Juan M. Jiménez‐Vacas
A5031887949- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- RNA Research and Splicing
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
- Cholesterol and Lipid Metabolism
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Cancer-related gene regulation
- Radiopharmaceutical Chemistry and Applications
- Pituitary Gland Disorders and Treatments
- Neuroendocrine Tumor Research Advances
- Metabolism, Diabetes, and Cancer
- Prostate Cancer Diagnosis and Treatment
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Adipose Tissue and Metabolism
- Receptor Mechanisms and Signaling
Instituto Maimónides de Investigación Biomédica de Córdoba
2017-2025
University of Córdoba
2017-2025
Institute of Cancer Research
2021-2025
Centro de Investigación Biomédica en Red
2017-2025
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition
2017-2024
Hospital Universitario Reina Sofía
2017-2024
Institute of Cancer Research
2023
Glioblastomas remain the deadliest brain tumour, with a dismal ∼12-16-month survival from diagnosis. Therefore, identification of new diagnostic, prognostic and therapeutic tools to tackle glioblastomas is urgently needed. Emerging evidence indicates that cellular machinery controlling splicing process (spliceosome) altered in tumours, leading oncogenic events associated tumour progression aggressiveness. Here, we identify for first time profound dysregulation expression relevant spliceosome...
Glioblastoma is one of the most devastating and incurable cancers due to its aggressive behaviour lack available therapies, being overall-survival from diagnosis ∼14-months. Thus, identification new therapeutic tools urgently needed. Interestingly, metabolism-related drugs (e.g., metformin/statins) are emerging as efficient antitumour agents for several cancers. Herein, we evaluated in vitro/in vivo effects metformin and/or statins on key clinical/functional/molecular/signalling parameters...
Abstract Endocrine resistance (EnR) in advanced prostate cancer is fatal. EnR can be mediated by androgen receptor (AR) splice variants, with AR variant 7 (AR-V7) arguably the most clinically important variant. In this study, we determined proteins key to generating AR-V7, validated our findings using clinical samples, and studied splicing regulatory mechanisms models. Triangulation studies identified JMJD6 as a regulator of evidenced its upregulation vitro EnR, downregulation alongside...
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and stem (CSCs). Altered splicing emerging as hallmark an attractive therapeutic target. The core factor SF3B1 heavily altered in can be inhibited by Pladienolide-B, but its actionability PDAC unknown. We explored the presence role of interrogated potential actionable target.SF3B1 was analyzed tissues, RNA-seq dataset, publicly available databases, examining associations...
Glioblastoma is one of the most devastating cancer worldwide based on its locally aggressive behavior and because it cannot be cured by current therapies. Defects in alternative splicing process are frequent cancer. Recently, we demonstrated that dysregulation spliceosome directly associated with glioma development, progression, aggressiveness.Different human cohorts a dataset from different mouse models were analyzed to determine mutation frequency as well gene protein expression levels...
The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, mechanisms actions variant prostate-cancer (PCa), completely unexplored. Herein, we aimed determine presence key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b)...
sst5TMD4, a splice variant of the sst5 gene, is overexpressed and associated with aggressiveness in various endocrine-related tumors, but its presence, functional role, mechanisms actions prostate cancer (PCa)-the most common type males-is completely unexplored. In this study, formalin-fixed, paraffin-embedded pieces from patients localized PCa, which included tumoral nontumoral adjacent regions (n = 45), fresh biopsies high-risk PCa 52), healthy prostates cystoprostatectomies 14) were...
Abstract Purpose: Therapies targeting the androgen receptor (AR) have improved outcome for patients with castration-sensitive prostate cancer (CSPC). Expression of constitutively active AR splice variant-7 (AR-V7) has shown clinical utility as a predictive biomarker AR-targeted therapy resistance in castration-resistant (CRPC), but its importance CSPC remains understudied. Experimental Design: We assessed different approaches to quantify AR-V7 mRNA and protein cell lines, patient-derived...
Abstract Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men advanced PCa, but treatment resistance inevitable and includes reactivation of signaling. Novel approaches targeting these mechanisms to block tumor growth an urgent unmet clinical need. One attractive strategy target heat shock proteins critical functional activity. Experimental Design: We first...
<p>NXP800-resistant 22Rv1 prostate cancer cell sublines demonstrate the reversal of NXP800-mediated phenotype. <b>A,</b> Long-term treatment cells with increasing concentrations (up to 2.5 μmol/L) DMSO (vehicle-C, white), CCT365248 (inactive-C, blue), and NXP800 (NXP800-R, red) led generation cell–derived sublines. Mean growth was determined after 5 days by CellTiter-Glo Luminescent Cell Viability Assay compared day 0 vehicle-C SD for each subline developed is shown....
<p>Supplementary figure 6: Inhibition of the unfolded protein response with ISRIB rescues NXP800-mediated suppression AR signaling and PCa model growth</p>
<p>GO cellular response to heat gene expression signature associates with AR signaling and poorer prognosis in men suffering from CRPC. <b>A</b> <b>G,</b> Two independent (PCF-SU2C ICR-RMH) transcriptome cohorts of patients Quantification GO each cohort CRPC the PCF-SU2C (<b>A</b>) ICR-RMH (<b>G</b>) cohorts. Biopsies (red dots) >80th percentile (dotted line) are shown. <b>B</b> <b>H,</b> Kaplan–Meier curves for...
<p>Supplementary figure 2: AR and AR-V7 bind members of the 70KDa heat shock protein family mediated cellular stress increases HSP72 expression, associates with GO Cellular Response to Heat gene expression signature, in PCa cells</p>
<p>NXP800 inhibits the growth of AR-dependent and AR-independent prostate cancer models with activation UPR inhibition key signaling pathways. <b>A</b> <b>B,</b> PDX-O [CP50, CP89, CP129, CP142 (<b>A</b>)], AR-positive (VCaP, LNCaP, LNCaP95, 22Rv1), AR-negative (PC3 DU145) cell lines (<b>B</b>) were treated vehicle (DMSO 0.1%) or various concentrations (5, 10, 50, 100, 250 nmol/L) NXP800 (active, red line), CCT365248 (inactive, blue in...
<p>Supplementary figure 1: Chemical structures of NXP800 and CCT365248</p>
<p>Supplementary figure 3: GO Cellular Response to Heat gene expression signature associates with AR signaling in CRPC transcriptomes</p>
<p>NXP800 activates the UPR and inhibits key signaling pathways identifying a novel mechanism of action in prostate cancer models. <b>A,</b> VCaP, LNCaP95, 22Rv1 cells were treated with 250 nmol/L CCT365248 (inactive) or NXP800 (active) for 24 hours prior to addition puromycin 30 minutes. PERK, phospho-eIF2α, ATF4 (PERK arm); ATF6 (ATF6 IRE1 (IRE1 arm) protein; E2F1; (incorporation surrogate protein synthesis); GAPDH (housekeeping) expression was determined by Western blot...
<p>Supplementary figure 4: NXP800 decreases basal HSP72 protein levels and blocks induction in response to HSP90 inhibition PCa cell lines</p>
<div>AbstractPurpose:<p>Advanced prostate cancer is invariably fatal, with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men advanced cancer, but treatment resistance inevitable and includes reactivation of signaling. Novel approaches targeting these mechanisms to block tumor growth an urgent unmet clinical need. One attractive strategy target heat shock proteins (HSP) critical functional...