Search results for "Apoptosis."
showing 10 items of 1794 documents
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
2021
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…
Digital control circuitry for the p53 dynamics in cancer cell and apoptosis
2010
Abstract Experimental work and theoretical models deduce a “digital” response of the p53 transcription factor when genomic integrity is damaged. The mutual influence of p53 and its antagonist, the Mdm2 oncogene, is closed in a feedback. This paper proposes an aerospace-based architecture for translating the p53/Mdm2/DNA damage network into a digital circuitry in which the optimal control theory is applied for obtaining the requested dynamic evolutions of some considered cell species for repairing a DNA damage. The purpose of this paper is to demonstrate the usefulness of such digital circuitry design to detect and predict the cell species dynamics for shedding light on their inner and mutua…
THE HDAC INHIBITOR ITF2357 (GIVINOSTAT) AS A KEY PLAYER IN EPIGENETIC TARGETING OF MELANOMA AND COLON CANCER CELLS
2023
Histone deacetylase inhibitors (HDACIs) are epigenetic compounds that have been recently considered for their promising anti-tumor activity. The aim of this PhD thesis was to elucidate and characterize the anti-tumor effect of the HDAC inhibitor ITF2357 (Givinostat) in melanoma and colon cancer cells that are characterized by oncogenic BRAF mutations. Interestingly, data reported in this thesis demonstrate that ITF2357 exerts a remarkable anti-tumor effect in melanoma cells by inducing a switch from a pro-survival autophagy to caspase-dependent apoptosis. The thesis provides the first evidences that ITF2357 is able to target oncogenic BRAF and oncogenic p53. The ITF2357 decreasing effect on…
Oncogenic BRAF and p53 Interplay in Melanoma Cells and the Effects of the HDAC Inhibitor ITF2357 (Givinostat)
2023
Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. Here, we show that oncogenic BRAF localises to the nucleus of these cells, and the compound decreases BRAF levels in both the nuclear and cytosolic compartments. Although mutations in the tumour suppressor p53 gene are not equally frequent in melanomas compared to BRAF, the functional impairment of the p53 pathway may also contribute to melanoma development and aggressiveness. To understand whether oncogenic BRAF and p53 may cooperate, a po…
TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia
2019
International audience; Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or T…
Adrb3 adrenergic receptor is a key regulator of human myometrial apoptosis and inflammation during chorioamnionitis1
2008
The pathophysiology underlying preterm labor triggered by inflammatory conditions such as chorioamnionitis remains largely unclear. It has already been suggested that beta-3 adrenergic (ADRB3) agonists might be of interest in the pharmacological management of preterm labor. Although there is evidence implicating ADRB receptors in the control of inflammation, there are minimal data relating specifically to ADRB3. To explore the cellular consequences of chorioamnionitis and detect apoptosis, we first performed immunostaining and Western blot experiments on human myometrial samples obtained from women with confirmed chorioamnionitis. We then developed an in vitro model of chorioamnionitis by i…
Efecto terapéutico del compuesto BO-110 en un modelo animal de leiomioma
2023
Los miomas son los tumores benignos más frecuentes en las mujeres en edad reproductiva y pueden asociar numerosos síntomas como dolor, sangrado y problemas reproductivos. Sin embargo, actualmente no existe una terapia totalmente satisfactoria por lo que es de suma importancia la evaluación de nuevos tratamientos. En la búsqueda de opciones terapéuticas alternativas, hemos seleccionado el ácido poliinosina-policitidílico (pIC) conjugado con polietilenimina (PEI) [pICPEI], cuyo nombre comercial es BO-100. El compuesto pIC es un ARN sintético de doble cadena sin toxicidad asociada, que induce de manera selectiva la autofagia y apoptosis en un gran espectro de células tumorales. Presen…
Significado pronóstico de las lesiones histopatológicas y de la expresión inmunohistoquímica de marcadores de apoptosis, proliferación y angiogénesis…
2008
Objetivo. Establecer una relación estadística entre características clínicas, histopatológicas con el grado de regresión tumoral Dworak y con el pronóstico. También se pretende estudiar distintos marcadores inmunohistoquímicos con el ojetivo de observar los cambios que sufre la la lesión neoplásica antes y después del tratamiento neoadyuvante en lo que respecta a la angiogénesis, proliferación, apoptosis y diferenciación neuroendocrina. Diseño de experimento: Se trata de un estudio epidemiológico retrospectivo con una muestra de 59 casos de carcinomas rectales diagnosticados en estadios avanzados y sometidos a neoadyuvancia. El análisis de las distintas variables histopatológicas e inmunohi…
Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…
2006
Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…
Biological and Proteomic Characterization of the Anti-Cancer Potency of Aqueous Extracts from Cell-Free Coelomic Fluid of Arbacia lixula Sea Urchin i…
2022
Echinoderms are an acknowledged source of bioactive compounds exerting various beneficial effects on human health. Here, we examined the potential in vitro anti-hepatocarcinoma effects of aqueous extracts of the cell-free coelomic fluid obtained from the sea urchin Arbacia lixula using the HepG2 cell line as a model system. This was accomplished by employing a combination of colorimetric, microscopic and flow cytometric assays to determine cell viability, cell cycle distribution, the possible onset of apoptosis, the accumulation rate of acidic vesicular organelles, mitochondrial polarization, cell redox state and cell locomotory ability. The obtained data show that exposed HepG2 cells under…