A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.

The Anaplastic Lymphoma Kinase (ALK) gene is a receptor tyrosine kinase (RTK) with expression restricted to the developing nervous system. Most neuroblastomas express native ALK protein on the cell surface and ALK is uniformly overexpressed in fusion-positive rhabdomyosarcoma and in subsets of metastatic colorectal carcinoma, melanoma, ovarian carcinoma, and breast carcinoma. Here, we first confirm that ALK RNA, protein, and tumor cell surface expression is elevated in multiple pediatric and adult malignancies with minimal expression in childhood normal tissues.

An automatic algorithm to exploit the symmetries of the system response matrix in positron emission tomography iterative reconstruction.

Positron emission tomography (PET) iterative 3D reconstruction is a very computational demanding task. One of the main issues of the iterative reconstruction concerns the management of the system response matrix (SRM). The SRM models the relationship between the projection and the voxel space and its memory footprint can easily exceed hundreds of GB.

The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma.

Recently we reported that direct injection of M1 macrophages significantly caused tumor regression . Despite the promising result, a major limitation in translating this approach is the induction of acute inflammatory response. To improve the strategy, a biocompatible scaffold for cell presentation and support is essential to control cell fate.

Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells.

Background: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity.

Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels.

Unlabelled: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation.

Cherenkov luminescence measurements with digital silicon photomultipliers: a feasibility study.

Background: A feasibility study was done to assess the capability of digital silicon photomultipliers to measure the Cherenkov luminescence emitted by a β source. Cherenkov luminescence imaging (CLI) is possible with a charge coupled device (CCD) based technology, but a stand-alone technique for quantitative activity measurements based on Cherenkov luminescence has not yet been developed. Silicon photomultipliers (SiPMs) are photon counting devices with a fast impulse response and can potentially be used to quantify β-emitting radiotracer distributions by CLI.

Quantitative micro-CT based coronary artery profiling using interactive local thresholding and cylindrical coordinates.

Background: Micro-CT is an established imaging technique for high-resolution non-destructive assessment of vascular samples, which is gaining growing interest for investigations of atherosclerotic arteries both in humans and in animal models. However, there is still a lack in the definition of micro-CT image metrics suitable for comprehensive evaluation and quantification of features of interest in the field of experimental atherosclerosis (ATS).

Objective: A novel approach to micro-CT image processing for profiling of coronary ATS is described, providing comprehensive visualization and quantification of contrast agent-free 3D high-resolution reconstruction of full-length artery walls.

Mesenchymal Stromal/Stem Cell and Minocycline-Loaded Hydrogels Inhibit the Growth of Staphylococcus aureus that Evades Immunomodulation of Blood-Derived Leukocytes.

Mesenchymal stromal/stem cells (MSCs) have demonstrated favorable wound healing properties in addition to their differentiation capacity. MSCs encapsulated in biomaterials such as gelatin and polyethylene glycol (PEG) composite hydrogels have displayed an immunophenotype change that leads to the release of cytokines and growth factors to accelerate wound healing. However, therapeutic potential of implanted MSC-loaded hydrogels may be limited by non-specific protein adsorption that facilitates adhesion of bacterial pathogens such as planktonic Staphylococcus aureus (SA) to the surface with subsequent biofilm formation resistant to immune cell recognition and antibiotic activity.

Multi-ray-based system matrix generation for 3D PET reconstruction.

Iterative image reconstruction algorithms for positron emission tomography (PET) require a sophisticated system matrix (model) of the scanner. Our aim is to set up such a model offline for the YAP-(S)PET II small animal imaging tomograph in order to use it subsequently with standard ML-EM (maximum-likelihood expectation maximization) and OSEM (ordered subset expectation maximization) for fully three-dimensional image reconstruction. In general, the system model can be obtained analytically, via measurements or via Monte Carlo simulations.

Development of the YAP-PEM scanner for breast cancer imaging.

A prototype for positron emission mammography is under development at the Department of Physics of Pisa University. The device will be composed of two opposing detectors (parallel plane geometry). The active part of each detector head consists of a matrix of 900 YAP: Ce pixel scintillators, with a 2x2 mm(2) pitch and a 30 mm thickness.