Publications by authors named "Pilar Puente"

Article Synopsis
  • Most ovarian cancer patients develop resistance to chemotherapy within five years, highlighting the need to better understand the tumor microenvironment (TME) and its effect on drug response.
  • Researchers created a 3D tumor-on-a-chip model with multiple chambers to mimic the TME and study how it influences drug resistance, using various cell combinations to explore different interactions.
  • The study found that the presence of cancer-associated fibroblasts (CAFs) increased drug resistance in ovarian cancer cells, but this could be mitigated using therapies targeting the extracellular matrix, suggesting new avenues for treatment.
View Article and Find Full Text PDF

Historical seroprevalence data for in Spain vary greatly depending on the sampling region owing to different fish consumption habits. As a result of European Regulation (EC) No. 853/2004, the Royal Decree 1420/2006 on the prevention of parasitosis by in fishery products supplied by establishments that serve food to final consumers or to communities came into force in Spain.

View Article and Find Full Text PDF
Article Synopsis
  • Cancer-associated fibroblasts (CAFs) play a crucial role in ovarian cancer progression and drug resistance by altering the extracellular matrix (ECM).
  • The study shows that media from ovarian cancer cells can activate normal fibroblasts, leading them to adopt a CAF-like phenotype, enhancing their function and increasing tumor growth.
  • Ultimately, this research suggests new strategies for developing targeted therapies against CAFs and ECM-related mechanisms that contribute to chemoresistance in ovarian cancer.
View Article and Find Full Text PDF

Introduction: The majority of ovarian cancer (OC) patients receiving standard of care chemotherapy develop chemoresistance within 5 years. The tumor microenvironment (TME) is a dynamic and influential player in disease progression and therapeutic response. However, there is a lack of models that allow us to elucidate the compartmentalized nature of TME in a controllable, yet physiologically relevant manner and its critical role in modulating drug resistance.

View Article and Find Full Text PDF

Cancer-associated fibroblasts (CAFs) are key contributors to ovarian cancer (OC) progression and therapeutic resistance through dysregulation of the extracellular matrix (ECM). CAFs are a heterogenous population derived from different cell types through activation and reprogramming. Current studies rely on uncharacterized heterogenous primary CAFs or normal fibroblasts that fail to recapitulate CAF-like tumor behavior.

View Article and Find Full Text PDF

Background: The dismal prognosis of advanced ovarian cancer calls for the development of novel therapies to improve disease outcome. In this regard, we set out to discover new molecular entities and to assess the preclinical effectiveness of their targeting.

Methods: Cell lines, mice and human ovarian cancer samples were used.

View Article and Find Full Text PDF

Micrograph comparison remains useful in bioscience. This technology provides researchers with a quick snapshot of experimental conditions. But sometimes a two- condition comparison relies on researchers' eyes to draw conclusions.

View Article and Find Full Text PDF

This study investigates the effects of a dual selective Class I histone deacetylase (HDAC)/lysine-specific histone demethylase 1A (LSD1) inhibitor known as 4SC-202 (Domatinostat) on tumor growth and metastasis in a highly metastatic murine model of Triple Negative Breast Cancer (TNBC). 4SC-202 is cytotoxic and cytostatic to the TNBC murine cell line 4T1 and the human TNBC cell line MDA-MB-231; the drug does not kill the normal breast epithelial cell line MCF10A. Furthermore, 4SC-202 reduces cancer cell migration.

View Article and Find Full Text PDF

Leukemia Inhibitory Factor (LIF) is a member of the IL-6 cytokine family and is expressed in almost every tissue type within the body. Although LIF was named for its ability to induce differentiation of myeloid leukemia cells, studies of LIF in additional diseases and solid tumor types have shown that it has the potential to contribute to many other pathologies. Exploring the roles of LIF in normal physiology and non-cancer pathologies can give important insights into how it may be dysregulated within cancers, and the possible effects of this dysregulation.

View Article and Find Full Text PDF

Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies.

View Article and Find Full Text PDF

Chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL) are hematological malignancies that remain incurable despite novel treatments. In order to improve current treatments and clinical efficacy, there remains a need for more complex models that mimic the intricate human leukemic microenvironment. This study aimed to use 3D tissue engineered plasma cultures (3DTEPC) derived from CML, AML and CLL patients to promote proliferation of leukemic cells for use as a drug screening tool for treatment.

View Article and Find Full Text PDF

Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity.

View Article and Find Full Text PDF

Oxygen deprivation within tumors is one of the most prevalent causes of resilient cancer cell survival and increased immune evasion in breast cancer (BCa). Current models do not adequately mimic physiological oxygen levels relevant to breast tissue and its tumor-immune interactions. In this study, we propose an approach to engineer a three-dimensional (3D) model (named 3D engineered oxygen, 3D-O) that supports the growth of BCa cells and generates physio- and pathophysiological oxygen levels to understand the role of oxygen availability in tumor-immune interactions.

View Article and Find Full Text PDF

Lack of efficacy and a low overall success rate of phase I-II clinical trials are the most common failures when it comes to advancing cancer treatment. Current drug sensitivity screenings present several challenges including differences in cell growth rates, the inconsistent use of drug metrics, and the lack of translatability. Here, we present a patient-derived 3D culture model to overcome these limitations in breast cancer (BCa).

View Article and Find Full Text PDF

The heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which modulate several intrinsic TME elements to promote immunosuppressive outcomes. Decoding these communications is necessary for designing effective therapeutic strategies that can effectively reduce tumor-associated chemotherapy resistance by employing the inherent potential of the immune system.

View Article and Find Full Text PDF

Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC's) and lysine demethylase (LSD1).

View Article and Find Full Text PDF

Purpose: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation.

Methods: Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia.

Results: We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells.

View Article and Find Full Text PDF

The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells.

View Article and Find Full Text PDF

Overall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation, and chemotherapy. GBM tumors are highly heterogeneous, and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (temozolomide [TMZ]) while retaining radioactive isotopes agents (iodine, [I]) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity.

View Article and Find Full Text PDF

Increased levels of the nuclear export protein, exportin 1 (XPO1), were demonstrated in multiple myeloma (MM) patients. Targeting XPO1 with selinexor (the selective inhibitor of nuclear export; SINE compound KPT-330) demonstrates broad antitumor activity also in patient cells resistant to bortezomib; hence, it is a promising target in MM patients. Hypoxia is known to mediate tumor progression and drug resistance (including bortezomib resistance) in MM cells.

View Article and Find Full Text PDF

Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance.

View Article and Find Full Text PDF

Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates >90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects.

View Article and Find Full Text PDF
Article Synopsis
  • Dexamethasone is a key treatment for multiple myeloma but often faces resistance, prompting the need for new strategies.
  • Researchers found that dexamethasone suppresses eIF2 signaling, a pathway involved in protein synthesis, and activates the phosphorylation of eIF2α, which helps induce apoptosis through increased ATF4 levels.
  • Targeting the eIF2α kinase HRI has shown promise in overcoming dex-resistant multiple myeloma, particularly when combined with other therapies like rapamycin, suggesting this approach could enhance existing treatment options.
View Article and Find Full Text PDF

Hypoxia is a non-physiological level of oxygen tension, a phenomenon common in a majority of malignant tumors. Tumor-hypoxia leads to advanced but dysfunctional vascularization and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence.

View Article and Find Full Text PDF