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  1. Article ; Online: Drug resistance in glioblastoma: from chemo- to immunotherapy.

    Sharma, Sachin / Chepurna, Oksana / Sun, Tao

    Cancer drug resistance (Alhambra, Calif.)

    2023  Volume 6, Issue 4, Page(s) 688–708

    Abstract: As the most common and aggressive type of primary brain tumor in adults, glioblastoma is estimated to end over 10,000 lives each year in the United States alone. Stand treatment for glioblastoma, including surgery followed by radiotherapy and ... ...

    Abstract As the most common and aggressive type of primary brain tumor in adults, glioblastoma is estimated to end over 10,000 lives each year in the United States alone. Stand treatment for glioblastoma, including surgery followed by radiotherapy and chemotherapy (i.e., Temozolomide), has been largely unchanged since early 2000. Cancer immunotherapy has significantly shifted the paradigm of cancer management in the past decade with various degrees of success in treating many hematopoietic cancers and some solid tumors, such as melanoma and non-small cell lung cancer (NSCLC). However, little progress has been made in the field of neuro-oncology, especially in the application of immunotherapy to glioblastoma treatment. In this review, we attempted to summarize the common drug resistance mechanisms in glioblastoma from Temozolomide to immunotherapy. Our intent is not to repeat the well-known difficulty in the area of neuro-oncology, such as the blood-brain barrier, but to provide some fresh insights into the molecular mechanisms responsible for resistance by summarizing some of the most recent literature. Through this review, we also hope to share some new ideas for improving the immunotherapy outcome of glioblastoma treatment.
    Language English
    Publishing date 2023-10-11
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2578-532X
    ISSN (online) 2578-532X
    DOI 10.20517/cdr.2023.82
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: β-Amyloid targeting nanodrug for neuron-specific delivery of nucleic acids in Alzheimer's disease mouse models.

    Israel, Liron L / Sun, Tao / Braubach, Oliver / Cox, Alysia / Shatalova, Ekaterina S / Rashid, Harun-Mohammad / Galstyan, Anna / Grodzinski, Zachary / Song, Xue Ying / Chepurna, Oksana / Ljubimov, Vladimir A / Chiechi, Antonella / Sharma, Sachin / Phebus, Connor / Wang, Yizhou / Ljubimova, Julia Y / Black, Keith L / Holler, Eggehard

    Journal of controlled release : official journal of the Controlled Release Society

    2023  Volume 361, Page(s) 636–658

    Abstract: Delivery of therapeutic substances into the brain poses a significant challenge in the treatment of neurological disorders. This is primarily due to the blood-brain barrier (BBB), which restricts access, alongside the limited stability and distribution ... ...

    Abstract Delivery of therapeutic substances into the brain poses a significant challenge in the treatment of neurological disorders. This is primarily due to the blood-brain barrier (BBB), which restricts access, alongside the limited stability and distribution of these agents within the brain tissue. Here we demonstrate an efficient delivery of microRNA (miRNA) and antisense RNA preferentially to neurons compared to astroglia in the brain of healthy and Alzheimer's disease mice, via disulfide-linked conjugation with poly(ß-L-malic acid-trileucine)-copolymer a biodegradable, amphiphilic, and multivalent platform. By conjugating a D-configured (D3)-peptide (vector) for specific targeting, highly efficient delivery across the BBB is achieved through the Low-Density Lipoprotein Receptor-Related Protein-1 (LRP-1) transcytosis pathway, amyloid beta (Aβ) peptides. Nanodrug distribution was determined by fluorescent labeling and analyzed by microscopy in neurons, astroglia, and in extracellular amyloid plaques typical for Alzheimer's disease. Whereas D-configured BBB-vectors can efficiently target neurons, L-configured (e.g., AP2-peptide) guided vector can only cross BBB but not seem to bind neurons. An analysis of post-injection fluorescence distribution, and RNA-seq followed by real-time PCR validation, confirmed a successful in vivo delivery of morpholino-miRNA-186 nanoconjugates into mouse brain. The size and fluorescence intensity of the intracellular nanodrug particulates were analyzed and verified by a competition with non-fluorescent conjugates. Differentially expressed genes (DEGs) from RNA-seq were identified in the nanodrug injected mice, and the changes of selected DEGs related to Alzheimer's disease were further validated by western blot and real-time PCR. Collectively, these results demonstrated that D3-peptide-conjugated nanopolymer drug is able to achieve neuron-selective delivery of miRNA and can serve as an efficient brain delivery vehicle in Alzheimer's disease (AD) mouse models.
    MeSH term(s) Mice ; Animals ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/metabolism ; Nucleic Acids/therapeutic use ; Brain/metabolism ; Blood-Brain Barrier/metabolism ; Nanoconjugates/therapeutic use ; MicroRNAs/therapeutic use ; Neurons/metabolism ; Disease Models, Animal ; Mice, Transgenic
    Chemical Substances Amyloid beta-Peptides ; Nucleic Acids ; Nanoconjugates ; MicroRNAs
    Language English
    Publishing date 2023-08-17
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2055: 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)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: New Boron Delivery Agents.

    Beck-Sickinger, Annette G / Becker, Daniel P / Chepurna, Oksana / Das, Bhaskar / Flieger, Sebastian / Hey-Hawkins, Evamarie / Hosmane, Narayan / Jalisatgi, Satish S / Nakamura, Hiroyuki / Patil, Rameshwar / Vicente, Maria da Graça H / Viñas, Clara

    Cancer biotherapy & radiopharmaceuticals

    2022  Volume 38, Issue 3, Page(s) 160–172

    Abstract: This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on ... ...

    Abstract This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on April 20-22, 2022. The most used boron sources are icosahedral boron clusters attached to peptides, proteins (such as albumin), porphyrin derivatives, dendrimers, polymers, and nanoparticles, or encapsulated into liposomes. These boron clusters and/or carriers can be labeled with contrast agents allowing for the use of imaging techniques, such as PET, SPECT, and fluorescence, that enable quantification of tumor-localized boron and their use as theranostic agents.
    MeSH term(s) Humans ; Boron/therapeutic use ; Neoplasms/diagnostic imaging ; Neoplasms/radiotherapy ; Neoplasms/drug therapy ; Liposomes ; Contrast Media ; Boron Neutron Capture Therapy/methods
    Chemical Substances Boron (N9E3X5056Q) ; Liposomes ; Contrast Media
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1315649-4
    ISSN 1557-8852 ; 1084-9785
    ISSN (online) 1557-8852
    ISSN 1084-9785
    DOI 10.1089/cbr.2022.0060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1896: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: β-Amyloid targeting nanodrug for neuron-specific delivery of nucleic acids in Alzheimer's disease mouse models

    Israel, Liron L. / Sun, Tao / Braubach, Oliver / Cox, Alysia / Shatalova, Ekaterina S. / Rashid, Harun-Mohammad / Galstyan, Anna / Grodzinski, Zachary / Song, Xue Ying / Chepurna, Oksana / Ljubimov, Vladimir A. / Chiechi, Antonella / Sharma, Sachin / Phebus, Connor / Wang, Yizhou / Ljubimova, Julia Y. / Black, Keith L. / Holler, Eggehard

    Journal of Controlled Release.

    2023  

    Abstract: Delivery of therapeutic substances into the brain poses a significant challenge in the treatment of neurological disorders. This is primarily due to the blood-brain barrier (BBB), which restricts access, alongside the limited stability and distribution ... ...

    Abstract Delivery of therapeutic substances into the brain poses a significant challenge in the treatment of neurological disorders. This is primarily due to the blood-brain barrier (BBB), which restricts access, alongside the limited stability and distribution of these agents within the brain tissue. Here we demonstrate an efficient delivery of microRNA (miRNA) and antisense RNA preferentially to neurons compared to astroglia in the brain of healthy and Alzheimer's disease mice, via disulfide-linked conjugation with poly(ß-L-malic acid-trileucine)-copolymer a biodegradable, amphiphilic, and multivalent platform. By conjugating a D-configured (D3)-peptide (vector) for specific targeting, highly efficient delivery across the BBB is achieved through the Low-Density Lipoprotein Receptor-Related Protein-1 (LRP-1) transcytosis pathway, amyloid beta (Aβ) peptides. Nanodrug distribution was determined by fluorescent labeling and analyzed by microscopy in neurons, astroglia, and in extracellular amyloid plaques typical for Alzheimer's disease. Whereas D-configured BBB-vectors can efficiently target neurons, L-configured (e.g., AP2-peptide) guided vector can only cross BBB but not seem to bind neurons. An analysis of post-injection fluorescence distribution, and RNA-seq followed by real-time PCR validation, confirmed a successful in vivo delivery of morpholino-miRNA-186 nanoconjugates into mouse brain. The size and fluorescence intensity of the intracellular nanodrug particulates were analyzed and verified by a competition with non-fluorescent conjugates. Differentially expressed genes (DEGs) from RNA-seq were identified in the nanodrug injected mice, and the changes of selected DEGs related to Alzheimer's disease were further validated by western blot and real-time PCR. Collectively, these results demonstrated that D3-peptide-conjugated nanopolymer drug is able to achieve neuron-selective delivery of miRNA and can serve as an efficient brain delivery vehicle in Alzheimer's disease (AD) mouse models.
    Keywords Alzheimer disease ; Western blotting ; amyloid ; astrocytes ; biodegradability ; blood-brain barrier ; brain ; drugs ; fluorescence ; gene expression regulation ; low density lipoprotein ; mice ; microRNA ; microscopy ; particulates ; peptides ; physiological transport ; quantitative polymerase chain reaction ; sequence analysis ; therapeutics ; Neuron targeting ; Blood-brain barrier ; Nanotechnology ; Nucleic acid delivery ; miRNA ; Alzheimer's disease
    Language English
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.08.001
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2055: 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)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Exposure to environmental airborne particulate matter caused wide-ranged transcriptional changes and accelerated Alzheimer's-related pathology: A mouse study.

    Israel, Liron L / Braubach, Oliver / Shatalova, Ekaterina S / Chepurna, Oksana / Sharma, Sachin / Klymyshyn, Dmytro / Galstyan, Anna / Chiechi, Antonella / Cox, Alysia / Herman, David / Bliss, Bishop / Hasen, Irene / Ting, Amanda / Arechavala, Rebecca / Kleinman, Michael T / Patil, Rameshwar / Holler, Eggehard / Ljubimova, Julia Y / Koronyo-Hamaoui, Maya /
    Sun, Tao / Black, Keith L

    Neurobiology of disease

    2023  Volume 187, Page(s) 106307

    Abstract: Air pollution poses a significant threat to human health, though a clear understanding of its mechanism remains elusive. In this study, we sought to better understand the effects of various sized particulate matter from polluted air on Alzheimer's ... ...

    Abstract Air pollution poses a significant threat to human health, though a clear understanding of its mechanism remains elusive. In this study, we sought to better understand the effects of various sized particulate matter from polluted air on Alzheimer's disease (AD) development using an AD mouse model. We exposed transgenic Alzheimer's mice in their prodromic stage to different sized particulate matter (PM), with filtered clean air as control. After 3 or 6 months of exposure, mouse brains were harvested and analyzed. RNA-seq analysis showed that various PM have differential effects on the brain transcriptome, and these effects seemed to correlate with PM size. Many genes and pathways were affected after PM exposure. Among them, we found a strong activation in mRNA Nonsense Mediated Decay pathway, an inhibition in pathways related to transcription, neurogenesis and survival signaling as well as angiogenesis, and a dramatic downregulation of collagens. Although we did not detect any extracellular Aβ plaques, immunostaining revealed that both intracellular Aβ1-42 and phospho-Tau levels were increased in various PM exposure conditions compared to the clean air control. NanoString GeoMx analysis demonstrated a remarkable activation of immune responses in the PM exposed mouse brain. Surprisingly, our data also indicated a strong activation of various tumor suppressors including RB1, CDKN1A/p21 and CDKN2A/p16. Collectively, our data demonstrated that exposure to airborne PM caused a profound transcriptional dysregulation and accelerated Alzheimer's-related pathology.
    Language English
    Publishing date 2023-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2023.106307
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4444: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  6. Article: Multifunctional Magneto-Plasmonic Fe

    Mukha, Iuliia / Chepurna, Oksana / Vityuk, Nadiia / Khodko, Alina / Storozhuk, Liudmyla / Dzhagan, Volodymyr / Zahn, Dietrich R T / Ntziachristos, Vasilis / Chmyrov, Andriy / Ohulchanskyy, Tymish Y

    Nanomaterials (Basel, Switzerland)

    2021  Volume 11, Issue 5

    Abstract: Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on ... ...

    Abstract Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe
    Language English
    Publishing date 2021-04-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano11051113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Synergy of Chemo- and Photodynamic Therapies with C

    Grebinyk, Anna / Prylutska, Svitlana / Chepurna, Oksana / Grebinyk, Sergii / Prylutskyy, Yuriy / Ritter, Uwe / Ohulchanskyy, Tymish Y / Matyshevska, Olga / Dandekar, Thomas / Frohme, Marcus

    Nanomaterials (Basel, Switzerland)

    2019  Volume 9, Issue 11

    Abstract: A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle ... ...

    Abstract A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C
    Language English
    Publishing date 2019-10-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano9111540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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