Publications by authors named "Mario Ciuffi"

7 Publications

  • Page 1 of 1

Reorganization of the endoscopic activity of Cancer Institutes during phase II of the Covid-19 emergency.

Dig Liver Dis 2020 11 15;52(11):1346-1350. Epub 2020 Jun 15.

Gastroenterologia Oncologica Sperimentale, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Franco Gallini, 2, 33081 Aviano, Italy. Electronic address:

After the lockdown during the emergency phase of the Covid-19 pandemic, we have to deal with phase 2, a period of uncertain duration, with a controlled and progressive return to normalization, in which we need to reconcile our work and our movements with the presence of the virus on our territory. Digestive endoscopic activity is a high-risk transmission procedure for Covid-19. The measures put in place to protect healthcare personnel and patients are stressful and "time-consuming" and lead to a reduction in the number of endoscopic procedures that can be performed. In this scenario, the Oncological Institutes are forced to make a rigorous selection of patients to undergo endoscopic examinations and treatments, according to lists of exceptional priorities, in order to guarantee cancer patients and subjects at high risk of developing digestive tumors, a preferential diagnostic and therapeutic process, protected from contagion risks. For this purpose, cuts and postponing times of endoscopic performances are here proposed, which go beyond the guidelines of scientific societies and have little evidences in the literature. These changes should be applied limited to this exceptional period and in proportion to the capacity of each operating unit in order to meet the demands of the patients.
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http://dx.doi.org/10.1016/j.dld.2020.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294252PMC
November 2020

TRPV2 Calcium Channel Gene Expression and Outcomes in Gastric Cancer Patients: A Clinically Relevant Association.

J Clin Med 2019 May 11;8(5). Epub 2019 May 11.

Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028 Rionero in Vulture (PZ), Italy.

Gastric cancer (GC) is characterized by poor efficacy and the modest clinical impact of current therapies. Apoptosis evasion represents a causative factor for treatment failure in GC as in other cancers. Since intracellular calcium homeostasis regulation has been found to be associated with apoptosis resistance, the aberrant expression of intracellular calcium regulator genes (CaRGs) could have a prognostic value in GC patients. We analyzed the association of the expression levels of 98 CaRGs with prognosis by the log-rank test in a collection of 1524 GC samples from four gene expression profiling datasets. We also evaluated differential gene expression in comparison with normal stomach tissue, and then we crossed results with tissue microarrays from the Human Protein Atlas. Among the investigated CaRGs, patients with high levels of expression were characterized by a shorter overall survival. expression was found to increase according to tumor stage. Both mRNA and protein levels were significantly higher in tumor than normal stomach samples. was also associated with poor prognosis in the Lauren's intestinal type GC and in patients treated with adjuvant therapy. Overall, we highlighted the relevance of not only as a prognostic biomarker but also as a potential therapeutic target to improve GC treatment efficacy.
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http://dx.doi.org/10.3390/jcm8050662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572141PMC
May 2019

Pyrido[1,2-a]pyrimidin-4-one derivatives as a novel class of selective aldose reductase inhibitors exhibiting antioxidant activity.

J Med Chem 2007 Oct 11;50(20):4917-27. Epub 2007 Sep 11.

Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.

2-Phenyl-pyrido[1,2-a]pyrimidin-4-one derivatives bearing a phenol or a catechol moiety in position 2 were tested as aldose reductase (ALR2) inhibitors and exhibited activity levels in the micromolar/submicromolar range. Introduction of a hydroxy group in position 6 or 9 gave an enhancement of the inhibitory potency (compare 18, 19, 28, and 29 vs 13 and 14). Lengthening of the 2-side chain to benzyl determined a general reduction in activity. The lack or the methylation of the phenol or catechol hydroxyls gave inactive (10-12, 21, 22, 25-27) or scarcely active (15, 17, 20) compounds, thus demonstrating that the phenol or catechol hydroxyls are involved in the enzyme pharmacophoric recognition. Moreover, all the pyridopyrimidinones displayed significant antioxidant properties, with the best activity shown by the catechol derivatives. The theoretical binding mode of the most active compounds obtained by docking simulations into the ALR2 crystal structure was fully consistent with the structure-activity relationships in the pyrido[1,2-a]pyrimidin-4-one series.
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http://dx.doi.org/10.1021/jm070398aDOI Listing
October 2007

Influence of resting tension on protease-activated receptor-mediated relaxation in guinea-pig tracheas.

Pulm Pharmacol Ther 2005 30;18(2):141-50. Epub 2004 Dec 30.

Department of Pharmacology, University of Florence, Viale Pieraccini, 6, 50139 Firenze, Italy.

We investigate the role of resting tension on thrombin (THR) induced relaxation of guinea-pig tracheas precontracted with acetylcholine (ACh). Isometric contractions of isolated guinea-pig tracheas were recorded at 4 and 6 g resting tension; and ACh dose-response curves were performed. THR relaxed ACh-precontracted tracheas and this effect was mimicked by the type 2 protease activating receptor agonist peptide (PAR-2 AP) and trypsin. The relaxant effect of 3 U ml(-1) THR and 100 nmol ml(-1) PAR-2 AP was prevented at 4 g by preincubation with the nitric oxide synthase (NOS) inhibitor l-NAME and at 6g resting tension by ibuprofen and diclofenac. However, adenosine trisphospahate (ATP) relaxation was totally prevented by cyclooxygenase (COX) inhibitors but not by NOS inhibitors at both resting tensions. Resting tension influenced the effect of PGE2 on contractile tone of isolated guinea-pig tracheas, the maximal relaxation being -11.1+/-2.97 and -2.0+/-0.4 6 mg mg(-1) tissue wet weight at 6 and 4 g, respectively. Moreover, 30 nmol ml(-1) PGE2 can relax ACh-precontracted tracheas, being the effect up to 91 and 30% at 6 and 4 g, respectively. These data demonstrate that trachea responsiveness is highly dependent on the smooth muscle length, revealing new aspects of stretch-activated receptors that can influence trachea responsiveness in vivo.
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http://dx.doi.org/10.1016/j.pupt.2004.11.006DOI Listing
May 2005

Pirenoxine prevents oxidative effects of argon fluoride excimer laser irradiation in rabbit corneas: biochemical, histological and cytofluorimetric evaluations.

J Photochem Photobiol B 2005 Jan;78(1):35-42

Department of Preclinical and Clinical Pharmacology, University of Florence, V.le Pierraccini, 6, Florence, Italy.

The production of reactive oxygen species (ROS) associated with excimer laser irradiation is recognized as a possible cause of corneal haze following photorefractive keratectomy (PRK). Our work was aimed at investigating in vitro the oxidative effects induced by subablative laser fluences and at demonstrating the protective effectiveness of pirenoxine. Comparative trials of subablative fluence on rabbit eyes with or without 10(-5) M pirenoxine were carried out. Superoxide anion (O(2)(-)), conjugated diene (CD), and thiobarbituric acid reagent substance (TBARS) formation were analyzed. Cellular death was evaluated by flow cytometry. Histological examinations were also performed. No appraisable differences in O(2)(-),CD,andTBARS formation were detected soon after irradiation, whereas they all increased following incubation. Pirenoxine inhibited such increases. Cytofluorimetric and histological observations gave coherent results. The experimental data indicate that oxidative and toxic effects are ascribable to ROS avalanches triggered by laser irradiation-induced photodissociation and are inhibited by pirenoxine.
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http://dx.doi.org/10.1016/j.jphotobiol.2004.09.005DOI Listing
January 2005

Antioxidant protection in cultured corneal cells and whole corneas submitted to UV-B exposure.

J Photochem Photobiol B 2003 Oct;71(1-3):59-68

Department of Preclinical and Clinical Pharmacology, University of Florence, V.le Pieraccini 6, Florence 50139, Italy.

Several corneal pathologies are characterized by the presence of reactive oxygen species (ROS); therefore, we evaluated the protection afforded by pirenoxine and melatonin to corneal cell culture and whole rabbit cornea from ultraviolet exposure and other oxidant systems. Rabbit cornea cell (SIRC) plates and whole corneas were exposed to UV-B (80 or 800 mJ/cm2) or incubated with fMLP-stimulated autologous macrophages, in the presence or absence of pirenoxine or melatonin (10(-5) M). The protective activity of compounds was assessed by measuring superoxide anion formation, inhibition of oxidation and mitochondrial viability. Moreover the ex vivo protective effect of pirenoxine and melatonin was verified in the whole cornea submitted to UV-B exposure in vitro. Our experimental data demonstrate that pirenoxine and melatonin were able to inhibit the superoxide formation and oxidative effect in cell culture and whole rabbit corneas submitted to UV-B exposure or to incubation with fMLP-stimulated autologous macrophages. Mitochondrial viability was restored in epithelial cells of rabbit cornea but not in SIRCs. Moreover, both compounds are also able to increase ex vivo epithelial corneal cell defences against the in vitro UV-B induced lipid peroxidation.
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http://dx.doi.org/10.1016/j.jphotobiol.2003.07.004DOI Listing
October 2003

The ACh-induced contraction in rat aortas is mediated by the Cys Lt1 receptor via intracellular calcium mobilization in smooth muscle cells.

Br J Pharmacol 2003 Feb;138(4):707-15

Department of Pharmacology, University of Florence, Viale Pieraccini, 6 50139 Florence, Italy.

1. Our previously published data indicate that an endogenously produced 5-lipoxygenase metabolite can strongly contract isolated endothelium-preserved rat aortic strips when cyclo-oxygenase isoenzymes are inhibited. Therefore, we decided to investigate if cysteinyl-containing leukotrienes (Cys Lts) are involved in this endothelium-dependent contraction. 2. The isometric contraction of endothelium-preserved rat aortic strips was recorded in preparations preincubated with 5 microM indomethacin and precontracted with phenylephrine, adjusting resting tension at 0.7 g. Acetylcholine (ACh) contracted control strips. Montelukast and MK-571, selective type 1 Cys Lts receptor (Cys Lt(1)) antagonists and the Cys Lt(1)/Cys Lt(2) (type 2 Cys Lts receptor) antagonist BAYu9773 dose-dependently prevented ACh-induced contraction, their IC(50)s being 2.2, 3.1 and 7.9 nM respectively. The leukotriene B4 receptor antagonist U75302 was far less potent (IC(50) 1.5 microM). 3. In rat aorta smooth muscle cells (RASMs), Western blot analysis showed the presence of Cys Lt(1) and Cys Lt(2) receptors, the Cys Lt(1) receptor being predominantly expressed. 4. In fura-2 loaded RASMs, LTD4 (0.01-100 nM) and LTC4 (200-800 nM) dose-dependently increased intracellular calcium concentration ([Ca(2+)](i)). Montelukast (1-100 nM) reduced LTD4-induced [Ca(2+)](i) increase, its IC(50) being approximately 10 nM. BAY u9773 exhibited significantly low effectiveness. 5. LTD4 (10 nM) induced a redistribution of smooth muscle actin fibres throughout the cytoplasm as visualized by confocal microscopy. 6. In conclusion, Cys Lt(1) activation by endogenously produced Cys Lts, can contract rat aortas, while Cys Lt(2) only marginally influences aortic tone. Intracellularly, this effect is mediated by an increase in [Ca(2+)](i). Therefore, Cys Lts, by inducing vascular contraction, can contribute to systemic hypertension.
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http://dx.doi.org/10.1038/sj.bjp.0705087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573698PMC
February 2003