A5052615349- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Histone Deacetylase Inhibitors Research
- Synthesis and Biological Activity
- Microtubule and mitosis dynamics
- Environmental Toxicology and Ecotoxicology
- HIV/AIDS drug development and treatment
- Synthesis and bioactivity of alkaloids
- Chronic Lymphocytic Leukemia Research
- Synthesis and Characterization of Heterocyclic Compounds
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Quinazolinone synthesis and applications
- Effects and risks of endocrine disrupting chemicals
- Cancer Treatment and Pharmacology
- Cancer Immunotherapy and Biomarkers
- Acute Myeloid Leukemia Research
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Pharmaceutical and Antibiotic Environmental Impacts
- Chronic Myeloid Leukemia Treatments
Universidad de Salamanca
2012-2024
Centro de Investigación del Cáncer
2014-2024
Instituto de Investigación Biomédica de Salamanca
2014-2024
Consejo Superior de Investigaciones Científicas
2013-2024
Complejo Hospitalario de Salamanca
2015-2024
Hospital de Sant Pau
2020
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
2013-2016
Institute of Agrifood Research and Technology
2011-2016
Background Combinations of drug treatments based on bortezomib or lenalidomide plus steroids have resulted in very high response rates multiple myeloma. However, most patients still relapse, indicating the need for novel combination partners to increase duration treat relapsed disease. We explored antimyeloma activity triple combinations these well-established schemes with panobinostat, a deacetylase inhibitor multi-targeted profile.Design and Methods The was vitro cell lines by using MTT...
// José Luis Ordóñez 1,4,* , Ana Teresa Amaral Angel M. Carcaboso 2 David Herrero-Martín 3 María del Carmen García-Macías 4 Vicky Sevillano Diego Alonso Guillem Pascual-Pasto Laura San-Segundo Monica Vila-Ubach Telmo Rodrigues Susana Fraile Cristina Teodosio Agustín Mayo-Iscar 5 Miguel Aracil 6 Carlos Galmarini Oscar Tirado Jaume Mora and Enrique de Álava 1,4 1 Laboratory of Molecular Pathology, Instituto Biomedicina Sevilla (IBiS), Hospital Universitario Virgen Rocio/CSIC/Universidad...
Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of immunosuppressive regimens administered control T alloreactivity. PI3K/AKT/mTOR pathway is crucial in activation and function and, therefore, represents an attractive therapeutic target prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies explored their effect.The effects a selective...
Multiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on marrow mesenchymal stromal cells (MSCs). MM-MSCs exhibit abnormal transcriptomes, suggesting the involvement of epigenetic mechanisms governing their tumor-promoting functions prolonged osteoblast suppression. Here, we identify widespread DNA methylation alterations marrow-isolated MSCs from distinct MM stages, particularly in Homeobox genes involved osteogenic differentiation that associate...
Abstract Purpose: PIM kinases are a family of serine/threonine recently proposed as therapeutic targets in oncology. In the present work, we have investigated effects novel pan-PIM kinase inhibitor, PIM447, on myeloma cells and myeloma-associated bone disease using different preclinical models. Experimental Design: vitro/ex vivo cytotoxicity PIM447 was evaluated cell lines patient samples. Synergistic combinations with standard treatments were analyzed Calcusyn Software. assessed osteogenic...
Preclinical evaluation of the simultaneous inhibition MCL-1 and BCL-2 with combination S63845 venetoclax in multiple myelomaApoptotic evasion has been postulated as one main mechanisms myeloma (MM) cell survival. 1,2The intrinsic apoptotic pathway, tightly regulated by protein family, is initiated intracellularly sensed stress signals ultimately leads to permeabilization outer mitochondrial membrane.Tumor cells can keep this pathway inactivated, part, through overexpression BCL-2, BCL-XL or...
Despite recent advances in the treatment of multiple myeloma (MM), prognosis most patients remains poor, and resistance to traditional new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as fusion histone deacetylase inhibitor radical bendamustine, with aim potentiating its alkylating activity. The efficacy was evaluated vitro, ex vivo vivo, alone, combination standard anti-myeloma agents. underlying mechanisms action were also on MM cell lines, patient samples,...
Abstract The deletion of 11q (del(11q)) invariably comprises ATM gene in chronic lymphocytic leukemia (CLL). Concomitant mutations this the remaining allele have been identified 1/3 CLL cases harboring del(11q), being biallelic loss associated with adverse prognosis. Although introduction targeted BCR inhibition has significantly favored outcomes del(11q) patients, responses patients functional through inactivation are unexplored, and development resistances to therapies increasingly...
Although new therapies have doubled the survival of multiple myeloma patients, this remains an incurable disease. It has been postulated that so-called cancer stem cells would be responsible for tumor initiation and relapse but their unequivocal identification unclear. Here, we investigated in a panel cell lines presence CD20+ harboring stem-cell phenotype. Thus, only small population CD20dim+ (0.3%) RPMI-8226 line was found. expressed plasma markers CD38 CD138 were CD19−CD27−. Additionally,...
Abstract Purpose: The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report first time potent antimyeloma activity amiloride, an old potassium-sparing diuretic approved treatment hypertension and edema due to heart failure. Experimental Design: Myeloma cell lines primary samples were used evaluate cytotoxicity amiloride. In vivo studies carried out in a xenograft mouse model. mechanisms action investigated using RNA-Seq experiments,...
// Víctor Martín-Granado 1, 2 , Sara Ortiz-Rivero Rita Carmona 3 Gutiérrez-Herrero Mario Barrera 1 Laura San-Segundo Celia Sequera 4 Pedro Perdiguero 2, 5 Francisco Lozano 6 Martín-Herrero José Ramón González-Porras 7 Muñoz-Chápuli Almudena Porras and Carmen Guerrero 8 Instituto de Biología Molecular y Celular del Cáncer, USAL-CSIC, Salamanca, Spain Investigación Biomédica Salamanca (IBSAL),...
Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to presence resistant cancer stem cells (MM-CSC). Although clonogenic MM was described three decades ago, phenotype MM-CSC is still controversial, especially with respect expression syndecan-1 (CD138). Here, we demonstrate two subpopulations - CD138++ (95–99%) and CD138low (1–5%) eight cell lines. To find out possible stem-cell-like features, have phenotypically, genomic...
Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), inhibitor of this protein, has demonstrated activity heavily pre-treated multiple myeloma patients. The aim the work herein was investigate filanesib combination with pomalidomide plus dexamethasone backbone, and mechanisms underlying potential synergistic effect. ability enhance studied vitro vivo models. Mechanisms were dissected by gene expression profiling,...
The mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function T cells, which play an essential role in development graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, mTORC1 inhibitor has shown encouraging results control GvHD. Therefore, we considered that simultaneous targeting both mTORC2 complexes could exert a more potent inhibition cell and, thus, have utility GvHD control. To assess this assumption, used dual...
In the present study, authors investigated effects of bisphenol A, chlorpyrifos, methylparaben, and 2 effluent samples from wastewater treatment plants located in province Madrid, Spain, on messenger RNA expression specific genes involved early development (ESR1, pax6, bmp4, myf5) a gene general stress response (hsp70) during Xenopus laevis embryo development. Gene was analyzed after 4 h, 24 96 h exposure by semiquantitative reverse-transcriptase-polymerase chain reaction. Concentration...
Abstract The current study describes the effect of cypermethrin, fluoxetine, and thiabendazole, at environmentally relevant concentrations, on expression heat shock protein 70 (HSP70) interleukin 1β (IL‐1β), using Xenopus laevis larvae as animal model. Cytokines interleukins are considered good predictors immunotoxic potential xenobiotics. Tadpoles stage 47 (normal tables X. ) were exposed under static conditions to: 0.3 30 µg/L 0.7 0.24 cypermethrin. effects evaluated 7, 24, 72 h, 6 9 d....
Background Although the majority of patients with acute myeloid leukemia initially respond to conventional chemotherapy, relapse is still leading cause death, probably because presence leukemic stem cells that are insensitive current therapies. We investigated antileukemic activity and mechanism action zalypsis, a novel alkaloid marine origin.Design Methods The zalypsis was studied in four cell lines freshly isolated blasts taken from before they started therapy. Zalypsis-induced apoptosis...
The regulation of hematopoietic stem cells (HSCs) depends on the integration multiple signals received from bone marrow niche. We show relevance protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control HSCs adhesiveness, cell cycling, quiescence. Lethally irradiated mice transplanted with Lin– in which or had been silenced showed a significant increase long-term (LT) short-term (ST) HSCs. A decrease cycling was also found, together an decreased...