Sameer Mohiuddin
A5102521508- Brain Metastases and Treatment
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Glycosylation and Glycoproteins Research
University of Nebraska Medical Center
2023-2025
Nebraska Medical Center
2023
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>
Abstract Outcomes from small cell lung cancer (SCLC) are dismal. Most SCLC patients have distant metastasis at diagnosis and the 5-year survival of these is around 2.8%. Despite initial response to chemotherapy immunotherapy, relapses very common. No targeted therapy available for SCLC. Thus, there an urgent need understand acquisition chemoresistance, identify novel targets therapeutic strategies this deadly disease. Recently, FOXM1 was identified as essential component in tumor growth. Our...