A5035633982- Cancer-related Molecular Pathways
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
- Salivary Gland Disorders and Functions
- Heat shock proteins research
- HIV/AIDS drug development and treatment
- Microtubule and mitosis dynamics
- Biochemical and Molecular Research
- NF-κB Signaling Pathways
- Cancer therapeutics and mechanisms
- Nutrition, Genetics, and Disease
- Oral microbiology and periodontitis research
- Gut microbiota and health
- Immune Response and Inflammation
Max Delbrück Center
2023
University of Trento
2018-2021
Abstract The dysbiosis of the oral microbiome is associated with both localized and systemic diseases. Modulating resident microbial communities by dietary consumption probiotics has become an appealing means to promote host health either restoring host-microbe balance or preventing dysbiosis. Most strategies target intestinal microbiome, but little known about their impact on microbiome. We analyzed here saliva from 21 volunteers, longitudinally collected before, during, after a commercial...
Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing activity has become one most appealing anticancer therapeutic strategies. Here, we disclose p53-activating drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates notable selectivity to pathway, activating wild-type (WT)p53 and restoring WT-like function mutant (mut)p53 human cancer cells. directly binds WT/mutp53 DNA-binding domain, enhancing protein...
Half of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation mutant (mutp53) through restoration wild-type-like function constitutes valuable anticancer therapeutic strategy. order to search for mutp53 reactivators, small library tryptophanol-derived oxazoloisoindolinones was synthesized and the potential compounds reactivators agents investigated in cells xenograft mouse models. By analysis their anti-proliferative effect on...
Transcription factor NF-κB potently activates anti-apoptotic genes, and its inactivation significantly reduces tumor cell survival following genotoxic stresses. We identified two structurally distinct lead compounds that selectively inhibit activation by DNA double-strand breaks, but not other stimuli, such as TNFα. Our do directly previously regulators of this pathway, most critically including IκB kinase (IKK), signal transmission in-between ATM, PARP1, IKKγ. Deconvolution strategies,...
DHX30 was recently implicated in the translation control of mRNAs involved p53-dependent apoptosis. Here, we show that exhibits a more general function by integrating activities its cytoplasmic isoform and abundant mitochondrial one. The depletion both isoforms HCT116 cells leads to constitutive changes polysome-associated mRNAs, enhancing coding for ribosomal proteins while reducing translational efficiency nuclear-encoded mitoribosome mRNAs. Furthermore, higher global but slower...
The finding that the well-known mammalian P53 protein can act as a transcription factor (TF) in yeast S. cerevisiae has allowed for development of different functional assays to study impacts 1) binding site [i.e., response element (RE)] sequence variants on transactivation specificity or 2) TP53 mutations, co-expressed cofactors, small molecules activity. Different basic and translational research applications have been developed. Experimentally, these approaches exploit two major...
Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 6. We investigated conformations of most stable prototropic tautomers one these N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), Density Functional Theory (DFT)...
The finding that the well-known mammalian P53 protein can act as a transcription factor (TF) in yeast S. cerevisiae has allowed for development of different functional assays to study impacts 1) binding site [i.e., response element (RE)] sequence variants on transactivation specificity or 2) TP53 mutations, co-expressed cofactors, small molecules activity. Different basic and translational research applications have been developed. Experimentally, these approaches exploit two major...
Material and methods Effect of metformin on A498 human renal cell carcinoma cells was studied.Morphological changes were visualised using a LM.Cellular DNA stained by applying PI the relative contents analysed FACS.Proteins such as anti-cFLIPL, anti-PARP, anti-Bcl-2, anti-Bcl-xL, anti-Mcl-1, anti-cIAP-2, anti-XIAP anti-actin antibodies detected Imaging System.c-FLIPL mRNA expression determined RT-PCR.ROS generation assessed dichlorofluoresence in fluorescence intensity flow cytometer.Data...
Abstract DHX30 was recently implicated in the translation control of mRNAs involved p53-dependent apoptosis. Here we show that exhibits a more general function by integrating activities its cytoplasmic isoform and abundant mitochondrial one. The depletion both isoforms HCT116 cells leads to constitutive changes polysome-associated mRNAs, enhancing coding for ribosomal proteins while reducing translational efficiency nuclear-encoded mitoribosome mRNAs. Furthermore, higher global but slower...