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71.
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72.
G. Decorti Luigi Candussio Fiora Bartoli Klugmann Antonella Strohmayer Maria Pia Mucci Alessandro Mosco Luciano Baldini 《Cancer chemotherapy and pharmacology》1997,40(4):363-366
It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells.
As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other
antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this
experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic
drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable
histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release
comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated
with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol
did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent
Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited
by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal
cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the
clinically employed formulation.
Received: 18 August 1996 / Accepted: 22 December 1996 相似文献
73.
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75.
Ghezzi F Cromi A Ciravolo G Volpi E Uccella S Rampinelli F Bergamini V 《Gynecologic oncology》2007,106(3):502-506
OBJECTIVE: To compare the surgicopathologic outcome of total laparoscopic radical hysterectomy (LRH) with that of abdominal radical hysterectomy (ARH) for the treatment of early-stage cervical cancer. METHODS: Radical hysterectomy specimens of sequential patients undergoing LRH (N=50) were compared with those of historical controls selected from consecutive women who have had conventional ARH (N=48), and who met the same criteria for eligibility as the cases. To evaluate the extent of parametrial resection, parametrial tissues were systematically measured at their widest dimensions before tissue processing. RESULTS: No difference was found in demographics, histologic type, tumor stage and grade between the two groups. The parametrial width was similar between LRH and ARH in both type II (right parametrium: 2.4 cm (1-3) vs. 2.3 (1.8-4.0), p=0.28; left parametrium: 2.3 cm (1.8-4) vs. 2.2 (1.2-3.0), p=0.54) and type III radical hysterectomy (right parametrium: 3.8 cm (2.3-6.5) vs. 3.4 (1.7-7.0), p=0.59; left parametrium: 3.6 cm (2-6) vs. 3.5 (1.5-6.5), p=0.82). There were no significant differences between the two groups with regard to lymph nodes yield and likelihood of identifying positive margins or metastatic disease. CONCLUSION: Our results suggest that laparoscopically managed patients with cervical cancer undergo a similar extent of surgery as those treated with the traditional ARH, as judged by objective pathologic criteria. 相似文献
76.
Scioscia M Vimercati A Maiorano A Depalo R Selvaggi L 《European journal of obstetrics, gynecology, and reproductive biology》2007,130(1):60-65
BACKGROUND: Perinatal mortality rate is used as an indicator of reproductive health worldwide. In western countries, national mortality registers are usually accurate and reliable. METHODS AND AIMS: We reviewed the data recorded in the past 50 years in Italy on perinatal and infant mortality. Each single class of mortality rate (according to WHO definitions) was assessed on temporal trends allowing a critical speculative analysis, mainly focusing on the last 20 years, in an attempt to evaluate the impact of prenatal diagnosis. RESULTS: Infant mortality rate (IMR) constantly decreased in the study period whereas early neonatal mortality rate progressively diminished in a 5-year comparison till the early 1990s. Perinatal mortality showed a linear negative trend until the 1980s, after which the decrease steadied at about 23% in the following 5-year period. Infant mortality attributable to congenital anomalies throughout a 20-year span (1980-2000) was steady at about 23% although a progressive reduction in general infant mortality was reported. CONCLUSIONS: A higher reduction in neonatal and perinatal mortality rate was found before the wide availability of the ultrasonographic prenatal diagnosis and the introduction of the law on voluntary abortion in Italy. Given these data, it seems that advances in neonatal care have improved the infant survival rates more than prenatal diagnosis, whereas obstetric care is linked to a reduction of the early perinatal mortality rate. 相似文献
77.
Pacchiarotti A Mohamed MA Micara G Linari A Tranquilli D Espinola SB Aragona C 《Journal of assisted reproduction and genetics》2007,24(10):459-462
Purpose To evaluate the effect of the hyperhomocysteinemia on pregnancy rate, implantation rate and abortion rate after IVF.
Method Data from a total of 48 infertile couples with hyperhomocysteinemia were prospectively collected for this study. All patients
underwent a standard down regulation protocol for ovarian stimulation. Oocytes recovery was performed at 36 h after hCG administration.
Embryo transfer took place at 48 h after insemination. The patients were matched in two groups that received or did not receive
therapy (group A and B respectively) to normalize homocysteine plasma level.
Results Pregnancy rate, implantation rate and abortion rate varied significantly (p ≤ 0.05) between the two groups. The number and quality of embryos transferred did not differ between the groups.
Conclusion The results suggest that hyperhomocysteinemia could affect IVF outcome 相似文献
78.
Maria Giovanna Cilberti Antonella Santillo Anna N. Polito Giovanni Messina Antonella della Malva Mariangela Caroprese Agostino Sevi Marzia Albenzio 《Nutrients》2022,14(11)
The objective of the present study was the evaluation of cytokine patterns in terms of TNF-α, IL-10, IL-6, and IL-1β secretion in peripheral blood mononuclear cell (PBMC) supernatants isolated from blood of children affected by generalized epilepsy and treated in vitro with myofibrillar, sarcoplasmic, and total protein fractions of meat and fish sources. Children with generalized epilepsy (EC group, n = 16) and children without any clinical signs of disease, representing a control group (CC group n = 16), were recruited at the Complex Structure of Neuropsychiatry Childhood-Adolescence of Policlinico Riuniti (Foggia, Italy). Myofibrillar (MYO), sarcoplasmic (SA), and total (TOT) protein fractions were obtained from longissimus thoracis muscle of beef (BF) and lamb (LA); from pectoralis muscle of chicken (CH); and from dorsal white muscle of sole (Solea solea, SO), European hake (Merluccius merluccius, EH), and sea bass fish (Dicentrarchus labrax, SB), respectively. PBMCs were isolated from peripheral blood of EC and CC groups, and an in vitro stimulation in the presence of 100 μg/mL for each protein fraction from different meat sources was performed. Data were classified according to three different levels of cytokines produced from the EC group relative to the CC group. TNF-α, IL-10, and IL-6 levels were not affected by different meat fractions and meat sources; on the contrary, IL-1β levels were found to be significantly affected by the tested proteins fractions, as well as different meat sources, in high-level cytokine group. On average, the protein fractions obtained from LB, BF, and CH meat sources showed a higher level of IL-1β than the protein fractions obtained from EH and SB fish samples. When all cytokine classes were analyzed, on average, a significant effect was observed for IL-10, IL-1β, and TNF-α. Data obtained in the present study evidence that the nutritional strategy based on protein from fish and meat sources may modulate the immunological cytokine pattern of infants with generalized epilepsy. 相似文献
79.
Cecilia Fazio Laura Daprai Arianna Neri Marcello Tirani Paola Vacca Milena Arghittu Luigina Ambrosio Danilo Cereda Maria Gramegna Annapina Palmieri Anna Carannante Maria Rosa Bertoli Lucia Crottogini Giorgio Gennati Eugenia Quinz Livia Trezzi Andrea Ciammaruconi Silvia Fillo Antonella Fortunato Giovanni Rezza Florigio Lista Paola Stefanelli 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(24)
In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain. 相似文献
80.
Xiang Li Chun-Hao Huang Francisco J. Snchez-Rivera Margaret C. Kennedy Darjus F. Tschaharganeh John P. Morris IV Antonella Montinaro Kevin P. O'Rourke Ana Banito John E. Wilkinson Chi-Chao Chen Yu-Jui Ho Lukas E. Dow Sha Tian Wei Luan Elisa de Stanchina Tinghu Zhang Nathanael S. Gray Henning Walczak Scott W. Lowe 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(17)