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  • 1
    Online Resource
    Online Resource
    Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 2 ( 2021-03-03), p. 636-654
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 2 ( 2021-03-03), p. 636-654
    Abstract: As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awaa408
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 2
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    Fam20C Kinase as a Key Regulator of Bevacizumab Resistance in Mesenchymal Glioblastoma
    Wiley ; 2023
    In:  Advanced Therapeutics
    Details
    In: Advanced Therapeutics, Wiley
    Abstract: A significant hurdle in treating glioblastoma (GBM) is addressing the development of drug resistance. In this study, the role of Family of Sequence Similarity 20, Member C (Fam20C) as a central player in bevacizumab resistant GBM mouse model is investigated. In vivo analyses confirm that Fam20C upregulation accelerates drug resistance and correlates with tumor progression. Proteomic analyses of conditioned media and cell lysates subsequent to Fam20C knockout (KO) in GBM cells reveal the regulatory role of Fam20C in both intracellular and extracellular aspects of epithelial‐mesenchymal transition (EMT) and genes associated with AKT signaling. Moreover, In vitro experiments demonstrate that Fam20C activates the AKT signaling pathway, promoting cell proliferation. Elevated levels of Fam20C are observed in human GBM, particularly in the mesenchymal subtype, which correlates with diminished survival rates and increased resistance to various drugs, including temozolomide (TMZ), bevacizumab, epidermal growth factor receptor (EGFR) inhibitors, and other antibody‐based drugs. Notably, even in cases of resistance to gefitinib and hepatocyte growth factor (HGF) antibodies, Fam20C expression is elevated. These findings highlight the pivotal role of Fam20C in driving drug resistance in GBM, suggesting it as a promising target for combination therapies aimed at surmounting this formidable resistance barrier.
    Type of Medium: Online Resource
    ISSN: 2366-3987 , 2366-3987
    URL: Article
    DOI: 10.1002/adtp.202300309
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2920320-X
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  • 3
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    Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPβ Signaling
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 18 ( 2017-09-15), p. 4973-4984
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 18 ( 2017-09-15), p. 4973-4984
    Abstract: Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage–inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973–84. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-17-0388
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
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    IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis
    Springer Science and Business Media LLC ; 2023
    In:  Nature Communications Vol. 14, No. 1 ( 2023-03-22)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-03-22)
    Abstract: Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-023-37306-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 5
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    Analysis of electric cigarette liquid effect on mouse brain tumor growth through EGFR and ERK activation
    Public Library of Science (PLoS) ; 2021
    In:  PLOS ONE Vol. 16, No. 9 ( 2021-9-8), p. e0256730-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-8), p. e0256730-
    Abstract: Recently, electric cigarettes with liquid (e-liquid) were introduced as an alternative to tobacco smoking. They were promoted as possible cessation aids and were considered to be potentially less harmful than traditional tobacco-based cigarettes. However, there is little information on the toxicants present in e-liquids and their possible carcinogenic effects. Methods Western blot analysis was performed to identify the protein levels of cancer progression related signal transducers. Patient-derived brain tumor cells (CSC2) were injected into mouse brains and tumor growth was then observed by performing magnetic resonance imaging (MRI) and hematoxylin and eosin (H & E) staining of the whole brain. Immunohistochemistry (IHC) staining and Immunofluorescence staining were performed to study the expression of pEGFR and pERK. Results Western blotting revealed that e-liquids increased pEGFR and pERK expression in a dose dependent manner. Animal experiments revealed that the e-liquid treated group had accelerated tumor growth and poor prognosis compared to the vehicle group. Histological staining showed activation of pEGFR and pERK in the e-liquid treated group. Conclusion Our study revealed that e-liquid activates pEGFR and pERK, leading to accelerated brain tumor growth and poor prognosis.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
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    DOI: 10.1371/journal.pone.0256730
    DOI: 10.1371/journal.pone.0256730.g001
    DOI: 10.1371/journal.pone.0256730.g002
    DOI: 10.1371/journal.pone.0256730.g003
    DOI: 10.1371/journal.pone.0256730.g004
    DOI: 10.1371/journal.pone.0256730.s001
    DOI: 10.1371/journal.pone.0256730.s002
    DOI: 10.1371/journal.pone.0256730.s003
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2021
    detail.hit.zdb_id: 2267670-3
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  • 6
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    Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme
    Public Library of Science (PLoS) ; 2021
    In:  PLOS ONE Vol. 16, No. 9 ( 2021-9-13), p. e0257375-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-13), p. e0257375-
    Abstract: Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
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    DOI: 10.1371/journal.pone.0257375
    DOI: 10.1371/journal.pone.0257375.g001
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    DOI: 10.1371/journal.pone.0257375.s004
    DOI: 10.1371/journal.pone.0257375.s005
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2021
    detail.hit.zdb_id: 2267670-3
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  • 7
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    Increased 18F-FDG Uptake on PET/CT is Associated With Poor Arterial and Portal Perfusion on Multiphase CT
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Clinical Nuclear Medicine Vol. 41, No. 4 ( 2016-04), p. 296-301
    Details
    In: Clinical Nuclear Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 4 ( 2016-04), p. 296-301
    Type of Medium: Online Resource
    ISSN: 0363-9762
    URL: Article
    DOI: 10.1097/RLU.0000000000001105
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2045053-9
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  • 8
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    Comparative Life Cycle Assessment of Multiple Liquid Laundry Detergent Packaging Formats
    MDPI AG ; 2020
    In:  Sustainability Vol. 12, No. 11 ( 2020-06-08), p. 4669-
    Details
    In: Sustainability, MDPI AG, Vol. 12, No. 11 ( 2020-06-08), p. 4669-
    Abstract: The emerging packaging industry trend of focusing on packaging sustainability is also occurring in the laundry detergent industry. This study presents a cradle-to-grave comparative life cycle assessment (LCA) of three different packaging systems for liquid laundry detergent: the conventional pourable bottle, polyethylene terephthalate (PET) container with pods, and flexible pouch with pods. The scope of this study included material production, intermediate processes, transportation, and end-of-life phases of each packaging system. The results showed that the conventional pourable bottle made of high-density polyethylene (HDPE) has less environmental impact than the other two packaging systems in all impact categories, except ecotoxicity, due to the higher amount of packaging material required to produce the pods. The rigid PET container with pods impacted the environment in all categories more than the multi-layered flexible pouch containing pods, due primarily to the amount of material production, heavier weight, and intermediate processing using injection molding.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su12114669
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518383-7
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  • 9
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    Investigation of the Effect of Pallet Top-Deck Stiffness on Corrugated Box Compression Strength as a Function of Multiple Unit Load Design Variables
    MDPI AG ; 2021
    In:  Materials Vol. 14, No. 21 ( 2021-11-03), p. 6613-
    Details
    In: Materials, MDPI AG, Vol. 14, No. 21 ( 2021-11-03), p. 6613-
    Abstract: Unit loads consisting of a pallet, packages, and a product securement system are the dominant way of shipping products across the United States. The most common packaging types used in unit loads are corrugated boxes. Due to the great stresses created during unit load stacking, accurately predicting the compression strength of corrugated boxes is critical to preventing unit load failure. Although many variables affect the compression strength of corrugated boxes, recently, it was found that changing the pallet’s top deck stiffness can significantly affect compression strength. However, there is still a lack of understanding of how these different factors influence this phenomenon. This study investigated the effect of pallet’s top-deck stiffness on corrugated box compression strength as a function of initial top deck thickness, pallet wood species, box size, and board grade. The amount of increase in top deck thickness needed to lower the board grade of corrugated boxes by one level from the initial unit load scenario was determined using PDS™. The benefits of increasing top deck thickness diminish as the initial top deck thickness increases due to less severe pallet deflection from the start. The benefits were more pronounced as higher board grade boxes were initially used, and as smaller-sized boxes were used due to the heavier weights of these unit loads. Therefore, supposing that a company uses lower stiffness pallets or heavy corrugated boxes for their unit loads, this study suggests that they will find more opportunities to optimize their unit loads by increasing their pallet’s top deck thickness.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    URL: Article
    DOI: 10.3390/ma14216613
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2487261-1
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  • 10
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    Sustainable and Secure Transport: Achieving Environmental Impact Reductions by Optimizing Pallet-Package Strength Interactions during Transport
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 17 ( 2023-08-22), p. 12687-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 17 ( 2023-08-22), p. 12687-
    Abstract: Increasing quantities of products are being transported across widely distributed supply networks; the sustainability of the packaging used to transport these goods, or unit loads, presents an area of potential concern. The most common type of unit load in the U.S. is wooden pallets supporting various configurations of stacked corrugated boxes. Research into unit load cost optimization revealed that increasing the stiffness of a pallet’s top deck can significantly affect the strength of the assembled, stacked corrugated boxes and provides opportunities to reduce the board grade required for accompanying corrugated boxes. However, there remains a knowledge gap regarding the environmental implications of this type of unit load optimization method. To address this, we conducted a life cycle analysis (LCA) to investigate the environmental implications of optimizing a unit load using this method. The environmental impacts of paired (pallet and box) unit load design scenarios (n = 108) were investigated using varied wood species, pallet top deck thicknesses, corrugated boxes sizes, corrugated flutes, and board grades. Initial and optimized unit load scenarios ensured that the unit loads offered equivalent performance. LCA results indicate that optimizing the unit load can reduce environmental impacts by up to 23%, with benefits accruing across most impact categories primarily due to the reduction in corrugated material used. Ozone depletion, the exception, was mainly affected by the increase in the amount of required pallet materials. This study provides minimum required conditions as preliminary guidance for determining the usefulness of unit load specific analysis, and a sensitivity analysis confirmed these values remain unchanged even with different transportation distances. Through the unit load optimization method, this study demonstrates that an effective way to reduce the overall environmental impact and cost of transported unit loads involves increasing the stiffness of the top decks and reducing the corrugated board grade.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su151712687
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518383-7
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