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Laura Pizzuti Maddalena Barba Diana Giannarelli Domenico Sergi Claudio Botti Paolo Marchetti Michele Anzà Marcello Maugeri‐Saccà Clara Natoli Simona Di Filippo Teresa Catenaro Federica Tomao Antonella Amodio Silvia Carpano Letizia Perracchio Marcella Mottolese Luigi Di Lauro Giuseppe Sanguineti Anna Di Benedetto Antonio Giordano Patrizia Vici 《Journal of cellular physiology》2016,231(11):2541-2547
To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 相似文献
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Genetic and Functional Analysis of Polymorphisms in the Human Dopamine Receptor and Transporter Genes in Small Cell Lung Cancer
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Improved Mitochondrial and Methylglyoxal‐Related Metabolisms Support Hyperproliferation Induced by 50 Hz Magnetic Field in Neuroblastoma Cells
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Renae K. Barr Giuseppe Verdile Linda K. Wijaya Michael Morici Kevin Taddei Veer B. Gupta Steve Pedrini Liang Jin Joseph A. Nicolazzo Erin Knock Paul E. Fraser Ralph N. Martins 《The Journal of biological chemistry》2016,291(2):547-559
Although the formation of β-amyloid (Aβ) deposits in the brain is a hallmark of Alzheimer disease (AD), the soluble oligomers rather than the mature amyloid fibrils most likely contribute to Aβ toxicity and neurodegeneration. Thus, the discovery of agents targeting soluble Aβ oligomers is highly desirable for early diagnosis prior to the manifestation of a clinical AD phenotype and also more effective therapies. We have previously reported that a novel 15-amino acid peptide (15-mer), isolated via phage display screening, targeted Aβ and attenuated its neurotoxicity (Taddei, K., Laws, S. M., Verdile, G., Munns, S., D''Costa, K., Harvey, A. R., Martins, I. J., Hill, F., Levy, E., Shaw, J. E., and Martins, R. N. (2010) Neurobiol. Aging 31, 203–214). The aim of the current study was to generate and biochemically characterize analogues of this peptide with improved stability and therapeutic potential. We demonstrated that a stable analogue of the 15-amino acid peptide (15M S.A.) retained the activity and potency of the parent peptide and demonstrated improved proteolytic resistance in vitro (stable to t = 300 min, c.f. t = 30 min for the parent peptide). This candidate reduced the formation of soluble Aβ42 oligomers, with the concurrent generation of non-toxic, insoluble aggregates measuring up to 25–30 nm diameter as determined by atomic force microscopy. The 15M S.A. candidate directly interacted with oligomeric Aβ42, as shown by coimmunoprecipitation and surface plasmon resonance/Biacore analysis, with an affinity in the low micromolar range. Furthermore, this peptide bound fibrillar Aβ42 and also stained plaques ex vivo in brain tissue from AD model mice. Given its multifaceted ability to target monomeric and aggregated Aβ42 species, this candidate holds promise for novel preclinical AD imaging and therapeutic strategies. 相似文献
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Lorenzo Lazzaro Bruno Foggi Giulio Ferretti Giuseppe Brundu 《Biological invasions》2016,18(5):1317-1333
For the first time, we tested the European and Mediterranean Plant Protection Organization (EPPO) prioritization process (EPP) on 212 alien plant species thriving in the Tuscan Archipelago, Central Italy. We compared the results of the EPPO procedure with those of the Australian Weed Risk Assessment (A-WRA) system. The two methods were also tested against the categorization performed at the national and local level by a panel of experts. Our results suggest that both methods accurately predict the invasiveness of species already present in the Tuscan Archipelago. However, the total numbers of species included in the highest risk categories by the two methods differed greatly, with the EPPO prioritization process including fewer species in the highest risk class. The two methods differed in the ability to correctly detect the invasive species, with the A-WRA method being more conservative, but at cost of more species in the highest risk class. Using Generalized Linear Models, we showed that both methods suffer from some degree of dependence from one or more of the tested explanatory variables (life span, year of first record). The results suggest that the choice of a risk assessment method should be driven by the main aim of the assessment, i.e., distinguishing between a more predictive tool (A-WRA) and a prioritization tool (EPP) for already introduced species. 相似文献