LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 21

Search options

  1. Article ; Online: Activated immune cells drive neurodegeneration in an Alzheimer's model.

    Guldner, Ian H / Wyss-Coray, Tony

    Nature

    2023  Volume 615, Issue 7953, Page(s) 588–589

    MeSH term(s) Humans ; Alzheimer Disease ; Amyloid beta-Peptides ; Positron-Emission Tomography
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-023-00600-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: A nanotherapeutic approach to selectively eliminate metastatic breast cancer cells by targeting cell surface GRP78.

    Shin, Jaeho / Kim, Baksun / Lager, Tyson W / Mejia, Franklin / Guldner, Ian / Conner, Clay / Zhang, Siyuan / Panopoulos, Athanasia D / Bilgicer, Basar

    Nanoscale

    2023  Volume 15, Issue 32, Page(s) 13322–13334

    Abstract: Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer ... ...

    Abstract Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer cells
    MeSH term(s) Animals ; Mice ; Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Cell Line, Tumor ; Prodrugs ; Glucose ; Peptides ; Doxorubicin/pharmacology ; Neoplasms
    Chemical Substances Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Prodrugs ; Glucose (IY9XDZ35W2) ; Peptides ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-08-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2515664-0
    ISSN 2040-3372 ; 2040-3364
    ISSN (online) 2040-3372
    ISSN 2040-3364
    DOI 10.1039/d3nr00800b
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Isolation of mouse brain-infiltrating leukocytes for single cell profiling of epitopes and transcriptomes.

    Guldner, Ian H / Golomb, Samantha M / Wang, Qingfei / Wang, Emilia / Zhang, Siyuan

    STAR protocols

    2021  Volume 2, Issue 2, Page(s) 100537

    Abstract: High dimensional compositional and transcriptional profiling of heterogeneous brain-infiltrating leukocytes can lead to novel biological and therapeutic discoveries. High-quality single-cell leukocyte preparations are a prerequisite for optimal single ... ...

    Abstract High dimensional compositional and transcriptional profiling of heterogeneous brain-infiltrating leukocytes can lead to novel biological and therapeutic discoveries. High-quality single-cell leukocyte preparations are a prerequisite for optimal single cell profiling. Here, we describe a protocol for epitope and RNA-preserving dissociation of adult mouse brains and subsequent leukocyte purification and staining, which is adaptable to homeostatic and pathogenic brains. Leukocyte preparation following this protocol permits exquisite single-cell surface protein and RNA profiling in applications including CyTOF and CITE-seq. For complete details on the use and execution of this protocol, please refer to Guldner et al. (2020) and Golomb et al. (2020).
    MeSH term(s) Animals ; Brain/pathology ; Cell Separation/methods ; Cells, Cultured ; Epitopes/genetics ; Female ; Leukocytes/cytology ; Leukocytes/metabolism ; Male ; Mice ; Single-Cell Analysis/methods ; Transcriptome/genetics
    Chemical Substances Epitopes
    Language English
    Publishing date 2021-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100537
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article: A journey to uncharted territory: new technical frontiers in studying tumor–stromal cell interactions

    Guldner, Ian H / Zhang, Siyuan

    Integrative biology. 2015 Feb. 10, v. 7, no. 2

    2015  

    Abstract: The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor–stroma interactions is tied to ... ...

    Abstract The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor–stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor–stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet methods currently applied to study the said crosstalk do not sufficiently address these features. Emerging imaging and genetic methods, however, can overcome limitations of traditional approaches and provide unprecedented insight into tumor–stroma crosstalk with unparalleled accuracy. The comprehensive data obtained by applying emerging methods will require processing and analysis by multidisciplinary teams, but the efforts will ultimately rejuvenate hope in developing novel therapies against pro-tumorigenic tumor–stroma crosstalk.
    Keywords cancer therapy ; image analysis ; neoplasm cells ; neoplasms
    Language English
    Dates of publication 2015-0210
    Size p. 153-161.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 2480063-6
    ISSN 1757-9708 ; 1757-9694
    ISSN (online) 1757-9708
    ISSN 1757-9694
    DOI 10.1039/c4ib00192c
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  5. Article ; Online: Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer.

    Palakurthi, Bhavana / Fross, Shaneann R / Guldner, Ian H / Aleksandrovic, Emilija / Liu, Xiyu / Martino, Anna K / Wang, Qingfei / Neff, Ryan A / Golomb, Samantha M / Lewis, Cheryl / Peng, Yan / Howe, Erin N / Zhang, Siyuan

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 2109

    Abstract: Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME) ...

    Abstract Chemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic and trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads to a characteristic co-evolution of divergent myeloid cell subsets in female triple-negative breast cancer (TNBC). Specifically, we identify that the proportion of CXCL16 + myeloid cells increase and a high STAT1 regulon activity distinguishes Programmed Death Ligand 1 (PD-L1) expressing immature myeloid cells. Chemical inhibition of STAT1 signaling in MCT-primed breast cancer sensitizes TNBC to ICB treatment, which underscores the STAT1's role in modulating TIME. In summary, we leverage single-cell analyses to dissect the cellular dynamics in the tumor microenvironment (TME) following neoadjuvant chemotherapy and provide a pre-clinical rationale for modulating STAT1 in combination with anti-PD-1 for TNBC patients.
    MeSH term(s) Humans ; Female ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Radioimmunotherapy ; Myeloid Cells ; Chemokine CXCL16 ; Tumor Microenvironment ; STAT1 Transcription Factor/genetics
    Chemical Substances Immune Checkpoint Inhibitors ; Chemokine CXCL16 ; STAT1 protein, human ; STAT1 Transcription Factor ; CXCL16 protein, human
    Language English
    Publishing date 2023-04-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-37727-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: A journey to uncharted territory: new technical frontiers in studying tumor-stromal cell interactions.

    Guldner, Ian H / Zhang, Siyuan

    Integrative biology : quantitative biosciences from nano to macro

    2014  Volume 7, Issue 2, Page(s) 153–161

    Abstract: The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to ... ...

    Abstract The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor-stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet methods currently applied to study the said crosstalk do not sufficiently address these features. Emerging imaging and genetic methods, however, can overcome limitations of traditional approaches and provide unprecedented insight into tumor-stroma crosstalk with unparalleled accuracy. The comprehensive data obtained by applying emerging methods will require processing and analysis by multidisciplinary teams, but the efforts will ultimately rejuvenate hope in developing novel therapies against pro-tumorigenic tumor-stroma crosstalk.
    MeSH term(s) Animals ; Cell Communication/genetics ; Cell Communication/physiology ; Computational Biology ; Diagnostic Imaging ; Humans ; Microscopy ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/physiopathology ; Stromal Cells/pathology ; Stromal Cells/physiology ; Tumor Microenvironment/genetics ; Tumor Microenvironment/physiology
    Language English
    Publishing date 2014-12-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2480063-6
    ISSN 1757-9708 ; 1757-9694
    ISSN (online) 1757-9708
    ISSN 1757-9694
    DOI 10.1039/c4ib00192c
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype.

    Bahcecioglu, Gokhan / Yue, Xiaoshan / Howe, Erin / Guldner, Ian / Stack, M Sharon / Nakshatri, Harikrishna / Zhang, Siyuan / Zorlutuna, Pinar

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2021  Volume 8, Issue 22, Page(s) e2100128

    Abstract: Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ... ...

    Abstract Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. Decellularized breast matrix from aged mice leads to loss of E-cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer-related proteins. The aged matrix upregulates cancer-related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial-mesenchymal transition-related genes. Lysyl oxidase knockdown reverts the aged matrix-induced changes to the young levels; it relocalizes E-cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer-like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.
    MeSH term(s) Aging/metabolism ; Animals ; Breast/metabolism ; Breast/pathology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Neoplasm Invasiveness ; Phenotype
    Language English
    Publishing date 2021-10-07
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202100128
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Atlas of the aging mouse brain reveals white matter as vulnerable foci.

    Hahn, Oliver / Foltz, Aulden G / Atkins, Micaiah / Kedir, Blen / Moran-Losada, Patricia / Guldner, Ian H / Munson, Christy / Kern, Fabian / Pálovics, Róbert / Lu, Nannan / Zhang, Hui / Kaur, Achint / Hull, Jacob / Huguenard, John R / Grönke, Sebastian / Lehallier, Benoit / Partridge, Linda / Keller, Andreas / Wyss-Coray, Tony

    Cell

    2023  Volume 186, Issue 19, Page(s) 4117–4133.e22

    Abstract: Aging is the key risk factor for cognitive decline, yet the molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA sequencing of the mouse brain, profiling 1,076 samples from 15 regions across 7 ages and ... ...

    Abstract Aging is the key risk factor for cognitive decline, yet the molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA sequencing of the mouse brain, profiling 1,076 samples from 15 regions across 7 ages and 2 rejuvenation interventions. Our analysis identified a brain-wide gene signature of aging in glial cells, which exhibited spatially defined changes in magnitude. By integrating spatial and single-nucleus transcriptomics, we found that glial aging was particularly accelerated in white matter compared with cortical regions, whereas specialized neuronal populations showed region-specific expression changes. Rejuvenation interventions, including young plasma injection and dietary restriction, exhibited distinct effects on gene expression in specific brain regions. Furthermore, we discovered differential gene expression patterns associated with three human neurodegenerative diseases, highlighting the importance of regional aging as a potential modulator of disease. Our findings identify molecular foci of brain aging, providing a foundation to target age-related cognitive decline.
    MeSH term(s) Animals ; Humans ; Mice ; Aging ; Cognitive Dysfunction/genetics ; Gene Expression Profiling ; Solitary Nucleus ; White Matter/pathology ; Single-Cell Gene Expression Analysis ; Brain/pathology
    Language English
    Publishing date 2023-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.07.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer.

    Wang, Qingfei / Guldner, Ian H / Golomb, Samantha M / Sun, Longhua / Harris, Jack A / Lu, Xin / Zhang, Siyuan

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 3817

    Abstract: Acquired resistance to targeted cancer therapy is a significant clinical challenge. In parallel with clinical trials combining CDK4/6 inhibitors to treat HER2+ breast cancer, we sought to prospectively model tumor evolution in response to this regimen in ...

    Abstract Acquired resistance to targeted cancer therapy is a significant clinical challenge. In parallel with clinical trials combining CDK4/6 inhibitors to treat HER2+ breast cancer, we sought to prospectively model tumor evolution in response to this regimen in vivo and identify a clinically actionable strategy to combat drug resistance. Despite a promising initial response, acquired resistance emerges rapidly to the combination of anti-HER2/neu antibody and CDK4/6 inhibitor Palbociclib. Using high-throughput single-cell profiling over the course of treatments, we reveal a distinct immunosuppressive immature myeloid cell (IMC) population to infiltrate the resistant tumors. Guided by single-cell transcriptome analysis, we demonstrate that combination of IMC-targeting tyrosine kinase inhibitor cabozantinib and immune checkpoint blockade enhances anti-tumor immunity, and overcomes the resistance. Furthermore, sequential combinatorial immunotherapy enables a sustained control of the fast-evolving CDK4/6 inhibitor-resistant tumors. Our study demonstrates a translational framework for treating rapidly evolving tumors through preclinical modeling and single-cell analyses.
    MeSH term(s) Animals ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4/antagonists & inhibitors ; Cyclin-Dependent Kinase 6/antagonists & inhibitors ; Drug Resistance, Neoplasm/drug effects ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/immunology ; Mammary Neoplasms, Experimental/drug therapy ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/pathology ; Mice ; Mice, Transgenic ; Models, Biological ; Myeloid Progenitor Cells/drug effects ; Myeloid Progenitor Cells/immunology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Single-Cell Analysis ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Treatment Outcome ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents, Immunological ; Protein Kinase Inhibitors ; Erbb2 protein, rat (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; CDK4 protein, human (EC 2.7.11.22) ; CDK6 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22)
    Language English
    Publishing date 2019-08-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-11729-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

    Haney, Michael S / Pálovics, Róbert / Munson, Christy Nicole / Long, Chris / Johansson, Patrik K / Yip, Oscar / Dong, Wentao / Rawat, Eshaan / West, Elizabeth / Schlachetzki, Johannes C M / Tsai, Andy / Guldner, Ian Hunter / Lamichhane, Bhawika S / Smith, Amanda / Schaum, Nicholas / Calcuttawala, Kruti / Shin, Andrew / Wang, Yung-Hua / Wang, Chengzhong /
    Koutsodendris, Nicole / Serrano, Geidy E / Beach, Thomas G / Reiman, Eric M / Glass, Christopher K / Abu-Remaileh, Monther / Enejder, Annika / Huang, Yadong / Wyss-Coray, Tony

    Nature

    2024  Volume 628, Issue 8006, Page(s) 154–161

    Abstract: Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial ... ...

    Abstract Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells
    MeSH term(s) Animals ; Female ; Humans ; Male ; Mice ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Apolipoprotein E4/genetics ; Apolipoprotein E4/metabolism ; Induced Pluripotent Stem Cells/cytology ; Lipid Droplets/metabolism ; Lipid Droplets/pathology ; Microglia/cytology ; Microglia/metabolism ; Microglia/pathology ; Triglycerides ; tau Proteins ; Culture Media, Conditioned ; Phosphorylation ; Genetic Predisposition to Disease
    Chemical Substances Amyloid beta-Peptides ; Apolipoprotein E4 ; ACSL1 protein, human (EC 6.2.1.3) ; Triglycerides ; tau Proteins ; Culture Media, Conditioned
    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-024-07185-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top