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101.
Gianni Sava Sonia Zorzet Claudia Turrin Francesca Vita MariaRosa Soranzo Giuliano Zabucchi Moreno Cocchietto Alberta Bergamo Stefano DiGiovine Gabriella Pezzoni Luigi Sartor Spiridione Garbisa 《Clinical cancer research》2003,9(5):1898-1905
NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases. 相似文献
102.
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
103.
Use of complementary and alternative medicine in cancer patients: a European survey. 总被引:6,自引:0,他引:6
104.
Lorenzo Fornaro Gianna Musettini Paola Orlandi Irene Pecora Caterina Vivaldi Marta Banchi Francesca Salani Elisabetta Fini Valentina Massa Silvia Catanese Federico Cucchiara Monica Lencioni Gianluca Masi Enrico Vasile Guido Bocci 《American journal of cancer research》2022,12(7):3347
Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with paclitaxel in pretreated metastatic GC patients. Plasma samples were collected at different time points (on days 1 and 15 of the first 3 cycles, at best radiologic response and at disease progression). VEGF-A, VEGF-D and sVEGFR-2 were analysed by ELISA. Correlations of biomarker baseline levels or dynamic changes with outcome measures were assessed. Progression-free survival (PFS) was the primary endpoint of the study. Forty-one patients were enrolled. VEGF-A and VEGF-D, but not sVEGFR-2, values significantly increased during treatment compared to baseline (P < 0.001). A positive correlation between VEGF-A and sVEGFR-2 at cycle 2 was found (P=0.045). At univariate analysis, higher baseline levels of VEGF-A were associated with worse OS (P=0.015). Early increase of sVEGFR-2 levels after the first treatment cycle was the only factor associated with longer PFS (6.6 vs. 3.6 months, P=0.049) and OS (18.6 vs. 5.2 months, P=0.008). Significance of sVEGFR-2 early increase was retained at multivariate analysis for OS (HR 0.32; 95% CI 0.12-0.91; P=0.032). The reported results confirmed the prognostic role of baseline VEGF-A and, with the limitations of the limited sample size and the lack of a control arm, suggested that the early increase of sVEGFR-2 after 1 cycle of treatment could be a potential predictive biomarker of benefit from second-line ramucirumab plus paclitaxel in GC. 相似文献
105.
Identification
of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based
Dynamic Combinatorial Chemistry
Greta Bagnolini Beatrice Balboni Fabrizio Schipani Dario Gioia Marina Veronesi Francesca De Franco Cansu Kaya Ravindra P. Jumde Jose Antonio Ortega Stefania Girotto Anna K. H. Hirsch Marinella Roberti Andrea Cavalli 《ACS medicinal chemistry letters》2022,13(8):1262
RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further 19F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors. 相似文献
106.
L Filippi P Fiorini M Daniotti S Catarzi S Savelli C Fonda L Bartalena A Boldrini M Giampietri R Scaramuzzo P Papoff F Del Balzo A Spalice G la Marca S Malvagia ML Della Bona G Donzelli F Tinelli G Cioni T Pisano M Falchi R Guerrini 《BMC pediatrics》2012,12(1):144
ABSTRACT: BACKGROUND: Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2--3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. METHODS: Term newborns (gestational age >= 36 weeks and birth weight >= 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. DISCUSSION: This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25. 相似文献
107.
Floriana Mascilini Lorena Quagliozzi Francesca Moro Maria Cristina Moruzzi Valerio Gallotta Salvatore Gueli Alletti Giovanni Scambia Antonia Carla Testa Anna Fagotti 《Journal of minimally invasive gynecology》2018,25(5):848-854
Study Objective
To describe the potential role of intraoperative ultrasound (IOUS) in the detection and localization of recurrent disease in gynecologic cancer patients during minimally invasive surgery (MIS).Design
A prospective cohort study (Canadian Task Force classification II-1).Setting
A university hospital.Patients
Fifty-one gynecologic cancer patients with isolated recurrent disease.Interventions
IOUS during secondary cytoreductive surgery (SCS) by MIS.Measurements and Main Results
From November 2015 to February 2017 51 gynecologic cancer patients with isolated recurrent disease and candidates for SCS were treated by MIS. Recurrent tumor was preoperatively assessed at clinical examination, transvaginal and transabdominal sonography, and radiologic evaluation in all women. Twelve of 51 women (23.5%) needed IOUS. Type of disease was ovarian in 5 women (42%), endometrial in 4 (33%), cervical in 1 (8%), vaginal cancer in 1 (8%), and uterine sarcoma in 1 (8%). Recurrence was localized deep in the pelvis in 7 cases (58%), lymph nodes in 3 (25%), and extraperitoneal in 2 cases (17%). Recurrence was dimmed in the surgical field, due to either presence of adherences, deep anatomic position, small size, and/or lack of tactile feeling. IOUS was able to identify the lesions in all women, allowing MIS (83% laparoscopy and 17% robotic) complete cytoreduction, with no conversion to laparotomy. Median operative time was 150 minutes (range, 77–280). No intraoperative/postoperative complications occurred. Histologic examination confirmed the presence of recurrence in 11 of 12 cases (92%), whereas the remaining case showed inflammatory tissue. With a median follow-up time of 15 months (range, 6–19), all patients except 2 were still alive.Conclusions
About 1 of 4 patients (25%) with single gynecologic cancer recurrence needs IOUS to benefit from MIS for complete secondary cytoreduction. 相似文献108.
Canosa Stefano Parmegiani Lodovico Charrier Lorena Gennarelli Gianluca Garello Cristina Granella Francesca Evangelista Francesca Monelli Giuseppe Guidetti Daniela Revelli Alberto Filicori Marco Bongioanni Francesca 《Journal of assisted reproduction and genetics》2022,39(1):67-73
Journal of Assisted Reproduction and Genetics - To study whether a new combination of different warming kits is clinically effective for vitrified human blastocysts. This is a longitudinal cohort... 相似文献
109.
110.
Alessandra Vergori Antonio Boschini Stefania Notari Patrizia Lorenzini Concetta Castilletti Francesca Colavita Giulia Matusali Eleonora Tartaglia Roberta Gagliardini Andrea Boschi Eleonora Cimini Markus Maeurer Pierluca Piselli Leila Angeli Andrea Antinori Chiara Agrati Enrico Girardi 《Viruses》2022,14(7)
The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination. 相似文献