Search results for "Biological target"
showing 10 items of 20 documents
K-nearest neighbor driving active contours to delineate biological tumor volumes
2019
Abstract An algorithm for tumor delineation in positron emission tomography (PET) is presented. Segmentation is achieved by a local active contour algorithm, integrated and optimized with the k-nearest neighbor (KNN) classification method, which takes advantage of the stratified k-fold cross-validation strategy. The proposed approach is evaluated considering the delineation of cancers located in different body districts (i.e. brain, head and neck, and lung), and considering different PET radioactive tracers. Data are pre-processed in order to be expressed in terms of standardized uptake value, the most widely used PET quantification index. The algorithm uses an initial, operator selected re…
Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.
2021
Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expressi…
Conf-VLKA: A structure-based revisitation of the Virtual Lock-and-key Approach
2016
In a previous work, we developed the in house Virtual Lock-and-Key Approach (VLKA) in order to evaluate target assignment starting from molecular descriptors calculated on known inhibitors used as an information source. This protocol was able to predict the correct biological target for the whole dataset with a good degree of reliability (80%), and proved experimentally, which was useful for the target fishing of unknown compounds. In this paper, we tried to remodel the previous in house developed VLKA in a more sophisticated one in order to evaluate the influence of 3D conformation of ligands on the accuracy of the prediction. We applied the same previous algorithm of scoring and ranking b…
Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs.
2018
Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis an…
Strategic Syntheses of Vine and Wine Resveratrol Derivatives to Explore their Effects on Cell Functions and Dysfunctions
2018
Trans-resveratrol, the most well-known polyphenolic stilbenoid, is found in grapes and accordingly in wine and it is considered to be beneficial for human health, especially towards the aging-linked cell alterations by providing numerous biological activities, such as anti-oxidant, antitumoral, antiviral, anti-inflammatory, neuroprotective, and platelet anti-aggregation properties. Although trans-resveratrol is a promising molecule, it cannot be considered as a drug, due to its weak bio-availability and fast metabolism. To overcome these weaknesses, several research teams have undertaken the synthesis of innovative trans-resveratrol derivatives, with the aim to increase its solubility in wa…
Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour
2017
Soft and flexible nanogels, produced by electron beam (e-beam) irradiation of poly(N-vinyl pyrrolidone) and acrylic acid, were evaluated as delivery devices of the inhibitor of miR-31, a small RNA molecule with an important role in colorectal cancer (CRC) progression. The nanogel carriers developed possess both carboxyl and primary amino groups; the former were activated to react with the primary amino group present in the purposely-functionalised AntimiR-31. Very high conjugation reaction yields were attained, as well as a remarkable colloidal and storage stability of the conjugates. The ability of these nanoconstructs to be internalized by cells and the specific interaction of conjugated …
Multivariate analysis in the identification of biological targets for designed molecular structures: The BIOTA protocol
2013
In this work the new protocol BIOlogical Target Assignation (BIOTA) for the prediction of the biological target from molecular structures is proposed. BIOTA is based on the Principal Components Analysis (PCA) application on a matrix of ligands versus molecular descriptors. The application of BIOTA could allow to hypothesize the mechanism of action of a candidate drug prior to its biological evaluation or to repurpose old drugs. The protocol can be fine-tuned by choosing opportune targets (biological or not) and molecular descriptors, and it can be useful in every fields in with it is possible to collect set of compounds with known properties. The robustness of the protocol depends from diff…
The In Silico Fischer Lock-and-Key Model: The Combined Use of Molecular Descriptors and Docking Poses for the Repurposing of Old Drugs
2019
Not always lead compound and/or derivatives are suitable for the specific biological target for which they are designed but, in some cases, discarded compounds proved to be good binders for other biological targets; therefore, drug repurposing constitute a valid alternative to avoid waste of human and financial resources. Our virtual lock-and-key methods, VLKA and Conf-VLKA, furnish a strong support to predict the efficacy of a designed drug a priori its biological evaluation, or the correct biological target for a set of the selected compounds, allowing thus the repurposing of known and unknown, active and inactive compounds.
A smart and operator independent system to delineate tumours in Positron Emission Tomography scans
2018
Abstract Positron Emission Tomography (PET) imaging has an enormous potential to improve radiation therapy treatment planning offering complementary functional information with respect to other anatomical imaging approaches. The aim of this study is to develop an operator independent, reliable, and clinically feasible system for biological tumour volume delineation from PET images. Under this design hypothesis, we combine several known approaches in an original way to deploy a system with a high level of automation. The proposed system automatically identifies the optimal region of interest around the tumour and performs a slice-by-slice marching local active contour segmentation. It automa…
A preliminary PET radiomics study of brain metastases using a fully automatic segmentation method
2020
AbstractBackgroundPositron Emission Tomography (PET) is increasingly utilized in radiomics studies for treatment evaluation purposes. Nevertheless, lesion volume identification in PET images is a critical and still challenging step in the process of radiomics, due to the low spatial resolution and high noise level of PET images. Currently, the biological target volume (BTV) is manually contoured by nuclear physicians, with a time expensive and operator-dependent procedure.This study aims to obtain BTVs from cerebral metastases in patients who underwent L-[11C]methionine (11C-MET) PET, using a fully automatic procedure and to use these BTVs to extract radiomics features to stratify between p…