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101.
102.
Prognostic value of CD40 in adult soft tissue sarcomas. 总被引:4,自引:0,他引:4
Alessandro Ottaiano Anna De Chiara Francesco Perrone Gerardo Botti Flavio Fazioli Vincenzo De Rosa Nicola Mozzillo Vincenzo Ravo Brunello Morrica Ciro Gallo Carmela Pisano Maria Napolitano Paolo Antonio Ascierto Rosario Vincenzo Iaffaioli Gaetano Apice 《Clinical cancer research》2004,10(8):2824-2831
PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas. 相似文献
103.
Marco Herling George Z Rassidakis L Jeffrey Medeiros Theodoros P Vassilakopoulos Kay-Oliver Kliche Gianpaolo Nadali Simonetta Viviani Valeria Bonfante Roberto Giardini Marco Chilosi Christos Kittas Alessandro M Gianni Gianni Bonadonna Giovanni Pizzolo Gerassimos A Pangalis Fernando Cabanillas Andreas H Sarris 《Clinical cancer research》2003,9(6):2114-2120
PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients. 相似文献
104.
p15INK4b, p14ARF, and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. 总被引:1,自引:0,他引:1
Federica Perrone Silvia Tabano Federica Colombo Gianpaolo Dagrada Sarah Birindelli Alessandro Gronchi Maurizio Colecchia Marco A Pierotti Silvana Pilotti 《Clinical cancer research》2003,9(11):4132-4138
PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) can arise sporadically or in association with neurofibromatosis type 1. Deletions at the 9p21 locus have been reported in these tumors. To additionally characterize the status of this chromosomal region, in this study we performed a comprehensive, mostly PCR-based molecular analysis of the three tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) located at the 9p21 locus in 26 cryopreserved MPNSTs. EXPERIMENTAL DESIGN: Fourteen neurofibromatosis type 1-related and 12 sporadic cases were investigated for homozygous deletion coupled with fluorescent in situ hybridization, promoter methylation, and mutational analysis, as well as m-RNA expression. RESULTS: The results showed that an inactivation of one or more genes occurred in 77% of MPNSTs and was mainly achieved through homozygous deletion (46%), which, in turn, encompassed all of the three tandemly linked genes in 83% of the deleted cases. Promoter methylation was at a less extent involved in gene silencing (18%), and no mutations were found. Loss of function at DNA level strongly correlated with loss of mRNA expression accounting for 80% of the cases. Because of the close relationship between p14(ARF) and TP53 and between p15(INK4b)/p16(INK4a) and Rb, these results support a model of a coinactivation of TP53 and Rb pathways in 75% of MPNSTs, with functional consequences on cell growth control and apoptosis. CONCLUSIONS: The inactivation of the 9p21 locus is a frequent and peculiar hallmark of MPNST genetic profile leading also to an impaired apoptosis that could be taken into account in treatment planning of these tumors. 相似文献
105.
Valeria Masciullo Tommaso Susini Alessandra Zamparelli Alessandro Bovicelli Corrado Minimo Daniela Massi Gianluigi Taddei Nicola Maggiano Pierandrea De Iaco Marcello Ceccaroni Luciano Bovicelli Gianni Amunni Salvatore Mancuso Giovanni Scambia Antonio Giordano 《Clinical cancer research》2003,9(14):5332-5338
PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P = 0.001). In addition to nuclear staining, cytoplasmic localization of p27 was noted in 193 (91%) of 217 specimens examined. When the clinical outcome of the patients was evaluated in relation to p27 status, we found no significant correlation between the presence of p27 staining and clinicopathological parameters or survival. CONCLUSIONS: These data indicate that p27 expression could progressively decrease from normal endometrium through hyperplastic endometrium to invasive endometrial carcinomas, suggesting that loss of this tumor suppressor may represent a novel and distinct molecular alteration involved in estrogen-related endometrial adenocarcinomas (type I). Despite the suggested role of the p27 protein in determining the prognosis of several human tumors, it was not found to be a predictor of clinical outcome in this large group of patients with endometrial cancer. 相似文献
106.
Gabriela F. Meresman Rosa I. Barañao A. Tenenbaum J. J. Singla N. R. Neuspiller Lia S. Rumi 《Archives of gynecology and obstetrics》1997,259(3):109-115
The aim of this study was to evaluate and compare the mitogenic effect of peritoneal fluid (PF) from women with mild and severe
endometriosis on the endometrial stromal cell proliferation. Increasing concentrations of PF from women with and without mild
or severe endometriosis were added to primary endometrial stromal cell cultures and3H-thymidine incorporation was used to assess DNA synthesis in these cultures. PF from women with mild endometriosis induced
a statistically significant dose-dependent increase in stromal cell thymidine uptake ranged from 5.8 to 14.5 fold, whereas
PF from women with severe endometriosis produced an average 51% inhibition of stromal cell proliferation of compared with
cells exposed to non-endometriosis PF or exposed to nutrient medium supplemented with 2.5% calf serum alone. PF samples from
patients with stage I endometriosis induced a statistically dose-dependent increase in stromal cell proliferation, whereas
PF from patients with stage IV endometriosis caused a significant inhibition. 相似文献
107.
Giancarlo Colombo Carla Lobina Paola Maccioni M Francesca Mascia Alessandro Orrù Gian Luigi Gessa Mauro A M Carai 《Alcohol》2005,35(1):35-41
In the current study, we investigated the effect of the concurrent presentation of saccharin on the maintenance of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Rats were initially given access to alcohol [10% (volume/volume) in water] and water under the home cage, two-bottle, free-choice regimen, with unlimited access for 24 h/day for eight consecutive weeks. Next, a third bottle, containing saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], was concomitantly offered for an additional 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, with the 0.1% saccharin solution being the highest accepted. Alcohol intake was a U function of saccharin concentration, being reduced by 65%-95% in the group of rats exposed to the 0.1% saccharin solution. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin markedly reduced alcohol intake in alcohol-experienced sP rats and (2) the reducing effect of saccharin solutions on the alcohol intake in sP rats was positively related to their degree of acceptability. We hypothesized that saccharin solutions may have functioned as a reinforcer, partially substituting for alcohol reinforcement and rendering alcohol drinking less urgent. 相似文献
108.
109.
110.
Gabriella Marucci Angeli Piero Livio Brasili Michela Buccioni Dario Giardinà Ugo Gulini Alessandro Piergentili Gianni Sagratini 《Medicinal chemistry research》2005,14(5):274-296
Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds
were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M1), guinea-pig heart (M2) and guinea-pig ileum (M3). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated.
Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors. 相似文献