LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article: Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19.

    Santoso, Clarissa S / Li, Zhaorong / Rottenberg, Jaice T / Liu, Xing / Shen, Vivian X / Fuxman Bass, Juan I

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 673485

    Abstract: Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify ... ...

    Abstract Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
    Language English
    Publishing date 2021-06-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.673485
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: BAG1L: a promising therapeutic target for androgen receptor-dependent prostate cancer.

    Lee, Irene I / Kuznik, Nane C / Rottenberg, Jaice T / Brown, Myles / Cato, Andrew C B

    Journal of molecular endocrinology

    2019  Volume 62, Issue 4, Page(s) R289–R299

    Abstract: Androgens are important determinants of normal and malignant prostate growth. They function by binding to the C-terminal ligand-binding domain (LBD) of the androgen receptor (AR). All clinically approved AR-targeting antiandrogens for prostate cancer ... ...

    Abstract Androgens are important determinants of normal and malignant prostate growth. They function by binding to the C-terminal ligand-binding domain (LBD) of the androgen receptor (AR). All clinically approved AR-targeting antiandrogens for prostate cancer therapy function by competing with endogenous androgens. Despite initial robust responses to androgen deprivation therapy, nearly all patients with advanced prostate cancer relapse with lethal castration-resistant prostate cancer (CRPC). Progression to CRPC is associated with ongoing AR signaling, which in part, is due to the expression of constitutively active AR splice variants that contain the N-terminus of the receptor but lack the C-terminus. Currently, there are no approved therapies specifically targeting the AR N-terminus. Current pharmacologic targeting strategies for inhibiting the AR N-terminal region have proven difficult, due to its intrinsically unstructured nature and lack of enzymatic activity. An alternative approach is to target key molecules such as the cochaperone BAG1L that bind to and enhance the activity of the AR AF1. Here, we review recent literature that suggest Bag-1L is a promising target for AR-positive prostate cancer.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Disease Susceptibility ; Humans ; Male ; Molecular Chaperones/chemistry ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Molecular Targeted Therapy ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/etiology ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/etiology ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Prostatic Neoplasms, Castration-Resistant/pathology ; Protein Binding ; Protein Interaction Domains and Motifs ; Receptors, Androgen/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Antineoplastic Agents ; BCL2-associated athanogene 1 protein ; Biomarkers, Tumor ; DNA-Binding Proteins ; Molecular Chaperones ; Receptors, Androgen ; Receptors, Cytoplasmic and Nuclear ; Transcription Factors
    Language English
    Publishing date 2019-03-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 645012-x
    ISSN 1479-6813 ; 0952-5041
    ISSN (online) 1479-6813
    ISSN 0952-5041
    DOI 10.1530/JME-19-0034
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2406: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: In vitro

    Santoso, Clarissa S / Li, Zhaorong / Rottenberg, Jaice T / Liu, Xing / Shen, Vivian X / Bass, Juan I Fuxman

    bioRxiv : the preprint server for biology

    2020  

    Abstract: Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify ... ...

    Abstract Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
    Language English
    Publishing date 2020-12-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.12.29.424728
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19

    Santoso, Clarissa S / Li, Zhaorong / Rottenberg, Jaice T / Liu, Xing / Shen, Vivian X / Fuxman Bass, Juan I

    bioRxiv

    Abstract: Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify ... ...

    Abstract Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
    Keywords covid19
    Language English
    Publishing date 2020-12-30
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.12.29.424728
    Database COVID19

    Full text online

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway.

    Kuznik, Nane C / Solozobova, Valeria / Lee, Irene I / Jung, Nicole / Yang, Linxiao / Nienhaus, Karin / Ntim, Emmanuel A / Rottenberg, Jaice T / Muhle-Goll, Claudia / Kumar, Amrish Rajendra / Peravali, Ravindra / Gräßle, Simone / Gourain, Victor / Deville, Célia / Cato, Laura / Neeb, Antje / Dilger, Marco / Cramer von Clausbruch, Christina A / Weiss, Carsten /
    Kieffer, Bruno / Nienhaus, G Ulrich / Brown, Myles / Bräse, Stefan / Cato, Andrew C B

    iScience

    2022  Volume 25, Issue 5, Page(s) 104175

    Abstract: BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis, and ... ...

    Abstract BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis, and transcription. The largest isoform, BAG1L, controls the activity of the androgen receptor (AR) and is upregulated in prostate cancer. Here, we show that BAG1L regulates AR dynamics in the nucleus and its ablation attenuates AR target gene expression especially those involved in oxidative stress and metabolism. We show that a small molecule, A4B17, that targets the BAG domain downregulates AR target genes similar to a complete BAG1L knockout and upregulates the expression of oxidative stress-induced genes involved in cell death. Furthermore, A4B17 outperformed the clinically approved antagonist enzalutamide in inhibiting cell proliferation and prostate tumor development in a mouse xenograft model. BAG1 inhibitors therefore offer unique opportunities for antagonizing AR action and prostate cancer growth.
    Language English
    Publishing date 2022-03-31
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104175
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.

    Cato, Laura / Neeb, Antje / Sharp, Adam / Buzón, Victor / Ficarro, Scott B / Yang, Linxiao / Muhle-Goll, Claudia / Kuznik, Nane C / Riisnaes, Ruth / Nava Rodrigues, Daniel / Armant, Olivier / Gourain, Victor / Adelmant, Guillaume / Ntim, Emmanuel A / Westerling, Thomas / Dolling, David / Rescigno, Pasquale / Figueiredo, Ines / Fauser, Friedrich /
    Wu, Jennifer / Rottenberg, Jaice T / Shatkina, Liubov / Ester, Claudia / Luy, Burkhard / Puchta, Holger / Troppmair, Jakob / Jung, Nicole / Bräse, Stefan / Strähle, Uwe / Marto, Jarrod A / Nienhaus, Gerd Ulrich / Al-Lazikani, Bissan / Salvatella, Xavier / de Bono, Johann S / Cato, Andrew Cb / Brown, Myles

    eLife

    2017  Volume 6

    Abstract: Targeting the activation function-1 (AF-1) domain located in the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is ... ...

    Abstract Targeting the activation function-1 (AF-1) domain located in the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the cochaperone Bag-1L. Mutations in the AR interaction domain or loss of Bag-1L abrogate AR signaling and reduce PCa growth. Clinically, Bag-1L protein levels increase with progression to castration-resistant PCa (CRPC) and high levels of Bag-1L in primary PCa associate with a reduced clinical benefit from abiraterone when these tumors progress. Intriguingly, residues in Bag-1L important for its interaction with the AR AF-1 are within a potentially druggable pocket, implicating Bag-1L as a potential therapeutic target in PCa.
    MeSH term(s) Androgen Receptor Antagonists/metabolism ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/metabolism ; Humans ; Male ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/therapy ; Protein Binding ; Protein Interaction Maps ; Receptors, Androgen/metabolism ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/metabolism
    Chemical Substances Androgen Receptor Antagonists ; BCL2-associated athanogene 1 protein ; DNA-Binding Proteins ; Receptors, Androgen ; Transcription Factors
    Language English
    Publishing date 2017-08-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.27159
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer.

    Cato, Laura / de Tribolet-Hardy, Jonas / Lee, Irene / Rottenberg, Jaice T / Coleman, Ilsa / Melchers, Diana / Houtman, René / Xiao, Tengfei / Li, Wei / Uo, Takuma / Sun, Shihua / Kuznik, Nane C / Göppert, Bettina / Ozgun, Fatma / van Royen, Martin E / Houtsmuller, Adriaan B / Vadhi, Raga / Rao, Prakash K / Li, Lewyn /
    Balk, Steven P / Den, Robert B / Trock, Bruce J / Karnes, R Jeffrey / Jenkins, Robert B / Klein, Eric A / Davicioni, Elai / Gruhl, Friederike J / Long, Henry W / Liu, X Shirley / Cato, Andrew C B / Lack, Nathan A / Nelson, Peter S / Plymate, Stephen R / Groner, Anna C / Brown, Myles

    Cancer cell

    2019  Volume 35, Issue 3, Page(s) 401–413.e6

    Abstract: Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, often ... ...

    Abstract Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, often through increased expression of full-length AR (ARfl) or expression of dominantly active splice variants such as ARv7. We show in ARv7-dependent CRPC models that ARv7 binds together with ARfl to repress transcription of a set of growth-suppressive genes. Expression of the ARv7-repressed targets and ARv7 protein expression are negatively correlated and predicts for outcome in PCa patients. Our results provide insights into the role of ARv7 in CRPC and define a set of potential biomarkers for tumors dependent on ARv7.
    MeSH term(s) Alternative Splicing ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Tissue Array Analysis ; Transcription, Genetic
    Chemical Substances AR protein, human ; Receptors, Androgen
    Language English
    Publishing date 2019-02-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2019.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 104: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top