A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury

Traumatic spinal cord injury (SCI) is a damage to the spinal cord that results in loss or impaired motor and/or sensory function. SCI is a sudden and unexpected event characterized by high morbidity and mortality rate during both acute and chronic stages, and it can be devastating in human, social and economical terms. Despite significant progresses in the clinical management of SCI, there remain no effective treatments to improve neurological outcomes. Among experimental strategies, bioengineered scaffolds have the potential to support and guide injured axons contributing to neural repair. The major aim of this study was to investigate a novel composite type I collagen scaffold with micropatterned porosity in a rodent model of severe spinal cord injury. After segment resection of the thoracic spinal cord we implanted the scaffold in female Sprague-Dawley rats. Controls were injured without receiving implantation. Behavioral analysis of the locomotor performance was monitored up to 55 days postinjury. Two months after injury histopathological analysis were performed to evaluate the extent of scar and demyelination, the presence of connective tissue and axonal regrowth through the scaffold and to evaluate inflammatory cell infiltration at the injured site. We provided evidence that the new collagen scaffold was well integrated with the host tissue, slightly ameliorated locomotor function, and limited the robust recruitment of the inflammatory cells at the injury site during both the acute and chronic stage in spinal cord injured rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016

From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers-A Multidisciplinary Perspective

Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents

enhanced sparcl1 expression in cancer stem cells improves preclinical modeling of glioblastoma by promoting both tumor infiltration and angiogenesis

Abstract Glioblastoma (GBM) is the most malignant brain tumor of adults and is characterized by extensive cell dissemination within the brain parenchyma and enhanced angiogenesis. Effective preclinical modeling of these key features suffers from several shortcomings. Aim of this study was to determine whether modulating the expression of extracellular matrix (ECM) modifiers in proneural (PN) and mesenchymal (MES) cancer stem cells (CSCs) and in conventional glioma cell lines (GCLs) might improve tumor invasion and vascularization. To this end, we selected secreted, acidic and rich in cysteine-like 1 (SPARCL1) as a potential mediator of ECM remodeling in GBM. SPARCL1 transcript and protein expression was assessed in PN and MES CSCs as well as GCLs, in their xenografts and in patient-derived specimens by qPCR, WB and IHC. SPARCL1 expression was then enforced in both CSCs and GCLs by lentiviral-based transduction. The effect of SPARCL1 gain-of-function on microvascular proliferation, microglia activation and advanced imaging features was tested in intracranial xenografts by IHC and MRI and validated by chorioallantoic membrane (CAM) assays. SPARCL1 expression significantly enhanced the infiltrative and neoangiogenic features of PN and MES CSC/GCL-induced tumors, with the concomitant activation of inflammatory responses associated with the tumor microenvironment, thus resulting in experimental GBMs that reproduced both the parenchymal infiltration and the increased microvascular density, typical of GBM. Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography

PURPOSE: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good

Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2)

A lower bone mass accompanied by a higher bone fragility with increased risk of fracture are observed in individuals with type 1 diabetes mellitus. Low C-peptide levels are associated with low lumbar mineral density in postmenopausal woman. In this work, we investigated the role of C-peptide on the osteoblast cell biology in vitro. We examined intracellular pathways and we found that C peptide activates ERK1/2 in human osteoblast-like cells (Saos-2). We also observed that proinsulin C-peptide prevents a reduction of type I collagen expression and decreases, in combination with insulin, receptor activator of nuclear factor-kappa B (RANKL) levels. In this work we show for the first time that Cpeptide activates a specific intracellular pathway in osteoblasts and it modulates the expression of protein involved in bone remodeling. Our results suggest that both C-peptide may have a role in bone metabolism. Further studies are needing to fully clarify its role