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Nathan Goodyear

IJMS | Free Full-Text | mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy | HTML - 0 views

www.mdpi.com/...htm

amino acids hypoxia mTOR protein cancer

shared by Nathan Goodyear on 27 Mar 19 - No Cached
hoangkimchi liked it
  • Nathan Goodyear on 27 Mar 19
     
    Incredible review on mTOR and carcinogenesis and promotion of cancer proliferation
Nathan Goodyear

Growth Inhibition of Ovarian Tumor-Initiating Cells by Niclosamide | Molecular Cancer Therapeutics - 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
  • 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 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
  • Our results showed that genes participating in protein complexes of oxidative phosphorylation were downregulated
  • 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

In vitro and in vivo inhibition of mTOR by 1,25-dihydroxyvitamin D 3 to improve early diabetic nephropathy via the DDIT4/TSC2/mTOR pathway - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/27395420

vitamin D mTOR

shared by Nathan Goodyear on 21 Jan 21 - No Cached
  • Nathan Goodyear on 21 Jan 21
     
    Vitamin D inhibits mTOR
Nathan Goodyear

mTOR Signaling in Growth, Metabolism, and Disease - 0 views

www.ncbi.nlm.nih.gov/...PMC5394987

cancer mTOR

shared by Nathan Goodyear on 03 Apr 19 - No Cached
hoangkimchi liked it
  • Nathan Goodyear on 03 Apr 19
     
    Great read on MTOR signaling and its impact of tumorigenesis.
Nathan Goodyear

Anticancer Effects of Niclosamide in Human Glioblastoma | Clinical Cancer Research - 0 views

clincancerres.aacrjournals.org/...4124.long

Niclosamide cancer Glioblastoma glioblastoma multiforme NOTCH mTOR Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • glioblastoma remains a fatal disease with a median overall survival time of only 15 months
  • inter- and intrapatient tumor heterogeneity
  • cellular and genetic diversity that characterizes glioblastoma
  • ...5 more annotations...
  • This broad effect could be a result of niclosamide's pleiotropic activity, similarly affecting signaling pathways that are known to be overly active in human malignant cells (i.e., mTOR, NOTCH, WNT/CTNNB1; refs. 44–46)
  • It is a salicylanilide that was introduced as a molluscide in 1959
  • Studies in animals suggested no mutagenic, oncogenic, or embryotoxic activity and no cumulative effects
  • its rate of absorption from the intestinal tract was estimated at only 33%
  • the potential mechanism of synergy between temozolomide and niclosamide as a “natural inducer” of NFKBIA
  • Nathan Goodyear on 16 Apr 18
     
    Niclosamide pilot animal study useful in the treatment of Glioblastoma.  Found to inhibit NOTCH, mTOR, and WNT and cancer signaling. Also found to reduce the malignant potential through cytostatic, cytotoxic and antimigratory effects of niclosamide on GBM
Nathan Goodyear

PLOS ONE: Alcohol Ingestion Impairs Maximal Post-Exercise Rates of Myofibrillar Protein Synthesis following a Single Bout of Concurrent Training - 0 views

journals.plos.org/...article

exercise recovery alcohol protein mTOR training

shared by Nathan Goodyear on 09 Feb 15 - No Cached
  • Nathan Goodyear on 09 Feb 15
     
    Alcohol in the recovery phase suppresses anabolic repair through inhibition of mTOR--even when taken with protein.
Nathan Goodyear

Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy | Molecular Cancer Therapeutics - 0 views

mct.aacrjournals.org/...1161.long

Cancer "breast cancer" CBD AKT mTOR

shared by Nathan Goodyear on 12 Nov 18 - No Cached
  • Nathan Goodyear on 12 Nov 18
     
    CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling through non-CBD receptor mechanism inducing apoptosis and autophagy.
Nathan Goodyear

Suppression of HSP27 increases the anti-tumor effects of quercetin in human leukemia U937 cells - 0 views

www.ncbi.nlm.nih.gov/...PMC4686121

quercetin cancer HSP heat shock proteins mTOR VEGF apoptosis

shared by Nathan Goodyear on 23 Feb 19 - No Cached
  • Nathan Goodyear on 23 Feb 19
     
    Quercetin effects in cancer i.e. decreased VEGF, apoptosis inhibition, mTOR inhibition... are augmented via HSP27 suppression
Nathan Goodyear

Metformin in cancer prevention and therapy - 0 views

www.ncbi.nlm.nih.gov/...PMC4200668

Metformin cancer mTOR IGF-1 insulin

shared by Nathan Goodyear on 27 Nov 17 - No Cached
  • relative risks imparted by diabetes are greatest (about two fold or higher) for cancers of the liver, pancreas, and endometrium, and lesser (about 1.2-1.5 fold) for cancers of the colon and rectum, breast, and bladder
  • Nathan Goodyear on 27 Nov 17
     
    Metformin useful in the prevention of cancer, but also on the treatment as an adjunct.  Good review through possible mechanisms, mToR, insulin, IGF-1...
Nathan Goodyear

Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/26002438

TA-1 peptides PI3K_Akt_mTOR breast cancer thymosin alpha-1 PTEN

shared by Nathan Goodyear on 15 Aug 21 - No Cached
  • Nathan Goodyear on 15 Aug 21
     
    TA-1 induces apoptosis through PTEN mediated PI3k/Akt/mTOR pathway inhibition. Sorry, only abstract available here. Significant in that TA-1 works beyond just immune stimulation.
Nathan Goodyear

Amino acid management in cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC4800996

amino acids cancer nutrition diet

shared by Nathan Goodyear on 15 Mar 19 - No Cached
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  • Nathan Goodyear on 15 Mar 19
     
    Serine, glycine, glutamine, glutamate, asparagine upregulated in cancer. Most glutamine is converted to glutamate to drive alpha-ketoglutarate production to drive energy production. It also upregulates mTOR signaling.
Nathan Goodyear

Protein Restriction, Epigenetic Diet, Intermittent Fasting as New Approaches for Preventing Age-associated Diseases - 0 views

www.ncbi.nlm.nih.gov/...PMC6036773

Cancer "calorie restriction" protein nutrition diet "amino amino acids

shared by Nathan Goodyear on 15 Mar 19 - No Cached
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  • Nathan Goodyear on 15 Mar 19
     
    Calorie restriction and protein restriction inhibit IGF-1, insulin, AkT, PI3K, and mTOR. In addition, those with protein intake >20%, compared to 10%, was associated with a 4 fold increase in cancer death risk and a 75% increase in overall mortality. Protein restriction inhibits tumor growth, associated with a 30-70% reduction in IGF-1, reduced the accumulation of oxidized proteins. The restriction of tryptophan alone reduced inflammation.
Nathan Goodyear

ScienceDirect - 0 views

www.sciencedirect.com/...S2212492618300745

"pancreatic cancer" cancer metformin chloroquine berberine

shared by Nathan Goodyear on 27 Nov 18 - No Cached
  • Nathan Goodyear on 27 Nov 18
     
    metformin augments chemotherapy in the treatment of pancreatic cancer. It promotes the anti-proliferative effects of mTORC and inhibits the proliferative PI3k/mTOR. It also works synergistically with the known anti-tumor anti-malarial drugs chloroquine and with the herb berberine.
Nathan Goodyear

Role of Growth Hormone in Breast Cancer - 0 views

academic.oup.com/...3098660

breast cancer growth hormone GH

shared by Nathan Goodyear on 12 Aug 19 - No Cached
  • Nathan Goodyear on 12 Aug 19
     
    Growth hormone plays critical role in breast cancer: promotes angiogenesis, stimulated mTOR, promotes chemoresistance, promotes breast stem activity, promotes metastasis via increase in epithelial to mesenchymal transition...
Nathan Goodyear

Role of the growth hormone-IGF-1 axis in cancer: Expert Review of Endocrinology & Metabolism: Vol 6, No 1 - 0 views

www.tandfonline.com/...eem.10.73

cancer growth hormone HGH

shared by Nathan Goodyear on 14 Aug 19 - No Cached
  • Nathan Goodyear on 14 Aug 19
     
    Great read on the different mechanisms by which GH promotes carcinogenesis and growth via STATs, P13K/Akt, mTOR, IGF-1...
Nathan Goodyear

Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition | Scientific Reports - 0 views

www.nature.com/...s41598-018-25524-3

mTOR PKM2 curcumin oncogenic metabolism pyruvate kinase M2 Warburg effect cancer

shared by Nathan Goodyear on 14 May 21 - No Cached
  • Nathan Goodyear on 14 May 21
     
    Curcumin inhibits PKM2 and thus the Warburg effect in cancer.
Nathan Goodyear

Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition - 0 views

www.ncbi.nlm.nih.gov/...PMC5974195

lactate Curcumin HIF-1 HIF-1alpha Warburg effect PKM2 oncogenic metabolism mTOR

shared by Nathan Goodyear on 07 May 21 - No Cached
  • Nathan Goodyear on 07 May 21
     
    Curcumin is anti-warburg effect through its inhibition of PKM2
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