A5083135497- Estrogen and related hormone effects
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Hormonal and reproductive studies
- Cell Adhesion Molecules Research
- Vitamin D Research Studies
- Cancer Genomics and Diagnostics
- Women's cancer prevention and management
- Advanced Proteomics Techniques and Applications
- Fibroblast Growth Factor Research
- S100 Proteins and Annexins
- RNA modifications and cancer
- Chemokine receptors and signaling
- Mechanisms of cancer metastasis
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Neutropenia and Cancer Infections
- Molecular Biology Techniques and Applications
- Effects and risks of endocrine disrupting chemicals
- Advanced Breast Cancer Therapies
Magdalena Villegas de Martínez el Hospital
2018-2025
Experimental Medicine and Biology Institute
2018
Sanatorio Otamendi y Miroli
2018
Moores Cancer Center
2018
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...
Abstract Progesterone receptors (PRs) ligands are being tested in luminal breast cancer. There mainly two PR isoforms, PRA and PRB, their ratio (PRA/PRB) may be predictive of antiprogestin response. Our aim was to investigate: the impact isoform on metastatic behaviour, paired primary tumours lymph node metastases (LNM) and, effect antiprogestin/progestins growth. Using murine human models, we demonstrated that with PRB > (PRB‐H) have a higher proliferation index but less ability than...
Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they still not therapeutic targets. We have proposed that the ratio between PR isoforms A B (PRA PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed benefit of 200 mg mifepristone, administered to patients with tumors a high PRA/PRB ratio, dose-ranging has been conducted. aim this study was establish plasma mifepristone levels from trial, along resultant steroid...
Abstract Seventy percent of breast cancers express estrogen (ER) and progesterone receptors (PR) respond to antiestrogen therapies. Emerging evidence from experimental studies human epidemiology, points a relevant role for progestins in carcinogenesis cancer growth. Others we have proposed that there is antiprogestins the therapeutic armamentarium, but challenge remains identify which patients would benefit targeting PR addition ER. Preclinical data indicates block cell proliferation...
Abstract Overcoming luminal breast cancer (BrCa) progression remains a critical challenge for improved overall patient survival. RUNX2 has emerged as protein related to aggressiveness in triple‐negative BrCa, however its role tumors elusive. We have previously shown that active FGFR2 (FGFR2‐CA) contributes increased tumor growth and expression was high hormone‐independent mouse mammary carcinomas. To elucidate the interaction between human we investigated their roles treatment...
Abstract Background: Different antiprogestins have been clinically evaluated in gynecological andbreast cancers. Mifepristone (MFP), as well onapristone and telapristone acetate, showedpartial responses breast cancer clinical trials. Preclinical data indicates that antiprogestinsinhibit cell proliferation of luminal carcinomas expressing higher levels progesteronereceptor isoform A (PRA) than those B (PRB) by western blots (WB). Thus,we designed a pre-surgical window trial to determine the...
<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>