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81.
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
82.
Arsenio Spinillo Consultant Ezio Capuzzo Clinical Assistant Gaia Piazzi Registrar Federica Baltaro Registrar Mauro Stronati Consultant Alessandra Ometto Consultant 《BJOG : an international journal of obstetrics and gynaecology》1997,104(6):668-673
Objective To estimate the risk of specific adverse neonatal events resulting from the combined effects of prematurity and low birthweight in very preterm infants (delivered at 24–31 weeks of gestation)
Design A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation.
Setting Pavia, Italy.
Population Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation.
Methods To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation.
Results After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS 0 ( 50th centile of birthweight), infants with birthweight SDS < −1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42–9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04–75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41–7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age.
Conclusions A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does. 相似文献
Design A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation.
Setting Pavia, Italy.
Population Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation.
Methods To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation.
Results After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS 0 ( 50th centile of birthweight), infants with birthweight SDS < −1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42–9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04–75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41–7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age.
Conclusions A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does. 相似文献
83.
84.
Mario Sanna Abdelkader Taibah Alessandra Russo Maurizio Falcioni Manoj Agarwal 《Otology & neurotology》2004,25(3):379-386
OBJECTIVE: Retrospective study and review of the complications other than those related to the facial nerve and hearing, encountered in acoustic neuroma surgery. Also, an evaluation of hospital stay and its relation with various factors. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotologic and skull base referral center. PATIENTS: A series of 707 patients who underwent surgical removal of acoustic neuroma from April 1987 to December 2001. INTERVENTIONS: The surgical approaches used were the enlarged translabyrinthine approach, the enlarged middle fossa approach, and the retrosigmoid approach. In a small number of cases, the operations were performed through other approaches. MAIN OUTCOME MEASURES: The duration of hospital stay and appearance of complications in the perioperative period along with their management. Results related to the facial nerve and hearing were not considered in this study. RESULTS: The most frequent complication was abdominal subcutaneous hematoma (site of fat harvest), which occurred in 23 patients (3.2%). Cerebrospinal fluid leak was present in 20 patients (2.8%), 15 of whom needed revision surgery. Other complications included VIth cranial nerve dysfunction in 12 cases (1.68%), subdural hematoma in 3 cases (0.4%), cerebellopontine angle hematoma in 4 cases (0.6%), cerebellar edema in 2 cases (0.28%), brainstem hematoma in 1 case (0.14%), transitory aphasia in 1 case (0.14%), and lower cranial nerve dysfunction in 1 case (0.14%). Mortality occurred in only one case (0.14%). Medical complications seldom occurred. The postoperative hospital stay ranged from 2 to 36 days, with an average of 6.4 days. The overall hospital stay diminished over time from 10.2 days in 1987 to 1990, to 4.9 days in 2001. There was a significant relation between hospital stay and tumor size, approach used, and presence/absence of complications. CONCLUSIONS: Perioperative complications in acoustic neuroma surgery do exist, but this study demonstrated how low the incidence is. The authors believe that the low percentage of complications is mainly attributable to the majority of operations being carried out in specialized clinics, where they are considered routine operations. They believe that following individualized approaches, depending on tumor size and on the preoperative function of the cranial nerves, is the proper way to reach a significant reduction in complications while maintaining a high percentage of total tumor removal. The results of this study, considered as a basis of comparison with other studies, will certainly be useful in preoperative patient counseling. 相似文献
85.
86.
Matrix‐assisted laser desorption/ionisation (MALDI) TOF analysis identifies serum angiotensin II concentrations as a strong predictor of all‐cause and breast cancer (BCa)‐specific mortality following breast surgery 下载免费PDF全文
Francesco Boccardo Alessandra Rubagotti Pier Vitale Nuzzo Francesca Argellati Grazia Savarino Paolo Romano Gianluca Damonte Mattia Rocco Aldo Profumo 《International journal of cancer. Journal international du cancer》2015,137(10):2394-2402
MALDI‐TOF MS was used to recognise serum peptidome profiles predictive of mortality in women affected by early BCa. Mortality was analysed based on signal profiling, and appropriate statistics were used. The results indicate that four signals were increased in deceased patients compared with living patients. Three of the four signals were individually associated with all‐cause mortality, but only one having mass/charge ratio (m/z) 1,046.49 was associated with BCa‐specific mortality and was the only peak to maintain an independent prognostic role after multivariate analysis. Two groups exhibiting different mortality probabilities were identified after clustering patients based on the expression of the four peptides, but m/z 1,046.49 was exclusively expressed in the cluster exhibiting the worst mortality outcome, thus confirming the crucial value of this peptide. The specific role of this peak was confirmed by competing risk analysis. MS findings were validated by ELISA analysis after demonstrating that m/z 1,046.49 structurally corresponded to Angiotensin II (ATII). In fact, mortality results obtained after arbitrarily dividing patients according to an ATII serum value of 255 pg/ml (which corresponds to the 66th percentile value) were approximately comparable to those previously demonstrated when the same patients were analysed according to the expression of signal m/z 1,046.49. Similarly, ATII levels were specifically correlated with BCa‐related deaths after competing risk analysis. In conclusion, ATII levels were increased in women who exhibited worse mortality outcomes, reinforcing the evidence that this peptide potentially significantly affects the natural history of early BCa. Our findings also confirm that MALDI‐TOF MS is an efficient screening tool to identify novel tumour markers and that MS findings can be rapidly validated through less complex techniques, such as ELISA. 相似文献
87.
Vanesa Gregorc Rabab M Gaafar Adolfo Favaretto Francesco Grossi Jacek Jassem Andreas Polychronis Paolo Bidoli Marcello Tiseo Riyaz Shah Paul Taylor Silvia Novello Alberto Muzio Alessandra Bearz Laurent Greillier Floriana Fontana Giulia Salini Antonio Lambiase Mary OBrien 《The lancet oncology》2018,19(6):799-811
88.
Sara Pilotto Antonio Rossi Tiziana Vavalà Alessandro Follador Marcello Tiseo Domenico Galetta Alessandro Morabito Massimo Di Maio Olga Martelli Orazio Caffo Pier Luigi Piovano Diego Cortinovis Nicoletta Zilembo Clelia Casartelli Giuseppe Luigi Banna Antonio Ardizzoia Maria Luisa Barzelloni Alessandra Bearz Silvia Novello 《Clinical lung cancer》2018,19(1):93-104
Background
Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a “real-life” Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study.Patients and Methods
Data of advanced NSCLC patients with uncommon EGFR mutations who received first-line first-generation EGFR-TKIs in 24 Italian Hospitals were collected. In this analysis we aimed to evaluate overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of EGFR-TKIs in NSCLC patients harboring uncommon EGFR mutations.Results
Thirty-five patients harboring uncommon EGFR mutations (any mutation other than deletion 19 or substitution of leucine by arginine at codon 858) were included of the original 312 EGFR-mutated cases. Most of them were female (n = 20, 57.1%), former smokers (n = 23, 65.7%), with adenocarcinoma (n = 31, 88.6%). The most frequent EGFR mutations were G719X (n = 6, 17.2%) and L861Q (n = 5, 14.2%). The population presented an ORR of 25.7%, a median PFS of 5.19 months, and a median OS of 14.49 months. When stratified according to type of EGFR mutation, median OS ranged from 3.65 months for unspecified mutations to 21.29 for double EGFR mutations. Median PFS ranged from 1.77 months for unspecified mutations to 20.83 months for concomitant EGFR-anaplastic lymphoma kinase alteration. ORR varied from 0% in exon 18, 20 and double gene alteration to 66.6% in exon 19.Conclusion
Our study supports the existence of a strong outcome heterogeneity within patients harboring uncommon EGFR mutations, which needs to be clarified to achieve a real personalized treatment strategy. 相似文献89.
A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells
Alessia Garufi Daniela Trisciuoglio Manuela Porru Carlo Leonetti Antonella Stoppacciaro Valerio D’Orazi Maria Laura Avantaggiati Alessandra Crispini Daniela Pucci Gabriella D’Orazi 《Journal of experimental & clinical cancer research : CR》2013,32(1):72
Background
Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.Methods
P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.Results
The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.Conclusions
Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth. 相似文献90.
Alessio Cortellini Juan Aguilar-Company Ramon Salazar Mark Bower Ailsa Sita-Lumsden Andrea Plaja Alvin J. X. Lee Alexia Bertuzzi Carlo Tondini Nikolaos Diamantis Clara Martinez-Vila Aleix Prat Eleanor Apthorp Alessandra Gennari David J. Pinato 《British journal of cancer》2022,127(10):1787
Background Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown.Methods We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid (), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19.Results As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients.Conclusion This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer.Subject terms: NCT04393974Oncology, Public health 相似文献