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Characterization of the antitumor activity of the PI3K δ-sparing inhibitor MEN1611 mediated by the PIK3γ inhibition on macrophages and tumour immune infiltrate
Full text linkCharacterization of the antitumor activity of the PI3K δ-sparing inhibitor MEN1611 mediated by the PIK3γ inhibition on macrophages and tumour immune infiltrate
The tumour microenvironment (TME) is a complex multicellular environment. The TME typically comprises immune cells, including tumour-associated macrophages (TAM), fibroblasts, blood vessels, lymphatics and cancer cells that regulates cancer progression and may influence therapeutic and clinical outcome.
The phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell cycle, growth and proliferation and its aberrant activation is one of the most frequent events in human cancer (Yang, J. et Al. Mol Cancer 18, 26 2019). Literature data have shown that PI3Kγ inhibition can reshape the inflammatory cells infiltrating the tumours towards a less immunosuppressive phenotype (Megan M. Kaneda et Al. Nature 2016).
MEN1611 is a PI3K inhibitor currently in clinical development targeting the p110 α, β, and γ isoforms, while sparing the δ subunit (J. Ohwada et Al. Bioorg Med Chem Lett. 2011). MEN1611 showed a long-lasting antitumor activity when combined with Trastuzumab (H. Tanaka et Al. Clin Cancer Res. 2011).
This project aim is to characterize the effects of MEN1611 inhibition of the PI3Kγ isoform, highly expressed in tumour-associated macrophages (TAMs), in order to investigate the possible anti-tumour activity of MEN1611 mediated by the inflammatory microenvironment modulation.
In-vitro and in-vivo models were established in order to evaluate the effect of MEN1611 on TAMs. Murine macrophages were differentiated from bone marrow-derived monocytes (A. Sica and A. Mantovani J Clin Invest. 2012). Obtained cells, were treated with MEN1611 or IPI-549 (as positive control).
In this project we characterized the effects of MEN1611 and IPI-549 on the gene expression of M1/M2 macrophages using RNA-Seq technology in order to understand similar and independent pathways modulated from the two compounds using Ingenuity Pathway Analysis (IPA).
A syngeneic xenograft model of breast cancer based on 4T1 cells was implemented to investigate the modulation of the inflammatory infiltrate mediated by MEN1611 and IPI-549. RNA-Seq analysis was performed on dissociated treated tumours. Subsequently, an in-silico IPA was done on genes modulated by MEN1611/IPI-549 to investigate the processes related to the immune-activating switch.
All these data were used to generate a gene signature associated with MEN1611 activity on the tumour immune-infiltrate that were used to investigate a subpopulation that could be targeted by MEN1611 using public databases.
In vivo and in vitro results together suggest that MEN1611 anti-tumoral activity might be also mediated by inflammatory cells infiltrating tumours through PI3Kγ inhibition. Moreover, in silico results suggest that the modulation of TAM induced by MEN1611 could improve overall survival of breast cancer patients
Automatic Alignment of Multiple Point Clouds by Image Processing and 3D Data Matching
No full textIn recent years, various methodologies of reverse engineering have been proposed with the aim at creating CAD models from digitization of target objects using optical sensors. Traditionally, the acquisition of 3D geometrical data includes crucial tasks, such as planning scanning strategies and aligning different point clouds by many alternative methodologies which differ for user interaction levels and costs. This paper describes a technology to acquire free form surfaces by combining a 3D vision system and a fully automatic point clouds alignment procedure based on fiducial marker recognition. The aim is to create accurate and complete digital representations of physical objects, even those presenting a few morphological singularities, in a very short time and with minimal human intervention. The technology has been tested acquiring target objects with complex shape
Large yacht hull measurement by integrating optical scanning with mechanical tracking-based methodologies
No full textIn the shipbuilding industry, the manufacturing of large yacht hulls is a complex process. Metal hulls are traditionally manufactured by welding pre fabricated large steel panels to form the external superstructure. A surface finishing process is then carried out in order to obtain a final target surface having a smooth curvature. The methodologies manly rely on manual processes based on the measurement of the as built hull shape through simple testing instrumentation. Well-experienced workers are required, and a great amount of time is usually wasted, thus affecting the overall shipyard competitiveness.
This paper introduces a methodology for automating the measurement process of as built hull yacht shapes. The methodology, which is based on the integration of a robotic system with an optical scanner, provides accurate non contact 3D full field measurements of the hull surface. The placement of the robotic system around the hull shape is determined by a laser total station thus allowing the automatic multi view data registration into a common reference frame. The proposed approach represents the basis for the automation of the whole surface finishing process of large yacht hulls. In this paper, the methodology has been tested by measuring a large broadside area of a 59 m hull assembled within a shipyard
An innovative methodology for the design of custom dental prostheses by optical scanning
No full textThe anchorage of dental prostheses to endosseous implants is a well defined procedure in clinical practice, allowing the restoration of the masticatory function, eliminating pain and providing esthetics. Traditional methods for the creation of implant surfaces are greatly dependent on experiences and skills of clinicians. In the last few years, the development of CAD/CAM technologies has been extended to the design of custom prosthetic frameworks. The weak point of the whole procedure is the accuracy in the determination of implant supporting positions and consequent prosthetic fit to these surfaces.
This paper concerns the study of an innovative methodology to obtain dental prostheses starting from endosseous implants. The method is based on optical scanning gypsum replicas in different times within the design phase of dental frameworks. A structured light scanning device has been developed to automatically capture 3D data relative to positions and orientations of endosseous implants in master models. Since inaccuracies in the measurement of dental cast models can seriously compromise the final clinical results, a proper test method for the precision of the dental scanner has been proposed and described
Customised 3D tooth modeling by minimally invasive imaging modalities
No full textDental panoramic tomography represents a standard imaging modality in dentistry since it provides a convenient and inexpensive method to visualize anatomic structures and pathologic conditions with low radiation doses. However, this technique does not provide comprehensive 3D geometries of dental shapes which are conventionally demanded to computerised tomography (CT) techniques. In this paper, a tooth reconstruction process is presented by integrating patient-specific information with general dental templates. A 2D panoramic radiograph and the digitised patient plaster cast are used to customise both shape and orientation of teeth templates thus allowing a consistent 3D tooth reconstruction with minimally invasive imaging modalities. The proposed methodology does not make any assumption about the tomographic device used to collect the panoramic radiograp
Multiple alignments of range maps by active stereo imaging and global marker framing
No full textThree-dimensional shapes can be digitised by using active imaging techniques, which reconstruct entire objects by capturing multiple range maps from different viewpoints. Multiple-view reconstructions require the computation of translation and rotation parameters to transform each range map with reference to a global coordinate frame.
In this paper, an automatic method has been developed to efficiently align 3D range maps acquired by an active stereo vision system. The methodology is based on referring range maps to a global frame of fiducial markers captured by the stereo system. The procedure includes a refinement of the marker frame in order to globally minimise the misalignment errors.
The methodology optimises the overall accuracy of 3D reconstructions regardless of the scanning strategies, even processing large data sets.
The proposed approach has been experienced and validated by measuring both nominal shapes and industrial models
Automation of the finishing process of steel yacht hulls based on optical scanning
No full textPurpose: The manufacturing of large yacht hulls is a complex process in the shipbuilding industry. The traditional approach is based on the pre-fabrication of large steel panels that are welded together to form 3D superstructure assemblies. One of the most relevant aspects of a yacht is its visual impact. For this reason, a finishing phase is usually carried out in order to obtain a final target surface with smooth curvature. Current methodologies mainly rely on manual processes thus requiring a great amount of time and well-experienced workers. Method: This paper introduces an innovative methodology representing the basis for the automation of the finishing phase of large yacht hulls. The proposed approach is based on the measurement of the as-built hull surface through the integration of an active stereo vision system and a complex mechanical tracking system. A procedure to define the target surface has been developed by integrating information deriving from both the design and the as-built shapes. Result: The developed methodology has been tested on a broadside region of the hull of a 59 metres yacht assembled within a shipyard. A target surface, differing as little as possible from the design surface, has been modelled in order to obtain a uniform curvature shape. A finishing phase has then been carried out by applying a layer of filler and by milling the hull’s surface. Discussion & Conclusion:
Results obtained have demonstrated the feasibility of the proposed approach, speeding up the whole process and guaranteeing fair reflection line patterns on the manufactured surface
Computer-aided modeling of 3D maxillofacial tissues through multi-modal imaging
No full textRecent developments in digital imaging techniques have allowed a wide spread of three-dimensional methodologies based on capturing anatomical tissues by different approaches, such as cone-beam computed tomography, three-dimensional photography and surface scanning. In oral rehabilitation, an objective method to predict surgical and orthodontic outcomes should be based on anatomical data belonging to soft facial tissue, facial skeleton and dentition (maxillofacial triad). However, none of the available imaging techniques can accurately capture the complete triad. This article presents a multi-modal framework, which allows image fusion of different digital techniques to create a three-dimensional virtual maxillofacial model, which integrates photorealistic face, facial skeleton and dentition. The methodology is based on combining structured light surface scanning and cone-beam computed tomography data processing. The fusion procedure provides multi-modal representations by aligning different tissues on the basis of common anatomical constraints
Validation of a No-Contact CMM System for Fast and Accurate 3D Shape Measurements
No full textThe measurement process of three-dimensional shapes has recently assumed a relevant role in various industrial applications due to its wide field of application such as reverse engineering or coordinate metrology in dimensional control. The acquisition of 3D geometrical data generally requires three main steps: planning the number and the right sequence of all the range scans, acquiring the single data sets and aligning the collected data in a common reference frame. The overall measurement accuracy directly depends on the planned strategy, the sensor precision and the alignment methodology used. Among these, the point cloud alignment phase represents the task having the main influence on the reliability of the measurement process and on required time.
This paper describes an integration between a 3D stereo vision system and 5 motorized axes with the aim at the definition of a no-contact Coordinate Measurement Machine (CMM) system for fast and accurate digital representations of target objects with minimum human intervention. An automatic alignment methodology, based on a calibration procedure of the vision system with respect to the 5 axes, allows rapid and high-precision 3D shape measurements with minimum human intervention
Automatic alignment of multi-view range maps by optical stereo-tracking
No full textPurpose: Industrial reverse engineering applications usually require reliable multi-view measurements of complex shapes obtained by full field techniques. One of the most challenging issues in this field is represented by the automatic computation of the best transformation parameters relating the different views into a common reference system. Method: A low cost optical tracking system has been developed with the aim at creating an automatic procedure to align 3D point clouds captured by a structured light system. The tracking system uses stereo images and retro-reflective infrared markers rigidly connected to the scanner. Markers are accurately tracked on the basis of automatic intensity-based analyses. Stereo correspondences are established by using epipolar and similarity constraints. Result: Experimental tests have been carried out in order to evaluate the capabilities of the developed system in the measurement process of nominal benchmarks and complex shapes. Discussion & Conclusion:
The accuracy obtained in the automatic alignment of multiple views justifies the use of the proposed approach in the speed up of the measurement process for reverse engineering applications, especially when conventional high-end systems cannot be applied
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