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6. Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

Author

Pagnamenta, Alistair T., Camps, Carme, Giacopuzzi, Edoardo, Taylor, John M., Hashim, Mona, Calpena, Eduardo, Kaisaki, Pamela J., Hashimoto, Akiko, Yu, Jing, Sanders, Edward, Schwessinger, Ron, Hughes, Jim R., Lunter, Gerton, Dreau, Helene, Ferla, Matteo, Lange, Lukas, Kesim, Yesim, Ragoussis, Vassilis, Vavoulis, Dimitrios V., Allroggen, Holger, Ansorge, Olaf, Babbs, Christian, Banka, Siddharth, Baños-Piñero, Benito, Beeson, David, Ben-Ami, Tal, Bennett, David L., Bento, Celeste, Blair, Edward, Brasch-Andersen, Charlotte, Bull, Katherine R., Cario, Holger, Cilliers, Deirdre, Conti, Valerio, Davies, E. Graham, Dhalla, Fatima, Dacal, Beatriz Diez, Dong, Yin, Dunford, James E., Guerrini, Renzo, Harris, Adrian L., Hartley, Jane, Hollander, Georg, Javaid, Kassim, Kane, Maureen, Kelly, Deirdre, Kelly, Dominic, Knight, Samantha J. L., Kreins, Alexandra Y., Kvikstad, Erika M., Langman, Craig B., Lester, Tracy, Lines, Kate E., Lord, Simon R., Lu, Xin, Mansour, Sahar, Manzur, Adnan, Maroofian, Reza, Marsden, Brian, Mason, Joanne, McGowan, Simon J., Mei, Davide, Mlcochova, Hana, Murakami, Yoshiko, Németh, Andrea H., Okoli, Steven, Ormondroyd, Elizabeth, Ousager, Lilian Bomme, Palace, Jacqueline, Patel, Smita Y., Pentony, Melissa M., Pugh, Chris, Rad, Aboulfazl, Ramesh, Archana, Riva, Simone G., Roberts, Irene, Roy, Noémi, Salminen, Outi, Schilling, Kyleen D., Scott, Caroline, Sen, Arjune, Smith, Conrad, Stevenson, Mark, Thakker, Rajesh V., Twigg, Stephen R. F., Uhlig, Holm H., van Wijk, Richard, Vona, Barbara, Wall, Steven, Wang, Jing, Watkins, Hugh, Zak, Jaroslav, Schuh, Anna H., Kini, Usha, Wilkie, Andrew O. M., Popitsch, Niko, and Taylor, Jenny C.

Published
2023
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10. The impact of survivorship bias in glioblastoma research

Author

Pasqualetti, Francesco, Barberis, Alessandro, Zanotti, Sofia, Montemurro, Nicola, De Salvo, Gian Luca, Soffietti, Riccardo, Mazzanti, Chiara Maria, Ius, Tamara, Caffo, Maria, Paiar, Fabiola, Bocci, Guido, Lombardi, Giuseppe, Harris, Adrian L., and Buffa, Francesca M.

Published
2023
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12. Landscape of transcriptomic interactions between breast cancer and its microenvironment.

Author

Fox, Natalie S, Haider, Syed, Harris, Adrian L, and Boutros, Paul C

Subjects
Biomarkers, Tumor, Breast Neoplasms, Clinical Decision-Making, Female, Gene Expression Profiling, Humans, Prognosis, RNA, Messenger, Tumor Microenvironment, Cancer, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, Biomarkers, Tumor, RNA, Messenger
Abstract

Solid tumours comprise mixtures of tumour cells (TCs) and tumour-adjacent cells (TACs), and the intricate interconnections between these diverse populations shape the tumour's microenvironment. Despite this complexity, clinical genomic profiling is typically performed from bulk samples, without distinguishing TCs from TACs. To better understand TC-TAC interactions, we computationally distinguish their transcriptomes in 1780 primary breast tumours. We show that TC and TAC mRNA abundances are divergently associated with clinical phenotypes, including tumour subtypes and patient survival. These differences reflect distinct responses of TCs and TACs to specific somatic driver mutations, particularly TP53. These data further elucidate how the molecular interplay between breast tumours and their microenvironment drives aggressive tumour phenotypes.

Published
2019

13. Author Correction: Normal tissue radioprotection by amifostine via Warburg-type effects.

Author

Koukourakis, Michael I., Giatromanolaki, Alexandra, Zois, Christos E., Kalamida, Dimitra, Pouliliou, Stamatia, Karagounis, Ilias V., Yeh, Tzu-Lan, Abboud, Martine I., Claridge, Timothy D. W., Schofield, Christopher J., Sivridis, Efthimios, Simopoulos, Costantinos, Tokmakidis, Savvas P., and Harris, Adrian L.

Subjects
CONFOCAL fluorescence microscopy, MEMBRANE potential, GENE expression, LIVER cells, CONFOCAL microscopy
Abstract

The correction notice in Scientific Reports addresses errors in the original article regarding the figure assembly process. The correction includes updated figures showing the correct images for specific time points related to the effects of amifostine on normal tissue radioprotection. The authors, including Michael I. Koukourakis and Adrian L. Harris, conducted experiments on mouse liver cells and hepatoma cells to analyze the impact of amifostine on anaerobic metabolism and mitochondrial function. The correction ensures the accuracy of the research findings presented in the article. [Extracted from the article]

Published
2025
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16. Consensus guidelines for the use and interpretation of angiogenesis assays

Author

Nowak-Sliwinska, Patrycja, Alitalo, Kari, Allen, Elizabeth, Anisimov, Andrey, Aplin, Alfred C, Auerbach, Robert, Augustin, Hellmut G, Bates, David O, van Beijnum, Judy R, Bender, R Hugh F, Bergers, Gabriele, Bikfalvi, Andreas, Bischoff, Joyce, Böck, Barbara C, Brooks, Peter C, Bussolino, Federico, Cakir, Bertan, Carmeliet, Peter, Castranova, Daniel, Cimpean, Anca M, Cleaver, Ondine, Coukos, George, Davis, George E, De Palma, Michele, Dimberg, Anna, Dings, Ruud PM, Djonov, Valentin, Dudley, Andrew C, Dufton, Neil P, Fendt, Sarah-Maria, Ferrara, Napoleone, Fruttiger, Marcus, Fukumura, Dai, Ghesquière, Bart, Gong, Yan, Griffin, Robert J, Harris, Adrian L, Hughes, Christopher CW, Hultgren, Nan W, Iruela-Arispe, M Luisa, Irving, Melita, Jain, Rakesh K, Kalluri, Raghu, Kalucka, Joanna, Kerbel, Robert S, Kitajewski, Jan, Klaassen, Ingeborg, Kleinmann, Hynda K, Koolwijk, Pieter, Kuczynski, Elisabeth, Kwak, Brenda R, Marien, Koen, Melero-Martin, Juan M, Munn, Lance L, Nicosia, Roberto F, Noel, Agnes, Nurro, Jussi, Olsson, Anna-Karin, Petrova, Tatiana V, Pietras, Kristian, Pili, Roberto, Pollard, Jeffrey W, Post, Mark J, Quax, Paul HA, Rabinovich, Gabriel A, Raica, Marius, Randi, Anna M, Ribatti, Domenico, Ruegg, Curzio, Schlingemann, Reinier O, Schulte-Merker, Stefan, Smith, Lois EH, Song, Jonathan W, Stacker, Steven A, Stalin, Jimmy, Stratman, Amber N, Van de Velde, Maureen, van Hinsbergh, Victor WM, Vermeulen, Peter B, Waltenberger, Johannes, Weinstein, Brant M, Xin, Hong, Yetkin-Arik, Bahar, Yla-Herttuala, Seppo, Yoder, Mervin C, and Griffioen, Arjan W

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cardiovascular, Animals, Biological Assay, Guidelines as Topic, Humans, Mice, Neoplasms, Neovascularization, Pathologic, Angiogenesis, Aortic ring, Endothelial cell migration, Proliferation, Microfluidic, Zebrafish, Chorioallantoic membrane, Vascular network, Intussusceptive angiogenesis, Retinal vasculature, Corneal angiogenesis, Hindlimb ischemia, Myocardial angiogenesis, Recombinant proteins, Tip cells, Plug assay, Vessel co-option, Clinical Sciences, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology
Abstract

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Published
2018

17. Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions

Author

Westbrook, Rebecca L., Bridges, Esther, Roberts, Jennie, Escribano-Gonzalez, Cristina, Eales, Katherine L., Vettore, Lisa A., Walker, Paul D., Vera-Siguenza, Elias, Rana, Himani, Cuozzo, Federica, Eskla, Kattri-Liis, Vellama, Hans, Shaaban, Abeer, Nixon, Colin, Luuk, Hendrik, Lavery, Gareth G., Hodson, David J., Harris, Adrian L., and Tennant, Daniel A.

Published
2022
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19. The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition

Author

Azzoni, Emanuele, Frontera, Vincent, Anselmi, Giorgio, Rode, Christina, James, Chela, Deltcheva, Elitza M., Demian, Atanasiu S., Brown, John, Barone, Cristiana, Patelli, Arianna, Harman, Joe R., Nicholls, Matthew, Conway, Simon J., Morrissey, Edward, Jacobsen, Sten Eirik W., Sparrow, Duncan B., Harris, Adrian L., Enver, Tariq, and de Bruijn, Marella F.T.R.

Published
2021
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22. Autophagy Blockage Up-Regulates HLA-Class-I Molecule Expression in Lung Cancer and Enhances Anti-PD-L1 Immunotherapy Efficacy.

Author

Xanthopoulou, Erasmia, Lamprou, Ioannis, Mitrakas, Achilleas G., Michos, Georgios D., Zois, Christos E., Giatromanolaki, Alexandra, Harris, Adrian L., and Koukourakis, Michael I.

Subjects
PROTEINS, IN vitro studies, PROTEIN kinase inhibitors, FLOW cytometry, AUTOPHAGY, T cells, RESEARCH funding, IMMUNOTHERAPY, PROGRAMMED death-ligand 1, APOPTOSIS, TREATMENT effectiveness, REVERSE transcriptase polymerase chain reaction, DESCRIPTIVE statistics, CHLOROQUINE, IMMUNODIAGNOSIS, CYTOSKELETAL proteins, IMMUNE checkpoint inhibitors, GENE expression, CELL lines, ANTIGENS, IMMUNOHISTOCHEMISTRY, MONOCLONAL antibodies, MESSENGER RNA, WESTERN immunoblotting, LUNG cancer, MACROLIDE antibiotics, HLA-B27 antigen, CELL surface antigens, PHARMACODYNAMICS, CHEMICAL inhibitors
Abstract

Simple Summary: The restoration of HLA-class-I expression in lung cancer cells may reverse immune evasion, enhance cytotoxic T-cell activity, and improve immune checkpoint inhibitors' therapeutic efficacy. In the current study, we provide experimental evidence that autophagy blockage either at the late stage (chloroquine and bafilomycin) or early stage of the autophagic process (ULK1 inhibitors and MAP1LC3A silencing) can up-regulate the expression of HLA-class-I molecules in the A549 and H1299 NSCLC cell lines and their CD133+ stem cells. This upregulation enhances the cytotoxic activity of activated CD8+ T-cells, in particular after pre-incubation with anti-PD-L1 monoclonal antibodies. The restoration of HLA-class-I-mediated antigen presentation with autophagy blockers in lung cancer is a promising avenue that urgently requires further exploration in clinical trials. Background/Objectives: Immune checkpoint inhibitors have an established role in non-small cell lung cancer (NSCLC) therapy. The loss of HLA-class-I expression allows cancer cell evasion from immune surveillance, disease progression, and failure of immunotherapy. The restoration of HLA-class-I expression may prove to be a game-changer in current immunotherapy strategies. Autophagic activity has been recently postulated to repress HLA-class-I expression in cancer cells. Methods: NSCLC cell lines (A549 and H1299) underwent late-stage (chloroquine and bafilomycin) and early-stage autophagy blockage (ULK1 inhibitors and MAP1LC3A silencing). The HLA-class-I expression was assessed with flow cytometry, a Western blot, and RT-PCR. NSCLC tissues were examined for MAP1LC3A and HLA-class-I expression using double immunohistochemistry. CD8+ T-cell cytotoxicity was examined in cancer cells pre-incubated with chloroquine and anti-PD-L1 monoclonal antibodies (Moabs); Results: A striking increase in HLA-class-I expression following incubation with chloroquine, bafilomycin, and IFNγ was noted in A549 and H1299 cancer cells, respectively. This effect was further confirmed in CD133+ cancer stem cells. HLA-class-I, β2-microglobulin, and TAP1 mRNA levels remained stable. Prolonged exposure to chloroquine further enhanced HLA-class-I expression. Similar results were noted following exposure to a ULK1 and a PIKfyve inhibitor. Permanent silencing of the MAP1LC3A gene resulted in enhanced HLA-class-I expression. In immunohistochemistry experiments, double LC3A+/HLA-class-I expression was seldom. Pre-incubation of H1299 cancer cells with chloroquine and anti-PD-L1 MoAbs increased the mean % of apoptotic/necrotic cells from 2.5% to 18.4%; Conclusions: Autophagy blockers acting either at late or early stages of the autophagic process may restore HLA-class-I-mediated antigen presentation, eventually leading to enhanced immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Liver glycogen phosphorylase is upregulated in glioblastoma and provides a metabolic vulnerability to high dose radiation

Author

Zois, Christos E., Hendriks, Anne M., Haider, Syed, Pires, Elisabete, Bridges, Esther, Kalamida, Dimitra, Voukantsis, Dimitrios, Lagerholm, B. Christoffer, Fehrmann, Rudolf S. N., den Dunnen, Wilfred F. A., Tarasov, Andrei I., Baba, Otto, Morris, John, Buffa, Francesca M., McCullagh, James S. O., Jalving, Mathilde, and Harris, Adrian L.

Published
2022
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24. APP and β-amyloid modulate protein aggregation and dissociation from recycling endosomal and exosomal membranes

Author

Singh, Preman J, primary, Verma, Bhavna, additional, Wells, Adam, additional, Mendes, Claudia C, additional, Dunn, Dali, additional, Chen, Ying-Ni, additional, Oh, Jade, additional, Blincowe, Lewis, additional, Wainwright, Mark, additional, Fischer, Roman, additional, Fan, Shih-Jung, additional, Harris, Adrian L, additional, Goberdhan, Deborah CI, additional, and Wilson, Clive, additional

Published
2024
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29. HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Author

de Heer, Ellen C., Jalving, Mathilde, and Harris, Adrian L.

Subjects
Physiological aspects, International economic relations, Development and progression, Prognosis, Health aspects, Cancer treatment -- Physiological aspects -- Health aspects, Bevacizumab -- Health aspects -- Physiological aspects, Amino acids -- Physiological aspects -- Health aspects, Breast cancer -- Development and progression -- Prognosis
Abstract

Introduction Breast cancer is the cancer type with the highest prevalence and, despite therapeutic advances, still has the second highest cancer-related mortality rate in women (1). In breast cancer, low [...], Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing of escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in patients with breast cancer. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

Published
2020
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31. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Author

Welsh, Joshua A., Goberdhan, Deborah C. I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A. P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing-Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., Faustino, Vroniqa Ku’ulei-Lyn, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M., Lötvall, Jan, Maddox, Adam L., Martens-Uzunova, Elena S., Mizenko, Rachel R., Newman, Lauren A., Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S., Saugstad, Julie A., Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P., Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J. C., Wauben, Marca H. M., Wehman, Ann M., Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J., MISEV Consortium, Thery, Clotilde, Witwer, Kenneth W., Welsh, Joshua A., Goberdhan, Deborah C. I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A. P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing-Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., Faustino, Vroniqa Ku’ulei-Lyn, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M., Lötvall, Jan, Maddox, Adam L., Martens-Uzunova, Elena S., Mizenko, Rachel R., Newman, Lauren A., Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S., Saugstad, Julie A., Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P., Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J. C., Wauben, Marca H. M., Wehman, Ann M., Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J., MISEV Consortium, Thery, Clotilde, and Witwer, Kenneth W.

Abstract

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly., Godkänd;2024;Nivå 0;2024-04-05 (marisr);Full text license: CC BY

Published
2024
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32. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Author

Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, null, Théry, Clotilde, Witwer, Kenneth W, Stoorvogel, Willem, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, null, Théry, Clotilde, Witwer, Kenneth W, and Stoorvogel, Willem

Abstract

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Published
2024

33. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Author

CDL extracellular vesicles, MS Nefrologie, Circulatory Health, CDL Nanomedicine, CDL Staf Research, CMM Groep Coffer, Cancer, Regenerative Medicine and Stem Cells, Zorgeenheid MKA/BT Medisch, MKA/BT Onderzoek, Experimentele Afd. Cardiologie 2, Centraal Diagnostisch Laboratorium, Experimental Cardiology Laboratory, Onderzoek Cardiovasculair Reg. Med., CDL Cluster Onderzoek en Onderwijs, Welsh, Joshua A., Goberdhan, Deborah C.I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A.P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., MISEV Consortium, CDL extracellular vesicles, MS Nefrologie, Circulatory Health, CDL Nanomedicine, CDL Staf Research, CMM Groep Coffer, Cancer, Regenerative Medicine and Stem Cells, Zorgeenheid MKA/BT Medisch, MKA/BT Onderzoek, Experimentele Afd. Cardiologie 2, Centraal Diagnostisch Laboratorium, Experimental Cardiology Laboratory, Onderzoek Cardiovasculair Reg. Med., CDL Cluster Onderzoek en Onderwijs, Welsh, Joshua A., Goberdhan, Deborah C.I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A.P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, M˜y, G. Mahoney, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Hendrix, An, Ivanov, Alexander R., Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A., and MISEV Consortium

Published
2024

34. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Author

Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, Théry, Clotilde, Witwer, Kenneth W, Stoorvogel, Willem, Celbiologie, Cell Biology, Metabolism & Cancer - Cellbiology, Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Buzas, Edit I, Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A P, Erdbrügger, Uta, Falcon-Perez, Juan M, Fu, Qing-Ling, Hill, Andrew F, Lenassi, Metka, Lim, Sai Kiang, Mahoney, Mỹ G, Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C, Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M, Brucale, Marco, Burger, Dylan, Carney, Randy P, Cocucci, Emanuele, Colombo, Federico, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L, Haughey, Norman J, Hendrix, An, Ivanov, Alexander R, Jovanovic-Talisman, Tijana, Kruh-Garcia, Nicole A, Ku'ulei-Lyn Faustino, Vroniqa, Kyburz, Diego, Lässer, Cecilia, Lennon, Kathleen M, Lötvall, Jan, Maddox, Adam L, Martens-Uzunova, Elena S, Mizenko, Rachel R, Newman, Lauren A, Ridolfi, Andrea, Rohde, Eva, Rojalin, Tatu, Rowland, Andrew, Saftics, Andras, Sandau, Ursula S, Saugstad, Julie A, Shekari, Faezeh, Swift, Simon, Ter-Ovanesyan, Dmitry, Tosar, Juan P, Useckaite, Zivile, Valle, Francesco, Varga, Zoltan, van der Pol, Edwin, van Herwijnen, Martijn J C, Wauben, Marca H M, Wehman, Ann M, Williams, Sarah, Zendrini, Andrea, Zimmerman, Alan J, Misev Consortium, Théry, Clotilde, Witwer, Kenneth W, and Stoorvogel, Willem

Published
2024

35. Minimal information for studies of extracellular vesicles (MISEV2023):From basic to advanced approaches

Author

Welsh, Joshua A., Goberdhan, Deborah C.I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A.P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, Mahoney, M. ỹ.G., Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Benediktsdóttir, Berglind E., Gargiulo, Ernesto, Gori, Alessandro, Guo, Wei, Hufnagel, Antonia, Di Ianni, Emilio, Jacobsen, Soren, Li, Bo, Mellergaard, Maiken, Nejsum, Peter, Nolan, John P., Østergaard, Ole, Yarani, Reza, Yin, Hang, Welsh, Joshua A., Goberdhan, Deborah C.I., O’Driscoll, Lorraine, Buzas, Edit I., Blenkiron, Cherie, Bussolati, Benedetta, Cai, Houjian, Di Vizio, Dolores, Driedonks, Tom A.P., Erdbrügger, Uta, Falcon-Perez, Juan M., Fu, Qing Ling, Hill, Andrew F., Lenassi, Metka, Lim, Sai Kiang, Mahoney, M. ỹ.G., Mohanty, Sujata, Möller, Andreas, Nieuwland, Rienk, Ochiya, Takahiro, Sahoo, Susmita, Torrecilhas, Ana C., Zheng, Lei, Zijlstra, Andries, Abuelreich, Sarah, Bagabas, Reem, Bergese, Paolo, Bridges, Esther M., Brucale, Marco, Burger, Dylan, Carney, Randy P., Cocucci, Emanuele, Crescitelli, Rossella, Hanser, Edveena, Harris, Adrian L., Haughey, Norman J., Benediktsdóttir, Berglind E., Gargiulo, Ernesto, Gori, Alessandro, Guo, Wei, Hufnagel, Antonia, Di Ianni, Emilio, Jacobsen, Soren, Li, Bo, Mellergaard, Maiken, Nejsum, Peter, Nolan, John P., Østergaard, Ole, Yarani, Reza, and Yin, Hang

Abstract

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly., Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Published
2024

40. Interferon- and STING-independent induction of type I interferon stimulated genes during fractionated irradiation

Author

Goedegebuure, Ruben S. A., Kleibeuker, Esther A., Buffa, Francesca M., Castricum, Kitty C. M., Haider, Syed, Schulkens, Iris A., ten Kroode, Luuk, van den Berg, Jaap, Jacobs, Maarten A. J. M., van Berkel, Anne-Marie, van Grieken, Nicole C. T., Derks, Sarah, Slotman, Ben J., Verheul, Henk M. W., Harris, Adrian L., and Thijssen, Victor L.

Published
2021
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44. Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER.

Author

van den Beucken, Twan, Koch, Elizabeth, Chu, Kenneth, Rupaimoole, Rajesha, Prickaerts, Peggy, Adriaens, Michiel, Voncken, Jan Willem, Harris, Adrian L, Buffa, Francesca M, Haider, Syed, Starmans, Maud HW, Yao, Cindy Q, Ivan, Mircea, Ivan, Cristina, Pecot, Chad V, Boutros, Paul C, Sood, Anil K, Koritzinsky, Marianne, and Wouters, Bradly G

Subjects
Humans, Breast Neoplasms, Ribonuclease III, Prognosis, Cell Hypoxia, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Silencing, RNA Processing, Post-Transcriptional, Phenotype, Female, DEAD-box RNA Helicases, Neoplastic Stem Cells, Promoter Regions, Genetic, Epithelial-Mesenchymal Transition, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, RNA Processing, Post-Transcriptional, Promoter Regions
Abstract

MicroRNAs are small regulatory RNAs that post transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet, the underlying mechanisms are not well understood. Here we identify tumour hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumour stem cell phenotypes that may underlie poor outcome in breast cancer.

Published
2014

45. Stress‐induced Rab11a‐exosomes induce amphiregulin‐mediated cetuximab resistance in colorectal cancer.

Author

Mason, John D., Marks, Ewan, Fan, Shih‐Jung, McCormick, Kristie, Wilson, Clive, Harris, Adrian L., Hamdy, Freddie C., Cunningham, Chris, and Goberdhan, Deborah C. I.

Subjects
CETUXIMAB, COLORECTAL cancer, EPIDERMAL growth factor receptors
Abstract

Exosomes are secreted vesicles made intracellularly in the endosomal system. We have previously shown that exosomes are not only made in late endosomes, but also in recycling endosomes marked by the monomeric G‐protein Rab11a. These vesicles, termed Rab11a‐exosomes, are preferentially secreted under nutrient stress from several cancer cell types, including HCT116 colorectal cancer (CRC) cells. HCT116 Rab11a‐exosomes have particularly potent signalling activities, some mediated by the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG). Mutant activating forms of KRAS, a downstream target of EGFR, are often found in advanced CRC. When absent, monoclonal antibodies, such as cetuximab, which target the EGFR and block the effects of EGFR ligands, such as AREG, can be administered. Patients, however, inevitably develop resistance to cetuximab, either by acquiring KRAS mutations or via non‐genetic microenvironmental changes. Here we show that nutrient stress in several CRC cell lines causes the release of AREG‐carrying Rab11a‐exosomes. We demonstrate that while soluble AREG has no effect, much lower levels of AREG bound to Rab11a‐exosomes from cetuximab‐resistant KRAS‐mutant HCT116 cells, can suppress the effects of cetuximab on KRAS‐wild type Caco‐2 CRC cells. Using neutralising anti‐AREG antibodies and an intracellular EGFR kinase inhibitor, we show that this effect is mediated via AREG activation of EGFR, and not transfer of activated KRAS. Therefore, presentation of AREG on Rab11a‐exosomes affects its ability to compete with cetuximab. We propose that this Rab11a‐exosome‐mediated mechanism contributes to the establishment of resistance in cetuximab‐sensitive cells and may explain why in cetuximab‐resistant tumours only some cells carry mutant KRAS. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer

Author

Lord, Simon R., Cheng, Wei-Chen, Liu, Dan, Gaude, Edoardo, Haider, Syed, Metcalf, Tom, Patel, Neel, Teoh, Eugene J., Gleeson, Fergus, Bradley, Kevin, Wigfield, Simon, Zois, Christos, McGowan, Daniel R., Ah-See, Mei-Lin, Thompson, Alastair M., Sharma, Anand, Bidaut, Luc, Pollak, Michael, Roy, Pankaj G., Karpe, Fredrik, James, Tim, English, Ruth, Adams, Rosie F., Campo, Leticia, Ayers, Lisa, Snell, Cameron, Roxanis, Ioannis, Frezza, Christian, Fenwick, John D., Buffa, Francesca M., and Harris, Adrian L.

Published
2018
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49. High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer

Author

Kawashima, Masahiro, Tokiwa, Mariko, Nishimura, Tomomi, Kawata, Yukiko, Sugimoto, Masahiro, Kataoka, Tatsuki R., Sakurai, Takaki, Iwaisako, Keiko, Suzuki, Eiji, Hagiwara, Masatoshi, Harris, Adrian L., and Toi, Masakazu

Published
2020
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50. Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin

Author

Lord, Simon R., Collins, Jennifer M., Cheng, Wei-Chen, Haider, Syed, Wigfield, Simon, Gaude, Edoardo, Fielding, Barbara A., Pinnick, Katherine E., Harjes, Ulrike, Segaran, Ashvina, Jha, Pooja, Hoefler, Gerald, Pollak, Michael N., Thompson, Alastair M., Roy, Pankaj G., English, Ruth., Adams, Rosie F., Frezza, Christian, Buffa, Francesca M., Karpe, Fredrik, and Harris, Adrian L.

Published
2020
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