Search results for "GENI"
showing 10 items of 6843 documents
Anticancer metal drugs and immunogenic cell death
2016
Conventional chemotherapeutics, but also innovative precision anticancer compounds, are commonly perceived to target primarily the cancer cell compartment. However, recently it was discovered that some of these compounds can also exert immunomodulatory activities which might be exploited to synergistically enhance their anticancer effects. One specific phenomenon of the interplay between chemotherapy and the anticancer immune response is the so-called “immunogenic cell death” (ICD). ICD was discovered based on a vaccination effect exerted by cancer cells dying from pretreatment with certain chemotherapeutics, termed ICD inducers, in syngeneic transplantation mouse models. Interestingly, onl…
Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards mu…
2018
Abstract Introduction Resistance of cancer cells is a serious impediment to chemotherapy and several phytochemicals are active against multi-drug resistant (MDR) phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1), mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone (5) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant cell lines. The modes of action of compound 5 were further investigated. Methods The resazurin reduction assay was used to evaluate cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase-Glo assay was used to detect the activation of caspases in CCR…
Taking up the cudgels for the traditional reactive oxygen and nitrogen species detection assays and their use in the cardiovascular system
2017
Reactive oxygen and nitrogen species (RONS such as H2O2, nitric oxide) confer redox regulation of essential cellular functions (e.g. differentiation, proliferation, migration, apoptosis), initiate and catalyze adaptive stress responses. In contrast, excessive formation of RONS caused by impaired break-down by cellular antioxidant systems and/or insufficient repair of the resulting oxidative damage of biomolecules may lead to appreciable impairment of cellular function and in the worst case to cell death, organ dysfunction and severe disease phenotypes of the entire organism. Therefore, the knowledge of the severity of oxidative stress and tissue specific localization is of great biological …
Sicilian Litchi Fruit Extracts Induce Autophagy versus Apoptosis Switch in Human Colon Cancer Cells
2018
Litchi chinensis Sonnerat is a tropical tree whose fruits contain significant amounts of bioactive polyphenols. Litchi cultivation has recently spread in Sicily where the climate conditions are particularly favorable for this crop. Recent findings have shown that Litchi extracts display anti-tumor and pro-apoptotic effects in vitro, but the precise underlying mechanisms have not been fully elucidated. In this study, we report for the first time the effects of Sicilian litchi fruit extracts on colon cancer cells. The results indicated that litchi exocarp, mesocarp and endocarp fractions reduce the viability and clonogenic growth of HT29 cells. These effects were due to cell cycle arrest in t…
Searching for Chymase Inhibitors among Chamomile Compounds Using a Computational-Based Approach
2018
Inhibitors of chymase have good potential to provide a novel therapeutic approach for the treatment of cardiovascular diseases. We used a computational approach based on pharmacophore modeling, docking, and molecular dynamics simulations to evaluate the potential ability of 13 natural compounds from chamomile extracts to bind chymase enzyme. The results indicated that some chamomile compounds can bind to the active site of human chymase. In particular, chlorogenic acid had a predicted binding energy comparable or even better than that of some known chymase inhibitors, interacted stably with key amino acids in the chymase active site, and appeared to be more selective for chymase than other …
Lunasin is a redox sensitive intrinsically disordered peptide with two transiently populated α-helical regions.
2016
Lunasin is a 43 amino acid peptide with anti-cancer, antioxidant, anti-inflammatory and cholesterol-lowering properties. Although the mechanism of action of lunasin has been characterized to some extent, its exact three-dimensional structure as well as the function of the N-terminal sequence remains unknown. We established a novel method for the production of recombinant lunasin that allows efficient isotope labeling for NMR studies. Initial studies showed that lunasin can exist in a reduced or oxidized state with an intramolecular disulfide bond depending on solution conditions. The structure of both forms of the peptide at pH 3.5 and 6.5 was characterized by CD spectroscopy and multidimen…
Cancer stem cell-based models of colorectal cancer reveal molecular determinants of therapy resistance
2016
Abstract Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines w…
Mandarin essential oils inhibit quorum sensing and virulence factors of Pseudomonas aeruginosa
2016
Pseudomonas aeruginosa produces biofilm and several virulence factors coordinated by quorum sensing (QS) in food. The interruption of QS is a target to control the bacterial virulence. Chemical preservatives used to control biofilm give rise to several food safety problems. For this reason, essential oils (EOs), generally recognized as safe products, are a hopeful alternative. The aim of this work was to determine the chemical composition of mandarin EOs obtained by cold-pressing (EOP) and cold-pressing followed by steam distillation (EOPD) and their antipathogenic properties against P. aeruginosa. Both EOs contained the highest quantities of monoterpene hydrocarbons, mainly limonene, follo…
Interleukin-17A Promotes Lung Tumor Progression through Neutrophil Attraction to Tumor Sites and Mediating Resistance to PD-1 Blockade
2017
Abstract Introduction Proinflammatory cytokine interleukin-17A (IL-17A) is overexpressed in a subset of patients with lung cancer. We hypothesized that IL-17A promotes a protumorigenic inflammatory phenotype and inhibits antitumor immune responses. Methods We generated bitransgenic mice expressing a conditional IL-17A allele along with conditional Kras G12D and performed immune phenotyping of mouse lungs, a survival analysis, and treatment studies with antibodies either blocking programmed cell death 1 (PD-1) or IL-6 or depleting neutrophils. To support the preclinical findings, we analyzed human gene expression data sets and immune profiled patient lung tumors. Results Tumors in IL-17:Kras…
A Tuft Cell-Like Signature Is Highly Prevalent in Thymic Squamous Cell Carcinoma and Delineates New Molecular Subsets Among the Major Lung Cancer His…
2020
Abstract Introduction In-depth genomic characterization of thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas (TCs), failed to identify targetable mutations and suggested unique biology of TETs, including KIT expression in most TCs. Recently, tuft cell–like medullary thymic epithelial cells were identified in the murine thymus, and our reanalysis of the published gene expression data revealed that these cells express KIT. In addition, recently, a minor subset of SCLCs with tuft cell–like features was described. Methods We interrogated mRNA expression data from our tumor cohorts (N = 60) and publicly available, independent data sets from TETs and NSCLC (N = 1199) for …