A5066642004- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Antibiotic Resistance in Bacteria
- Gene expression and cancer classification
- T-cell and B-cell Immunology
- Antibiotic Use and Resistance
- Urinary Tract Infections Management
- Mathematical Biology Tumor Growth
University of Cambridge
2024
University of Miami
2019-2020
Policlinico S.Orsola-Malpighi
2014
<p>Supplementary Figures 1-20</p>
<div>Abstract<p>The intertumor and intratumor heterogeneity of triple-negative breast cancers, which is reflected in diverse drug responses, interplays with tumor evolution. In this study, we developed a preclinical experimental analytical framework using patient-derived xenografts (PDTX) from patients treatment-naïve cancers to test their predictive value personalized cancer treatment approaches. Patients matched PDTXs exhibited concordant responses neoadjuvant therapy two trial...
<p>Short-term olaparib treatment does not cause major genomic changes. <b>A,</b> Growth curves displaying raw data of model 1006 treated with for 11 weeks (purple) or untreated controls (black). Dotted line indicates end treatment, after which, tumors were left to progress until size limits. <b>B,</b> Correlation plots comparing mean VAFs mutations between and (left) post-treated (right) samples. <i>R</i> value calculated using the Spearman...
<p><i>In vivo</i> treatment causes permanent changes to a tumor’s drug response profile. <b>A,</b> Experimental framework of <i>in and <i>ex profiling. <b>B,</b> High-throughput screening data dissociated PDTX cells. AUC plots display the each tumor drugs tested vivo</i>. Color indicates which was previously exposed. <b>C,</b> Dose–response curves models 1040 (top) 1141 (bottom) olaparib BMN-673. Plots compare untreated...
<p>Supplementary Figures 1-20 and Supplementary Tables 1-10 Legends</p>
<p>Olaparib treatment causes permanent phenotypic changes due to TF reprogramming. <b>A,</b> Heatmap displaying <i>z</i>-score (scaled by row) of the top 250 strong and variable genes. Clustering analysis performed using Euclidean distances. Columns indicate PDTX samples (labeled mouse number). <b>B,</b> Top 10 significant gene sets normalized enrichment score (NES) between untreated post-treated samples, identified GSEA (Hallmark sets). DN, down....
<p>A preclinical platform of TNBC PDTXs. <b>A,</b> Clinical treatment and responses the patient cohort from which PDTX models used in this study were derived. <b>B,</b> Experimental framework coclinical trial. <b>C,</b> Top, correlation plots comparing GSEA enrichment scores (Hallmark C6 gene sets) for 1006, 1040, 1022, 1141. Bottom, mutation VAFs model 1006. Correlation was calculated between passages, sister mice, multiple regions same tumor using...
<p>A coclinical trial framework reveals concordant patient–PDTX drug responses. <b>A,</b> Experimental (consisting of two designs) and associated analytical approach, with modeling metrics used to assess response. <b>B</b> <b>C,</b> TV growth curves displaying linear mixed model fits designs 1 (<b>B</b>) 2 (<b>C</b>) over treatment duration. Treatment arm for each PDTX corresponds the clinical matched patient....
<p>PDTXs identify patient-specific drug responses and model patient- treatment-specific regrowth dynamics. <b>A,</b> Experimental framework to test alternative treatments <b>B</b> <b>C,</b> Mean difference in daily growth rate between the treated untreated groups during treatment (<b>B</b>) after has ceased (<b>C</b>). <b>D</b> <b>E</b>, TV curves displaying linear mixed fits of PDTX models 1040 (left)...
Tumors induce tolerance toward their antigens by producing the chemokine CCL21, leading to formation of tertiary lymphoid organs (TLOs). Ins2-CCL21 transgenic, nonobese diabetic (NOD) mice express CCL21 in pancreatic β-cells and do not develop autoimmune diabetes. We investigated which mechanisms expression prevented TLOs 4 weeks age, consisting naive CD4+ T cells compartmentalized within networks CD45−gp38+CD31− fibroblastic reticular cell (FRC)–like cells. Importantly, 12-week-old...
The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental analytical framework using treatment-naive TNBC patient-derived xenografts (PDTX) to test their predictive value personalized cancer treatment approaches. Patients matched PDTX exhibited concordant responses neoadjuvant therapy two trial designs dosing schedules. This platform enabled...