Search results for "target"
showing 10 items of 1196 documents
mTOR Driven Gene Transcription Is Required for Cholesterol Production in Neurons of the Developing Cerebral Cortex
2021
AbstractDysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the stero…
Detection, validation, and downstream analysis of allelic variation in gene expression.
2009
AbstractCommon sequence variants within a gene often generate important differences in expression of corresponding mRNAs. This high level of local (allelic) control—or cis modulation—rivals that produced by gene targeting, but expression is titrated finely over a range of levels. We are interested in exploiting this allelic variation to study gene function and downstream consequences of differences in expression dosage. We have used several bioinformatics and molecular approaches to estimate error rates in the discovery of cis modulation and to analyze some of the biological and technical confounds that contribute to the variation in gene expression profiling. Our analysis of SNPs and alter…
Targeting the aryl hydrocarbon receptor with a novel set of triarylmethanes
2020
International audience; The aryl hydrocarbon receptor (AhR) is a chemical sensor upregulating the transcription of responsive genes associated with endocrine homeostasis, oxidative balance and diverse metabolic, immunological and inflammatory processes, which have raised the pharmacological interest on its modulation. Herein, a novel set of 32 unsymmetrical triarylmethane (TAM) class of structures has been synthesized, characterized and their AhR transcriptional activity evaluated using a cell-based assay. Eight of the assayed TAM compounds (14, 15, 18, 19, 21, 22, 25, 28) exhibited AhR agonism but none of them showed antagonist effects. TAMs bearing benzotrifluoride, naphthol or heteroarom…
Expression of a reporter gene is reduced by a ribozyme in transgenic plants
1994
A chimeric gene encoding a ribozyme under the control of the cauliflower mosaic virus (CaMV) 35S promoter was introduced into transgenic tobacco plants. In vivo activity of this ribozyme, which was designed to cleave npt mRNA, was previously demonstrated by transient expression assays in plant protoplasts. The ribozyme gene was transferred into transgenic tobacco plants expressing an rbcS-npt chimeric gene as an indicator. Five double transformants out of sixteen exhibited a reduction in the amount of active NPT enzyme. To measure the amount of ribozyme produced, in the absence of its target, the ribozyme and target genes were separated by genetic segregation. The steady-state concentration…
Potential impact of genetically modified Lepidoptera-resistant Brassica napus in biodiversity hotspots: Sicily as a theoretical model
2016
The general increase of the cultivation and trade of Bt transgenic plants resistant to Lepidoptera pests raises concerns regarding the conservation of animal and plant biodiversity. Demand for biofuels has increased the cultivation and importation of oilseed rape (Brassica napus L.), including transgenic lines. In environmental risk assessments (ERAs) for its potential future cultivation as well as for food and feed uses, the impact on wild Brassicaeae relatives and on non-target Lepidoptera should be assessed. Here we consider the potential exposure of butterflies as results of possible cultivation or naturalization of spilled seed in Sicily (Italy). Diurnal Lepidoptera, which are pollinat…
Generator-Based Radiopharmaceuticals for PET Dosimetry Before, During, and After Endoradiotherapy
2014
Generator-derived radionuclides for PET/CT imaging are promising for optimizing targeted radiotherapy by an individual patient-based approach, applying pre-therapeutic evaluation, dosimetric calculations, and for measuring treatment response after radionuclide therapy. To realize this vision, sophisticated nuclear chemistry and radiopharmaceutical chemistry should coincide with quantitative molecular imaging and dosimetric calculations.
Generator-based PET radiopharmaceuticals for molecular imaging of tumours: on the way to THERANOSTICS.
2011
Generator-derived radionuclides for PET/CT imaging are promising for optimizing targeted radiotherapy by an individual patient-based approach, applying pre-therapeutic evaluation, as well as dosimetric calculations, and for measuring treatment response after radionuclide therapy.
Targeting cancer stem cells and the tumor microenvironment
2015
Compelling evidence indicates that the survival and behavior of cancer stem cells (CSCs) are positively regulated by specific stimuli received from the tumor microenvironment, which dictates the maintenance of stemness, invasiveness, and protection against drug-induced apoptotic signals. CSCs are per se endowed with multiple treatment resistance capabilities, thus the eradication of CSC pools offers a precious strategy in achieving a long-term cancer remission. Numerous therapies, aimed at eradicating CSCs, have been elaborated such as: (i) selective targeting of CSCs, (ii) modulating their stemness and (iii) influencing the microenvironment. In this context, markers commonly exploited to i…
Death receptors as targets in cancer
2014
Anti-tumour therapies based on the use PARAs (pro-apoptotic receptor agonists), including TRAIL (TNF-Related Apoptosis inducing Ligand) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future…
Not just for tumor targeting: unmet medical needs and opportunities for nanomedicine.
2015
During the last 3 decades, nanomedicines have provided novel opportunities to improve the delivery of chemotherapeutics in cancer therapy effectively. However, many principles learnt from there have the potential to be transferred to other diseases. This perspective article, on the one hand, critically reflects the limitations of nanomedicines in tumor therapy and, on the other hand, provides alternative examples of nanomedicinal applications in immunotherapy, noninvasive drug deliveries across epithelial barriers and strategies to combat intra- and extra-cellular bacterial infections. Looking ahead, access to highly complex nanoparticular delivery vehicles given nowadays may allow further…