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101.
Cimini A Mei S Benedetti E Laurenti G Koutris I Cinque B Cifone MG Galzio R Pitari G Di Leandro L Giansanti F Lombardi A Fabbrini MS Ippoliti R 《Journal of cellular physiology》2012,227(3):939-951
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of ~12-18 months post-diagnosis. GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4-Pseudomonas aeruginosa exotoxin A (IL4-PE, NBI-3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha-TP-38, IL13-PE38, and a transferrin-C diphtheriae toxin mutant (Tf-CRM107). In this work, we studied the effects of the plant ribosome-inactivating saporin and of its chimera transferrin-saporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways. 相似文献
102.
Lombardi R Donini M Villani ME Brunetti P Fujiyama K Kajiura H Paul M Ma JK Benvenuto E 《Transgenic research》2012,21(5):1005-1021
We previously described the expression of a tumour-targeting antibody (mAb H10) in Nicotiana benthamiana by vacuum-agro-infiltration and the remarkable yields of highly pure protein achieved. The objective of the present work was to investigate different strategies for transient overexpression of the mAb H10 in which glycan configuration was modulated and assess how these strategies affect the accumulation yield and stability of the antibody. To this aim, three procedures have been assayed: (1) Site-directed mutagenesis to abolish the glycosylation site; (2) endoplasmic reticulum retention (C-terminal SEKDEL fusion) to ensure predominantly high-mannose type glycans; and (3) expression in a N. benthamiana RNAi down-regulated line in which β1,2-xylosyltransferase and α1,3-fucosyltransferase gene expression is silenced. The three antibody variants (H10-Mut) (H10-SEKDEL) (H10(XylT/FucT)) were transiently expressed, purified and characterised for their glycosylation profile, expression/purification yield and antibody degradation pattern. Glycosylation analysis of H10(XylT/FucT) demonstrated the absence of plant complex-type sugars, while H10-SEKDEL, although substantially retained in the ER, revealed the presence of β1,2-xylose and α1,3-fucose residues, indicating a partial escape from the ER retrieval system. Antibody accumulation and purification yields were not enhanced by ER retention. All H10 antibody glyco-forms revealed greater degradation compared to the original, resulting mostly in the formation of Fab fragments. In the case of aglycosylated H10-Mut, more than 95% of the heavy chain was cleaved, confirming the pivotal role of the sugar moiety in protein stability. Identification of possible 'fragile' sites in the H10 antibody hinge region could be of general interest for the development of new strategies to reduce antibody degradation and increase the yield of intact IgGs in plants. 相似文献
103.
The most commonly cited definition of industrial symbiosis (IS), by Chertow (2000) , has served well to foster discussion and research for more than a decade. The definition reflected the state of research and practice at the time; as both have advanced, some terms have been interpreted in substantially different ways. In this article we analyze those generally used terms for their connection to the ecological metaphor that is the root of industrial ecology, and their varied interpretations in IS research and practice over time. We then propose an updated definition intended to communicate the essence of IS as a tool for innovative green growth: IS engages diverse organizations in a network to foster eco‐innovation and long‐term culture change. Creating and sharing knowledge through the network yields mutually profitable transactions for novel sourcing of required inputs and value‐added destinations for non‐product outputs, as well as improved business and technical processes. We posit that, although geographic proximity is often associated with IS, it is neither necessary nor sufficient—nor is a singular focus on physical resource exchange. 相似文献
104.
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106.
M. C. Di Lonardo F. Lombardi R. Gavasci 《Reviews in Environmental Science and Biotechnology》2012,11(4):353-363
Mechanical?Cbiological treatment (MBT) plants treat municipal solid waste (MSW), residual after source separation, with the aim to minimize the environmental impact associated with the residues landfilling and to add values to waste outflows for a potential utilization. MBT consists in a combination of mechanical processes (shredding, size, density and magnetic separation, densification, etc.) and biological treatment (aerobic or anaerobic degradation) of the organic fraction mechanically separated. In this work a review regarding the MBT input and outputs characterization is presented with the aim to evaluate the quality of them and the effectiveness of MBT plants to produce materials that can be utilized for material/energy recovery. A strong variability of the different flows characteristics, mainly due to the heterogeneity of the input MSW and to the different configurations of processing units employed in MBT plants, was highlighted. Therefore most suitable end-uses or disposal for the MBT outputs are site-specific and should be related to prior detailed characterizations of the materials able to identify specific quality classes defined by proper technical standards. 相似文献
107.
Mainini V Gianazza E Chinello C Bilo G Revera M Giuliano A Caldara G Lombardi C Piperno A Magni F Parati G 《Molecular bioSystems》2012,8(4):959-966
The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia and to evaluate pharmacological approaches potentially useful as a therapy for chronic diseases related to hypoxia. We explored the urinary peptidome to detect alterations induced by the exposure of subjects to different altitudes (sea level, high altitude = 3500 m, very high altitude = 5400 m) and to pharmacological treatment. Urine samples were collected from 47 subjects, randomly and blindly assigned to placebo (n = 24) or Telmisartan (n = 23). Samples were purified by the use of magnetic beads, then analysed by MALDI-TOF MS. Results showed that the urinary peptidome is not affected by the administration of Telmisartan, neither at the sea level nor at high and very high altitudes. In contrast, the urinary protein profiles are modified when subjects are exposed to high and very high altitudes, and we detected six peptides differentially expressed in hypobaric hypoxia at high or very high altitude compared to the sea level. Two of them were identified as fragments of the glycoprotein uromodulin and of the α1-antitrypsin. This is the first proteomic study showing that hypobaric hypoxia conditions affect the urinary peptidome. 相似文献
108.
McKimmie CS Fraser AR Hansell C Gutiérrez L Philipsen S Connell L Rot A Kurowska-Stolarska M Carreno P Pruenster M Chu CC Lombardi G Halsey C McInnes IB Liew FY Nibbs RJ Graham GJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3353-3363
D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes. 相似文献
109.
Marra M Lombardi A Agostinelli E Giuberti G Zappavigna S Tempera G Vitale G Bifulco M Abbruzzese A Caraglia M 《Biochimica et biophysica acta》2008,1783(12):2269-2278
It was previously demonstrated that bovine serum amine-oxidase (BSAO) and SPM (SPM) addition to cancer cells induces cell growth inhibition and over-run the multi-drug resistance (MDR) phenotype through the oxidative stress caused by polyamine metabolites. In this study, it is reported that BSAO/SPM enzymatic system antagonizes the survival pathway induced by either docetaxel (DTX) or interferon alpha (IFNalpha) in human epidermoid cancer KB cells. The combination of BSAO/SPM with either DTX or IFNalpha had a synergistic effect on cell growth inhibition through apoptosis in both human epidermoid KB and breast cancer MCF-7 cell lines. The effects of the BSAO/SPM-DTX combination on apoptosis were caspase 3 and 9-dependent and were paralleled by the enhancement of intracellular O(2-), nitric oxide levels and of lipo-oxidation. The scavenger moiety N-acetyl-cysteine antagonized the effects on apoptosis and cell growth inhibition induced by the combination suggesting a role of the oxidative products of SPM. These effects occurred together with a decrease of the physiological scavenger MnSOD and an increase of both p38 kinase activity and DNA damage. The results suggest that DTX and IFNalpha could sensitize tumour cells to the oxidative stress and apoptosis induced by BSAO/SPM through the induction of a survival ras-dependent pathway and the consequent elevation of the intracellular polyamine pool. These data allow the design of new therapeutic strategy based on the use of this combination in human neoplasms. 相似文献
110.
Racial disparity in spontaneous preterm birth (PTB) between African Americans and Caucasians in the US is unexplained, but
is probably related to differences in amniotic fluid (AF) inflammatory cytokine profiles. Therefore, this study analyzed the
association of 34 single nucleotide polymorphisms (SNPs) in TNF-α and its receptor genes (TNFR1 and TNFR2) with AF TNF-α and soluble TNF receptor (R1 and R2) concentrations in PTB. Samples consisted of African American and Caucasian
cases (PTB), and controls (term birth) for which both cytokine, and maternal and fetal genotype data were available. Analyses
were performed with genotype, case, and maker-status interaction in the model for log transformed cytokine concentrations.
In Caucasians, two interactions between genotype and pregnancy outcome associated with cytokine concentrations, whereas 14
gene variants in African Americans showed interactions with pregnancy outcome, and 13 showed association with genetic markers.
In conclusion, cytokine concentrations in African American preterm births can be partially explained by interactions between
pregnancy outcome, SNPs and infection. This does not appear to be the case in Caucasians. These findings may be important
in understanding disparity in rates of PTB between the two populations.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献