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SRC homology-2-containing protein tyrosine phosphatase-1 restrains cell proliferation in human medullary thyroid carcinoma 总被引:3,自引:0,他引:3
Zatelli MC Piccin D Tagliati F Bottoni A Luchin A degli Uberti EC 《Endocrinology》2005,146(6):2692-2698
Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells, where, in the inherited form, constitutive activation of the RET protooncogene is responsible for unrestrained cell proliferation. We previously demonstrated that somatostatin (SRIF) reduces cell growth in the human MTC cell line TT, which expresses all SRIF receptor (SSTR) subtypes and responds differently to selective SSTR agonists. The antiproliferative mechanism of SRIF and its analogs in MTC is still unclear. Src homology-2-containing protein tyrosine phosphatase-1 (SHP-1), a cytoplasmic protein tyrosine phosphatase (PTP), is activated by somatotropin release-inhibiting factor and reduces mutated RET autophosphorylation in a heterologous system. In this study, we explore the role of PTP activation, in particular of SHP-1, in TT cells, where RET is constitutively activated. In TT cells, SRIF stimulated the PTP activity of SHP-1, which was associated with proliferation inhibition and with reduction in the MAPK pathway activation. Blockade of PTP activity with sodium orthovanadate induced cell proliferation and MAPK phosphorylation and blunted the inhibitory effects of SRIF. Moreover, SHP-1 associates with SSTR2 depending on its activation. By using a MAPK kinase inhibitor, we demonstrated that TT cell growth depends on MAPK pathway activation. Furthermore, in TT cells overexpressing SHP-1, cell proliferation and MAPK signaling were strongly down-regulated, whereas in TT cells transfected with a dominant negative form of SHP-1, cell proliferation and MAPK signaling were markedly induced. Our data demonstrate that SRIF inhibitory effects on TT cell proliferation are mediated, at least in part, by SHP-1, which acts through a MAPK-dependent mechanism. 相似文献
34.
Ettore Beghi Elisa Gervasoni Elisabetta Pupillo Elisa Bianchi Angelo Montesano Irene Aprile Michela Agostini Marco Rovaris Davide Cattaneo 《Archives of physical medicine and rehabilitation》2018,99(4):641-651
Objective
To compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design.Design
Multicenter prospective cohort study.Setting
Institutions for physical therapy and rehabilitation.Participants
Patients (N=299) with PD (n=94), MS (n=111), and stroke (n=94) seen for rehabilitation.Interventions
Not applicable.Main Outcome Measures
Functional scales were applied to investigate balance, disability, daily performance, self-confidence with balance, and social integration. Patients were followed for 6 months. Telephone interviews were organized at 2, 4, and 6 months to record falls and fall-related injuries. Incidence ratios, Kaplan-Meier survival curves, and Cox proportional hazards models were used.Results
Of the 299 patients enrolled, 259 had complete follow-up. One hundred and twenty-two patients (47.1%) fell at least once; 82 (31.7%) were recurrent fallers and 44 (17.0%) suffered injuries; and 16%, 32%, and 40% fell at 2, 4, and 6 months. Risk of falls was associated with disease type (PD, MS, and stroke in decreasing order) and confidence with balance (Activities-specific Balance Confidence [ABC] scale). Recurrent fallers were 7%, 15%, and 24% at 2, 4, and 6 months. The risk of recurrent falls was associated with disease type, high educational level, and ABC score. Injured fallers were 3%, 8%, and 12% at 2, 4, and 6 months. The only predictor of falls with injuries was disease type (PD).Conclusions
PD, MS, and stroke carry a high risk of falls. Other predictors include perceived balance confidence and high educational level. 相似文献35.
Edmondo Falleti Carlo Fabris Mario Pirisi Giorgio Soardo Daniela Vitulli Pierluigi Toniutto Nadia Bortolotti Fabio Gonano Ettore Bartoli 《Journal of cancer research and clinical oncology》1996,122(6):366-369
Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R=–0.397,P<0.001), aspartate aminotransferase (R=0.421,P<0.001), bilirubin (R=0.231,P<0.05) and cICAM-1 (R=0.430,P<0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.Abbreviations
AFP
1-fetoprotein
-
cICAM-1
circulating intercellular adhesion molecule 1 相似文献
36.
Dr. Ettore Zuccato MD Marco Venturi MD Giuseppe Di Leo BSc Laura Colombo BSc Cristina Bertolo BSc Santo Bressani Doldi MD Emilio Mussini MD 《Digestive diseases and sciences》1993,38(3):514-519
Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer. 相似文献
37.
Ettore Porreca Concetta Di Febbo Assunta Pandolfi Andria D''Orazio Nicola Martelli Andrea Mezzetti Franco Cuccurullo Andreina Poggi 《Atherosclerosis》1993,100(2):141-148
We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4–6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase,
-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10−4 M, after 48–72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10−4 M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation. 相似文献
38.
Claudio Borghi Ettore Ambrosioni 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1996,10(5):519-525
Summary The purpose of the present article was to review the current evidence on the use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI). This article is based on published information as well as on our personal experience derived from an extensive analysis of the SMILE study. All the randomized trials have been included irrespective of the primary endpoint, and the results are presented in terms of either hemodynamic or clinical benefit. Short- and long-term treatment with ACE inhibitors in patients with acute MI results in a significant reduction in mortality, which is more evident in high risk patients (i.e., patients with left ventricular dysfunction, congestive heart failure on admission, or anterior myocardial infarction). Development and progression of congestive heart failure after myocardial infarction was significantly reduced by ACE inhibition, which also reduced the rate of reinfarction, the need for revascularization procedures, as well as the occurrence of ventricular arrhythmias, probably through a mechanism involving some drug-dependent effects. In conclusion, the available data strongly support a wide benefit associated with the use of ACE inhibitors in patients with high-risk acute MI. 相似文献
39.
40.
Riccardo D’Ambrosi Carlo Perfetti Guido Garavaglia Ettore Taverna 《International journal of shoulder surgery》2015,9(3):94-98
This case presents the challenges of the surgical management for a patient with a history of recurrent posterior shoulder instability and subsequently traumatic anterior dislocation. The patient was already on the waiting list for an arthroscopic posterior stabilization with anchors, when a car accident caused an additional anterior shoulder dislocation. This traumatic anterior dislocation created a bone loss with a glenoid fracture and aggravated the preexisting posterior instability. In order to address both problems, we decided to perform an arthroscopically assisted Latarjet procedure for anterior instability and to stabilize with a bone graft for posterior instability. To our best knowledge, this type of surgical procedure has so far never been reported in the literature. The purpose of this report is to present the surgical technique and to outline the decision making process. 相似文献