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101. Inhibiting extracellular vesicles formation and release: a review of EV inhibitors.

Author

Catalano, Mariadelva and O'Driscoll, Lorraine

Subjects
*EXTRACELLULAR vesicles, *CELL membranes, *GLYCOPROTEINS, *LIPIDS
Abstract

It is now becoming well established that vesicles are released from a broad range of cell types and are involved in cell-to-cell communication, both in physiological and pathological conditions. Once outside the cell, these vesicles are termed extracellular vesicles (EVs). The cellular origin (cell type), subcellular origin (through the endosomal pathway or pinched from the cell membrane) and content (what proteins, glycoproteins, lipids, nucleic acids, metabolites) are transported by the EVs, and their size, all seem to be contributing factors to their overall heterogeneity. Efforts are being invested into attempting to block the release of subpopulations of EVs or, indeed, all EVs. Some such studies are focussed on investigating EV inhibitors as research tools; others are interested in the longerterm potential of using such inhibitors in pathological conditions such as cancer. This review, intended to be of relevance to both researchers already well established in the EV field and newcomers to this field, provides an outline of the compounds that have been most extensively studied for this purpose, their proposed mechanisms of actions and the findings of these studies. [ABSTRACT FROM AUTHOR]

Published
2020
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102. European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD)

Author

O'Driscoll, Lorraine, Stoorvogel, Willem, Théry, Clotilde, Buzas, Edit, Nazarenko, Irina, Siljander, Pia, Yáñez-Mó, María, Fais, Stefano, Giebel, Bernd, Yliperttula, Marjo, LS Celbiologie-Algemeen, dB&C I&I, LS Celbiologie-Algemeen, and dB&C I&I

Subjects
0301 basic medicine, Societies, Scientific, Biomedical Research, Chemistry, Network on, Microvesicle, International Cooperation, Australia, Medizin, Pharmaceutical Science, Extracellular vesicle, Disease, Extracellular vesicles, Exosome, Microvesicles, United States, Cell biology, Europe, 03 medical and health sciences, Extracellular Vesicles, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis
Published
2017

103. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, primary, Witwer, Kenneth W, additional, Aikawa, Elena, additional, Alcaraz, Maria Jose, additional, Anderson, Johnathon D, additional, Andriantsitohaina, Ramaroson, additional, Antoniou, Anna, additional, Arab, Tanina, additional, Archer, Fabienne, additional, Atkin-Smith, Georgia K, additional, Ayre, D Craig, additional, Bach, Jean-Marie, additional, Bachurski, Daniel, additional, Baharvand, Hossein, additional, Balaj, Leonora, additional, Baldacchino, Shawn, additional, Bauer, Natalie N, additional, Baxter, Amy A, additional, Bebawy, Mary, additional, Beckham, Carla, additional, Bedina Zavec, Apolonija, additional, Benmoussa, Abderrahim, additional, Berardi, Anna C, additional, Bergese, Paolo, additional, Bielska, Ewa, additional, Blenkiron, Cherie, additional, Bobis-Wozowicz, Sylwia, additional, Boilard, Eric, additional, Boireau, Wilfrid, additional, Bongiovanni, Antonella, additional, Borràs, Francesc E, additional, Bosch, Steffi, additional, Boulanger, Chantal M, additional, Breakefield, Xandra, additional, Breglio, Andrew M, additional, Brennan, Meadhbh Á, additional, Brigstock, David R, additional, Brisson, Alain, additional, Broekman, Marike LD, additional, Bromberg, Jacqueline F, additional, Bryl-Górecka, Paulina, additional, Buch, Shilpa, additional, Buck, Amy H, additional, Burger, Dylan, additional, Busatto, Sara, additional, Buschmann, Dominik, additional, Bussolati, Benedetta, additional, Buzás, Edit I, additional, Byrd, James Bryan, additional, Camussi, Giovanni, additional, Carter, David RF, additional, Caruso, Sarah, additional, Chamley, Lawrence W, additional, Chang, Yu-Ting, additional, Chen, Chihchen, additional, Chen, Shuai, additional, Cheng, Lesley, additional, Chin, Andrew R, additional, Clayton, Aled, additional, Clerici, Stefano P, additional, Cocks, Alex, additional, Cocucci, Emanuele, additional, Coffey, Robert J, additional, Cordeiro-da-Silva, Anabela, additional, Couch, Yvonne, additional, Coumans, Frank AW, additional, Coyle, Beth, additional, Crescitelli, Rossella, additional, Criado, Miria Ferreira, additional, D’Souza-Schorey, Crislyn, additional, Das, Saumya, additional, Datta Chaudhuri, Amrita, additional, de Candia, Paola, additional, De Santana, Eliezer F, additional, De Wever, Olivier, additional, del Portillo, Hernando A, additional, Demaret, Tanguy, additional, Deville, Sarah, additional, Devitt, Andrew, additional, Dhondt, Bert, additional, Di Vizio, Dolores, additional, Dieterich, Lothar C, additional, Dolo, Vincenza, additional, Dominguez Rubio, Ana Paula, additional, Dominici, Massimo, additional, Dourado, Mauricio R, additional, Driedonks, Tom AP, additional, Duarte, Filipe V, additional, Duncan, Heather M, additional, Eichenberger, Ramon M, additional, Ekström, Karin, additional, EL Andaloussi, Samir, additional, Elie-Caille, Celine, additional, Erdbrügger, Uta, additional, Falcón-Pérez, Juan M, additional, Fatima, Farah, additional, Fish, Jason E, additional, Flores-Bellver, Miguel, additional, Försönits, András, additional, Frelet-Barrand, Annie, additional, Fricke, Fabia, additional, Fuhrmann, Gregor, additional, Gabrielsson, Susanne, additional, Gámez-Valero, Ana, additional, Gardiner, Chris, additional, Gärtner, Kathrin, additional, Gaudin, Raphael, additional, Gho, Yong Song, additional, Giebel, Bernd, additional, Gilbert, Caroline, additional, Gimona, Mario, additional, Giusti, Ilaria, additional, Goberdhan, Deborah CI, additional, Görgens, André, additional, Gorski, Sharon M, additional, Greening, David W, additional, Gross, Julia Christina, additional, Gualerzi, Alice, additional, Gupta, Gopal N, additional, Gustafson, Dakota, additional, Handberg, Aase, additional, Haraszti, Reka A, additional, Harrison, Paul, additional, Hegyesi, Hargita, additional, Hendrix, An, additional, Hill, Andrew F, additional, Hochberg, Fred H, additional, Hoffmann, Karl F, additional, Holder, Beth, additional, Holthofer, Harry, additional, Hosseinkhani, Baharak, additional, Hu, Guoku, additional, Huang, Yiyao, additional, Huber, Veronica, additional, Hunt, Stuart, additional, Ibrahim, Ahmed Gamal-Eldin, additional, Ikezu, Tsuneya, additional, Inal, Jameel M, additional, Isin, Mustafa, additional, Ivanova, Alena, additional, Jackson, Hannah K, additional, Jacobsen, Soren, additional, Jay, Steven M, additional, Jayachandran, Muthuvel, additional, Jenster, Guido, additional, Jiang, Lanzhou, additional, Johnson, Suzanne M, additional, Jones, Jennifer C, additional, Jong, Ambrose, additional, Jovanovic-Talisman, Tijana, additional, Jung, Stephanie, additional, Kalluri, Raghu, additional, Kano, Shin-ichi, additional, Kaur, Sukhbir, additional, Kawamura, Yumi, additional, Keller, Evan T, additional, Khamari, Delaram, additional, Khomyakova, Elena, additional, Khvorova, Anastasia, additional, Kierulf, Peter, additional, Kim, Kwang Pyo, additional, Kislinger, Thomas, additional, Klingeborn, Mikael, additional, Klinke, David J, additional, Kornek, Miroslaw, additional, Kosanović, Maja M, additional, Kovács, Árpád Ferenc, additional, Krämer-Albers, Eva-Maria, additional, Krasemann, Susanne, additional, Krause, Mirja, additional, Kurochkin, Igor V, additional, Kusuma, Gina D, additional, Kuypers, Sören, additional, Laitinen, Saara, additional, Langevin, Scott M, additional, Languino, Lucia R, additional, Lannigan, Joanne, additional, Lässer, Cecilia, additional, Laurent, Louise C, additional, Lavieu, Gregory, additional, Lázaro-Ibáñez, Elisa, additional, Le Lay, Soazig, additional, Lee, Myung-Shin, additional, Lee, Yi Xin Fiona, additional, Lemos, Debora S, additional, Lenassi, Metka, additional, Leszczynska, Aleksandra, additional, Li, Isaac TS, additional, Liao, Ke, additional, Libregts, Sten F, additional, Ligeti, Erzsebet, additional, Lim, Rebecca, additional, Lim, Sai Kiang, additional, Linē, Aija, additional, Linnemannstöns, Karen, additional, Llorente, Alicia, additional, Lombard, Catherine A, additional, Lorenowicz, Magdalena J, additional, Lörincz, Ákos M, additional, Lötvall, Jan, additional, Lovett, Jason, additional, Lowry, Michelle C, additional, Loyer, Xavier, additional, Lu, Quan, additional, Lukomska, Barbara, additional, Lunavat, Taral R, additional, Maas, Sybren LN, additional, Malhi, Harmeet, additional, Marcilla, Antonio, additional, Mariani, Jacopo, additional, Mariscal, Javier, additional, Martens-Uzunova, Elena S, additional, Martin-Jaular, Lorena, additional, Martinez, M Carmen, additional, Martins, Vilma Regina, additional, Mathieu, Mathilde, additional, Mathivanan, Suresh, additional, Maugeri, Marco, additional, McGinnis, Lynda K, additional, McVey, Mark J, additional, Meckes, David G, additional, Meehan, Katie L, additional, Mertens, Inge, additional, Minciacchi, Valentina R, additional, Möller, Andreas, additional, Møller Jørgensen, Malene, additional, Morales-Kastresana, Aizea, additional, Morhayim, Jess, additional, Mullier, François, additional, Muraca, Maurizio, additional, Musante, Luca, additional, Mussack, Veronika, additional, Muth, Dillon C, additional, Myburgh, Kathryn H, additional, Najrana, Tanbir, additional, Nawaz, Muhammad, additional, Nazarenko, Irina, additional, Nejsum, Peter, additional, Neri, Christian, additional, Neri, Tommaso, additional, Nieuwland, Rienk, additional, Nimrichter, Leonardo, additional, Nolan, John P, additional, Nolte-’t Hoen, Esther NM, additional, Noren Hooten, Nicole, additional, O’Driscoll, Lorraine, additional, O’Grady, Tina, additional, O’Loghlen, Ana, additional, Ochiya, Takahiro, additional, Olivier, Martin, additional, Ortiz, Alberto, additional, Ortiz, Luis A, additional, Osteikoetxea, Xabier, additional, Østergaard, Ole, additional, Ostrowski, Matias, additional, Park, Jaesung, additional, Pegtel, D. Michiel, additional, Peinado, Hector, additional, Perut, Francesca, additional, Pfaffl, Michael W, additional, Phinney, Donald G, additional, Pieters, Bartijn CH, additional, Pink, Ryan C, additional, Pisetsky, David S, additional, Pogge von Strandmann, Elke, additional, Polakovicova, Iva, additional, Poon, Ivan KH, additional, Powell, Bonita H, additional, Prada, Ilaria, additional, Pulliam, Lynn, additional, Quesenberry, Peter, additional, Radeghieri, Annalisa, additional, Raffai, Robert L, additional, Raimondo, Stefania, additional, Rak, Janusz, additional, Ramirez, Marcel I, additional, Raposo, Graça, additional, Rayyan, Morsi S, additional, Regev-Rudzki, Neta, additional, Ricklefs, Franz L, additional, Robbins, Paul D, additional, Roberts, David D, additional, Rodrigues, Silvia C, additional, Rohde, Eva, additional, Rome, Sophie, additional, Rouschop, Kasper MA, additional, Rughetti, Aurelia, additional, Russell, Ashley E, additional, Saá, Paula, additional, Sahoo, Susmita, additional, Salas-Huenuleo, Edison, additional, Sánchez, Catherine, additional, Saugstad, Julie A, additional, Saul, Meike J, additional, Schiffelers, Raymond M, additional, Schneider, Raphael, additional, Schøyen, Tine Hiorth, additional, Scott, Aaron, additional, Shahaj, Eriomina, additional, Sharma, Shivani, additional, Shatnyeva, Olga, additional, Shekari, Faezeh, additional, Shelke, Ganesh Vilas, additional, Shetty, Ashok K, additional, Shiba, Kiyotaka, additional, Siljander, Pia R-M, additional, Silva, Andreia M, additional, Skowronek, Agata, additional, Snyder, Orman L, additional, Soares, Rodrigo Pedro, additional, Sódar, Barbara W, additional, Soekmadji, Carolina, additional, Sotillo, Javier, additional, Stahl, Philip D, additional, Stoorvogel, Willem, additional, Stott, Shannon L, additional, Strasser, Erwin F, additional, Swift, Simon, additional, Tahara, Hidetoshi, additional, Tewari, Muneesh, additional, Timms, Kate, additional, Tiwari, Swasti, additional, Tixeira, Rochelle, additional, Tkach, Mercedes, additional, Toh, Wei Seong, additional, Tomasini, Richard, additional, Torrecilhas, Ana Claudia, additional, Tosar, Juan Pablo, additional, Toxavidis, Vasilis, additional, Urbanelli, Lorena, additional, Vader, Pieter, additional, van Balkom, Bas WM, additional, van der Grein, Susanne G, additional, Van Deun, Jan, additional, van Herwijnen, Martijn JC, additional, Van Keuren-Jensen, Kendall, additional, van Niel, Guillaume, additional, van Royen, Martin E, additional, van Wijnen, Andre J, additional, Vasconcelos, M Helena, additional, Vechetti, Ivan J, additional, Veit, Tiago D, additional, Vella, Laura J, additional, Velot, Émilie, additional, Verweij, Frederik J, additional, Vestad, Beate, additional, Viñas, Jose L, additional, Visnovitz, Tamás, additional, Vukman, Krisztina V, additional, Wahlgren, Jessica, additional, Watson, Dionysios C, additional, Wauben, Marca HM, additional, Weaver, Alissa, additional, Webber, Jason P, additional, Weber, Viktoria, additional, Wehman, Ann M, additional, Weiss, Daniel J, additional, Welsh, Joshua A, additional, Wendt, Sebastian, additional, Wheelock, Asa M, additional, Wiener, Zoltán, additional, Witte, Leonie, additional, Wolfram, Joy, additional, Xagorari, Angeliki, additional, Xander, Patricia, additional, Xu, Jing, additional, Yan, Xiaomei, additional, Yáñez-Mó, María, additional, Yin, Hang, additional, Yuana, Yuana, additional, Zappulli, Valentina, additional, Zarubova, Jana, additional, Žėkas, Vytautas, additional, Zhang, Jian-ye, additional, Zhao, Zezhou, additional, Zheng, Lei, additional, Zheutlin, Alexander R, additional, Zickler, Antje M, additional, Zimmermann, Pascale, additional, Zivkovic, Angela M, additional, Zocco, Davide, additional, and Zuba-Surma, Ewa K, additional

Published
2018
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106. European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD)

Author

LS Celbiologie-Algemeen, dB&C I&I, O'Driscoll, Lorraine, Stoorvogel, Willem, Théry, Clotilde, Buzas, Edit, Nazarenko, Irina, Siljander, Pia, Yáñez-Mó, María, Fais, Stefano, Giebel, Bernd, Yliperttula, Marjo, LS Celbiologie-Algemeen, dB&C I&I, O'Driscoll, Lorraine, Stoorvogel, Willem, Théry, Clotilde, Buzas, Edit, Nazarenko, Irina, Siljander, Pia, Yáñez-Mó, María, Fais, Stefano, Giebel, Bernd, and Yliperttula, Marjo

Published
2017

107. European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD)

Author

dB&C I&I, LS Celbiologie-Algemeen, O'Driscoll, Lorraine, Stoorvogel, Willem, Théry, Clotilde, Buzas, Edit, Nazarenko, Irina, Siljander, Pia, Yáñez-Mó, María, Fais, Stefano, Giebel, Bernd, Yliperttula, Marjo, dB&C I&I, LS Celbiologie-Algemeen, O'Driscoll, Lorraine, Stoorvogel, Willem, Théry, Clotilde, Buzas, Edit, Nazarenko, Irina, Siljander, Pia, Yáñez-Mó, María, Fais, Stefano, Giebel, Bernd, and Yliperttula, Marjo

Published
2017

114. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Author

Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A, Del Portillo, Hernando A, O'Driscoll, Lorraine, Fais, Stefano, Falcon-Perez, Juan M, Felderhoff-Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C, Hendrix, An, Hermann, Dirk M, Hill, Andrew F, Hochberg, Fred, Horn, Peter A, de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W, Krämer-Albers, Eva-Maria, Laner-Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J, Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A, Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G, Rivera, Francisco J, Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper-Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W M, Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, Giebel, Bernd, Infection & Immunity, Fertility & Reproduction, dI&I I&I-1, dB&C I&I, LS Celbiologie-Algemeen, Infection & Immunity, Fertility & Reproduction, dI&I I&I-1, dB&C I&I, LS Celbiologie-Algemeen, Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), RS: MHeNs - R3 - Neuroscience, RS: GROW - Developmental Biology, and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
Bioquímica clínica, Medizin, ISCHEMIA-REPERFUSION INJURY, Bioinformatics, immunology, neurobiology, haematology, stem cells, tissue regeneration, tumour vaccination, regulation, 0302 clinical medicine, Clinical trials, Clinical investigation, VERSUS-HOST-DISEASE, Medicine and Health Sciences, FIELD-FLOW FRACTIONATION, Medicine, Immunologia, media_common, 0303 health sciences, lcsh:Cytology, OUTER-MEMBRANE VESICLES, Hematology, Biologia experimental, 3. Good health, TUMOR-DERIVED EXOSOMES, 030220 oncology & carcinogenesis, Drug delivery, Position Paper, Cèl·lules mare, Neurobiologia, Histology, Medicina Investigació, Cèl·lules, NANOPARTICLE TRACKING ANALYSIS, Extracellular vesicles, MESENCHYMAL STEM-CELLS, 03 medical and health sciences, Journal Article, media_common.cataloged_instance, REGULATORY T-CELLS, European union, lcsh:QH573-671, ENDOTHELIAL PROGENITOR CELLS, Hematologia, 030304 developmental biology, business.industry, Cell Biology, Microvesicles, Clinical trial, Position paper, Pharmaceutical manufacturing, UMBILICAL-CORD BLOOD, business, Neuroscience, Assaigs clínics
Abstract

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Published
2015

117. Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

Author

Fais, Stefano, primary, O’Driscoll, Lorraine, additional, Borras, Francesc E., additional, Buzas, Edit, additional, Camussi, Giovanni, additional, Cappello, Francesco, additional, Carvalho, Joana, additional, Cordeiro da Silva, Anabela, additional, Del Portillo, Hernando, additional, El Andaloussi, Samir, additional, Ficko Trček, Tanja, additional, Furlan, Roberto, additional, Hendrix, An, additional, Gursel, Ihsan, additional, Kralj-Iglic, Veronika, additional, Kaeffer, Bertrand, additional, Kosanovic, Maja, additional, Lekka, Marilena E., additional, Lipps, Georg, additional, Logozzi, Mariantonia, additional, Marcilla, Antonio, additional, Sammar, Marei, additional, Llorente, Alicia, additional, Nazarenko, Irina, additional, Oliveira, Carla, additional, Pocsfalvi, Gabriella, additional, Rajendran, Lawrence, additional, Raposo, Graça, additional, Rohde, Eva, additional, Siljander, Pia, additional, van Niel, Guillaume, additional, Vasconcelos, M. Helena, additional, Yáñez-Mó, María, additional, Yliperttula, Marjo L., additional, Zarovni, Natasa, additional, Zavec, Apolonija Bedina, additional, and Giebel, Bernd, additional

Published
2016
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118. Biological properties of extracellular vesicles and their physiological functions

Author

Yáñez-Mó, María, Siljander, Pia R-M, Andreu, Zoraida, Zavec, Apolonija Bedina, Borràs, Francesc E, Buzas, Edit I, Buzas, Krisztina, Casal, Enriqueta, Cappello, Francesco, Carvalho, Joana, Colás, Eva, Cordeiro-da Silva, Anabela, Fais, Stefano, Falcon-Perez, Juan M, Ghobrial, Irene M, Giebel, Bernd, Gimona, Mario, Graner, Michael, Gursel, Ihsan, Gursel, Mayda, Heegaard, Niels H H, Hendrix, An, Kierulf, Peter, Kokubun, Katsutoshi, Kosanovic, Maja, Kralj-Iglic, Veronika, Krämer-Albers, Eva-Maria, Laitinen, Saara, Lässer, Cecilia, Lener, Thomas, Ligeti, Erzsébet, Linē, Aija, Lipps, Georg, Llorente, Alicia, Lötvall, Jan, Manček-Keber, Mateja, Marcilla, Antonio, Mittelbrunn, Maria, Nazarenko, Irina, Nolte-'t Hoen, Esther N M, Nyman, Tuula A, O'Driscoll, Lorraine, Olivan, Mireia, Oliveira, Carla, Pállinger, Éva, Del Portillo, Hernando A, Reventós, Jaume, Rigau, Marina, Rohde, Eva, Sammar, Marei, Sánchez-Madrid, Francisco, Santarém, N, Schallmoser, Katharina, Ostenfeld, Marie Stampe, Stoorvogel, Willem, Stukelj, Roman, Van der Grein, Susanne G, Vasconcelos, M Helena, Wauben, Marca H M, De Wever, Olivier, Yáñez-Mó, María, Siljander, Pia R-M, Andreu, Zoraida, Zavec, Apolonija Bedina, Borràs, Francesc E, Buzas, Edit I, Buzas, Krisztina, Casal, Enriqueta, Cappello, Francesco, Carvalho, Joana, Colás, Eva, Cordeiro-da Silva, Anabela, Fais, Stefano, Falcon-Perez, Juan M, Ghobrial, Irene M, Giebel, Bernd, Gimona, Mario, Graner, Michael, Gursel, Ihsan, Gursel, Mayda, Heegaard, Niels H H, Hendrix, An, Kierulf, Peter, Kokubun, Katsutoshi, Kosanovic, Maja, Kralj-Iglic, Veronika, Krämer-Albers, Eva-Maria, Laitinen, Saara, Lässer, Cecilia, Lener, Thomas, Ligeti, Erzsébet, Linē, Aija, Lipps, Georg, Llorente, Alicia, Lötvall, Jan, Manček-Keber, Mateja, Marcilla, Antonio, Mittelbrunn, Maria, Nazarenko, Irina, Nolte-'t Hoen, Esther N M, Nyman, Tuula A, O'Driscoll, Lorraine, Olivan, Mireia, Oliveira, Carla, Pállinger, Éva, Del Portillo, Hernando A, Reventós, Jaume, Rigau, Marina, Rohde, Eva, Sammar, Marei, Sánchez-Madrid, Francisco, Santarém, N, Schallmoser, Katharina, Ostenfeld, Marie Stampe, Stoorvogel, Willem, Stukelj, Roman, Van der Grein, Susanne G, Vasconcelos, M Helena, Wauben, Marca H M, and De Wever, Olivier

Abstract

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Published
2015

119. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Author

Infection & Immunity, Fertility & Reproduction, dI&I I&I-1, dB&C I&I, LS Celbiologie-Algemeen, Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A, Del Portillo, Hernando A, O'Driscoll, Lorraine, Fais, Stefano, Falcon-Perez, Juan M, Felderhoff-Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C, Hendrix, An, Hermann, Dirk M, Hill, Andrew F, Hochberg, Fred, Horn, Peter A, de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W, Krämer-Albers, Eva-Maria, Laner-Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J, Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A, Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G, Rivera, Francisco J, Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper-Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W M, Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, Giebel, Bernd, Infection & Immunity, Fertility & Reproduction, dI&I I&I-1, dB&C I&I, LS Celbiologie-Algemeen, Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A, Del Portillo, Hernando A, O'Driscoll, Lorraine, Fais, Stefano, Falcon-Perez, Juan M, Felderhoff-Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C, Hendrix, An, Hermann, Dirk M, Hill, Andrew F, Hochberg, Fred, Horn, Peter A, de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W, Krämer-Albers, Eva-Maria, Laner-Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J, Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A, Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G, Rivera, Francisco J, Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper-Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W M, Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, and Giebel, Bernd

Published
2015

120. Biological properties of extracellular vesicles and their physiological functions

Author

Infection & Immunity, Fertility & Reproduction, dB&C I&I, LS Celbiologie-Algemeen, Yáñez-Mó, María, Siljander, Pia R-M, Andreu, Zoraida, Zavec, Apolonija Bedina, Borràs, Francesc E, Buzas, Edit I, Buzas, Krisztina, Casal, Enriqueta, Cappello, Francesco, Carvalho, Joana, Colás, Eva, Cordeiro-da Silva, Anabela, Fais, Stefano, Falcon-Perez, Juan M, Ghobrial, Irene M, Giebel, Bernd, Gimona, Mario, Graner, Michael, Gursel, Ihsan, Gursel, Mayda, Heegaard, Niels H H, Hendrix, An, Kierulf, Peter, Kokubun, Katsutoshi, Kosanovic, Maja, Kralj-Iglic, Veronika, Krämer-Albers, Eva-Maria, Laitinen, Saara, Lässer, Cecilia, Lener, Thomas, Ligeti, Erzsébet, Linē, Aija, Lipps, Georg, Llorente, Alicia, Lötvall, Jan, Manček-Keber, Mateja, Marcilla, Antonio, Mittelbrunn, Maria, Nazarenko, Irina, Nolte-'t Hoen, Esther N M, Nyman, Tuula A, O'Driscoll, Lorraine, Olivan, Mireia, Oliveira, Carla, Pállinger, Éva, Del Portillo, Hernando A, Reventós, Jaume, Rigau, Marina, Rohde, Eva, Sammar, Marei, Sánchez-Madrid, Francisco, Santarém, N, Schallmoser, Katharina, Ostenfeld, Marie Stampe, Stoorvogel, Willem, Stukelj, Roman, Van der Grein, Susanne G, Vasconcelos, M Helena, Wauben, Marca H M, De Wever, Olivier, Infection & Immunity, Fertility & Reproduction, dB&C I&I, LS Celbiologie-Algemeen, Yáñez-Mó, María, Siljander, Pia R-M, Andreu, Zoraida, Zavec, Apolonija Bedina, Borràs, Francesc E, Buzas, Edit I, Buzas, Krisztina, Casal, Enriqueta, Cappello, Francesco, Carvalho, Joana, Colás, Eva, Cordeiro-da Silva, Anabela, Fais, Stefano, Falcon-Perez, Juan M, Ghobrial, Irene M, Giebel, Bernd, Gimona, Mario, Graner, Michael, Gursel, Ihsan, Gursel, Mayda, Heegaard, Niels H H, Hendrix, An, Kierulf, Peter, Kokubun, Katsutoshi, Kosanovic, Maja, Kralj-Iglic, Veronika, Krämer-Albers, Eva-Maria, Laitinen, Saara, Lässer, Cecilia, Lener, Thomas, Ligeti, Erzsébet, Linē, Aija, Lipps, Georg, Llorente, Alicia, Lötvall, Jan, Manček-Keber, Mateja, Marcilla, Antonio, Mittelbrunn, Maria, Nazarenko, Irina, Nolte-'t Hoen, Esther N M, Nyman, Tuula A, O'Driscoll, Lorraine, Olivan, Mireia, Oliveira, Carla, Pállinger, Éva, Del Portillo, Hernando A, Reventós, Jaume, Rigau, Marina, Rohde, Eva, Sammar, Marei, Sánchez-Madrid, Francisco, Santarém, N, Schallmoser, Katharina, Ostenfeld, Marie Stampe, Stoorvogel, Willem, Stukelj, Roman, Van der Grein, Susanne G, Vasconcelos, M Helena, Wauben, Marca H M, and De Wever, Olivier

Published
2015

121. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Author

CMM Groep Coffer, Apotheek Celtherapie Faciliteit, Regenerative Medicine and Stem Cells, CDL Nanomedicine, Circulatory Health, MS Nefrologie, Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A, Del Portillo, Hernando A, O'Driscoll, Lorraine, Fais, Stefano, Falcon-Perez, Juan M, Felderhoff-Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C, Hendrix, An, Hermann, Dirk M, Hill, Andrew F, Hochberg, Fred, Horn, Peter A, de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W, Krämer-Albers, Eva-Maria, Laner-Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J, Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A, Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G, Rivera, Francisco J, Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper-Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W M, Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, Giebel, Bernd, CMM Groep Coffer, Apotheek Celtherapie Faciliteit, Regenerative Medicine and Stem Cells, CDL Nanomedicine, Circulatory Health, MS Nefrologie, Lener, Thomas, Gimona, Mario, Aigner, Ludwig, Börger, Verena, Buzas, Edit, Camussi, Giovanni, Chaput, Nathalie, Chatterjee, Devasis, Court, Felipe A, Del Portillo, Hernando A, O'Driscoll, Lorraine, Fais, Stefano, Falcon-Perez, Juan M, Felderhoff-Mueser, Ursula, Fraile, Lorenzo, Gho, Yong Song, Görgens, André, Gupta, Ramesh C, Hendrix, An, Hermann, Dirk M, Hill, Andrew F, Hochberg, Fred, Horn, Peter A, de Kleijn, Dominique, Kordelas, Lambros, Kramer, Boris W, Krämer-Albers, Eva-Maria, Laner-Plamberger, Sandra, Laitinen, Saara, Leonardi, Tommaso, Lorenowicz, Magdalena J, Lim, Sai Kiang, Lötvall, Jan, Maguire, Casey A, Marcilla, Antonio, Nazarenko, Irina, Ochiya, Takahiro, Patel, Tushar, Pedersen, Shona, Pocsfalvi, Gabriella, Pluchino, Stefano, Quesenberry, Peter, Reischl, Ilona G, Rivera, Francisco J, Sanzenbacher, Ralf, Schallmoser, Katharina, Slaper-Cortenbach, Ineke, Strunk, Dirk, Tonn, Torsten, Vader, Pieter, van Balkom, Bas W M, Wauben, Marca, Andaloussi, Samir El, Théry, Clotilde, Rohde, Eva, and Giebel, Bernd

Published
2015

122. Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth):a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study

Author

Bohl, Mette, Bjørnshave, Ann, Rasmussen, Kia V, Schioldan, Anne Grethe, Amer, Bashar, Larsen, Mette K, Dalsgaard, Trine K, Holst, Jens Juul, Herrmann, Annkatrin, O'Neill, Sadhbh, O'Driscoll, Lorraine, Afman, Lydia, Jensen, Erik, Christensen, Merete M, Gregersen, Søren, Hermansen, Kjeld, Bohl, Mette, Bjørnshave, Ann, Rasmussen, Kia V, Schioldan, Anne Grethe, Amer, Bashar, Larsen, Mette K, Dalsgaard, Trine K, Holst, Jens Juul, Herrmann, Annkatrin, O'Neill, Sadhbh, O'Driscoll, Lorraine, Afman, Lydia, Jensen, Erik, Christensen, Merete M, Gregersen, Søren, and Hermansen, Kjeld

Abstract

BACKGROUND: Abdominal obesity and exaggerated postprandial lipemia are independent risk factors for cardiovascular disease (CVD) and mortality, and both are affected by dietary behavior.OBJECTIVE: We investigated whether dietary supplementation with whey protein and medium-chain saturated fatty acids (MC-SFAs) improved postprandial lipid metabolism in humans with abdominal obesity.DESIGN: We conducted a 12-wk, randomized, double-blinded, diet intervention study. Sixty-three adults were randomly allocated to one of 4 diets in a 2 × 2 factorial design. Participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (with high or low MC-SFA content) daily. Before and after the intervention, a high-fat meal test was performed. We measured changes from baseline in fasting and postprandial triacylglycerol, apolipoprotein B-48 (apoB-48; reflecting chylomicrons of intestinal origin), free fatty acids (FFAs), insulin, glucose, glucagon, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP). Furthermore, changes in the expression of adipose tissue genes involved in lipid metabolism were investigated. Two-factor ANOVA was used to examine the difference between protein types and fatty acid compositions, as well as any interaction between the two.RESULTS: Fifty-two participants completed the study. We found that the postprandial apoB-48 response decreased significantly after whey compared with casein (P = 0.025) independently of fatty acid composition. Furthermore, supplementation with casein resulted in a significant increase in the postprandial GLP-1 response compared with whey (P = 0.003). We found no difference in postprandial triacylglycerol, FFA, insulin, glucose, glucagon, or GIP related to protein type or MC-SFA content. We observed no interaction between milk protein and milk fat on postprandial lipemia.CONCLUSION: We found that a whey protein supplement decreased the postprandial chylomicron response compare

Published
2015

123. When E-Cadherin Becomes Unstuck in Cancer.

Author

O'Driscoll, Lorraine

Subjects
*CADHERINS, *MEDICAL sciences, *METASTATIC breast cancer, *LOBULAR carcinoma
Abstract

The article offers information on the clinical implications of the E-cadherin in Cancer. It mentions the Transcriptomic and histologic characteristics of the process as associated with resistance to therapy and a poor prognosis. It discusses about the loss of the E-cadherin bond, which occurs when cancer cells break away from the original tumor mass.

Published
2020
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129. Biological properties of extracellular vesicles and their physiological functions

Author

Yáñez-Mó, María, primary, Siljander, Pia R.-M., additional, Andreu, Zoraida, additional, Bedina Zavec, Apolonija, additional, Borràs, Francesc E., additional, Buzas, Edit I., additional, Buzas, Krisztina, additional, Casal, Enriqueta, additional, Cappello, Francesco, additional, Carvalho, Joana, additional, Colás, Eva, additional, Cordeiro-da Silva, Anabela, additional, Fais, Stefano, additional, Falcon-Perez, Juan M., additional, Ghobrial, Irene M., additional, Giebel, Bernd, additional, Gimona, Mario, additional, Graner, Michael, additional, Gursel, Ihsan, additional, Gursel, Mayda, additional, Heegaard, Niels H. H., additional, Hendrix, An, additional, Kierulf, Peter, additional, Kokubun, Katsutoshi, additional, Kosanovic, Maja, additional, Kralj-Iglic, Veronika, additional, Krämer-Albers, Eva-Maria, additional, Laitinen, Saara, additional, Lässer, Cecilia, additional, Lener, Thomas, additional, Ligeti, Erzsébet, additional, Linē, Aija, additional, Lipps, Georg, additional, Llorente, Alicia, additional, Lötvall, Jan, additional, Manček-Keber, Mateja, additional, Marcilla, Antonio, additional, Mittelbrunn, Maria, additional, Nazarenko, Irina, additional, Nolte-‘t Hoen, Esther N.M., additional, Nyman, Tuula A., additional, O'Driscoll, Lorraine, additional, Olivan, Mireia, additional, Oliveira, Carla, additional, Pállinger, Éva, additional, del Portillo, Hernando A., additional, Reventós, Jaume, additional, Rigau, Marina, additional, Rohde, Eva, additional, Sammar, Marei, additional, Sánchez-Madrid, Francisco, additional, Santarém, N., additional, Schallmoser, Katharina, additional, Stampe Ostenfeld, Marie, additional, Stoorvogel, Willem, additional, Stukelj, Roman, additional, Van der Grein, Susanne G., additional, Helena Vasconcelos, M., additional, Wauben, Marca H. M., additional, and De Wever, Olivier, additional

Published
2015
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130. Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal carcinoma

Author

Walsh, Naomi, Larkin, Anne-Marie, Kennedy, Susan, Connolly, Lisa, Ballot, Jo, Ooi, Wei, Gullo, Giuseppe, Crown, John, Clynes, Martin, and O'Driscoll, Lorraine

Subjects
multidrug resistance, immunohistochemistry, renal cell carcinoma, cancer, MDR1/P-glycoprotein, multi drug resistance protein 1, Cancer
Abstract

Background: Renal cancer patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. Methods: The aim of this prospective study was to analyse by immunohistochemistry the expression of two of these transporter efflux pumps, namely MDR-1/P-gp (ABCB1) and MRP-1 (ABCC1) in archival material from 113 renal carcinoma patients. Results: In the largest study of its kind, results presented here show 100% of cases stained positively for P-gp and MRP-1 protein expression. Conclusion: However, although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

Published
2009

132. Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors

Author

Rani, Sweta, primary, Corcoran, Claire, additional, Shiels, Liam, additional, Germano, Serena, additional, Breslin, Susan, additional, Madden, Stephen, additional, McDermott, Martina S., additional, Browne, Brigid C., additional, O'Donovan, Norma, additional, Crown, John, additional, Gogarty, Martina, additional, Byrne, Annette T., additional, and O'Driscoll, Lorraine, additional

Published
2014
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133. Predictive biomarkers for dasatinib treatment in melanoma

Author

Eustace, Alex J., primary, Kennedy, Susan, additional, Larkin, Anne-Marie, additional, Mahgoub, Thamir, additional, Tryfonopoulos, Dimitrios, additional, O'Driscoll, Lorraine, additional, Clynes, Martin, additional, Crown, John, additional, and O'Donovan, Norma, additional

Published
2014
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134. Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma

Author

Rani, Sweti, Gately, Kathy, Crown, John, O'Byrne, Kenneth, O'Driscoll, Lorraine, Rani, Sweti, Gately, Kathy, Crown, John, O'Byrne, Kenneth, and O'Driscoll, Lorraine

Abstract

Free to read Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNA s have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNA s have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNA s were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNA s. Overall, approximately 390 and 370 miRNA s were detected in ADC and control sera, respectively. A group of 6 miRNA s, miR-30c-1* (AU C = 0.74; P < 0.002), miR-616(AU C = 0.71; P = 0.001), miR-146b-3p (AU C = 0.82; P < 0.0001), miR-566 (AU C = 0.80; P < 0.0001), miR-550 (AU C = 0.72; P = 0.0006), and miR-939 (AU C = 0.82; P < 0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AU C = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNA s having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNA s as minimally invasive biomarkers for ADC.

Published
2013

139. The use of LC-MS to identify differentially expressed proteins in docetaxel-resistant prostate cancer cell lines

Author

O'Connell, Kathleen, Prencipe, Maria, O'Neill, Amanda, Corcoran, Claire, Rani, Sweta, Henry, Michael, Dowling, Paul, Meleady, Paula, O'Driscoll, Lorraine, Watson, William, O'Connor, Robert, O'Connell, Kathleen, Prencipe, Maria, O'Neill, Amanda, Corcoran, Claire, Rani, Sweta, Henry, Michael, Dowling, Paul, Meleady, Paula, O'Driscoll, Lorraine, Watson, William, and O'Connor, Robert

Abstract

Docetaxel is a taxane-derived chemotherapy drug that has been approved for treatment of prostate cancer. While docetaxel is frequently used as a treatment for hormone-refractory prostate cancer, a subset of patients either do not respond to this treatment or those that do respond eventually become resistant to the drug over time. Resistance to docetaxel is complex and multi-factoral and further understanding of the cellular biochemistry underlying resistance is vital to improve treatment efficacy. To identify proteins altered in the resistant phenotype, three parental cell lines DU145, 22RV1 and PC-3, as well as their docetaxel resistant sub-lines, were subjected to quantitative label-free LC-MS proteomic profiling. A total of 189 significant (p < 0.05) protein abundance changes were identified in the DU145 resistant sub-lines, 254 in the 22RV1 sub-lines, and 51 and 72 in the 8 and 12 nM resistant PC-3 sub-lines, respectively. From these, 29 proteins demonstrated a significant (p < 0.05) fold change across two or more resistant variants. These included proteins indicative of an epithelial-to-mesenchemyl transition as well as altered heat shock response elements.

Published
2012

140. Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis

Author

Walsh, Naomi, Kennedy, Susan, Larkin, Anne-Marie, Tryfonopoulos, Dimitrios, Eustace, Alexander J., Mahgoub, Thamir, Conway, Catherine, Oglesby, Irene, Collins, Denis, Ballot, Jo, Ooi, Wei, Gullo, Giuseppe, Clynes, Martin, Crown, John, O'Driscoll, Lorraine, Walsh, Naomi, Kennedy, Susan, Larkin, Anne-Marie, Tryfonopoulos, Dimitrios, Eustace, Alexander J., Mahgoub, Thamir, Conway, Catherine, Oglesby, Irene, Collins, Denis, Ballot, Jo, Ooi, Wei, Gullo, Giuseppe, Clynes, Martin, Crown, John, and O'Driscoll, Lorraine

Abstract

BACKGROUND: Malignant melanoma, generally described as incurable, is notoriously refractory to chemotherapy. The mechanisms contributing to this have not yet been defined and the contributions of drug efflux pumps, implicated in chemo-resistance of many other cancer types, have not been extensively investigated in melanoma. METHODS: In this study, expression of multi-drug resistant (MDR1/P-gp and MRP-1) proteins was examined, by immunohistochemistry, in archival specimens from 134 melanoma patients. This included 92 primary tumours and 42 metastases. RESULTS: On assessing all specimens, MRP-1 and MDR1/P-gp expression was found to be common, with the majority (81%) of melanomas expressing at least one of these efflux pumps. Although there is significant association between expression of these pumps (P=0.007), MRP-1 was found to be the predominant (67% of cases) form detected. chi(2) analysis showed significant associations between expression of MRP-1 and/or MDR1/P-gp and the aggressive nature of this disease specifically increased Breslow's depth, Clark's level and spread to lymph nodes. This association with aggressiveness and spread is further supported by the observation that a significantly higher percentage of metastases, than primary tumours, express MRP-1 (91% vs 57%; P<0.0001) and MDR1/P-gp (74% vs 50%; P=0.010). CONCLUSION: The predominant expression of these pumps and, in particular, MRP-1 suggests that they may be important contributors to the inherent aggressive and resistant nature of malignant melanoma.

Published
2010

141. Molecular medicine of microRNAs: structure, function and implications for diabetes

Author

Hennessy, Erica, O'Driscoll, Lorraine, Hennessy, Erica, and O'Driscoll, Lorraine

Abstract

MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19–28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic β-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes.

Published
2008

142. Proteomic analysis of conditioned media from glucose responsive and glucose nonresponsive phenotypes reveals a panel of secreted proteins associated with beta cell dysfunction

Author

Dowling, Paul, Shields, William, Rani, Sweta, Meleady, Paula, Henry, Michael, Jeppesen, Per Bendix, O'Driscoll, Lorraine, Clynes, Martin, Dowling, Paul, Shields, William, Rani, Sweta, Meleady, Paula, Henry, Michael, Jeppesen, Per Bendix, O'Driscoll, Lorraine, and Clynes, Martin

Abstract

Media conditioned by dysfunctioning pancreatic beta cells offer an excellent source of potential protein markers associated with this phenotype. Proteins identified from cell culture model systems are often found to be of importance clinically. Previous work by us and others have shown that low-passage MIN-6 cells (MIN-6(L)) respond to changes in glucose concentrations, producing an approximately 5.5-fold glucose-stimulated insulin secretion (GSIS) in response to 26.7 mmol/L, compared with 3.3 mmol/L, glucose. After continuous culture or high-passage (MIN-(H)), this GSIS was no longer present and thus represents an excellent model system for investigating beta cell dysfunction. Employing 2-D difference gel electrophoresis and mass spectrometry a panel of protein markers were identified in conditioned media (CM) from MIN-6(L) and MIN-6(H) beta cells. These proteins, including secretogranin II, secretogranin III and transthyretin, are associated with secretory granule biogenesis and were found to have substantially increased levels in the CM from the non-responsive high-passage MIN-6 beta cells. A panel of protein markers found to have increased abundance levels in CM from MIN- 6(H) compared with MIN-6(L) beta cells may have the potential to be used clinically for assessing beta cell function and to monitor the effects of specific therapeutics.

Published
2008

148. 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteins

Author

Dowling, Paul, O'Driscoll, Lorraine, Meleady, Paula, Henry, Michael, Roy, Shunil, Ballot, Jo, Moriarty, Michael, Crown, John, Clynes, Martin, Dowling, Paul, O'Driscoll, Lorraine, Meleady, Paula, Henry, Michael, Roy, Shunil, Ballot, Jo, Moriarty, Michael, Crown, John, and Clynes, Martin

Abstract

Most lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples. Proteins found to have increased abundance levels in squamous cell carcinoma sera compared to normal sera included apolipoprotein A-IV precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A protein precursor and Ras-related protein Rab-7b. Proteins found to have lower abundance levels in squamous cell carcinoma sera compared to normal sera included alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III and SP40; 40. The data presented here demonstrate that high-abundant protein removal combined with 2-D DIGE is a powerful strategy for the discovery of potential biomarkers. The identification of lung cancer-specific biomarkers is crucial to early detection, which in turn could lead to a dramatic increase in survival rates.

Published
2007

149. Docetaxel-Resistance in Prostate Cancer: Evaluating Associated Phenotypic Changes and Potential for Resistance Transfer via Exosomes

Author

Corcoran, Claire, primary, Rani, Sweta, additional, O’Brien, Keith, additional, O’Neill, Amanda, additional, Prencipe, Maria, additional, Sheikh, Rizwan, additional, Webb, Glenn, additional, McDermott, Ray, additional, Watson, William, additional, Crown, John, additional, and O’Driscoll, Lorraine, additional

Published
2012
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150. Proteomic screening of glucose-responsive and glucose non-responsive MIN-6 beta cells reveals differential expression of proteins involved in protein folding, secretion and oxidative stress

Author

Dowling, Paul, O'Driscoll, Lorraine, O'Sullivan, Finbarr, Dowd, Andrew, Henry, Michael, Jeppesen, Per Bendix, Meleady, Paula, Clynes, Martin, Dowling, Paul, O'Driscoll, Lorraine, O'Sullivan, Finbarr, Dowd, Andrew, Henry, Michael, Jeppesen, Per Bendix, Meleady, Paula, and Clynes, Martin

Abstract

The glucose-sensitive insulin-secretion (GSIS) phenotype is relatively unstable in long-term culture of beta cells. The purpose of this study was to investigate relative changes in the proteome between glucose-responsive (low passage) and glucose non-responsive (high passage) murine MIN-6 pancreatic beta cells. The 2D-DIGE and subsequent DeCyder analysis detected 3351 protein spots in the pH range of 4–7. Comparing MIN-6(H) to MIN-6(L) and using a threshold of 1.2-fold, the number of proteins with a decrease in expression level was 152 (4.5%), similar was 3140 (93.7%) and increased 59 (1.8%). From the differentially expressed proteins identified in this study, groups of proteins associated with the endoplasmic reticulum (ER) and proteins involved in oxidative stress were found to be significantly decreased in the high-passage (H passage) cells. These proteins included endoplasmic reticulum protein 29 (ERp29); 78-kDa glucoserelated protein, (GRP78); 94-kDa glucose-related protein (GRP94); protein disulphide isomerase; carbonyl reductase 3; peroxidoxin 4 and superoxide dismutase 1. These results suggest that non- GSIS MIN-6 cells do not have the same ability/capacity of glucose-responsive MIN-6 cells to successfully fold, modify or secrete proteins and counteract the problems associated with oxidative stress.

Published
2006

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