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S Caporali

Publications and source records attributed to S Caporali.

8 recordsLinked to original sources
PubMed2001

Estrogens do not modify MAP kinase-dependent nuclear signaling during stimulation of early G(1) progression in human breast cancer cells.

Estrogens are direct mitogens for hormone-responsive human breast cancercells, where they promote cell cycle progression and induce transcriptional activation of "immediate early" and cyclin genes. Nongenomic signaling by estrogens, including rapid changes of mitogen-activated protein(MAP) kinase and other signal-transduction-cascades activity, has been proposed to be essential for the mitogenic actions of these hormones and their nuclear receptors. Because regulation of gene transcription is considered a key step in cell cycle control by mitogenic protein kinase cascades, here we investigated the possibility that estrogen might induce the activation of extracellular signal-regulated kinase (Erk) 1/2-, c-Jun NH(2)-terminal kinase-, p38- or protein kinase A-responsive transcription factors in the cell nucleus during stimulation of early G(1) progression, a timing coincident with the maximum effects of these hormones on such enzyme activity. No significant changes in protein kinase-mediated transcription factor activity could be detected here after estrogen stimulation of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb phosphorylation, all key events in cell cycle stimulation by mitogens, even in the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase (Mek)1/2 inhibitor. Thus, estrogens do not appear to convey significant protein kinase-dependent signaling to the cell nucleus during the early phases of human breast cancer cell stimulation. Furthermore, hormonal regulation of G(1) gene transcription can occur even without additional activation of the Mek-Erk1/2 pathway by estrogen receptors.

Breast Neoplasms↗
PubMed2001

beta-estradiol stimulation of DNA synthesis requires different PKC isoforms in HepG2 and MCF7 cells.

The role exerted by protein kinase C (PKC) on estrogen-induced DNA synthesis has been investigated in hepatic and mammary gland cells, HepG2 and MCF7. 17-beta-estradiol stimulated DNA synthesis in HepG2 and MCF7 cells, maximal effect occurring at 10 nM. DNA synthesis stimulation was prevented by anti-estrogen ICI 182,780 and by inhibitor of PKC, Ro 31-8220. The rapid estradiol effects in MCF7 cells were determined by following the inositol trisphosphate (IP(3)) production and PKC-alpha membrane translocation. After estradiol treatment the increase of IP(3) production, prevented by anti-estrogen or by phospholipase C (PLC) inhibitor (neomycin), was present in MCF7 cells. In MDA cells, devoid of estrogen receptor, no effect was observed. The PKC-alpha presence on the membranes appeared unchanged in MCF7 cells. The PLC inhibitors, neomycin and U73,122, and PKC-alpha down regulator, phorbol 12-myristate 13-acetate (PMA), were able to prevent estradiol-induced DNA synthesis in hepatoma cells, but ineffective in mammary cells; wortmannin, an inhibitor of phosphoinositide 3-kinases (PI3-K), blocked DNA synthesis in both cell lines. These data show that beta-estradiol, via an estrogen receptor-mediated mechanism, activates more signal transduction pathways, and consequently different PKC isoforms in two responsive cell lines. In both cell lines PI3-K/PKC pathway is functional to the estrogen regulation of DNA synthesis, whereas in HepG2 cells the parallel involvement of the PLC/PKC-alpha pathway is present. The reported results indicate that the DNA synthesis stimulation by beta-estradiol requires the estrogen receptor and utilises one or more activated pathways in dependence on the cell equipment.

Androstadienes↗
PubMed2001

Activation of IP(3)-protein kinase C-alpha signal transduction pathway precedes the changes of plasma cholesterol, hepatic lipid metabolism and induction of low-density lipoprotein receptor expression in 17-beta-oestradiol-treated rats.

The intracellular concentration of cholesterol is regulated by the balance between endogenous synthesis and exogenous uptake. Oestrogens have been reported to be involved in the physiological regulation of cellular cholesterol content. Relevant reports have focused on long-term responses and there is a lack of information about the relationship between the timing of the oestrogen effect and the regulation of cholesterol homeostasis. The aim of this work has been to set up a systematic picture of the short-term effects induced by oestrogen on hepatic lipid metabolism in vivo and the involvement of some relevant signal transduction pathways. At intervals after oestrogen administration (30 min to 6 h), oestrogen receptor expression and changes in liver cAMP, IP(3) and protein kinase C-alpha (PKC-alpha) were followed. Changes in the expression of the low density lipoprotein receptor at mRNA and protein levels, and of hydroxy-methyl-glutaryl-CoA reductase activity have been verified. At the same time, the content of hepatic cholesterol, ubiquinone and dolichol and of plasma cholesterol have been determined. Changes of rab 5 and rab 8, small GTP-binding prenylated proteins involved in the transfer of neosynthesised proteins through the cell, have been also checked. In vivo treatment with oestradiol produced no change in cyclic AMP but a rapid increase in IP(3), increased PKC-alpha localisation on the membranes and enhanced expression of the low density lipoprotein receptor in the liver occurred. PKC inhibition completely prevented any increase in low density lipoprotein receptor mRNA in isolated and perfused rat liver. Early changes of ubiquinone and dolichol content and a later reduction in hepatic hydroxy-methyl-glutaryl-CoA reductase activity and plasma cholesterol content were also detectable. A functional role of the IP(3) -protein kinase C-alpha pathway in the induction of the low density lipoprotein receptor is suggested. Experimental Physiology (2001) 86.1, 39-45.

Animals↗
PubMed2000

Predictive factors for early success of endovascular abdominal aortic aneurysm repair.

To identify predictive factors for postoperative success and potential predictors for satisfactory outcome of endovascular grafting for abdominal aortic aneurysm (AAA), we collected data from our prospective database, which includes a series of consecutive patients undergoing endovascular repair at the Vascular Surgery Unit, Policlinico Monteluce, Perugia, Italy. From April 1997 to July 1998, 202 patients were referred to our Unit for elective AAA repair; 94 patients (47%) were selected for endografting. Placement of the graft using endovascular technique without conversion to open laparotomy, in addition to no mortality, major morbidity, or endoleak at 30-day follow-up, was defined as postoperative success. The influence of anatomical features on postoperative results was analyzed by univariate and multivariate analysis. Our experience shows that endoluminal repair of AAA is safe and effective in the short term and male patients with small aneurysms are optimal candidates for successful repair.

Aged↗
PubMed1999

Epidural anesthesia reduces length of hospitalization after endoluminal abdominal aortic aneurysm repair.

PURPOSE: The low invasiveness of endoluminal abdominal aneurysm repair (EAAR) appears optimal for the use of epidural anesthesia (EA). However, reported series on EAAR show that general anesthesia (GA) is generally preferred. To evaluate the feasibility and problems encountered with EA for EAAR, patients undergoing EAAR with EA and patients undergoing EAAR with GA were examined. METHODS: From April 1997 through October 1998, EAAR was performed on 119 patients at the Unit of Vascular Surgery at Policlinico Monteluce in Perugia, Italy. Four patients (3%) required conversion to open repair and were excluded from the analysis because they were not suitable candidates for evaluating the feasibility of EA. The study cohort thus comprised 115 patients undergoing abdominal aortic aneurysm (AAA) repair with the AneuRx Medtronic stent graft. The incidence of risk factors and anatomical features of the aneurysm were compared in patients selected for EA or GA on the basis of intention-to-treat analysis. Intraoperative and perioperative data were compared and analyzed on the basis of intention-to-treat and on-treatment analysis. RESULTS: Sixty-one patients (54%) underwent the surgical procedure with EA (group A), and 54 (46%) underwent the surgical procedure with GA (group B). Conversion from EA to GA was required in four patients (3 of 61 patients, 5%). There were no statistically significant differences between the two study groups in demographics, clinical characteristics, and American Society of Anesthesiology classification (ASA). There was no perioperative mortality. Major morbidity occurred in 3% of patients (group B). According to intention-to-treat analysis, no significant differences were observed between the two groups in mean operating time, fluoro time, blood loss, amount of contrast media used, mean units of transfused blood, need of intensive care unit, mean postoperative hospital stay, and postoperative endoleak. Conversely, significant differences were found by means of on-treatment analysis in the need of intensive care unit (0 vs 5 patients; P =.02), and length of hospitalization (2.5 vs 3.2 days; P =.04). Multivariate logistic regression analysis showed that GA and ASA 4 were positive independent predictors of prolonged (more than 2 days) postoperative hospitalization (hazard ratio, 2.5; 95% CI, 1.1 to 5.8; P =.03, and hazard ratio, 5.1; 95% CI, 1.5 to 17.9; P =.007, respectively). CONCLUSION: EA for EAAR is feasible in a high percentage of patients in whom it is attempted, and it ensures a technical outcome comparable with that of patients undergoing EAAR with GA. Successful completion of EAAR with EA is associated with a short period of hospitalization.

Aged↗
PubMed1999

Endoluminal repair of infrarenal abdominal aortic aneurysms using a modular stent-graft: one-year clinical results from a European multicentre trial.

This is a report of a prospective study to evaluate the safety and efficacy of the Medtronic AneuRx stent-graft. Patients with an infrarenal aneurysm with a proximal neck length of greater than 10 mm and a neck diameter not greater than 26 mm and iliac artery diameters of at least 6 mm were accepted for endovascular repair using the Medtronic AneuRx modular stent-graft. A total of 104 patients were included in the study. Transfemoral placement of the bifurcated stent-graft was successful in 102 of 104 patients. Two conversions were performed. The mean operating time was 148 min (range 75-480) and the mean blood loss was 605 ml (range 100-2900). The mean follow-up was 15 months (range 12-21). Complications were rare and no kinking or migration occurred. At follow-up, four endoleaks persisted after 12 months. The Medtronic AneuRx stent-graft is a safe and efficacious alternative to open abdominal aortic aneurysm repair with excellent early results.

Aged↗
PubMed1997

Eversion versus conventional carotid endarterectomy: a prospective study.

OBJECTIVES: To analyse comparatively eversion and conventional CEA for later association with restenosis, perioperative stroke/death and ipsilateral cerebrovascular events (early, late, disabling and non-disabling). DESIGN: Prospective non-randomised clinical study. MATERIALS AND METHODS: A total of 469 patients underwent 514 procedures; 274 (53%) eversion CEA and 240 (47%) conventional CEA. Perioperative monitoring was carried out by clinical evaluation under local anaesthesia or by transcranial Doppler under general anaesthesia. Follow-up was carried out by clinical evaluation and Duplex scanning. RESULTS: Clamping time was significantly shorter in the eversion group (25.5 +/- 7.4 vs. 28.3 +/- 10.1 min; p = 0.0001; CI delta 4.40/1.12). The perioperative disabling stroke/death rate was 0.7% for eversion vs. 1.2% for conventional CEA, p = 0.6; odds ratio (OR), 0.58. There were two early carotid occlusions (within 30 days) in both groups. According to life-table analysis, after 3 years the probability of > 50% carotid restenosis was significantly lower in the eversion group (2.2% vs. 6.9%, p = 0.03; relative risk reduction 67%). There were no significant differences between the two groups relative to new cerebrovascular events (92% in both groups, p = 0.6). Using multivariate analysis (Cox regression), eversion CEA, and to a lesser extent standard CEA with patch, appeared to protect the vessel from restenosis. CONCLUSIONS: The eversion technique was associated with reduced clamping time and probability of restenosis. However, because of the nature of a non-randomised study, the present analysis should be confirmed by a multicentre randomised trial.

Aged↗