Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl To evaluate the potential theranostic role of [64Cu]CuClin GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuClto simulate single-and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy

Exploitation of wasted bread as substrate for polyhydroxyalkanoates production through the use of Haloferax mediterranei and seawater

The use of the halophile microorganism Haloferax mediterranei, able to synthesize poly(hydroxybutyrate-hydroxyvalerate) (PHBV), is considered as a promising tool for the industrial production of bioplastic through bioprocessing. A consistent supplementation of the growth substrate in carbohydrates and minerals is overall necessary to allow its PHBV production. In this work, wasted bread was used as substrate for bioplastic production by microbial fermentation. Instead of the consistent and expensive minerals supplement required for Hfx. mediterranei DSM1411 growth, microfiltered seawater was added to the wasted bread-derived substrate. The suitable ratio of wasted bread homogenate and seawater, corresponding to 40:60, was selected. The addition of proteases and amylase to the bread homogenate promoted the microbial growth but it did not correspond to the increase of bioplastic production by the microorganism, that reach, under the experimental conditions, 1.53 g/L. An extraction procedure of the PHBV from cells, based on repeated washing with water, followed or not by a purification through ethanol precipitation, was applied instead of the conventional extraction with chloroform. Yield of PHBV obtained using the different extraction methods were 21.6 ± 3.6 (standard extraction/purification procedure with CHCl3:H2O mixture), 24.8 ± 3.0 (water-based extraction), and 19.8 ± 3.3 mg PHAs/g of wasted bread (water-based extraction followed by ethanol purification). Slightly higher hydroxyvalerate content (12.95 vs 10.78%, w/w) was found in PHBV obtained through the water-based extraction compared to the conventional one, moreover, the former was characterized by purity of 100% (w/w). Results demonstrated the suitability of wasted bread, supplemented with seawater, to be used as substrate for bioplastic production through fermentation. Results moreover demonstrated that a solvent-free extraction, exclusively based on osmotic shock, could be used to recover the bioplastic from cells

Annali storici di Principato Citra, A. 10, n. 1.1 (2012)

A.10, n.1.1(2012): G. Guardia, Editoriale, P. 3 ; F. Astone, Alle origini del toponimo Cilento: la fondazione di Poseidonia ed i Tirreni-Etruschi del golfo di Salerno. Riflessioni ed ipotesi, P. 5 ; F. La Greca, Paestum e il suo territorio nella cartografia medievale e moderna, P. 45 ; A. Capano, Casalvelino e la sua frazione Acquavella. Note storiche e il catasto provvisorio del decennio napoleonico, P. 96 ; C. Bellotta, Il monachesimo basiliano nel Cilento. Il cenobio di S. Giovanni a Piro, P. 130 ; S. Villano, Città e patriziato nel Regno di Napoli attraverso le consulte della Camera di S. Chiara, P. 146 ; M. Rinaldi, Agropoli: il territorio, le fonti e la ricerca archeologica, P. 162

Microbial fuel cells: From fundamentals to applications. A review

© 2017 The Author(s) In the past 10–15 years, the microbial fuel cell (MFC) technology has captured the attention of the scientific community for the possibility of transforming organic waste directly into electricity through microbially catalyzed anodic, and microbial/enzymatic/abiotic cathodic electrochemical reactions. In this review, several aspects of the technology are considered. Firstly, a brief history of abiotic to biological fuel cells and subsequently, microbial fuel cells is presented. Secondly, the development of the concept of microbial fuel cell into a wider range of derivative technologies, called bioelectrochemical systems, is described introducing briefly microbial electrolysis cells, microbial desalination cells and microbial electrosynthesis cells. The focus is then shifted to electroactive biofilms and electron transfer mechanisms involved with solid electrodes. Carbonaceous and metallic anode materials are then introduced, followed by an explanation of the electro catalysis of the oxygen reduction reaction and its behavior in neutral media, from recent studies. Cathode catalysts based on carbonaceous, platinum-group metal and platinum-group-metal-free materials are presented, along with membrane materials with a view to future directions. Finally, microbial fuel cell practical implementation, through the utilization of energy output for practical applications, is described

Imaging of Brain Tumors with Copper-64 Chloride: Early Experience and Results

Objectives: To conduct the first investigational study that is aimed at evaluating the ability of the simple salt 64CuCl2 to diagnose cerebral tumors in patients affected by glioblastoma multiforme (GBM). Methods: Nineteen patients with a documented history and radiologic evidence of brain tumors were enrolled in the study. Eighteen patients were diagnosed with GBM, and one patient was diagnosed with grade II astrocytoma. After initial cerebral magnetic resonance imaging (MRI), patients were administered with 64CuCl2 (13 MBq/kg) and brain positron emission tomography (PET)/computed tomography (CT) imaging was performed at 1, 3, and 24 hours after administration. Standardized uptake values (SUVs) were calculated and used to figure out the pharmacokinetic profile of the tracer. Absorbed radiation doses were estimated using OLINDA/EXM. Results: Copper-64 chloride clearly visualized brain cancerous lesions within 1 hour after injection, with stable retention of radioactivity at 3 and 24 hours. Excellent agreement was found between PET/CT and MRI. No uptake of the tracer was observed in low-grade astrocytoma. The agent cleared rapidly from the blood and was mostly excreted through the liver, without significant kidney washout. Analysis of time variation of SUVmax values showed persistent uptake in malignant tissues with a slight increase of radioactive concentration at 24 hours. Conclusions: Copper-64 chloride has favorable biological properties for brain imaging and warrants further investigation as a diagnostic tracer for GBM

Serpin B3 transgenic mice are more susceptible to lung fibrosis and epithelial proliferation

SERPIN B3/B4, members of the serpin superfamily, are fundamental for the control of proteolysis through a known inhibitory function of different proteases. Several studies have documented an important role of SERPIN B3 in the modulation of inflammation, programmed cell death and fibrosis. To confirm the role of SERPIN B3 in lung fibrosis and overall investigate its influence on epithelial dysfunction, a stratified controlled trial randomly assigning bleomycin (BLM) treatment was performed on both SERPIN B3 transgenic (TG) and wild-type (WT) mice. TG and WT animals were killed 48\u2009h (group T48\u2009h) and 20 days (group T20d) after BLM treatment. Lung fibrosis was assessed by histology and hydroxyproline measurement. Architectural remodeling, inflammation, epithelial apoptosis and proliferation were quantified. Moreover, the profibrogenetic cytokine transforming growth factor (TGF)-\u3b2, cathepsin K, L and S were also investigated. No significant differences were observed between TG and WT mice of group T48\u2009h in any parameters. In group T20d, less inflammation and a significant increase in epithelial proliferation were detected in treated TG than WT mice despite a similar apoptotic index, thus resulting in a different apoptosis/proliferation imbalance with a significant gain of epithelial proliferation. Moreover, TG mice showed higher TGF-\u3b2 expression and more extended fibrosis. General linear model analysis, applied on morphological data, showed that interaction between SERPIN B3 expression and treatment was mainly significant for fibrosis. This study provides in vivo evidence for a role of SERPIN B3 in inhibiting inflammation and favoring epithelial proliferation with increased TGF-\u3b2 secretion and thus the likelihood of consequent fibrogenesis

SERPINB3 transgenic mice are more susceptible to lung fibrosis and epithelial proliferation

none8- ISSN:noneLUNARDI FRANCESCA; PONTISSO PATRIZIA; REA FEDERICO; VILLANO G.; GNOATO MARIANNA; AGOSTINI CARLO; VALENTE MARIALUISA; CALABRESE FIORELLALunardi, Francesca; Pontisso, Patrizia; Rea, Federico; Villano, Gianmarco; Gnoato, Marianna; Agostini, Carlo; Valente, Marialuisa; Calabrese, Fiorell