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  1. Article ; Online: Making HSP90 Inhibitors Great Again? Unite for Better Cancer Immunotherapy.

    Graner, Michael W

    Cell chemical biology

    2021  Volume 28, Issue 2, Page(s) 118–120

    Abstract: HSP90 inhibitors are in numerous cancer clinical trials, but treatments often induce toxicity at effective dosages. In this issue of Cell Chemical Biology, Zavareh et al. (2020) serendipitously found that HSP90 inhibitors, at manageable doses, can reduce ...

    Abstract HSP90 inhibitors are in numerous cancer clinical trials, but treatments often induce toxicity at effective dosages. In this issue of Cell Chemical Biology, Zavareh et al. (2020) serendipitously found that HSP90 inhibitors, at manageable doses, can reduce target cell expression of immune checkpoint molecules, potentially enabling improved anti-cancer immunotherapy.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Humans ; Immunotherapy ; Neoplasms/drug therapy
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2021-02-19
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2451-9448
    ISSN (online) 2451-9448
    DOI 10.1016/j.chembiol.2021.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Conference report for the 2nd annual American Society for Intercellular Communication (ASIC) meeting, 2022.

    Russell, Ashley E / Graner, Michael W / Buch, Shilpa

    Extracellular vesicles and circulating nucleic acids

    2023  Volume 4, Issue 3, Page(s) 323–337

    Language English
    Publishing date 2023-07-04
    Publishing country United States
    Document type Journal Article
    DOI 10.20517/evcna.2022.43
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Roles of Extracellular Vesicles in High-Grade Gliomas: Tiny Particles with Outsized Influence.

    Graner, Michael W

    Annual review of genomics and human genetics

    2019  Volume 20, Page(s) 331–357

    Abstract: High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has ... ...

    Abstract High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has remained essentially unchanged for almost 15 years, with little new therapeutic progress. We desperately need a better biologic understanding of these complicated tumors in a complicated organ. One area of rejuvenated study relates to extracellular vesicles (EVs)-membrane-enclosed nano- or microsized particles that originate from the endosomal system or are shed from the plasma membrane. EVs contribute to tumor heterogeneity (including the maintenance of glioma stem cells or their differentiation), the impacts of hypoxia (angiogenesis and coagulopathies), interactions amid the tumor microenvironment (concerning the survival of astrocytes, neurons, endothelial cells, blood vessels, the blood-brain barrier, and the ensuing inflammation), and influences on the immune system (both stimulatory and suppressive). This article reviews glioma EVs and the ways that EVs manifest themselves as autocrine, paracrine, and endocrine factors in proximal and distal intra- and intercellular communications. The reader should note that there is much controversy, and indeed confusion, in the field over the exact roles for EVs in many biological processes, and we will engage some of these difficulties herein.
    MeSH term(s) Animals ; Astrocytes ; Brain Neoplasms/immunology ; Brain Neoplasms/metabolism ; Brain Neoplasms/physiopathology ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/physiology ; Glioma/immunology ; Glioma/metabolism ; Glioma/physiopathology ; Humans ; Immune System ; Inflammation ; Tumor Microenvironment
    Language English
    Publishing date 2019-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037670-4
    ISSN 1545-293X ; 1527-8204
    ISSN (online) 1545-293X
    ISSN 1527-8204
    DOI 10.1146/annurev-genom-083118-015324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Se 2016: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Immunopathology of Extracellular Vesicles in Macrophage and Glioma Cross-Talk.

    Kopper, Timothy J / Yu, Xiaoli / Graner, Michael W

    Journal of clinical medicine

    2023  Volume 12, Issue 10

    Abstract: Glioblastomas (GBM) are a devastating disease with extremely poor clinical outcomes. Resident (microglia) and infiltrating macrophages are a substantial component of the tumor environment. In GBM and other cancers, tumor-derived extracellular vesicles ( ... ...

    Abstract Glioblastomas (GBM) are a devastating disease with extremely poor clinical outcomes. Resident (microglia) and infiltrating macrophages are a substantial component of the tumor environment. In GBM and other cancers, tumor-derived extracellular vesicles (EVs) suppress macrophage inflammatory responses, impairing their ability to identify and phagocytose cancerous tissues. Furthermore, these macrophages then begin to produce EVs that support tumor growth and migration. This cross-talk between macrophages/microglia and gliomas is a significant contributor to GBM pathophysiology. Here, we review the mechanisms through which GBM-derived EVs impair macrophage function, how subsequent macrophage-derived EVs support tumor growth, and the current therapeutic approaches to target GBM/macrophage EV crosstalk.
    Language English
    Publishing date 2023-05-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm12103430
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Extracellular vesicles in cancer immune responses: roles of purinergic receptors.

    Graner, Michael W

    Seminars in immunopathology

    2018  Volume 40, Issue 5, Page(s) 465–475

    Abstract: Extracellular vesicles (EVs) are nano- to micro-scale membrane-enclosed vesicles that are released from presumably all cell types. Tumor cells and immune cells are prodigious generators of EVs often with competing phenotypes in terms of immune ... ...

    Abstract Extracellular vesicles (EVs) are nano- to micro-scale membrane-enclosed vesicles that are released from presumably all cell types. Tumor cells and immune cells are prodigious generators of EVs often with competing phenotypes in terms of immune suppression versus immune stimulation. Purinergic receptors, proteins that bind diverse purine nucleotides and nucleosides (ATP, ADP, AMP, adenosine), are widely expressed across tissues and cell types, and are prominent players in immune and tumor cell nucleotide metabolism. The effects of purinergic receptor stimulation or agonism tend to produce inflammatory responses that may aid immune stimulation but may also provoke various immune suppression mechanisms, particularly in the tumor microenvironment. EVs released by cells following receptor stimulation are frequently pro-inflammatory, but often also pro-thrombolytic; these EVs may generate an environment that favors tumor progression at the cost of an effective immune response. Purinergic signaling pathways are becoming more recognized as valuable targets in various therapeutic scenarios, including cancer. It is possible that some of those clinically relevant compounds might also impact EV secretion and/or phenotype, which would hopefully capitalize on the immune stimulatory properties of purinergic signaling while minimizing the immune suppressive consequences. This review covers a relatively understudied area in EV biology, but even so, focuses almost exclusively on the purinergic receptors in a very limited capacity. There is much more to evaluate and incorporate into our understanding of extracellular nucleotides in EV biology, and we hope this work prompts further discovery.
    MeSH term(s) Adenosine Triphosphate/metabolism ; Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Antigens, Neoplasm/immunology ; Biological Transport ; Cancer Vaccines/immunology ; Extracellular Vesicles/metabolism ; Humans ; Immunity ; Immunomodulation ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Receptors, Purinergic/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tumor Microenvironment/immunology
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines ; Receptors, Purinergic ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2018-09-12
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2316828-6
    ISSN 1863-2300 ; 1863-2297
    ISSN (online) 1863-2300
    ISSN 1863-2297
    DOI 10.1007/s00281-018-0706-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1425: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article: A report on ASIC2021: a conference on extracellular vesicle communication mechanisms.

    Russell, Ashley E / Sil, Susmita / Buch, Shilpa / Graner, Michael W

    Extracellular vesicles and circulating nucleic acids

    2022  Volume 3, Issue 3, Page(s) 249–263

    Language English
    Publishing date 2022-08-29
    Publishing country United States
    Document type Journal Article
    DOI 10.20517/evcna.2022.31
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: HSP90 and Immune Modulation in Cancer.

    Graner, Michael W

    Advances in cancer research

    2016  Volume 129, Page(s) 191–224

    Abstract: Heat-shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays prominent functional roles in nearly all aspects of cell biology. As a chaperone, it interacts with literally hundreds of "clients," many of which are important drivers, ... ...

    Abstract Heat-shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays prominent functional roles in nearly all aspects of cell biology. As a chaperone, it interacts with literally hundreds of "clients," many of which are important drivers, regulators, and promoters of cancer. Thus, HSP90 is a high-value target in the development of anticancer therapeutics. Despite its popularity, our overall knowledge of HSP90 in immune function has lagged behind its well-recognized tumor-supportive roles. The use of inhibitors of HSP90 as chemical biological probes has been invaluable in revealing important roles for the chaperone in multiple aspects of immune function. Given this critical link, we must now consider the question of how immune outcomes may be affected by the HSP90 inhibitors currently in clinical development for the treatment of cancer. This chapter will review some of the immunological aspects of HSP90 function in terms of its intracellular and extracellular roles in antigen presentation, immune effector cell tasks, and regulation of inflammatory processes. This review will further examine the value of HSP90 inhibitors within the context of cancer immunotherapy and will discuss how these drugs might be optimally utilized in combination with immune stimulatory approaches against cancer.
    MeSH term(s) Animals ; Antigen Presentation ; Antigens, Surface/immunology ; Antigens, Surface/metabolism ; Antineoplastic Agents/therapeutic use ; Apoptosis/immunology ; Exosomes/immunology ; Exosomes/metabolism ; Extracellular Space/immunology ; Extracellular Space/metabolism ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/immunology ; HSP90 Heat-Shock Proteins/metabolism ; Heat-Shock Response/immunology ; Humans ; Immunity, Innate ; Immunomodulation ; Inflammation/immunology ; Membrane Glycoproteins/immunology ; Mice ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/therapy
    Chemical Substances Antigens, Surface ; Antineoplastic Agents ; HSP90 Heat-Shock Proteins ; Membrane Glycoproteins ; endoplasmin
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 127-2
    ISSN 2162-5557 ; 0065-230X
    ISSN (online) 2162-5557
    ISSN 0065-230X
    DOI 10.1016/bs.acr.2015.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.178: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  8. Article ; Online: Specific Binding of Alzheimer's Aβ Peptides to Extracellular Vesicles.

    Coughlan, Christina / Lindenberger, Jared / Jacot, Jeffrey G / Johnson, Noah R / Anton, Paige / Bevers, Shaun / Welty, Robb / Graner, Michael W / Potter, Huntington

    International journal of molecular sciences

    2024  Volume 25, Issue 7

    Abstract: Alzheimer's disease (AD) is the fifth leading cause of death among adults aged 65 and older, yet the onset and progression of the disease is poorly understood. What is known is that the presence of amyloid, particularly polymerized Aβ42, defines when ... ...

    Abstract Alzheimer's disease (AD) is the fifth leading cause of death among adults aged 65 and older, yet the onset and progression of the disease is poorly understood. What is known is that the presence of amyloid, particularly polymerized Aβ42, defines when people are on the AD continuum. Interestingly, as AD progresses, less Aβ42 is detectable in the plasma, a phenomenon thought to result from Aβ becoming more aggregated in the brain and less Aβ42 and Aβ40 being transported from the brain to the plasma via the CSF. We propose that extracellular vesicles (EVs) play a role in this transport. EVs are found in bodily fluids such as blood, urine, and cerebrospinal fluid and carry diverse "cargos" of bioactive molecules (e.g., proteins, nucleic acids, lipids, metabolites) that dynamically reflect changes in the cells from which they are secreted. While Aβ42 and Aβ40 have been reported to be present in EVs, it is not known whether this interaction is specific for these peptides and thus whether amyloid-carrying EVs play a role in AD and/or serve as brain-specific biomarkers of the AD process. To determine if there is a specific interaction between Aβ and EVs, we used isothermal titration calorimetry (ITC) and discovered that Aβ42 and Aβ40 bind to EVs in a manner that is sequence specific, saturable, and endothermic. In addition, Aβ incubation with EVs overnight yielded larger amounts of bound Aβ peptide that was fibrillar in structure. These findings point to a specific amyloid-EV interaction, a potential role for EVs in the transport of amyloid from the brain to the blood, and a role for this amyloid pool in the AD process.
    MeSH term(s) Adult ; Humans ; Alzheimer Disease ; Peptides ; Extracellular Vesicles ; Amyloidogenic Proteins ; Plasma
    Chemical Substances Peptides ; Amyloidogenic Proteins
    Language English
    Publishing date 2024-03-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25073703
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  9. Article: The unfolded protein response in glioblastomas: targetable or trouble?

    Graner, Michael W

    Future science OA

    2015  Volume 1, Issue 2, Page(s) FSO45

    Abstract: Glioblastomas are devastating central nervous system tumors with abysmal prognoses. These tumors are often difficult to resect surgically, are highly invasive and proliferative, and are resistant to virtually all therapeutic attempts, making them ... ...

    Abstract Glioblastomas are devastating central nervous system tumors with abysmal prognoses. These tumors are often difficult to resect surgically, are highly invasive and proliferative, and are resistant to virtually all therapeutic attempts, making them universally lethal diseases. One key enabling feature of their tumor biology is the engagement of the unfolded protein response (UPR), a stress response originating in the endoplasmic reticulum (ER) designed to handle the pathologies of aggregating malfolded proteins in that organelle. Glioblastomas and other tumors have co-opted this stress response to allow their continued uncontrolled growth by enhanced protein production (maintained by chaperone-assisted protein folding) and lipid biosynthesis driven downstream of the UPR. These features can account for the extensive extracellular remodeling/invasiveness/angiogenesis and proliferative capacity, and ultimately result in tumor phenotypes of chemo- and radio-resistance. The UPR in general, and its chaperoning capacity in particular, are thus putative high-value targets for treatment intervention. Such therapeutic strategies, and potential problems with them, will be discussed and analyzed.
    Language English
    Publishing date 2015-09-01
    Publishing country England
    Document type Review ; Journal Article
    ISSN 2056-5623
    ISSN 2056-5623
    DOI 10.4155/fso.15.45
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Editorial: Blood-Based Biomarkers in Acute Ischemic Stroke and Hemorrhagic Stroke.

    Uphaus, Timo / Audebert, Heinrich J / Graner, Michael W / Tiedt, Steffen / Kowalski, Robert G

    Frontiers in neurology

    2022  Volume 13, Page(s) 866166

    Language English
    Publishing date 2022-02-24
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2022.866166
    Database MEDical Literature Analysis and Retrieval System OnLINE

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