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41.
HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors. 相似文献
42.
Serena Montalbano Francesca Degola Jennifer Bartoli Franco Bisceglie Annamaria Buschini Mauro Carcelli Donatella Feretti Serena Galati Laura Marchi Nicol Orsoni Giorgio Pelosi Marianna Pioli Francesco M. Restivo Dominga Rogolino Mirco Scaccaglia Olga Serra Giorgio Spadola Gaia C. V. Viola Ilaria Zerbini Claudia Zani 《International journal of molecular sciences》2021,22(9)
The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem. 相似文献
43.
Rosalinda Madonna Stefania Moscato Enza Polizzi Damiana Pieragostino Maria Concetta Cufaro Piero Del Boccio Francesco Bianchi Raffaele De Caterina Letizia Mattii 《International journal of molecular sciences》2021,22(11)
Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity. 相似文献
44.
Maria Chiara Mistretta Luigi Botta Francesco Paolo La Mantia Antonino Di Fiore Marco Cascone 《大分子材料与工程》2021,306(9):2100177
Films for agricultural applications, such as greenhouses films or mulching films are generally made of polyolefins such as linear low-density polyethylene (LLDPE) or low-density polyethylene. However, the use of biodegradable and/or compostable polymers is increasing, which enjoy the additional advantage that they can be left on the site since a fine life would be gradually assimilated to the underlying soil. Nevertheless, biodegradable polymeric films often do not have suitable mechanical performances. In this work, biodegradable polymer-based nanocomposite films are prepared by film blowing and compared with traditional LLDPE based nanocomposites. In particular, a biodegradable polymer blend and two different inorganic nanofillers (an organo-modified clay and a calcium carbonate with a hydrophobic coating) are used for the preparation of the nanocomposites. A detailed investigation of obtained materials is performed through rheological, mechanical, and optical characterizations. Adding nanofillers led to an increase of rigidity and tear strength of blown films without negatively affecting their ductility. 相似文献
45.
Raffaele Sacchi Isabel Medina Santiago P. Aubourg Francesco Addeo Livio Paolillo 《Journal of the American Oil Chemists' Society》1993,70(3):225-228
Based on proton nuclear magnetic resonance (1H-NMR) spectroscopy, a rapid and structure-specific method for the determination of ω-3 polyunsaturated fatty acids (PUFAs)
in fish lipids is presented. The different chemical shift observed for the methyl resonance of ω-3 PUFAs (δ=0.95 ppm) with
respect to the methyl resonance of all other fatty acids (δ=0.86 ppm) has provided the possibility of proposing a new and
rapid method for the determination of ω-3 PUFA content. Twenty-four fish lipid samples (raw, cooked and canned albacore tuna)
produced results that showed good agreement between1H-NMR analysis and gas chromatographic determination. Raw and cooked samples showed significantly higher levels of ω-3 PUFA
than canned tuna. 相似文献
46.
Summary Copolymers containing -S-CO-S-and/or -O-CO-S-groups have been synthesized mainly by interfacial polycondensation.Different chemical structures were obtained by reacting 1,3-benzene dithiol (BDT) respectively with phosgene alone, phosgene and bisphenol-A (BPA), bischloroformate of BPA, BPA polycarbonate oligomers and by reacting phosgene with the products of BPA polycarbonate degraded with BDT. The chemical structures of the copolymers were investigated by IR, 1H-NMR and 13C-NMR; molecular weights were determined by viscometry and vapor pressure osmometry. Although no attempt was made to find the optimum conditions for high molecular weight, some copolymers with fairly high mol. weight were obtained. 相似文献
47.
The emergence of synchronization in a network of coupled oscillators is a fascinating subject of multidisciplinary research. This survey reviews the vast literature on the theory and the applications of complex oscillator networks. We focus on phase oscillator models that are widespread in real-world synchronization phenomena, that generalize the celebrated Kuramoto model, and that feature a rich phenomenology. We review the history and the countless applications of this model throughout science and engineering. We justify the importance of the widespread coupled oscillator model as a locally canonical model and describe some selected applications relevant to control scientists, including vehicle coordination, electric power networks, and clock synchronization. We introduce the reader to several synchronization notions and performance estimates. We propose analysis approaches to phase and frequency synchronization, phase balancing, pattern formation, and partial synchronization. We present the sharpest known results about synchronization in networks of homogeneous and heterogeneous oscillators, with complete or sparse interconnection topologies, and in finite-dimensional and infinite-dimensional settings. We conclude by summarizing the limitations of existing analysis methods and by highlighting some directions for future research. 相似文献
48.
Francesco Ranzato 《Acta Informatica》2014,51(2):107-125
A number of algorithms for computing the simulation preorder (and equivalence) on Kripke structures are available. Let $\varSigma $ denote the state space, ${\rightarrow }$ the transition relation and $P_{\mathrm {sim}}$ the partition of $\varSigma $ induced by simulation equivalence. While some algorithms are designed to reach the best space bounds, whose dominating additive term is $|P_{\mathrm {sim}}|^2$ , other algorithms are devised to attain the best time complexity $O(|P_{\mathrm {sim}}||{\rightarrow }|)$ . We present a novel simulation algorithm which is both space and time efficient: it runs in $O(|P_ {\mathrm {sim}}|^2 \log |P_{\mathrm {sim}}| + |\varSigma |\log |\varSigma |)$ space and $O(|P_{\mathrm {sim}}||{\rightarrow }|\log |\varSigma |)$ time. Our simulation algorithm thus reaches the best space bounds while closely approaching the best time complexity. 相似文献
49.
Maria?Antonietta BresciaEmail author Vincenzo?Mazzilli Angela?Sgaramella Stefano?Ghelli Francesco?Paolo Fanizzi Antonio?Sacco 《Journal of the American Oil Chemists' Society》2004,81(5):431-436
Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia,
a region of southern Italy, were performed by means of 1H NMR. The aim of this work was to establish whether FA composition data obtained by 1H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the
signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out
by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the
results of the quantification, permitted buffalo and cow milks to be distinguished. 相似文献
50.
Oxidation reactivity studies are imperative for improving carbon re-burn technologies and valuing the heat content of unburned carbon within coal combustion ashes. Non-isothermal, thermal gravimetric analysis (TGA) was used to examine the oxidation kinetics of unburned carbon in coal combustion fly ashes having different particle size distributions; TGA results were related to combustion efficiencies as measured in a bench-scale rotary kiln. The activation energy and pre-exponential factor were determined for the chemically-controlled reaction regime; the transition temperatures between chemically-controlled and partially diffusion-controlled combustion regimes were obtained for unburned carbon particles of different sizes. After the oxidation reaction rates were evaluated, the residence time distribution (RTD) of fly ashes in the rotary kiln were experimentally measured and the mean residence times related to process parameters, including the rotating velocity and kiln inclination. By comparing these results with an advective-dispersive model, the axial dispersion coefficient of fly ashes was determined. The reaction rates obtained by thermal analyses and the RTDs were used to predict combustion efficiencies within the kiln and oxidation conditions of unburned carbon using various processing options. 相似文献