A5019852413- Estrogen and related hormone effects
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- Vitamin D Research Studies
- Hormonal and reproductive studies
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Cytokine Signaling Pathways and Interactions
Abstract Purpose: Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas express higher levels progesterone receptor isoform A (PRA) than B (PRB). Thus, we designed a presurgical window opportunity trial to determine therapeutic effects mifepristone in patients with cancer, based on their high PRA/PRB ratio (MIPRA; NCT02651844). Patients and Methods: Twenty > 1.5 (determined by Western blots), PR ≥ 50%, naïve from previous treatment, were included...
<div>AbstractPurpose:<p>Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas express higher levels progesterone receptor isoform A (PRA) than B (PRB). Thus, we designed a presurgical window opportunity trial to determine therapeutic effects mifepristone in patients with cancer, based on their high PRA/PRB ratio (MIPRA; NCT02651844).</p>Patients and Methods:<p>Twenty > 1.5 (determined by Western blots), PR ≥ 50%, naïve from...
<div>AbstractPurpose:<p>Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas express higher levels progesterone receptor isoform A (PRA) than B (PRB). Thus, we designed a presurgical window opportunity trial to determine therapeutic effects mifepristone in patients with cancer, based on their high PRA/PRB ratio (MIPRA; NCT02651844).</p>Patients and Methods:<p>Twenty > 1.5 (determined by Western blots), PR ≥ 50%, naïve from...
<p>Mutations identified in RNA-Seq analysis. The data obtained studies were graphed using the Oviz-Bio tool (https://academic.oup.com/nar/article/48/W1/W415/5835823). Only driver breast cancer genes (99) selected from Intogene base (https://www.intogen.org/download) and we found mutations 19 after read depth filtering (DP >50). Of note is missense mutation ESR1 M070 patient. Left, Percentage of samples with mutations. Color defines type mutations.</p>
<p>Morphological features after mifepristone treatment. A-D, Images illustrating increased stromal tissue (A), thin and scarce collagen fibers, matrix (arrow; B), an area of remodeling (C), differentiation (D) observed in the surgical samples (S) compared to respective core needle biopsies (CNB). E, Image illustrates necrosis (dotted arrow) together with a differentiated structure (black sample. F, Cells Alcian blue+ (left), PAS+ (middle) MUC-1+ (immunohistochemistry; right) vacuoles...
<p>A, Prevailing PR isoforms before and after mifepristone treatment their prevailing nuclear (Nuc) or cytosolic (Cyt) localization in western blot studies. *: Western studies; #: Distribution of the Nuc Cyt compartments; CNB: Core needle biopsy, S: Surgical sample. In grey font: Mifepristone unresponsive tumors by Ki67 criteria. B, Representative blots CNB surgical samples from all patients. The upper band is PRB lower PRA, as labeled first set.</p>
<p>Morphological features after mifepristone treatment. A-D, Images illustrating increased stromal tissue (A), thin and scarce collagen fibers, matrix (arrow; B), an area of remodeling (C), differentiation (D) observed in the surgical samples (S) compared to respective core needle biopsies (CNB). E, Image illustrates necrosis (dotted arrow) together with a differentiated structure (black sample. F, Cells Alcian blue+ (left), PAS+ (middle) MUC-1+ (immunohistochemistry; right) vacuoles...
<p>Mutations identified in RNA-Seq analysis. The data obtained studies were graphed using the Oviz-Bio tool (https://academic.oup.com/nar/article/48/W1/W415/5835823). Only driver breast cancer genes (99) selected from Intogene base (https://www.intogen.org/download) and we found mutations 19 after read depth filtering (DP >50). Of note is missense mutation ESR1 M070 patient. Left, Percentage of samples with mutations. Color defines type mutations.</p>
<p>RNA-Seq and Proteomics analysis. A B, Dot plot of relevant enriched pathways from GSEA results (Reactome Hallmark databases) separating responsive (A) unresponsive tumors (B). C, Immune cell deconvolution (xcell) in the different analyzed by RNA-Seq. Plots with significant p values Wilcoxon test T CD8+ are shown. D, Kegg diagram Cell cycle pathway, that may explain mifepristone therapeutics effects. colored code was used: first half box is according to RNA-Seq data (8 tumors) last...
<p>RNA-Seq and Proteomics analysis. A B, Dot plot of relevant enriched pathways from GSEA results (Reactome Hallmark databases) separating responsive (A) unresponsive tumors (B). C, Immune cell deconvolution (xcell) in the different analyzed by RNA-Seq. Plots with significant p values Wilcoxon test T CD8+ are shown. D, Kegg diagram Cell cycle pathway, that may explain mifepristone therapeutics effects. colored code was used: first half box is according to RNA-Seq data (8 tumors) last...
<p>A, Library size before and after low count filtering. B, P-value histogram distribution observed in the differential expression analysis. C, Pairwise scatter plots of first five principal components from component analysis RNA-Seq data.</p>
<p>A, Prevailing PR isoforms before and after mifepristone treatment their prevailing nuclear (Nuc) or cytosolic (Cyt) localization in western blot studies. *: Western studies; #: Distribution of the Nuc Cyt compartments; CNB: Core needle biopsy, S: Surgical sample. In grey font: Mifepristone unresponsive tumors by Ki67 criteria. B, Representative blots CNB surgical samples from all patients. The upper band is PRB lower PRA, as labeled first set.</p>
<p>Mifepristone plasma levels and mifepristone-related side effects. A, Plasma of mifepristone 7 or 14 days after treatment. The data from 9-10 patients are shown. Data were analyzed with ANOVA for matched samples (Friedman test). B, Clinical adverse effects grade 1 recorded in (MFP)-treated patients. C, Laboratory values. Patients M049, M095 M140 treated diabetes. M009, M019, M023, M042, M062, M070, M077, M090, M095, M105 hypertension M019 M124 hypothyroidism. Dotted areas represent...
<p>Morphological evaluation of CNBs and matched surgical samples; RNA-Seq analysis; Proteomics</p>
<p>Mifepristone plasma levels and mifepristone-related side effects. A, Plasma of mifepristone 7 or 14 days after treatment. The data from 9-10 patients are shown. Data were analyzed with ANOVA for matched samples (Friedman test). B, Clinical adverse effects grade 1 recorded in (MFP)-treated patients. C, Laboratory values. Patients M049, M095 M140 treated diabetes. M009, M019, M023, M042, M062, M070, M077, M090, M095, M105 hypertension M019 M124 hypothyroidism. Dotted areas represent...
<p>A, Library size before and after low count filtering. B, P-value histogram distribution observed in the differential expression analysis. C, Pairwise scatter plots of first five principal components from component analysis RNA-Seq data.</p>