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29 results on '"Abels, Erik R."'

2. Overcoming Barriers in Glioblastoma—Advances in Drug Delivery Strategies.

Author

ter Linden, Esther, Abels, Erik R., van Solinge, Thomas S., Neefjes, Jacques, and Broekman, Marike L. D.

Subjects
*BRAIN tumors, *GLIOBLASTOMA multiforme, *BLOOD-brain barrier, *PATIENTS' attitudes, *DRUGS
Abstract

The world of cancer treatment is evolving rapidly and has improved the prospects of many cancer patients. Yet, there are still many cancers where treatment prospects have not (or hardly) improved. Glioblastoma is the most common malignant primary brain tumor, and even though it is sensitive to many chemotherapeutics when tested under laboratory conditions, its clinical prospects are still very poor. The blood–brain barrier (BBB) is considered at least partly responsible for the high failure rate of many promising treatment strategies. We describe the workings of the BBB during healthy conditions and within the glioblastoma environment. How the BBB acts as a barrier for therapeutic options is described as well as various approaches developed and tested for passing or opening the BBB, with the ultimate aim to allow access to brain tumors and improve patient perspectives. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Potential Transfer of Polyglutamine and CAG-Repeat RNA in Extracellular Vesicles in Huntington’s Disease: Background and Evaluation in Cell Culture

Author

Zhang, Xuan, Abels, Erik R, Redzic, Jasmina S, Margulis, Julia, Finkbeiner, Steve, and Breakefield, Xandra O

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurodegenerative, Brain Disorders, Orphan Drug, Neurosciences, Huntington's Disease, Biotechnology, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Cells, Cultured, Extracellular Vesicles, Green Fluorescent Proteins, Humans, Huntingtin Protein, Huntington Disease, Mice, Neostriatum, Peptides, RNA, Real-Time Polymerase Chain Reaction, Trinucleotide Repeat Expansion, Exosomes, Trinucleotide repeat, Neurodegeneration, Huntington's disease, Huntington’s disease, Pharmacology and Pharmaceutical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

In Huntington's disease (HD) the imperfect expanded CAG repeat in the first exon of the HTT gene leads to the generation of a polyglutamine (polyQ) protein, which has some neuronal toxicity, potentially mollified by formation of aggregates. Accumulated research, reviewed here, implicates both the polyQ protein and the expanded repeat RNA in causing toxicity leading to neurodegeneration in HD. Different theories have emerged as to how the neurodegeneration spreads throughout the brain, with one possibility being the transport of toxic protein and RNA in extracellular vesicles (EVs). Most cell types in the brain release EVs and these have been shown to contain neurodegenerative proteins in the case of prion protein and amyloid-beta peptide. In this study, we used a model culture system with an overexpression of HTT-exon 1 polyQ-GFP constructs in human 293T cells and found that the EVs did incorporate both the polyQ-GFP protein and expanded repeat RNA. Striatal mouse neural cells were able to take up these EVs with a consequent increase in the green fluorescent protein (GFP) and polyQ-GFP RNAs, but with no evidence of uptake of polyQ-GFP protein or any apparent toxicity, at least over a relatively short period of exposure. A differentiated striatal cell line expressing endogenous levels of Hdh mRNA containing the expanded repeat incorporated more of this mRNA into EVs as compared to similar cells expressing this mRNA with a normal repeat length. These findings support the potential of EVs to deliver toxic expanded trinucleotide repeat RNAs from one cell to another, but further work will be needed to evaluate potential EV and cell-type specificity of transfer and effects of long-term exposure. It seems likely that expanded HD-associated repeat RNA may appear in biofluids and may have use as biomarkers of disease state and response to therapy.

Published
2016

12. Additional file 3 of Glioblastoma hijacks microglial gene expression to support tumor growth

Author

Maas, Sybren L. N., Abels, Erik R., Haar, Lieke L. Van De, Zhang, Xuan, Morsett, Liza, Srinjoy Sil, Guedes, Joana, Pritha Sen, Prabhakar, Shilpa, Hickman, Suzanne E., Lai, Charles P., Ting, David T., Breakefield, Xandra O., Broekman, Marike L. D., and Khoury, Joseph El

Subjects
nervous system
Abstract

Additional file 3: Figure S2. IL4, IL10, IL6 and IFNγ pathways genes were upregulated in tumor-associated microglia. (A) The IL4 associated genes were mostly upregulated in tumor-associated microglia with increased expression in EV-GFPpos microglia. The significantly upregulated genes in EV-GFPpos versus EV-GFPneg microglia included known tumor supportive genes such as Mmp12, Adam19 and Wnt5a. (B) IL10 related genes were upregulated in tumor microglia. Sod2, a tumor supportive gene, was among the genes significantly upregulated in EV-GFPpos microglia. (C) IL6 related genes were upregulated in tumor-associated microglia. Among the significantly upregulated IL6 genes is Ccl7 (MCP-3), a secreted chemokine involved in the attraction of microglia and macrophages to the tumor suggesting a tumor supportive infiltration loop. (D) Overall, increased expression of IFNγ related genes was observed with the strongest expression in EV-GFPpos microglia. Among the significantly upregulated genes in EV-GFPpos microglia was Irf7, a key regulator of pro-inflammatory to anti-inflammatory switching in microglia.

Published
2020
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13. Additional file 2 of Glioblastoma hijacks microglial gene expression to support tumor growth

Author

Maas, Sybren L. N., Abels, Erik R., Haar, Lieke L. Van De, Zhang, Xuan, Morsett, Liza, Srinjoy Sil, Guedes, Joana, Pritha Sen, Prabhakar, Shilpa, Hickman, Suzanne E., Lai, Charles P., Ting, David T., Breakefield, Xandra O., Broekman, Marike L. D., and Khoury, Joseph El

Abstract

Additional file 2: Figure S1. RNA levels correlated with protein levels in control and tumor-bearing brains. (A) The microglial marker Iba1 was equally expressed in control and tumor-associated microglia, whereas Cd74 and Arg1 expression was increased in tumor-associated microglia as measured by RNAseq. (B) Immunofluorescence staining of IBA1, CD74 and ARG1 in control and tumor-bearing mouse brains. (C) Quantification of immunofluorescent staining seen in (B) Fluorescent intensity was quantified per pixel within all identified cells. Tumor and control tissues were individually compared for each marker. IBA1, CD74 and ARG1 fluorescence quantification correlated with RNA data whereas Scale bars 100 μm, asterisk indicates multiple testing adjusted p-value

Published
2020
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14. Versatile Role of Rab27a in Glioma:Effects on Release of Extracellular Vesicles, Cell Viability, and Tumor Progression

Author

van Solinge, Thomas S, Abels, Erik R, van de Haar, Lieke L, Hanlon, Killian S, Maas, Sybren L N, Schnoor, Rosalie, de Vrij, Jeroen, Breakefield, Xandra O, Broekman, Marike L D, van Solinge, Thomas S, Abels, Erik R, van de Haar, Lieke L, Hanlon, Killian S, Maas, Sybren L N, Schnoor, Rosalie, de Vrij, Jeroen, Breakefield, Xandra O, and Broekman, Marike L D

Abstract

Introduction: Glioma cells exert influence over the tumor-microenvironment in part through the release of extracellular vesicles (EVs), membrane-enclosed structures containing proteins, lipids, and RNAs. In this study, we evaluated the function of Ras-associated protein 27a (Rab27a) in glioma and evaluated the feasibility of assessing its role in EV release in glioma cells in vitro and in vivo. Methods: Rab27a was knocked down via a short hairpin RNA (shRNA) stably expressed in mouse glioma cell line GL261, with a scrambled shRNA as control. EVs were isolated by ultracentrifugation and quantified with Nanoparticle Tracking Analysis (NTA) and Tunable Resistive Pulse Sensing (TRPS). CellTiter-Glo viability assays and cytokine arrays were used to evaluate the impact of Rab27a knockdown. GL261.shRab27a cells and GL261.shControl were implanted into the left striatum of eight mice to assess tumor growth and changes in the tumor microenvironment. Results:Knockdown of Rab27a in GL261 glioma cells decreased the release of small EVs isolated at 100,000 × g in vitro (p = 0.005), but not the release of larger EVs, isolated at 10,000 × g. GL261.shRab27a cells were less viable compared to the scramble control in vitro (p < 0.005). A significant increase in CCL2 expression in shRab27a GL261 cells was also observed (p < 0.001). However, in vivo there was no difference in tumor growth or overall survival between the two groups, while shRab27a tumors showed lower proliferation at the tumor borders. Decreased infiltration of IBA1 positive macrophages and microglia, but not FoxP3 positive regulatory T cells was observed. Conclusion: Rab27a plays an important role in the release of small EVs from glioma cells, and also in their viability and expression of CCL2 in vitro. As interference in Rab27a expression influences glioma cell viability and expression profiles, future studies should be cautious in us

Published
2020

15. Versatile Role of Rab27a in Glioma: Effects on Release of Extracellular Vesicles, Cell Viability, and Tumor Progression

Author

Pathologie Algemene Pat.zorg, Pathologie Opleiding, Cancer, Brain, Zorglijn FNE Medisch, van Solinge, Thomas S., Abels, Erik R., van de Haar, Lieke L., Hanlon, Killian S., Maas, Sybren L.N., Schnoor, Rosalie, de Vrij, Jeroen, Breakefield, Xandra O., Broekman, Marike L.D., Pathologie Algemene Pat.zorg, Pathologie Opleiding, Cancer, Brain, Zorglijn FNE Medisch, van Solinge, Thomas S., Abels, Erik R., van de Haar, Lieke L., Hanlon, Killian S., Maas, Sybren L.N., Schnoor, Rosalie, de Vrij, Jeroen, Breakefield, Xandra O., and Broekman, Marike L.D.

Published
2020

16. Glioblastoma hijacks microglial gene expression to support tumor growth

Author

Cancer, Pathologie Opleiding, ZL Neuro-Oncologie Medisch, TN groep Pasterkamp, Brain, Maas, Sybren L.N., Abels, Erik R., Van De Haar, Lieke L., Zhang, Xuan, Morsett, Liza, Sil, Srinjoy, Guedes, Joana, Sen, Pritha, Prabhakar, Shilpa, Hickman, Suzanne E., Lai, Charles P., Ting, David T., Breakefield, Xandra O., Broekman, Marike L.D., El Khoury, Joseph, Cancer, Pathologie Opleiding, ZL Neuro-Oncologie Medisch, TN groep Pasterkamp, Brain, Maas, Sybren L.N., Abels, Erik R., Van De Haar, Lieke L., Zhang, Xuan, Morsett, Liza, Sil, Srinjoy, Guedes, Joana, Sen, Pritha, Prabhakar, Shilpa, Hickman, Suzanne E., Lai, Charles P., Ting, David T., Breakefield, Xandra O., Broekman, Marike L.D., and El Khoury, Joseph

Published
2020

19. Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function

Author

Sen, Pritha, primary, Wilkie, Adrian R., additional, Ji, Fei, additional, Yang, Yiming, additional, Taylor, Ian J., additional, Velazquez-Palafox, Miguel, additional, Vanni, Emilia A. H., additional, Pesola, Jean M., additional, Fernandez, Rosio, additional, Chen, Han, additional, Morsett, Liza M., additional, Abels, Erik R., additional, Piper, Mary, additional, Lane, Rebekah J., additional, Hickman, Suzanne E., additional, Means, Terry K., additional, Rosenberg, Eric S., additional, Sadreyev, Ruslan I., additional, Li, Bo, additional, Coen, Donald M., additional, Fishman, Jay A., additional, and El Khoury, Joseph, additional

Published
2020
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20. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21

Author

Abels, Erik R., Maas, Sybren L.N., Nieland, Lisa, Wei, Zhiyun, Cheah, Pike See, Tai, Eric, Kolsteeg, Christy Joy, Dusoswa, Sophie A., Ting, David T., Hickman, Suzanne, El Khoury, Joseph, Krichevsky, Anna M., Broekman, Marike L.D., Breakefield, Xandra O., Abels, Erik R., Maas, Sybren L.N., Nieland, Lisa, Wei, Zhiyun, Cheah, Pike See, Tai, Eric, Kolsteeg, Christy Joy, Dusoswa, Sophie A., Ting, David T., Hickman, Suzanne, El Khoury, Joseph, Krichevsky, Anna M., Broekman, Marike L.D., and Breakefield, Xandra O.

Published
2019

21. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21

Author

UMC Utrecht, ZL Neuro-Oncologie Medisch, Pathologie Opleiding, Brain, Cancer, Abels, Erik R., Maas, Sybren L.N., Nieland, Lisa, Wei, Zhiyun, Cheah, Pike See, Tai, Eric, Kolsteeg, Christy Joy, Dusoswa, Sophie A., Ting, David T., Hickman, Suzanne, El Khoury, Joseph, Krichevsky, Anna M., Broekman, Marike L.D., Breakefield, Xandra O., UMC Utrecht, ZL Neuro-Oncologie Medisch, Pathologie Opleiding, Brain, Cancer, Abels, Erik R., Maas, Sybren L.N., Nieland, Lisa, Wei, Zhiyun, Cheah, Pike See, Tai, Eric, Kolsteeg, Christy Joy, Dusoswa, Sophie A., Ting, David T., Hickman, Suzanne, El Khoury, Joseph, Krichevsky, Anna M., Broekman, Marike L.D., and Breakefield, Xandra O.

Published
2019

22. Glioma EVs Contribute to Immune Privilege in the Brain

Author

ZL Neuro-Oncologie Medisch, Brain, Cancer, UMC Utrecht, Pathologie Histochemie en Em, Pathologie Opleiding, Abels, Erik R., Broekman, Marike L.D., Breakefield, Xandra O., Maas, Sybren L.N., ZL Neuro-Oncologie Medisch, Brain, Cancer, UMC Utrecht, Pathologie Histochemie en Em, Pathologie Opleiding, Abels, Erik R., Broekman, Marike L.D., Breakefield, Xandra O., and Maas, Sybren L.N.

Published
2019

23. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21

Author

Abels, Erik R., primary, Maas, Sybren L.N., additional, Nieland, Lisa, additional, Wei, Zhiyun, additional, Cheah, Pike See, additional, Tai, Eric, additional, Kolsteeg, Christy-Joy, additional, Dusoswa, Sophie A., additional, Ting, David T., additional, Hickman, Suzanne, additional, El Khoury, Joseph, additional, Krichevsky, Anna M., additional, Broekman, Marike L.D., additional, and Breakefield, Xandra O., additional

Published
2019
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24. Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

Author

Alieva, Maria, Margarido, Andreia S., Wieles, Tamara, Abels, Erik R., Colak, Burcin, Boquetale, Carla, Jan Noordmans, Herke, Snijders, Tom J., Broekman, Marike L., Van Rheenen, Jacco, Alieva, Maria, Margarido, Andreia S., Wieles, Tamara, Abels, Erik R., Colak, Burcin, Boquetale, Carla, Jan Noordmans, Herke, Snijders, Tom J., Broekman, Marike L., and Van Rheenen, Jacco

Published
2017

25. Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

Author

Team Innovatie Research MTKF, Other research (not in main researchprogram), ZL Neuro-Oncologie Medisch, Brain, Cancer, CMM Sectie Molecular Cancer Research, Alieva, Maria, Margarido, Andreia S., Wieles, Tamara, Abels, Erik R., Colak, Burcin, Boquetale, Carla, Jan Noordmans, Herke, Snijders, Tom J., Broekman, Marike L., Van Rheenen, Jacco, Team Innovatie Research MTKF, Other research (not in main researchprogram), ZL Neuro-Oncologie Medisch, Brain, Cancer, CMM Sectie Molecular Cancer Research, Alieva, Maria, Margarido, Andreia S., Wieles, Tamara, Abels, Erik R., Colak, Burcin, Boquetale, Carla, Jan Noordmans, Herke, Snijders, Tom J., Broekman, Marike L., and Van Rheenen, Jacco

Published
2017

27. Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain

Author

van der Vos, Kristan E., primary, Abels, Erik R., additional, Zhang, Xuan, additional, Lai, Charles, additional, Carrizosa, Esteban, additional, Oakley, Derek, additional, Prabhakar, Shilpa, additional, Mardini, Osama, additional, Crommentuijn, Matheus H. W., additional, Skog, Johan, additional, Krichevsky, Anna M., additional, Stemmer-Rachamimov, Anat, additional, Mempel, Thorsten R., additional, El Khoury, Joseph, additional, Hickman, Suzanne E., additional, and Breakefield, Xandra O., additional

Published
2015
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29. Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function.

Author

Pritha Sen, Wilkie, Adrian R., Fei Ji, Jiming Yang, Taylor, Ian J., Velazquez-Palafox, Miguel, Vanni, Emilia A. H., Pesola, Jean M., Fernandez, Rosio, Han Chen, Morsett, Liza M., Abels, Erik R., Piper, Mary, Lane, Rebekah J., Hickman, Suzanne E., Means, Terry K., Rosenberg, Eric S., Sadreyev, Ruslan I., Bo Li, and Coen, Donald M.

Subjects
*CYTOMEGALOVIRUS diseases, *MONOCYTES, *BIOCHEMISTRY, *HUMAN cytomegalovirus diseases, *BACTERIAL artificial chromosomes, *CELL receptors, *GREEN fluorescent protein
Abstract

The article focuses on the Cytomegalovirus (CMV), an important cause of morbidity and mortality in the immunocompromised host. It mentions that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors; and also mentions that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes.

Published
2020
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