A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl).

Background: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients.

Methods: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified.

Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study.

Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking.

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.

Aim: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

Material And Methods: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.

High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series.

: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. : Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/- ifosfamide (MAP+/-I)] with measurable disease according to RECIST1.

Efficacy of the DigniCap System in preventing chemotherapy-induced alopecia in breast cancer patients is not related to patient characteristics or side effects of the device.

Background: The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients.

Aim: This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction.

Methods: Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled.

Denosumab in patients with aneurysmal bone cysts: A case series with preliminary results.

Purpose:: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC.

Methods:: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed.

Circulating Candidate Biomarkers in Giant Cell Tumors of Bone.

Purpose: Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression.

Experimental Design: The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control.

Complexity in internal medicine wards: A novel screening method and implications for management.

Rationale: Complexity is increasingly recognized as a critical variable in health care. However, there is still lack of practical tools to assess it and tackle the challenges that stem from it, particularly within hospitals.

Aims And Objective: To validate a simple novel screening method based on both objective and subjective criteria to identify patients with clinically complex hospitalization events.

Fabrication of Innovative Silk/Alginate Microcarriers for Mesenchymal Stem Cell Delivery and Tissue Regeneration.

The aim of this study was to exploit silk fibroin's properties to develop innovative composite microcarriers for mesenchymal stem cell (MSCs) adhesion and proliferation. Alginate microcarriers were prepared, added to silk fibroin solution, and then treated with ethanol to induce silk conformational transition. Microcarriers were characterized for size distribution, coating stability and homogeneity.

A new holistic 3D non-invasive analysis of cellular distribution and motility on fibroin-alginate microcarriers using light sheet fluorescent microscopy.

Cell interaction with biomaterials is one of the keystones to developing medical devices for tissue engineering applications. Biomaterials are the scaffolds that give three-dimensional support to the cells, and are vectors that deliver the cells to the injured tissue requiring repair. Features of biomaterials can influence the behaviour of the cells and consequently the efficacy of the tissue-engineered product.

Identification of a T cell gene expression clock obtained by exploiting a MZ twin design.

Many studies investigated age-related changes in gene expression of different tissues, with scarce agreement due to the high number of affecting factors. Similarly, no consensus has been reached on which genes change expression as a function of age and not because of environment. In this study we analysed gene expression of T lymphocytes from 27 healthy monozygotic twin couples, with ages ranging over whole adult lifespan (22 to 98 years).

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel-coated OSPROLIFE(®) HA/TTCP granules and bone marrow concentrate.

The purpose of this study was to examine the in vitro cytocompatibility of a novel injectable multiphasic bone substitute (MBS) based on polysaccharide gel-coated OSPROLIFE(®) hydroxyapatite (HA)/tetracalcium phosphate (TTCP) granules combined with bone marrow concentrate (BMC). Polysaccharide gel-coated granules loaded in syringe were combined with BMC diluted in ionic crosslinking solution. The product was then maintained in culture to investigate the cytocompatibility, distribution, and osteogenic differentiation function of cells contained in the BMC.

Semi-quantitative monitoring of confluence of adherent mesenchymal stromal cells on calcium-phosphate granules by using widefield microscopy images.

The analysis of cell confluence and proliferation is essential to design biomaterials and scaffolds to use as bone substitutes in clinical applications. Accordingly, several approaches have been proposed in the literature to estimate the area of the scaffold covered by cells. Nevertheless, most of the approaches rely on sophisticated equipment not employed for routine analyses, while the rest of them usually do not provide significant statistics about the cell distribution.

The posterior iliac crest outperforms the anterior iliac crest when obtaining mesenchymal stem cells from bone marrow.

Background: The clinical application of freshly isolated connective-tissue progenitors, as well as the potential preparation of culture-expanded mesenchymal stem cell populations for therapeutic applications, will benefit from clinical methods that maximize the yield of the starting population. We compared the number of cells, concentration, and prevalence of colony-founding connective-tissue progenitors from the anterior and posterior iliac crest. In addition, we compared the expansion kinetics and multilineage differentiation potential of their culture-expanded progeny when processed to form mesenchymal stem cells.

Space/population and time/age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age.

Little is known about the impact of space (geography/ancestry) and time (age of the individuals) on DNA methylation variability in humans. We investigated DNA methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals homogeneous for age and gender (males with restricted age range: 30-50 years) belonging to four Italian districts representative of the major genetic clines, informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for the temporal dimension. DNA methylation of the analyzed regions displayed high levels of inter-individual variability that could not be ascribed to any geographical cline.

A rapid method for obtaining mesenchymal stem cells and platelets from bone marrow aspirate.

Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are currently used alone or in combination for therapeutic applications especially for bone repair. We tested whether MSCs can be isolated from bone marrow (BM) aspirate using a commercially available kit commonly used to obtain PRP from peripheral blood (PB). Results revealed that mononuclear cells and platelets from both PB and BM could be efficiently isolated by obtaining a mononuclear and platelet rich fraction (PB-MPRF and BM-MPRF, respectively).

Efficient isolation and enrichment of mesenchymal stem cells from bone marrow.

Background Aims: Bone marrow (BM) mesenchymal stromal cells (MSC) have been identified as a source of pluripotent stem cells used in clinical practice to regenerate damaged tissues. BM MSC are commonly isolated from BM by density-gradient centrifugation. This process is an open system that increases the risk of sample contamination.

Cell growth inhibition and apoptotic effect of the rexinoid 6-OH-11-O-hydroxyphenantrene on human osteosarcoma and mesenchymal stem cells.

Natural derivatives of vitamin A, including all-trans-retinoic acid (ATRA), commonly known as retinoids, currently produce favorable results in the treatment of many types of tumors. The rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) is a synthetic derivative of ATRA. Previous in vitro and in vivo studies demonstrated that IIF is able to induce growth inhibition of various cancer cells and is a potent apoptosis-inducing agent with clinical potential.

Molecular remodeling of potassium channels in fibroblasts from centenarians: a marker of longevity?

Aging is a complex process resulting from, among other, dynamic non-linear interactions between genetics and environment. Centenarians are the best example of successful aging in humans, as they escaped from, or largely postponed, major age-related diseases. Ionic fluxes changes play a key role in several patho-physiological cellular processes, but their relation to human aging is largely unexplored.

Complex patterns of gene expression in human T cells during in vivo aging.

Human aging is associated with complex alterations that contribute to remodelling of physiological processes and ultimately manifests in loss of tissue/organ function. Peripheral blood T cells do not escape this phenomenon and undergo profound remodelling with aging. Thus, investigating the effects of aging on T cells transcriptomics and identifying the underlying regulatory mechanisms can be of extreme importance to understand the aging process in the Immune System (IS).

Structural characterization of p53 isoforms due to the polymorphism at codon 72 by mass spectrometry and circular dichroism.

A common polymorphism at codon 72 of human TP53 gene determines a proline to arginine aminoacidic substitution within the proline-rich domain of p53 protein. The two resulting isoforms (p53P(72) and p53R(72)) are different from a biochemical and biological point of view and many reports suggest that they can modulate individual cancer susceptibility and overall survival. In the attempt to explain the observed biological differences, we characterized the two isoforms by mass spectrometry and circular dichroism (CD) to evaluate the possible alteration in the secondary structure of p53 introduced by this polymorphism.

The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing.

Plasminogen activator inhibitor 1 (PAI-1) is over-expressed during ageing and it has been linked to cellular senescence. Recently, PAI-1 has been also identified in vitro as a critical downstream target of p53. TP53, the p53 gene, has a common functional polymorphism at codon 72 which influences the capability to modulate both apoptosis and cell senescence.

The frequency of Klotho KL-VS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect.

In mice a defect of Klotho gene expression results in multiple aging-like phenotypes including short lifespan, osteoporosis and atherosclerosis, while its over-expression suppresses aging and extends lifespan. Contrasting data have been reported as far as the importance of the functional variant of Klotho termed "KL-VS" on human longevity, depending on the average age of the old subjects that were compared with young controls. We therefore performed a study on a large Italian population sample including people from very young to very old age (centenarians).

Different types of cell death in organismal aging and longevity: state of the art and possible systems biology approach.

Cell death is as important as cell proliferation for cell turn-over, and susceptibility to cell death is affected by a number of parameters that change with time. A time-dependent derangement of such a crucial process, or even the simple cell loss mediated by cell death impinges upon aging and longevity. In this review we will discuss how cell death phenomena are modulated during aging and what is their possible role in the aging process.