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Biomedical subjects

Francesca Tosetti

Publications and source records attributed to Francesca Tosetti.

7 recordsLinked to original sources
PubMed2006

Identification of a new truncated form and deamidation products of fibrinopeptide B released by thrombin from human fibrinogen.

Quantification of fibrinopeptides release is widely used to investigate fibrinogen activation, and standard chromatographic or capillary electrophoretic procedures are readily available. However, in the analyses of fibrinopeptide mixtures derived from the action of thrombin on human fibrinogen, a few unidentified peaks are usually present. The composition of these peaks was studied by reverse-phase HPLC/MS, revealing a single major anomalous peptide having a molecular mass of 1384.4. A further MS/MS analysis allowed the identification of this form, as a Nterminally truncated fibrinopeptide B (fpB) lacking the first two residues (pyroglutamic acid and glycine). This previously unidentified, relatively low-abundance form ( approximately 7%) has been found consistently in our fibrinopeptides preparations, and analysis of the parent Bbeta-chain suggest that it is likely present in circulating fibrinogen. In addition, deamidated forms of all fpB species (including desArgB), resulting from the conversion of asparagine to aspartic acid, were also identified. Overall, these previously unreported forms constitute a substantial amount of fpB (up to approximately 17% of the total), and should be taken into account for a reliable quantitative analysis of fpB release.

Blood Coagulation Factors↗
PubMed2005

Tumor inflammatory angiogenesis and its chemoprevention.

The importance of angiogenesis for the growth of tumors is widely recognized. Drugs that successfully target the endothelium, such as antivascular endothelial growth factor antibodies, are beginning to have an effect on the life expectancy of cancer patients. However, the endothelial cell is not the only possible target for antiangiogenic therapy or prevention of vascularization (angioprevention). It is evident from the literature that native immune cells recruited into tumors in turn stimulate the endothelium and are responsible for an indirect pathway of tumor vascularization. Inflammation-dependent angiogenesis seems to be a central force in tumor growth and expansion, a concept supported by the observation that the use of "classic" anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs, leads to angiogenesis inhibition. The mechanisms of inflammatory angiogenesis provide new approaches to target, cure, or even better, prevent tumor angiogenesis by treatment with synthetic or natural agents with anti-inflammatory properties. We propose chemoprevention of inflammatory angiogenesis as a way of checking the cancer before it progresses.

Angiogenesis Inhibitors↗
PubMed2003

Transient modulation of cytoplasmic and nuclear retinoid receptors expression in differentiating human teratocarcinoma NT2 cells.

Human embryonal carcinoma Ntera2/D1 (NT2) cells treated with retinoic acid (RA) differentiate into several cell types including post-mitotic neurons. In this study we asked if RA-induced differentiation alters the expression of RA and retinol (ROL) binding proteins. The regulation of the intracellular carrier proteins for ROL and RA, cellular retinol binding protein I (CRBP-I), and cellular retinoic acid binding protein I and II (CRABP-I, CRABP-II) were studied along with the nuclear RA receptors RARalpha, RARbeta and RARgamma2. PCR analysis of total mRNA from RA-treated cells showed a biphasic early induction of CRBP-I, CRABP-II, and RARgamma2 genes. The immediate early gene Krox-24, a zinc finger transcription factor which is up-regulated during neuronal differentiation, was also induced, but after 1 week of treatment. The induction of CRBP-I protein synthesis in differentiating NT2 cells was confirmed by western blotting and immunofluorescence experiments. Conversely, the synthetic retinoid N-(4-hydroxyphenyl)retinamide, which induces cell death, but not differentiation in different tumour cell types, did not produce the same modulation on gene expression in NT2 cells. These data suggest that the RA-specific induction of CRBP-I and CRABP-II could be an early event in the process leading to neuronal differentiation of NT2 cells.

Cell Differentiation↗
PubMed2003

N-(4-hydroxyphenyl)retinamide inhibits retinoblastoma growth through reactive oxygen species-mediated cell death.

Retinoblastoma arises from a subset of developing retinal cells lacking the RB-1 gene product pRB, which have lost the ability to respond to apoptotic signals. A better understanding of retinoblastoma biological response to therapeutic agents with low toxicity could improve the development of novel approaches for treatment and prevention of the disease. Naturally occurring retinoids inhibit growth and induce differentiation of Y79 human retinoblastoma cells in vitro. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been shown to induce apoptosis and/or necrosis of tumor cells of neuroectodermal origin. We examined the sensitivity of Y79 retinoblastoma cells to 4HPR in vitro, and in a xenograft model of tumor growth in nude mice in vivo. 4HPR treatment in the range 2.5 to 10 microM induced a loss of Y79 cell viability, as determined by crystal violet, trypan blue exclusion, and long-term clonogenic assays, and impairment of mitochondrial function detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Reactive oxygen species were elevated in 4HPR-treated cells and antioxidants rescued cell viability, indicating that 4HPR-induced cell death was mediated by oxidative stress. 4HPR inhibited growth of Y79 xenografts in vivo in both chemoprevention and intervention settings. Tumor growth inhibition by 4HPR was also associated with significant inhibition of angiogenesis in vivo. These findings could have an important translational value for chemoprevention or early intervention in the treatment of retinoblastoma.

Animals↗
PubMed2002

Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents.

The potential to block tumor growth by inhibition of the neoangiogenic process represents an intriguing approach to the treatment of solid tumors. The high proliferation rate in the tumor deprived of proper vascularization would be balanced by cell death due to lack of diffusion of nutrients and oxygen. Matrix metalloproteinases (MMPs), angiogenic growth factors, and their receptors are the main targets of an increasing number of clinical trials approved to test the tolerance and therapeutic efficacy of antiangiogenic agents. We observed that a series of substances proposed as possible cancer chemopreventive agents show antiangiogenic properties when tested in in vitro and in vivo angiogenesis models. We demonstrated that N-acetyl-l-cysteine is able to reduce the invasive and metastatic potential of melanoma cells, and to inhibit endothelial cell invasion by direct inhibition of MMP activity. We also showed that epigallocatechin gallate (EGCG), a flavonoid from green tea that possesses chemopreventive activity in experimental and epidemiological studies, is a potent inhibitor of MMP-2 and MMP-9. Angiogenesis has also been demonstrated to be a target for nonsteroidal anti-inflammatory drug chemopreventive activity. Based on these data, we hypothesize that other chemopreventive agents, including natural or synthetic retinoids, steroid hormone antagonists, peroxisome proliferator-activated receptor gamma ligands, vitamin D, and protease inhibitors, might have antiangiogenesis as an important mechanism of action, a novel concept we will term 'angioprevention'. We analyze the mechanisms on how and why chemopreventive agents could exert antiangiogenic effects aimed at controlling tumor growth, and their potential use in the clinic.

Acetylcysteine↗