A5030018274- Brain Metastases and Treatment
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Melanoma and MAPK Pathways
- Single-cell and spatial transcriptomics
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Mathematical Biology Tumor Growth
- Cancer Genomics and Diagnostics
- Ocular Oncology and Treatments
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- interferon and immune responses
- Computational Drug Discovery Methods
Moffitt Cancer Center
2019-2023
Melanoma brain metastases (MBM) and leptomeningeal melanoma (LMM) are two different manifestations of CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape MBM, LMM, skin metastases.scRNA-seq was undertaken on 43 patient specimens, including 8 metastases, 14 19 serial LMM specimens. Detailed cell type curation performed, landscapes were mapped, key results validated by IHC flow cytometry. Association analyses identify subsets correlated with...
Melanoma is a heterogeneous tumour, but the impact of this heterogeneity upon therapeutic response not well understood.Single cell mRNA analysis was used to define transcriptional melanoma and its dynamic BRAF inhibitor therapy treatment holidays. Discrete states were defined in lines patient specimens that predicted initial sensitivity inhibition potential for effective re-challenge following resistance. A mathematical model developed maintain competition between drug-sensitive resistant...
Melanoma is known to be a heterogeneous tumor, but the impact of this heterogeneity upon therapeutic response not well understood. In current study, we used single cell mRNA analysis and our Single Cell HETerogeneity (SinCHET) platform define transcriptional diversity melanoma its dynamic both BRAF inhibitor therapy treatment holidays. Our analyses showed lines patient specimens composed >3 co-existent, transcriptionally distinct states. Among these, State #1 had increased expression cyclin...
<p>Poor responder LMM CSF vs no significantly altered proteins and their IPA analysis</p>
<p>Kinase Array densitometry quantification</p>
<p>TMT Batch Setup</p>
<p>The fold changes in gene expression between the vemurafenib treated and vehicle cells for each cell culture condition</p>
<p>Poor responder LMM CSF vs no significantly altered proteins and their IPA analysis</p>
<p>Summary of significantly altered gene expression with BRAF inhibitor treatment</p>
<p>TMT Batch Setup</p>
<p>Supplementary Figures 1-11. 1. CSF cytology of leptomeningeal patient cohort. 2. Additional clinical timelines cohort 3. Patient MRIs 4. RNAseq Workflow 5. Differential responses to BRAFi treatment in 6. shows from 4 elicit transcriptional modulation melanoma cell response BRAF inhibition 7. LMM patients elicits changes cells 8. protects inhibitor therapy 9. activates AKT WM164 10. No-LMM does not induce expression TGFbeta or activation 11. ELISA assay showing the levels TGFβ1...
<p>Kinase Array densitometry quantification</p>
<p>The fold changes in gene expression between the vemurafenib treated and vehicle cells for each cell culture condition</p>
<p>Supplemental Figure 1. Expression of T, NK, B and Plasma cell markers by metastatic site. Supplemental 2. myeloid site gene expression associated with classical alternative macrophage activation. 3. Baseline therapy induced changes in the LMM immune landscape. 4. therapy-mediated to MBM 5. MHC class I II melanoma cells from samples without DC3s. 6. Cell-cell interactions between DC3s T defined SingleCellR. 7. Detection DC3 clinical using multiplexed IHC. 8. Validation analysis...
<div>AbstractPurpose:<p>The development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication the late-stage disease, for which no effective treatments exist. Here, we performed multi-omics analysis cerebrospinal fluid (CSF) from patients with LMM to determine how microenvironment shapes biology therapeutic responses cells.</p>Experimental Design:<p>A total 45 serial CSF samples were collected 16 patients, 8 these confirmed LMM. Of those...
<div>AbstractPurpose:<p>Melanoma brain metastases (MBM) and leptomeningeal melanoma (LMM) are two different manifestations of CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape MBM, LMM, skin metastases.</p>Experimental Design:<p>scRNA-seq was undertaken on 43 patient specimens, including 8 metastases, 14 19 serial LMM specimens. Detailed cell type curation performed, landscapes were mapped, key results validated by IHC...
<div>AbstractPurpose:<p>The development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication the late-stage disease, for which no effective treatments exist. Here, we performed multi-omics analysis cerebrospinal fluid (CSF) from patients with LMM to determine how microenvironment shapes biology therapeutic responses cells.</p>Experimental Design:<p>A total 45 serial CSF samples were collected 16 patients, 8 these confirmed LMM. Of those...