Search results for "CF"
showing 10 items of 701 documents
Pyrithione-based ruthenium complexes as inhibitors of aldo-keto reductase 1C enzymes and anticancer agents.
2016
Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo–keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell…
Theoretical Research on the Photophysics and Photochemistry of Water Aggregates and DNA/RNA Nucleobases
2014
La presente Tesis Doctoral provee una serie de conclusiones basadas en los estudios realizados durante la realización de la misma. En líneas generales, la caracterización teórica de las propiedades espectroscópicas asociadas al agua ha sido completada y ampliada. Diferentes modelos de agua han sido postulados para mejorar la cararcterización tanto del agua tipo “bulk”, generalmente asignada a la parte interior del agua líquida en la que hay un equilibrio dinámico de los enlaces de hidrógeno, así como del agua denominada estructurada u ordenada, presente generalmente en la interfase entre sólidos y biomoléculas y la propia agua líquida. Ambos tipos de agua poseen señales espectroscópicas dif…
Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells
2021
Abstract DNA is intrinsically dynamic and folds transiently into alternative higher-order structures such as G-quadruplexes (G4s) and three-way DNA junctions (TWJs). G4s and TWJs can be stabilised by small molecules (ligands) that have high chemotherapeutic potential, either as standalone DNA damaging agents or combined in synthetic lethality strategies. While previous approaches have claimed to use ligands that specifically target either G4s or TWJs, we report here on a new approach in which ligands targeting both TWJs and G4s in vitro demonstrate cellular effects distinct from that of G4 ligands, and attributable to TWJ targeting. The DNA binding modes of these new, dual TWJ-/G4-ligands w…
Modeling of the Achilles Subtendons and Their Interactions in a Framework of the Absolute Nodal Coordinate Formulation
2022
Experimental results have revealed the sophisticated Achilles tendon (AT) structure, including its material properties and complex geometry. The latter incorporates a twisted design and composite construction consisting of three subtendons. Each of them has a nonstandard cross-section. All these factors make the AT deformation analysis computationally demanding. Generally, 3D finite solid elements are used to develop models for AT because they can discretize almost any shape, providing reliable results. However, they also require dense discretization in all three dimensions, leading to a high computational cost. One way to reduce degrees of freedom is the utilization of finite beam elements…
Erratum: By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
2019
Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which sho…
A Phase I Study of Intravenous LBH589, a Novel Cinnamic Hydroxamic Acid Analogue Histone Deacetylase Inhibitor, in Patients with Refractory Hematolog…
2006
Abstract Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m2): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasm…
Activity of the antiestrogenic cajanin stilbene acid towards breast cancer
2014
Antiestrogenic therapy is a mainstay for estrogen receptor (ERα)-positive breast cancer. Due to the development of resistance to established antihormones such as tamoxifen, novel compounds are required. The low abundant cajanin stilbene acid (CSA) recently isolated by us from Pigeon Pea (Cajanus cajan) has structural similarities with estrogen. We analyzed the cytotoxic and anticancer activity of CSA in ERα-positive and -negative human breast cancer cells in vitro, in vivo and in silico. CSA exerts anticancer and antiestrogenic activities towards ERα-positive breast cancer, and it showed cytotoxicity towards tamoxifen-resistant MCF-7 cells, implying that CSA may be active against tamoxifen-…
Prismatic Adaptation as a Novel Tool to Directionally Modulate Motor Cortex Excitability: Evidence From Paired-pulse TMS
2014
Abstract Background The prismatic adaptation (PA) is a visuo-motor procedure that has captured the attention of neuroscientists in the last decades, hence it seems to affect high-order cognition. However, the basic neural processes related to PA and its effects on cortical plasticity are not clear yet. Objective/hypothesis The aim of the present study is to explore whether PA induces a direct effect on the motor cortices (M1) excitability. Methods Fourteen healthy participants were submitted to paired-pulse TMS to measure short-intracortical-inhibition (SICI) and intracortical-facilitation (ICF) on both the left and the right M1, before and after PA, that could induce a leftward or rightwar…
Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci
2012
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium id…
Predicting hypoxia in cystic fibrosis patients during exposure to high altitudes
2006
Abstract Background For patients with cystic fibrosis (CF)-related partial respiratory insufficiency and reduced arterial oxygen tension at ground level, the mild hypobaric environment on commercial jet aircraft poses the risk of severe hypoxemia. Thus, physicians should be able to estimate the extent of in-flight hypoxia. Objectives To derive tools for estimating the expected drop in arterial oxygen partial pressure (paO 2 ) and oxygen saturation (saO 2 ) in young adult CF patients with mild to moderate airway obstruction during exposure to the hypobaric conditions aboard commercial aircraft and to test the predictive power of a hypobaric chamber simulation. Methods Blood gases of 12 CF pa…