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20. A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors

Author

Orienti, I., Francescangeli, F., De Angelis, M. L., Fecchi, K., Bongiorno-Borbone, L., Signore, M., Peschiaroli, A., Boe, A., Bruselles, A., Costantino, A., Eramo, A., Salvati, V., Sette, G., Contavalli, P., Zolla, L., Oki, T., Kitamura, T., Spada, M., Giuliani, A., Baiocchi, M., La Torre, F., Melino, G., Tartaglia, M., De Maria, R., Zeuner, A., Salvati V., Sette G., Contavalli P., Spada M., De Maria R. (ORCID:0000-0003-2255-0583), Orienti, I., Francescangeli, F., De Angelis, M. L., Fecchi, K., Bongiorno-Borbone, L., Signore, M., Peschiaroli, A., Boe, A., Bruselles, A., Costantino, A., Eramo, A., Salvati, V., Sette, G., Contavalli, P., Zolla, L., Oki, T., Kitamura, T., Spada, M., Giuliani, A., Baiocchi, M., La Torre, F., Melino, G., Tartaglia, M., De Maria, R., Zeuner, A., Salvati V., Sette G., Contavalli P., Spada M., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention.

Published
2019

21. A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells

Author

Orienti, I., Salvati, Valentina, Sette, Giovanni, Zucchetti, M., Bongiorno-Borbone, L., Peschiaroli, A., Zolla, L., Francescangeli, F., Ferrari, M., Matteo, C., Bello, E., Di Virgilio, A., Falchi, M., De Angelis, M. L., Baiocchi, M., Melino, G., De Maria Marchiano, Ruggero, Zeuner, A., Eramo, A., Salvati V., Sette G., De Maria R. (ORCID:0000-0003-2255-0583), Orienti, I., Salvati, Valentina, Sette, Giovanni, Zucchetti, M., Bongiorno-Borbone, L., Peschiaroli, A., Zolla, L., Francescangeli, F., Ferrari, M., Matteo, C., Bello, E., Di Virgilio, A., Falchi, M., De Angelis, M. L., Baiocchi, M., Melino, G., De Maria Marchiano, Ruggero, Zeuner, A., Eramo, A., Salvati V., Sette G., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background: An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials. Methods: Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy. Results: Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent. Conclusion: Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin.

Published
2019

22. Redox status, procoagulant activity, and metabolome of fresh frozen plasma in glucose 6-phosphate dehydrogenase deficiency

Author

Tzounakas, V.L. Gevi, F. Georgatzakou, H.T. Zolla, L. Papassideri, I.S. Kriebardis, A.G. Rinalducci, S. Antonelou, M.H.

Abstract

Objective: Transfusion of fresh frozen plasma (FFP) helps in maintaining the coagulation parameters in patients with acquired multiple coagulation factor deficiencies and severe bleeding. However, along with coagulation factors and procoagulant extracellular vesicles (EVs), numerous bioactive and probably donor-related factors (metabolites, oxidized components, etc.) are also carried to the recipient. The X-linked glucose 6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme genetic defect, mainly affects males. By undermining the redox metabolism, the G6PD- cells are susceptible to the deleterious effects of oxidants. Considering the preferential transfusion of FFP from male donors, this study aimed at the assessment of FFP units derived from G6PD- males compared with control, to show whether they are comparable at physiological, metabolic and redox homeostasis levels. Methods: The quality of n = 12 G6PD- and control FFP units was tested after 12 months of storage, by using hemolysis, redox, and procoagulant activity-targeted biochemical assays, flow cytometry for EV enumeration and phenotyping, untargeted metabolomics, in addition to statistical and bioinformatics tools. Results: Higher procoagulant activity, phosphatidylserine positive EVs, RBC-vesiculation, and antioxidant capacity but lower oxidative modifications in lipids and proteins were detected in G6PD- FFP compared with controls. The FFP EVs varied in number, cell origin, and lipid/protein composition. Pathway analysis highlighted the riboflavin, purine, and glycerolipid/glycerophospholipid metabolisms as the most altered pathways with high impact in G6PD-. Multivariate and univariate analysis of FFP metabolomes showed excess of diacylglycerols, glycerophosphoinositol, aconitate, and ornithine but a deficiency in riboflavin, flavin mononucleotide, adenine, and arginine, among others, levels in G6PD- FFPs compared with control. Conclusion: Our results point toward a different redox, lipid metabolism, and EV profile in the G6PD- FFP units. Certain FFP-needed patients may be at greatest benefit of receiving FFP intrinsically endowed by both procoagulant and antioxidant activities. However, the clinical outcome of G6PD- FFP transfusion would likely be affected by various other factors, including the signaling potential of the differentially expressed metabolites and EVs, the degree of G6PD-, the redox status in the recipient, the amount of FFP units transfused, and probably, the storage interval of the FFP, which deserve further investigation by future studies. © 2018 Tzounakas, Gevi, Georgatzakou, Zolla, Papassideri, Kriebardis, Rinalducci and Antonelou.

Published
2018

25. The european hematology association roadmap for european hematology research: A consensus document

Author

Engert, A. Balduini, C. Brand, A. Coiffier, B. Cordonnier, C. Döhner, H. De Wit, T.D. Eichinger, S. Fibbe, W. Green, T. De Haas, F. Iolascon, A. Jaffredo, T. Rodeghiero, F. Sall Es, G. Schuringa, J.J. André, M. Andre-Schmutz, I. Bacigalupo, A. Bochud, P.-Y. Den Boer, M. Bonini, C. Camaschella, C. Cant, A. Cappellini, M.D. Cazzola, M. Celso, C.L. Dimopoulos, M. Douay, L. Dzierzak, E. Einsele, H. Ferreri, A. De Franceschi, L. Gaulard, P. Gottgens, B. Greinacher, A. Gresele, P. Gribben, J. De Haan, G. Hansen, J.-B. Hochhaus, A. Kadir, R. Kaveri, S. Kouskoff, V. Kühne, T. Kyrle, P. Ljungman, P. Maschmeyer, G. Méndez-Ferrer, S. Milsom, M. Mummery, C. Ossenkoppele, G. Pecci, A. Peyvandi, F. Philipsen, S. Reitsma, P. Ribera, J.M. Risitano, A. Rivella, S. Ruf, W. Schroeder, T. Scully, M. Socie, G. Staal, F. Stanworth, S. Stauder, R. Stilgenbauer, S. Tamary, H. Theilgaard-Mönch, K. Thein, S.L. Tilly, H. Trneny, M. Vainchenker, W. Vannucchi, A.M. Viscoli, C. Vrielink, H. Zaaijer, H. Zanella, A. Zolla, L. Zwaginga, J.J. Martinez, P.A. Van Den Akker, E. Allard, S. Anagnou, N. Andolfo, I. Andrau, J.-C. Angelucci, E. Anstee, D. Aurer, I. Avet-Loiseau, H. Aydinok, Y. Bakchoul, T. Balduini, A. Barcellini, W. Baruch, D. Baruchel, A. Bayry, J. Bento, C. Van Den Berg, A. Bernardi, R. Bianchi, P. Bigas, A. Biondi, A. Bohonek, M. Bonnet, D. Borchmann, P. Borregaard, N. Brækkan, S. Van Den Brink, M. Brodin, E. Bullinger, L. Buske, C. Butzeck, B. Cammenga, J. Campo, E. Carbone, A. Cervantes, F. Cesaro, S. Charbord, P. Claas, F. Cohen, H. Conard, J. Coppo, P. Vives Corron, J.-L. Da Costa, L. Davi, F. Delwel, R. Dianzani, I. Domanović, D. Donnelly, P. Drnovšek, T.D. Dreyling, M. Du, M.-Q. Dufour, C. Durand, C. Efremov, D. Eleftheriou, A. Elion, J. Emonts, M. Engelhardt, M. Ezine, S. Falkenburg, F. Favier, R. Federico, M. Fenaux, P. Fitzgibbon, J. Flygare, J. Foà, R. Forrester, L. Galacteros, F. Garagiola, I. Gardiner, C. Garraud, O. Van Geet, C. Geiger, H. Geissler, J. Germing, U. Ghevaert, C. Girelli, D. Godeau, B. Gökbuget, N. Goldschmidt, H. Goodeve, A. Graf, T. Graziadei, G. Griesshammer, M. Gruel, Y. Guilhot, F. Von Gunten, S. Gyssens, I. Halter, J. Harrison, C. Harteveld, C. Hellström-Lindberg, E. Hermine, O. Higgs, D. Hillmen, P. Hirsch, H. Hoskin, P. Huls, G. Inati, A. Johnson, P. Kattamis, A. Kiefel, V. Kleanthous, M. Klump, H. Krause, D. Hovinga, J.K. Lacaud, G. Lacroix-Desmazes, S. Landman-Parker, J. Legouill, S. Lenz, G. Von Lilienfeld-Toal, M. Von Lindern, M. Lopez-Guillermo, A. Lopriore, E. Lozano, M. Macintyre, E. Makris, M. Mannhalter, C. Martens, J. Mathas, S. Matzdorff, A. Medvinsky, A. Menendez, P. Migliaccio, A.R. Miharada, K. Mikulska, M. Minard, V. Montalbán, C. De Montalembert, M. Montserrat, E. Morange, P.-E. Mountford, J. Muckenthaler, M. Müller-Tidow, C. Mumford, A. Nadel, B. Navarro, J.-T. El Nemer, W. Noizat-Pirenne, F. O’Mahony, B. Oldenburg, J. Olsson, M. Oostendorp, R. Palumbo, A. Passamonti, F. Patient, R. De Latour, R.P. Pflumio, F. Pierelli, L. Piga, A. Pollard, D. Raaijmakers, M. Radford, J. Rambach, R. Koneti Rao, A. Raslova, H. Rebulla, P. Rees, D. Ribrag, V. Rijneveld, A. Rinalducci, S. Robak, T. Roberts, I. Rodrigues, C. Rosendaal, F. Rosenwald, A. Rule, S. Russo, R. Saglio, G. Sanchez, M. Scharf, R.E. Schlenke, P. Semple, J. Sierra, J. So-Osman, C. Soria, J.M. Stamatopoulos, K. Stegmayr, B. Stunnenberg, H. Swinkels, D. Barata, J.P.T. Taghon, T. Taher, A. Terpos, E. Thachil, J. Tissot, J.D. Touw, I. Toye, A. Trappe, R. Traverse-Glehen, A. Unal, S. Vaulont, S. Viprakasit, V. Vitolo, U. Van Wijk, R. Wójtowicz, A. Zeerleder, S. Zieger, B. EHA Roadmap for European Hematology Research

Abstract

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. © 2016 Ferrata Storti Foundation.

Published
2016

28. A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

Author

Mondanelli, G, Bianchi, R, Pallotta, MT, Orabona, C, Albini, E, Iacono, A, Belladonna, ML, Vacca, C, Fallarino, F, Macchiarulo, A, Ugel, S, Bronte, V, Gevi, F, Zolla, L, Verhaar, Auke, Peppelenbosch, Maikel, Mazza, EMC, Bicciato, S, Laouar, Y, Santambrogio, L, Puccetti, P, Volpi, C, Grohmann, U, Mondanelli, G, Bianchi, R, Pallotta, MT, Orabona, C, Albini, E, Iacono, A, Belladonna, ML, Vacca, C, Fallarino, F, Macchiarulo, A, Ugel, S, Bronte, V, Gevi, F, Zolla, L, Verhaar, Auke, Peppelenbosch, Maikel, Mazza, EMC, Bicciato, S, Laouar, Y, Santambrogio, L, Puccetti, P, Volpi, C, and Grohmann, U

Published
2017

29. Nicotiana tabacum protoplasts secretome can evidence relations among regulatory elements of exocytosis mechanisms

Author

Ul-Rehman, R., Rinalducci, S., Zolla, L., Dalessandro, G., Gian-Pietro Di Sansebastiano, Rehman, REIAZ UL, Rinalducci, S, Zolla, L, Dalessandro, Giuseppe, and DI SANSEBASTIANO, Gian Pietro

Subjects
secretion, SNAP33, secretome, SNARE, protoplast, GUS
Abstract

An alternative study involving proteome analysis of the 24 hour Nicotiana tabacum protoplast culture medium was performed with the aim to confirm relations among regulatory elements of exocytotic processes. Protoplasts present many convenient features to study cellular processes during transient over-expression or suppression of specific gene's products. We performed a proteomic analysis of the culture medium fraction of protoplasts transiently expressing transgenes for 24 hours to characterize the effect of various regulatory proteins dominant negative mutants. A total number of 49 spots were found reproducible in the medium. 24 of these spots were identified with nano RP-HPLC-ESI-MS/MS. Only three and six spots were respectively identified as canonical and non-canonical secreted cell wall proteins. The low number of spots present in the culture medium fraction allowed us the ambitious experiment to analyze the influence of various SNAREs (SYP121, SYP122, SNAP33) and Rab (Rab11) dominant negative mutants. Missing a reasonable number of identified proteins the analyses gave rise to a similarity matrix statistically analyzed considering variation within the presence of 24 spots reproducible in presence of transient over-expression of SNAREs (SYP121 and SYP122) and Rab11 native cDNAs. The similarity confirmed the closer relation between the function of SYP122 and Rab11 as evidenced by the secRGUS based analysis. This analysis included the effect of SNAP33 DN mutant and showed that this Qb-c-SNARE influence both SYP121 and SYP122 SNARE complexes.

Published
2011

30. An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies

Author

D'Alessandro, A. Kriebardis, A.G. Rinalducci, S. Antonelou, M.H. Hansen, K.C. Papassideri, I.S. Zolla, L.

Abstract

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high-energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long-stored RBCs and promote the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects. © 2014 AABB.

Published
2015

32. The many lives of Hsp10: From Early Pregnancy Factor to Potential Antitumoral Agent. New Proteomic Data and a Review of the Literature Focusing on Its Immunologic Properties

Author

LA ROCCA, Giampiero, ANZALONE, Rita, CAPPELLO, Francesco, CORRAO, Simona, FARINA, Felicia, ZUMMO, Giovanni, Timperio, AM, Zolla, L, Conway de Macario, E, Macario AJ, La Rocca, G, Anzalone, R, Cappello, F, Corrao, S, Timperio, AM, Zolla, L, Conway de Macario, E, Macario AJ, Farina, F, and Zummo, G

Subjects
heat shock protein, Hsp10, oxidative stress, early pregnancy factor, antitumoral agent, immune response, cancer, Settore BIO/16 - Anatomia Umana
Published
2008

33. CIGARETTE SMOKE EXPOSURE DOWNREGULATES TWO ISOELECTRIC VARIANTS OF HUMAN Hsp10 IN LUNG EPITHELIAL CELLS AND FIBROBLASTS: A PROTEOMIC STUDY

Author

MACARIO AJL, LA ROCCA G, ANZALONE, Rita, CORRAO S, LO IACONO M, MARASÀ L, FARINA, Felicia, TIMPERIO AM, ZOLLA L, CONWAY DE MACARIO E, Loria, Tiziana, CAPPELLO, Francesco, ZUMMO, Giovanni, ALBERTO JL MACARIO, LA ROCCA G, ANZALONE R, CORRAO S, LORIA T, LO IACONO M, MARASA' L, FARINA F, CAPPELLO F, TIMPERIO AM, ZOLLA L, CONWAY DE MACARIO E, ZUMMO G, MACARIO AJL, and MARASÀ L

Subjects
Settore BIO/16 - Anatomia Umana, Hsp10, cigarette smoke, oxidative stress, proteomics
Published
2008

34. Cigarette smoke exposure downregulates two isoelectric variants of human HSP10 in airway epithelial cells: A Proteomic study

Author

LA ROCCA, Giampiero, ANZALONE, Rita, CORRAO, Simona, MAGNO, Francesca, Loria, Tiziana, LO IACONO, Melania, FARINA, Felicia, CAPPELLO, Francesco, ZUMMO, Giovanni, Timperio, A, Zolla, L, Conway de Macario, E, Macario, A, La Rocca, G, Anzalone, R, Corrao, S, Magno, F, Loria, T, Lo Iacono, M, Farina, F, Cappello, F, Timperio, A, Zolla, L, Conway de Macario, E, Macario, A, and Zummo, G

Subjects
Settore BIO/16 - Anatomia Umana, cigarette smoke, Hsp, epithelial cells, lung, proteomics
Published
2008

35. Two isoelectric variants of HSP10 are down-regulated by cigarette smoke exposure in airway cells: A Proteomic study

Author

LA ROCCA, Giampiero, ANZALONE, Rita, CORRAO, Simona, MAGNO, Francesca, Loria, Tiziana, LO IACONO, Melania, FARINA, Felicia, ZUMMO, Giovanni, CAPPELLO, Francesco, Timperio,AM, Zolla, L, Conway de Macario,E, Macario,AJL, La Rocca,G, Anzalone,R, Corrao,S, Magno, F, Loria,T, Lo Iacono, M, Farina,F, Timperio,AM, Zolla, L, Conway de Macario,E, Macario,AJL, Zummo, G, and Cappello, F

Subjects
Settore BIO/16 - Anatomia Umana, Heat shock protein, HSP10, epithelial cells, lung, proteomics, oxidative stress, mass spectrometry, carcinogenesis
Published
2008

37. The european hematology association roadmap for european hematology research: A consensus document

Author

Engert, A. Balduini, C. Brand, A. Coiffier, B. Cordonnier, C. Döhner, H. De Wit, T.D. Eichinger, S. Fibbe, W. Green, T. De Haas, F. Iolascon, A. Jaffredo, T. Rodeghiero, F. Sall Es, G. Schuringa, J.J. André, M. Andre-Schmutz, I. Bacigalupo, A. Bochud, P.-Y. Den Boer, M. Bonini, C. Camaschella, C. Cant, A. Cappellini, M.D. Cazzola, M. Celso, C.L. Dimopoulos, M. Douay, L. Dzierzak, E. Einsele, H. Ferreri, A. De Franceschi, L. Gaulard, P. Gottgens, B. Greinacher, A. Gresele, P. Gribben, J. De Haan, G. Hansen, J.-B. Hochhaus, A. Kadir, R. Kaveri, S. Kouskoff, V. Kühne, T. Kyrle, P. Ljungman, P. Maschmeyer, G. Méndez-Ferrer, S. Milsom, M. Mummery, C. Ossenkoppele, G. Pecci, A. Peyvandi, F. Philipsen, S. Reitsma, P. Ribera, J.M. Risitano, A. Rivella, S. Ruf, W. Schroeder, T. Scully, M. Socie, G. Staal, F. Stanworth, S. Stauder, R. Stilgenbauer, S. Tamary, H. Theilgaard-Mönch, K. Thein, S.L. Tilly, H. Trneny, M. Vainchenker, W. Vannucchi, A.M. Viscoli, C. Vrielink, H. Zaaijer, H. Zanella, A. Zolla, L. Zwaginga, J.J. Martinez, P.A. Van Den Akker, E. Allard, S. Anagnou, N. Andolfo, I. Andrau, J.-C. Angelucci, E. Anstee, D. Aurer, I. Avet-Loiseau, H. Aydinok, Y. Bakchoul, T. Balduini, A. Barcellini, W. Baruch, D. Baruchel, A. Bayry, J. Bento, C. Van Den Berg, A. Bernardi, R. Bianchi, P. Bigas, A. Biondi, A. Bohonek, M. Bonnet, D. Borchmann, P. Borregaard, N. Brækkan, S. Van Den Brink, M. Brodin, E. Bullinger, L. Buske, C. Butzeck, B. Cammenga, J. Campo, E. Carbone, A. Cervantes, F. Cesaro, S. Charbord, P. Claas, F. Cohen, H. Conard, J. Coppo, P. Vives Corron, J.-L. Da Costa, L. Davi, F. Delwel, R. Dianzani, I. Domanović, D. Donnelly, P. Drnovšek, T.D. Dreyling, M. Du, M.-Q. Dufour, C. Durand, C. Efremov, D. Eleftheriou, A. Elion, J. Emonts, M. Engelhardt, M. Ezine, S. Falkenburg, F. Favier, R. Federico, M. Fenaux, P. Fitzgibbon, J. Flygare, J. Foà, R. Forrester, L. Galacteros, F. Garagiola, I. Gardiner, C. Garraud, O. Van Geet, C. Geiger, H. Geissler, J. Germing, U. Ghevaert and Engert, A. Balduini, C. Brand, A. Coiffier, B. Cordonnier, C. Döhner, H. De Wit, T.D. Eichinger, S. Fibbe, W. Green, T. De Haas, F. Iolascon, A. Jaffredo, T. Rodeghiero, F. Sall Es, G. Schuringa, J.J. André, M. Andre-Schmutz, I. Bacigalupo, A. Bochud, P.-Y. Den Boer, M. Bonini, C. Camaschella, C. Cant, A. Cappellini, M.D. Cazzola, M. Celso, C.L. Dimopoulos, M. Douay, L. Dzierzak, E. Einsele, H. Ferreri, A. De Franceschi, L. Gaulard, P. Gottgens, B. Greinacher, A. Gresele, P. Gribben, J. De Haan, G. Hansen, J.-B. Hochhaus, A. Kadir, R. Kaveri, S. Kouskoff, V. Kühne, T. Kyrle, P. Ljungman, P. Maschmeyer, G. Méndez-Ferrer, S. Milsom, M. Mummery, C. Ossenkoppele, G. Pecci, A. Peyvandi, F. Philipsen, S. Reitsma, P. Ribera, J.M. Risitano, A. Rivella, S. Ruf, W. Schroeder, T. Scully, M. Socie, G. Staal, F. Stanworth, S. Stauder, R. Stilgenbauer, S. Tamary, H. Theilgaard-Mönch, K. Thein, S.L. Tilly, H. Trneny, M. Vainchenker, W. Vannucchi, A.M. Viscoli, C. Vrielink, H. Zaaijer, H. Zanella, A. Zolla, L. Zwaginga, J.J. Martinez, P.A. Van Den Akker, E. Allard, S. Anagnou, N. Andolfo, I. Andrau, J.-C. Angelucci, E. Anstee, D. Aurer, I. Avet-Loiseau, H. Aydinok, Y. Bakchoul, T. Balduini, A. Barcellini, W. Baruch, D. Baruchel, A. Bayry, J. Bento, C. Van Den Berg, A. Bernardi, R. Bianchi, P. Bigas, A. Biondi, A. Bohonek, M. Bonnet, D. Borchmann, P. Borregaard, N. Brækkan, S. Van Den Brink, M. Brodin, E. Bullinger, L. Buske, C. Butzeck, B. Cammenga, J. Campo, E. Carbone, A. Cervantes, F. Cesaro, S. Charbord, P. Claas, F. Cohen, H. Conard, J. Coppo, P. Vives Corron, J.-L. Da Costa, L. Davi, F. Delwel, R. Dianzani, I. Domanović, D. Donnelly, P. Drnovšek, T.D. Dreyling, M. Du, M.-Q. Dufour, C. Durand, C. Efremov, D. Eleftheriou, A. Elion, J. Emonts, M. Engelhardt, M. Ezine, S. Falkenburg, F. Favier, R. Federico, M. Fenaux, P. Fitzgibbon, J. Flygare, J. Foà, R. Forrester, L. Galacteros, F. Garagiola, I. Gardiner, C. Garraud, O. Van Geet, C. Geiger, H. Geissler, J. Germing, U. Ghevaert

Abstract

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. © 2016 Ferrata Storti Foundation.

Published
2016

38. Red Blood Cell Homeostasis: Pharmacological Interventions to Explore Biochemical, Morphological and Mechanical Properties

Author

Cluitmans, J.C.A., Gevi, F., Siciliano, A., Matte, A., Leal, J.K., Franceschi, L. De, Zolla, L., Brock, R.E., Adjobo-Hermans, M.J.W., Bosman, G.J.C.G.M., Cluitmans, J.C.A., Gevi, F., Siciliano, A., Matte, A., Leal, J.K., Franceschi, L. De, Zolla, L., Brock, R.E., Adjobo-Hermans, M.J.W., and Bosman, G.J.C.G.M.

Abstract

Contains fulltext : 168094.pdf (publisher's version ) (Open Access), During their passage through the circulation, red blood cells (RBCs) encounter severe physiological conditions consisting of mechanical stress, oxidative damage and fast changes in ionic and osmotic conditions. In order to survive for 120 days, RBCs adapt to their surroundings by subtle regulation of membrane organization and metabolism. RBC homeostasis depends on interactions between the integral membrane protein band 3 with other membrane and cytoskeletal proteins, and with key enzymes of various metabolic pathways. These interactions are regulated by the binding of deoxyhemoglobin to band 3, and by a signaling network revolving around Lyn kinase and Src family kinase-mediated phosphorylation of band 3. Here we show that manipulation of the interaction between the lipid bilayer and the cytoskeleton, using various pharmacological agents that interfere with protein-protein interactions and membrane lipid organization, has various effects on: (1) morphology, as shown by high resolution microscopy and quantitative image analysis; (2) organization of membrane proteins, as indicated by immunofluorescence confocal microscopy and quantitative as well as qualitative analysis of vesicle generation; (3) membrane lipid organization, as indicated by flow cytometric analysis of phosphatidylserine exposure; (4) deformability, as assessed in capillary-mimicking circumstances using a microfluidics system; (5) deformability as determined using a spleen-mimicking device; (6) metabolic activity as indicated by metabolomics. Our data show that there is a complex relationship between red cell morphology, membrane organization and deformability. Also, our data show that red blood cells have a relatively high resistance to disturbance of membrane organization in vitro, which may reflect their capacity to withstand mechanical, oxidative and osmotic stress in vivo.

Published
2016

39. The European Hematology Association Roadmap for European Hematology Research: a consensus document.

Author

EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., de Wit, T.D., Schuringa, J.J., EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., de Wit, T.D., and Schuringa, J.J.

Abstract

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at euro23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

Published
2016

40. The european hematology association roadmap for european hematology research: A consensus document

Author

Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De Wit, T, Eichinger, S, Fibbe, W, Green, T, De Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Zieger, B., ZANELLA, ALBERTO, BIONDI, ANDREA, Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De Wit, T, Eichinger, S, Fibbe, W, Green, T, De Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Zieger, B., ZANELLA, ALBERTO, and BIONDI, ANDREA

Abstract

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

Published
2016

42. Proteomic analysis of platelets treated with gamma irradiation versus a commercial photochemical pathogen reduction technology

Author

Marrocco, C, D'Alessandro, A, Girelli, Gabriella, and Zolla, L.

Subjects
Blood Platelets, Male, Proteomics, Photosensitizing Agents, Proteome, Ultraviolet Rays, Blood Safety, Riboflavin, Platelet Activation, Mass Spectrometry, Oxidative Stress, Gamma Rays, Humans, Electrophoresis, Gel, Two-Dimensional, Chromatography, High Pressure Liquid
Abstract

Several strategies are currently being tested to reduce the risk of pathogen transmission associated with platelet (PLT) transfusion. Within the framework of the Italian Platelet Technology Assessment Study, we investigated the variations of the protein profiles (proteomics) of apheresis PLT concentrates (PCs) upon treatment with riboflavin and ultraviolet (UV) light (Mirasol; 6.24 J/mL; 280-400 nm).Control, gamma-irradiated, and Mirasol-treated apheresis PCs were assayed on Days 1 and 5 of storage by means of gel-based analytical approaches (two-dimensional gel electrophoresis) and mass spectrometry-based identification of significant (p 0.05 analysis of variance) differential proteins. Supernatants were then assayed for metabolism and oxidative stress-related metabolites through multiple reaction monitoring mass spectrometry.Only a handful of modifications could be observed in the PLT proteome profiles in response to the Mirasol treatment, which included proteins involved in oxidative stress responses, PLT metabolism, and activation. Results confirmed increased metabolic rate and oxidative stress in the supernatants of treated PLTs (both gamma irradiated and Mirasol treated).From this investigation, it emerges that, from a proteomics standpoint, gamma irradiation results in the acceleration of PLT storage lesions and the Mirasol treatment only moderately exacerbates these phenomena.

Published
2012

44. Peroxiredoxin-2 as a candidate biomarker to test oxidative stress levels of stored red blood cells under blood bank conditions

Author

Rinalducci, S., D'Amici, G. m., Blasi, B., Vaglio, Stefania, Grazzini, G., and Zolla, L.

Subjects
Oxidative Stress, Erythrocytes, Quality Assurance, Health Care, Blood Preservation, Blood Banks, Humans, Peroxiredoxins, Erythrocyte Transfusion, Biomarkers
Abstract

Several researches on aging red blood cells (RBCs)--performed both in vivo and under blood bank conditions--revealed that RBC membrane proteins undergo a number of irreversible alterations, mainly due to oxidative stress. The individuation of proteins to be used as indicators of irreversible RBC injury and to be proposed as candidate biomarkers of oxidative damage or aging status during blood storage is therefore of great interest.Based on this purpose we performed proteomic analysis of the membranes of RBCs during various storage periods under blood bank conditions. Changes in protein composition of RBC membranes were monitored as a function of the storage period by means of polyacrylamide gel electrophoresis coupled with immunoblotting and mass spectrometry analyses.During storage, a progressive linkage of typical cytosolic proteins to the membrane was detected, including both antioxidant and metabolic enzymes (such as catalase, peroxiredoxin-2 [Prx2], and 2,3-bisphosphoglycerate-mutase), as well as nonreducible cross-linkings of probably oxidized or denatured hemoglobin. This phenomenon was unequivocally related to oxidative stress, since storage of RBCs under anaerobic conditions showed a suppression of these protein recruitments to the membrane.The detailed analysis of these protein associations to the membrane of aged RBCs allowed Prx2 to be suggested as a potential RBC oxidative stress marker for the sake of developing new approaches in quality assurance of blood components.

Published
2011

46. Redox Proteomics

Author

Scaloni A and Zolla L.

Abstract

We believe that this JoP special issue on Redox Proteomics not only represents one of the numerous attempts to start a network of information among multiplelaboratories working on this delicate topic, but it also promises to start bridging the persisting gaps between the clinical and the academic milieu, hopping that, for the foreseeable future, this field of investigation will find a widespread diffusion in the clinical routine as well

Published
2011
Full Text
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47. Chromate reduction by the photosynthetic bacterium Rhodobacter sphaeroides

Author

Italiano F., Rinalducci S., Zolla L., R Ceci L., De Leo F., Agostiano A., and Trotta M.

Subjects
Rhodobacter sphaeroides, Photosynthesis, Chromate
Abstract

Chromate is a highly soluble and toxic non-essential oxyanion for most organisms. A number of chromate resistant bacteria have been investigated and diverse resistance mechanisms were found [1]. We are investigating the potentialities of the photosynthetic facultative bacterium Rhodobacter sphaeroides, known for its ability to tolerate high concentrations of several heavy metal ions [2] and bioaccumulate some of them, such as nickel and cobalt [3, 4], in the bioremediation of chromate polluted sites. Employing an interdisciplinary approach, the response to chromate stress was investigated by combining biochemical and spectroscopic measurements, proteomic characterization and cell imaging. An efficient resistance mechanism to chromate is suggested both by the high EC50 value and the lag-phase lengthening induced at concentrations above 0.05 mM. R. sphaeroides is also able to reduce chromate to the less toxic and soluble form Cr(III) with reductase activity preferentially associated with the protein soluble fraction. Chromate effect on soluble enzymes was investigated by a proteomic approach: soluble protein expression profiles of cells exposed to chromate were compared with those of untreated control cells through two-dimensional gel electrophoresis analysis. Upon exposure to chromate at least 30 soluble proteins were differentially expressed. The wide variety of differentially expressed proteins suggests that different metabolic pathways are involved as response to chromate exposure. The accompanying physiological response to Cr(VI) exposure included marked changes in cellular morphology as revealed by atomic force microscopy.

Published
2011

48. The bovine milk proteome: cherishing, nourishing and fostering molecular complexity. An interactomics and functional overview

Author

D'Alessandro A, Zolla L, and Scaloni A.

Abstract

Bovine milk represents an essential source of nutrients for lactating calves and a key raw material for human food preparations. A wealth of data are present in the literature dealing with massive proteomic analyses of milk fractions and independent targeted studies on specific groups of proteins, such as caseins, globulins, hormones and cytokines. In this study, we merged data from previous investigations to compile an exhaustive list of 573 non-redundant annotated protein entries. This inventory was exploited for integrated in silico studies, including functional GO term enrichment (FatiGO/Babelomics), multiple pathway and network analyses. As expected, most of the milk proteins were grouped under pathways/networks/ontologies referring to nutrient transport, lipid metabolism and objectification of the immune system response. Notably enough, another functional family was observed as the most statistically significant one, which included proteins involved in the induction of cellular proliferation processes as well as in anatomical and haematological system development. Although the latter function for bovine milk proteins has long been postulated, studies reported so far mainly focused on a handful of molecules and missed the whole overview resulting from an integrated holistic analysis. A preliminary map of the bovine milk proteins interactome was also built up, which will be refined in future as result of the widespread use of quantitative methods in protein interaction studies and consequent reduction of false-positives within associated databases.

Published
2011
Full Text
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49. p63 supports aerobic respiration through hexokinase II.

Author

Viticchiè, G., Agostini, M., Lena, A.M., Mancini, M., Zhou, Huiqing, Zolla, L., Dinsdale, D., Saintigny, G., Melino, G., Candi, E., Viticchiè, G., Agostini, M., Lena, A.M., Mancini, M., Zhou, Huiqing, Zolla, L., Dinsdale, D., Saintigny, G., Melino, G., and Candi, E.

Abstract

Item does not contain fulltext

Published
2015

50. Comparison among plasma-derived clotting factor VIII by using monodimensional gel electrophoresis and mass spectrometry

Author

Timperio, A. M., Gevi, F., Grazzini, G., Vaglio, Stefania, and Zolla, L.

Subjects
contaminants, haemophilia a, mass spectrometry, plasma derived fviii, sds-page, Factor VIII, Humans, Proteins, Electrophoresis, Polyacrylamide Gel, Original Article, Drug Contamination, Hemophilia A, Mass Spectrometry
Abstract

Deficiency or dysfunction of coagulation factor VIII (FVIII) is the underlying cause of haemophilia A. Haemophilic patients are at present treated with plasma-derived FVIII (pdFVIII) or recombinant FVIII (rFVIII) in order to correct their clotting deficiency. pdFVIII concentrates are exclusively produced from human plasma upon pooling from multiple donors. It is not know whether the presence of excess of other plasma proteins, in addition to von Willebrand factor, could stimulate untoward immune responses in the recipient. Thus, information regarding the presence of contaminants in commercial products is of concern.Two commercially available pdFVIII concentrates were characterized through SDS-PAGE and mass spectrometry Emoclot and Beriate.The components of two pdFVIII products considered in this study were well identified by mass spectrometry analysis, in both cases we found abundant components coming from blood plasma, and some other contaminants. Only in Beriate we also found truncated form of pdFVIII.The two pdFVIII examined showed the presence of vWF, Fibrinogen in excess, and other substances that could be considered as contaminants or impurities.

Published
2010

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