucin 5AC (MUC5AC) to be upregulated therefore sought define the role of MUC5AC BCBrM. Experimental design: In-silico dataset analysis, RNA-sequence profiling on patients cell lines, analysis patients’ serum samples, in-vitro/vivo knockdown experiments were...
<p>Supplementary Figure 2. MUC5AC IHC staining using Aperio Digital Imaging revealed strong to medium scores in BrM patient samples. Tumor areas were defined by annotations (green color) and necrotic or not corresponding tumor excluded as negative (blue color). Pixel Positive algorithm was with 4 scales: 1. Negative (blue), Weak positive (yellow), 3. Medium (orange) 4. Strong (red). Controls for development DAB. A. Annotation (tumor area) tissue of pancreas cancer without antibody...
<p>Supplementary Figure 3. MUC5AC promotes brain metastasis. A. Western blot for HER2 expression in MDA-231BR cells. B. showing knockout of the HCC1954BR C-F. Wound healing assay and quantification reduced migration shMUC5AC cells (C D) KO (E F). Representative images (G) (H) trans-endothelial cell SCR (HCC1954BR). I. Schematic representation 3D ex-vivo culture J. fluorescence microscopy slices (organotypic culture) GFP+ MDA-231P, invasion into tissue. Data presented as mean ± SD from...
<p>Supplementary Figure 6. PLB1001 inhibit cMET and CD44v6 expression. A. Representative IHC images showing MUC5AC expression in G5-3 PDXs B. fluorescence microscopy GFP+ C. of MUC5AC, cMET, cleaved caspase3 PDX treated with vehicle or (50mg/kg).</p>
<p>Supplementary Figure 5. MUC5AC silencing inhibits cMET and CD44v6 expression Astrocytes induce in breast cancer cells. A-B. Western blots showing knockdown of MDA-231BR HER2 (A) knockout HCC1954BR (B) reduces CD44v6. C. IHC staining for on brain tissue sections from mice injected with shSCR shMUC5AC D. SKBR3 cells were treated human astrocyte conditioned media 24h lysed subjected expression. HGF induced signaling (E) (F); (100ng/mL) indicated times. After treatment p-cMET using...
<div>AbstractPurpose:<p>Breast cancer brain metastasis remains a significant clinical problem. Mucins have been implicated in metastasis; however, whether they are also involved breast unknown. We queried databases of patients with and found mucin 5AC (MUC5AC) to be upregulated therefore sought define the role MUC5AC metastasis.</p>Experimental Design:<p><i>In silico</i> dataset analysis, RNA-sequence profiling patient samples cell lines, analysis serum...
<p>Supplementary Figure 1. Expression of MUC5AC is high in breast cancer brain metastasis. A. Heatmap showing the expression upregulated genes BC BrM cells as compared to primary (MDA-231BR vs MDA-231P). B. Comparison (z-score) between and metastasis samples, using online available Gene Omnibus (GEO) public datasets, probe (214385_s_at). C. goblet marker cell lines Data represents upregulation proteins. D. Pie chart representing H-score for tissues originating from (Breast cancer), LC...
<p>Supplementary Figure 4. MUC5AC silencing inhibits brain metastasis. A. Fluorescence microscopy images showing Cytokeratin 8/18 and in the tissue sections of mice intracardially injected with shSCR shMUC5AC KD MDA-231BR HER2 cells. B. The IHC show expression cMET. C. H-score quantification cMET different cohorts BC BrM patients. D. CD44v6. E. Clustering gene interaction network analysis (http://string-db.org/) shows MUC5AC, CD44v6 interaction.</p>
Lung cancer (LC) is the leading cause of cancer-related mortality. However, molecular mechanisms associated with development metastasis are poorly understood. Understanding biology LC critical to unveil for designing targeted therapies. We developed two genetically engineered mouse models KrasG12D/+ ; Trp53R172H/+ Ad-Cre (KPA) and (KA). Survival analysis showed significantly (P = 0.0049) shorter survival in KPA tumor-bearing mice as compared KA, suggesting aggressiveness model. Our...
Abstract Background Glioblastoma (GBM) has a devastating median survival of only one year. Treatment includes resection, radiation therapy, and temozolomide (TMZ); however, the latter increased by 2.5 months in pivotal study. A desperate need remains to find an effective treatment. Methods We used Connectivity Map (CMap) bioinformatic tool identify candidates for repurposing based on GBM’s specific genetic profile. CMap identified histone deacetylase (HDAC) inhibitors as top candidates. In...