A5028939517- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Click Chemistry and Applications
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Sphingolipid Metabolism and Signaling
- Chronic Lymphocytic Leukemia Research
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Pediatric Urology and Nephrology Studies
- NF-κB Signaling Pathways
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Prostate Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Spectroscopy Techniques in Biomedical and Chemical Research
- Advanced Breast Cancer Therapies
Discovery Institute
2020-2022
Sanford Burnham Prebys Medical Discovery Institute
2020-2022
Sidney Kimmel Cancer Center
2018-2020
Universidad de Navarra
2012-2020
Thomas Jefferson University
2018-2020
Icahn School of Medicine at Mount Sinai
2018
University of Dundee
2016
University Medical Center
2014
Oregon Health & Science University
2014
Howard Hughes Medical Institute
2014
The SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia. We evaluated efficacy antagonism chronic myeloid leukemia (CML) and acute (AML) cell lines, murine model, primary patient samples using OP449, specific, cell-penetrating peptide that antagonizes SET's inhibition PP2A.In vitro cytotoxicity specificity OP449 CML AML lines were measured proliferation, apoptosis, clonogenic assays. Efficacy target by was immunoblotting PP2A assay. In vivo...
Abstract Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that 73-amino-acid protein encoded ORF9c of viral genome contains a putative transmembrane domain, interacts membrane proteins in multiple cellular compartments, and impairs processes lung epithelial cell line. Proteomic, interactome, transcriptomic analyses, combined bioinformatic analysis, revealed expression only this highly unstable small impaired interferon...
The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able mediate aberrant effects in have not been characterized. Integrins are major players mediating functions. We previously reported that αVβ3 integrin detected sEVs prostate (PrCa) and transferred into recipient cells. Here, we investigate whether from αVβ3-expressing affect tumour growth differently than control do express αVβ3. compared stimulate growth,...
// Raffaella Pippa 1 , Ana Dominguez Raquel Malumbres Akinori Endo 2 Elena Arriazu 1, 3 Nerea Marcotegui Elizabeth Guruceaga and María D. Odero 3, 4 Hematology/Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain Centre Gene Regulation Expression, College Life Sciences, Dundee, UK Instituto de Investigación Sanitaria Navarra (IdiSNA), Department Biochemistry Genetics, Correspondence to: Odero, email: modero@unav.es Pippa, raffa80@gmail.com...
Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to pathogenesis various cancers. Here we demonstrate both and c-MYC expression are frequently elevated in T-ALL cell lines primary samples compared healthy T cells. Treatment cells with antagonist OP449 restored PP2A reduced interaction catalytic subunit, resulting a decrease viability dose-dependent manner. Since tight balance between phosphatases kinases...
Abstract Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches required. PP2A phosphatase a key regulator of cell homeostasis recurrently inactivated in AML. The anticancer activity several PP2A-activating (e.g., FTY720) depends on their interaction with SET oncoprotein, endogenous inhibitor that overexpressed 30% AML cases. Elucidation regulatory mechanisms may...
Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed aggressive We analyzed the predictive value of urine extracellular vesicle mRNA alone and combination with a multigene panel to improve detection cancer high risk disease.
Protein phosphatase 2A (PP2A) is a serin-threonin that regulates many proteins critical for malignant cell behavior; therefore, PP2A considered to be human tumor suppressor. In this study, we assessed the pharmacokinetic profile and antileukemic effects of activator FTY720, free or encapsulated in lipid nanoparticles, vitro vivo models acute myeloid leukemia. FTY720 nanoparticles presented diameters around 210 nm, with an encapsulation efficiency up 75% significantly increased oral...
Abstract Mesothelioma is an aggressive tumor that affects thousands of people every year. The therapeutic options for patients are limited; hence, a better understanding mesothelioma biology crucial to improve patient survival. To find new molecular targets and strategies related the protein phosphatase 2A (PP2A) network, we analyzed gene expression known PP2A inhibitors in samples. Our analysis disclosed general overexpression all PP2A‐negative regulators patients. Moreover, ANP32E CIP2A...
Abstract Accurate prediction of drug response using machine learning (ML) remains a significant challenge in development as well personalized cancer therapy. Furthermore, there is scarcity rigorous external validation studies for evaluating models. Even when available, such validations are often confined to in-vitro studies. Orthotopic patient-derived xenograft (O-PDX) mice serve essential preclinical models that closely replicate the human tumor microenvironment and assess therapeutic...
Abstract Glioblastoma (GBM) is a devastating primary brain cancer with approximately 10,000 new US diagnoses annually. The current standard of care (SOC) for GBM includes surgical resection followed by radiation therapy (RT) and temozolomide (TMZ), however, there near universal recurrence development resistance after treatment. Relapse in disease tightly linked dynamic changes gene expression during tumor evolution, highlighting the need stronger preclinical models. Here, we report...
18 Background: Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility discriminating tumors at high risk of progression from indolent-low tumors, which leads PCa overtreatment and highlights the need identify better biomarkers clinically significant (Gleason Score; GS ≥ 7). Here, we introduce a novel mRNA GATA2 exosomal biomarker detected urine useful diagnose PCa. Exosomes are 50-120 nm sized vesicles shed body...
Abstract Dysregulated alternative pre-mRNA splicing (AS) is commonly associated with human malignancies, producing pathological proteomes that underlie disease initiation, progression, and therapeutic resistance. The CDC2-like kinases (CLKs) dual-specificity tyrosine-regulated (DYRKs) are thought to govern AS efficiency specificity by directly phosphorylating factors influence splice junction selection. Cirtuvivint (SM08502) a first-in-class small molecule ATP-competitive inhibitor of...