Search

Bioactive glasses are widely studied as biomaterials for bone contact applications. In this research work, the opportunity to modify the surface of a bioactive glass with polyphenols (gallic acid, and natural polyphenols extracted from red grape skin and green tea leaves) has been investigated in order to induce a selective anti-tumor activity in vitro. The presence of surface grafted molecules has been optically proved by fluorescence microscopy exploiting their auto-fluorescence. Direct and indirect cytotoxicity assays have been performed with human bone osteosarcoma cells (U2OS) and human fetal pre-osteoblasts (hFOB), as well as the quantification of oxygen and nitrogen reactive species (RONS) engendered from cells in response to the materials. Finally, the DNA damage of U2OS cells upon contact with the bioactive glass has been evaluated in order to verify any selective cytotoxic activity of functionalized materials against cancer cells. Results showed a selective cytotoxic activity of functionalized bioactive glasses toward osteosarcoma cells that was particularly evident when cells were cultivated directly onto glasses surface. Moreover, the presence of grafted polyphenols increased the RONS production and induced a permanent DNA damage on the U2SOS cells while they promote a certain anti-inflammatory action toward hFOB. These preliminary results suggest polyphenols grafted bioactive glasses as promising material for bone substitution in cancer treatment. [ABSTRACT FROM AUTHOR]

Background Recent reports have revealed the therapeutic potential of cell-mediated immunity in neoplasms such as cutaneous squamous cell carcinoma ( SCC). Objectives To define the antigenic coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells ( pDCs) and assess the CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours. Methods We evaluated the content and distribution of Foxp3+CD25+ Treg and CD123+ pDC infiltration and assessed CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in 40 SCCs (20 well-differentiated, G1; and 20 moderately to poorly differentiated, G2-G3) to investigate a correlation with their aggressiveness. We determined the profiles of Tregs and CD123+ cells; immunostained for CD4, CD8, CD123, interleukin (IL)-1 and transforming growth factor (TGF)-β1; and unequivocally double stained for Foxp3CD25. Results Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123+ cells were fewer in G2-G3 ( P = 0·0005), while Foxp3+ CD25+ cells were more numerous ( P = 0·0005). The Foxp3+ CD25+/Foxp3+ ratio was higher in G2-G3 cases ( P = 0·0005), confirming the trend in this group of activated T lymphocytes towards total Treg Foxp3+ cells, while the CD8+/Foxp3+ CD25+ ratio was higher in G1 ( P = 0·0005). Intratumorally, CD4+ and CD8+ cells infiltrated G2-G3 ( P = 0·048) more than G1 ( P = 0·004), whereas almost all cells were CD123 negative. Regarding Foxp3 CD25, TGF-β1 and IL-10, they were less expressed in G1, whereas they were positive in G2-G3 ( P < 0·05). The CD8+/Foxp3+ CD25+ ratio was similar to that observed in peritumoral infiltration. Conclusions Our data suggest that intratumoral recruitment of Tregs, high expression of TGF-β1 and IL-10, almost negative CD123+, and a low CD8+/Foxp3+ CD25+ T-cell ratio may contribute to the aggressiveness of cutaneous SCC, as already evidenced for other solid tumours. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases. METHODS: Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined. RESULTS: Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti-IFI16 IgG antibody levels compared with normal controls (for SLE, P < 0.002; for primary SS, P < 0.001; for SSc, P < 0.0005). Anti-IFI16 titers above the ninety-fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc]). In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection. CONCLUSION: The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether the expression of interferon (IFN)-inducible gene IFI16 inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. Met hods: Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. Results: HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HP V-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. Conclusions: To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. [ABSTRACT FROM AUTHOR]

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes' poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na2SO4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis. [ABSTRACT FROM AUTHOR]