Skip to main content

Home/ Dr. Goodyear/ Group items tagged survivin

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Growth Inhibition of Ovarian Tumor-Initiating Cells by Niclosamide | Molecular Cancer T... - 0 views

mct.aacrjournals.org/...1703.long

Niclosamide Tumor-initiation cells TIC ovarian cancer cancer CSC cancer stem cells

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Ovarian cancer is the most lethal gynecologic malignancy and the fifth-most cause of overall cancer death of women in developed countries
  • An increasingly accepted cancer stem cell hypothesis regards tumors as caricatures of normal organs, possessing a hierarchy of cell types, at various stages of aberrant differentiation, descended from precursor tumor-initiating cells (TIC) cells that are highly resistant to conventional cytotoxics
  • Significant changes of gene expression in 2,928 genes were identified after niclosamide treatment for different time periods
  • ...14 more annotations...
  • uncoupling of mitochondrial oxidative phosphorylation is believed to be its anti-helminthic mechanism of action
  • we hypothesized that niclosamides antagonistic effects on OTICs could, in part, be due to its disruption of metabolism
  • Our results showed that genes participating in protein complexes of oxidative phosphorylation were downregulated
  • niclosamide treatment resulted in a more than 20% increase in reactive oxygen species (ROS) in cultured OTICs
  • niclosamide, which has proved to be safe and effective for the past 2 decades against numerous parasites, inhibited OTIC growth both in vitro and in vivo
  • niclosamide represses metabolic enzymes responsible for bioenergetics, biosynthesis, and redox regulation specifically in OTICs, presumably leading to mitochondrial intrinsic apoptosis pathways, loss of tumor stemness, and growth inhibition
  • Niclosamide is believed to inhibit mitochondrial oxidative phosphorylation
  • Niclosamide was reported to inactivate NF-κB, causing mitochondrial damage and the generation of ROS, leading to apoptosis of leukemic stem cells
  • niclosamide were identified in a screen for mTOR-signaling inhibitors
  • mTOR was reported to maintain stemness properties of HSCs by inhibiting mitochondrial biogenesis and ROS levels (39), implying that mTOR inhibitors (such as niclosamide) may interfere with mitochondria and various metabolic pathways in TICs via disruption of antioxidant responses
  • We observed Wnt hyperactivity in OTICs, in agreement with previous hypotheses of Wnt inhibitor effectiveness as an ovarian cancer therapy
  • niclosamide has now been independently identified in screens for Wnt inhibitors
  • downregulation of the Wnt/β-catenin target oncogenes survivin and c-Myc
  • ovarian carcinogenesis, the cell-to-cell signaling pathway Notch (8), were also suppressed by niclosamide (data not shown). These results agree with another recent niclosamide study in leukemia (49), and it has been widely hypothesized that disruption of Notch signaling may represent a highly effective therapy for ovarian and other solid tumors, via its essentiality to maintaining TIC stemness
  • Nathan Goodyear on 16 Apr 18
     
    Niclosamide, common anti-parasitic medication, inhibits cellular metabolism and increases ROS; both of which provide powerful anti-proliferative, anti-cancer treatment mechanism in TICs. Powerful target therapy for cancer stem cells. Also shown to inhibit Wnt stimulated oncogenes survivin and c-Myc, disrupts Notch signaling, inactivates NF-kappaBeta, and inhibits mTOR-signaling.  This has been found in in vitro and in vivo studies.
Nathan Goodyear

Effect of artesunate on apoptosis and autophagy in tamoxifen resistant breast cancer ce... - 0 views

tcr.amegroups.com/...html

tamoxifen artesunate breast cancer

shared by Nathan Goodyear on 07 May 20 - No Cached
  • Nathan Goodyear on 07 May 20
     
    Artesunate effective in Tamoxifen resistant breast cancer cells lines via reduction in Bcl-2, survivin, and increase in Caspase-7.
Nathan Goodyear

The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Si... - 0 views

europepmc.org/...37112680

COVID19 Wnt_Beta catenin survivin EGFR Wnt cancer COVID ERK SARS-CoV-2 COVID-19

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway.
  • Nathan Goodyear on 01 Sep 23
     
    WTF!!
1 - 6 of 6
Showing 20▼ items per page