Search results for "dynamics."
showing 10 items of 9637 documents
A versatile bioreactor for dynamic suspension cell culture. Application to the culture of cancer cell spheroids.
2016
A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein prese…
Chemotherapeutic efficacy of curcumin and resveratrol against cancer: Chemoprevention, chemoprotection, drug synergism and clinical pharmacokinetics
2021
The frequent inefficiency of conventional cancer therapies due to drug resistance, non-targeted drug delivery, chemotherapy-associated toxic side effects turned the focus to bioactive phytochemicals. In this context, curcumin and resveratrol have emerged as potent chemopreventive and chemoprotective compounds modulating apoptotic and autophagic cell death pathways in cancer in vitro and in vivo. As synergistic agents in combination with clinically established anticancer drugs, the enhanced anticancer activity at reduced chemotherapy-associated toxicity towards normal organs can be explained by improved pharmacokinetics, pharmacodynamics, bioavailability and metabolism. With promising precli…
2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells.
2017
Background/aim Dysregulation of mitochondrial pathways is implicated in several diseases, including cancer. Notably, mitochondrial respiration and mitochondrial biogenesis are favored in some invasive cancer cells, such as osteosarcoma. Hence, the aim of the current work was to investigate the effects of 2-methoxyestradiol (2-ME), a potent anticancer agent, on the mitochondrial biogenesis of osteosarcoma cells. Materials and methods Highly metastatic osteosarcoma 143B cells were treated with 2-ME separately or in combination with L-lactate, or with the solvent (non-treated control cells). Protein levels of α-syntrophin and peroxisome proliferator-activated receptor gamma, coactivator 1 alph…
Abstract OT1-08-04: A first-in-human phase Ia dose escalation study of GDC-0077, a p110a-selective and mutant-degrading PI3K inhibitor, in patients w…
2020
Abstract Background: Activating mutations in PIK3CA, encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3K), are highly prevalent in breast cancer and solid tumor malignancies. GDC-0077 is a potent p110α-selective inhibitor with a novel mechanism of action that degrades mutant p110α and anti-tumor activity in PIK3CA-mutant breast cancer xenograft models as a single agent and in combination with anti-estrogens with or without a CDK4/6 inhibitor. An open-label, Phase I dose-escalation study of GDC-0077 monotherapy and GDC-0077 combined with endocrine therapies and palbociclib is underway in patients (pts) with locally advanced or metastatic PIK3CA-mutant solid tumors. Data from th…
Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease
2019
Intrarenal hemodynamic alterations are independent predictors of cardiovascular events in different populations. It has been hypothesized that there is an association between renal hemodynamics and coronary atherosclerotic burden in patients with hypertension. Therefore, the present study examined the associations between renal hemodynamics, coronary atherosclerotic burden and carotid atherosclerotic disease. A total of 130 patients with hypertension aged between 30-80 years who had been referred for an elective coronary angiography were enrolled in the present study. A duplex ultrasound of the intrarenal vasculature was performed to evaluate the resistive index (RI), pulsatility index (PI)…
Abstract P1-19-46: A phase Ib dose escalation study evaluating the mutant selective PI3K-alpha inhibitor GDC-0077 (G) in combination with letrozole (…
2020
Abstract Background: Dysregulation of the PI3K/AKT/mTOR signaling pathway occurs in solid tumor malignancies. GDC-0077 (G) is a potent p110α-selective, p110α-mutant degrading inhibitor with anti-tumor activity in PIK3CA-mutant breast cancer xenograft models as a single agent and in combination with endocrine therapies (ET) with or without a CDK4/6 inhibitor (i). An open-label, Phase I dose escalation study of Galone and in combination with ET and P is underway in patients (pts) with locally advanced or metastatic PIK3CA-mutant solid tumors. Data from the combinations of G and L with and without P in pts with PIK3CA-mutant HR+/HER2- breast cancer are presented herein. Methods: This study (NC…
The genomic footprint of climate adaptation inChironomus riparius
2017
The gradual heterogeneity of climatic factors produces continuously varying selection pressures across geographic distances that leave signatures of clinal variation in the genome. Separating signatures of clinal adaptation from signatures of other evolutionary forces, such as demographic processes, genetic drift, and adaptation to specific non-clinal conditions of the immediate local environment is a major challenge. Here, we examine climate adaptation in five natural populations of the non-biting midge Chironomus riparius sampled along a climatic gradient across Europe. Our study integrates experimental data, individual genome resequencing, Pool-Seq data, and population genetic modelling.…
Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs)
2017
This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k2nd = 67 × 106 M-1 min-1), endowed with a picomolar b…
PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.
2019
Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatmen…
A Dehydrogenase Dual Hydrogen Abstraction Mechanism Promotes Estrogen Biosynthesis: Can We Expand the Functional Annotation of the Aromatase Enzyme?
2018
Cytochrome P450 (CYP450) enzymes are involved in the metabolism of exogenous compounds and in the synthesis of signaling molecules. Among the latter, human aromatase (HA) promotes estrogen biosynthesis, which is a key pharmacological target against breast cancers. After decades of debate, interest in gaining a comprehensive picture of HA catalysis has been renewed by the recent discovery that compound I (Cpd I) is the reactive species of the peculiar aromatization step. Herein, for the first time, a complete atomic-level picture of all controversial steps of estrogen biosynthesis is presented. By performing cumulative quantum-classical molecular dynamics and metadynamics simulations of abou…