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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
35.
Otavio Rizzi Coelho-Filho Ravi Shah Carlos Fernando Ramos Lavagnoli Jose Carlos Barros Tomas G. Neilan Venkatesh L. Murthy Pedro Paulo Martins de Oliveira Jose Roberto Matos Souza Elaine Soraya Barbosa de Oliveira Severino Karlos Alexandre de Souza Vilarinho Lindemberg da Mota Silveira Filho Jose Garcia Marc J. Semigran Otavio Rizzi Coelho Michael Jerosch-Herold Orlando Petrucci 《The international journal of cardiovascular imaging》2018,34(1):15-24
After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47?±?7 years, 30?% female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5?±?15 years; LVEF 63.5?±?7?%). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3?±?11?%) with higher LV mass relative to age-matched healthy volunteers (114?±?27 vs. 85.8?±?18 g; p?<?0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39?±?0.06 vs. 0.28?±?0.03, p?<?0.0001; τic: 0.12?±?0.08 vs. 0.08?±?0.03, p?<?0.001). ECV was associated with LV mass (r?=?0.74, p?<?0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35?±?0.02 for 0R vs. 0.45?±?0, p?<?0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings. 相似文献
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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38.
Morgan K. Boes Rachel E. Bollaert Richard M. Kesler Yvonne C. Learmonth Mazharul Islam Matthew N. Petrucci Robert W. Motl Elizabeth T. Hsiao-Wecksler 《Archives of physical medicine and rehabilitation》2018,99(3):484-490
Objective
To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS).Design
Short-term intervention.Setting
University research laboratory.Participants
Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO.Interventions
Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb.Main Outcome Measures
Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions.Results
Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions.Conclusions
The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS. 相似文献39.
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
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cICAM-1
circulating intercellular adhesion molecule 1 相似文献
40.
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