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Nathan Goodyear

Radiation treatment generates therapy‐resistant cancer stem cells from less a... - 0 views

acsjournals.onlinelibrary.wiley.com/...cncr.27701

CSC cancer stem cells radiation resistance

shared by Nathan Goodyear on 06 Feb 21 - No Cached
  • Nathan Goodyear on 06 Feb 21
     
    Radiation induces CSC radiation resistance.
Nathan Goodyear

Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer... - 0 views

www.ncbi.nlm.nih.gov/...PMC5282724

TME radiation epithelial to mesenchymal transition cancer stem cells tumor microenvironment CSC metastasis EMT

shared by Nathan Goodyear on 06 Feb 21 - No Cached
  • Nathan Goodyear on 06 Feb 21
     
    This study focuses on the molecular mechanisms of IR-induced EMT, CSCs, oncogenic metabolism, alterations in the TME, and treatment resistance.
Nathan Goodyear

Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/29432735

IV vitamin C CSC High dose IV vitamin C cancer stem cells vitamin C high dose vitamin C high-dose IV vitamin C cancer

shared by Nathan Goodyear on 03 Sep 22 - No Cached
  • Nathan Goodyear on 03 Sep 22
     
    High dose vitamin C preferentially targets CSC but not differentiated cells.
Nathan Goodyear

Ivermectin as an inhibitor of cancer stem‑like cells - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/29257278

CSC ivermectin cancer stem cells

shared by Nathan Goodyear on 16 Jan 24 - No Cached
  • Nathan Goodyear on 16 Jan 24
     
    Cell and computational study, so limited to take; however, it did showed that ivermectin inhibited CSC.
Nathan Goodyear

Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking m... - 0 views

www.ncbi.nlm.nih.gov/...PMC3777479

Niclosamide cancer NF-kappaB Wnt ROS mTOR

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Accumulating evidence suggests that niclosamide targets multiple signaling pathways such as nuclear factor-kappaB (NF-kB), Wnt/β-catenin, and Notch, most of which are closely involved with cancer stem cell proliferation
  • The transcription factor NF-κB has been demonstrated to promote cancer growth, angiogenesis, escape from apoptosis, and tumorigenesis
  • NF-κB is sequestered in the cytosol of resting cells through binding the inhibitory subunit IκBα
  • ...13 more annotations...
  • Niclosamide blocked TNFα-induced IκBα phosphorylation, translocation of p65, and the expression of NF-κB-regulated genes
  • Niclosamide also inhibited the DNA binding of NF-κB to the promoter of its target genes
  • niclosamide has two independent effects: NF-kB activation and ROS elevation
  • The Wnt signaling pathway plays fundamental roles in directing tissue patterning in embryonic development, in maintaining tissue homeostasis in differentiated tissue, and in tumorigenesis
  • niclosamide is a potent inhibitor of the Wnt/β-catenin pathway
  • The Notch signaling pathway plays important roles in a variety of cellular processes such as proliferation, differentiation, apoptosis, cell fate decisions, and maintenance of stem cells
  • niclosamide potently suppresses the luciferase activity of a CBF-1-dependent reporter gene in both a dose-dependent and a time-dependent manners in K562 leukemia cells
  • niclosamide treatment abrogated the epidermal growth factor (EGF)-stimulated dimerization and nuclear translocation and transcriptional activity of Stat3, and induced cell growth inhibition and apoptosis in several types of cancer cells (e.g. Du145, Hela, A549) that exhibit relatively higher levels of Stat3 constitutive activation
  • niclosamide can rapidly increase autophagosome formation
  • niclosamide induced autophagy and inhibited mammalian target of rapamycin complex 1 (mTORC1)
  • Niclosamide has low toxicity in mammals (oral median lethal dose in rats >5000 mg/kg
  • Niclosamide is active against cancer cells such as AML and colorectal cancer cells, not only as a monotherapy but also as part of combination therapy, in which it has been found to be synergistic with frontline chemotherapeutic agents (e.g., oxaliplatin, cytarabine, etoposide, and daunorubicin)
  • Because niclosamide targets multiple signaling pathways (e.g., NF-κB, Wnt/β-catenin, and Notch), most of which are closely involved with cancer stem cells, it holds promise in eradicating cancer stem cells
  • Nathan Goodyear on 16 Apr 18
     
    Review article: common anti-parasitic medication, niclosamide, provides anti-proliferative effect in cancer stem cells (CSC), via inhibition of NF-kappaBeta, Wnt/B-catenin, Notch, ROS, mTORC1, and STAT2 pathways.
Nathan Goodyear

Epithelial‐to‐mesenchymal transition (EMT) to sarcoma in recurrent lung adeno... - 0 views

www.ncbi.nlm.nih.gov/...PMC6718027

chemotherapy EMT epithelial to mesenchymal transition

shared by Nathan Goodyear on 19 Apr 20 - No Cached
  • facilitates the dissemination of cancer cells to distant organs. In addition to facilitating metastasis, EMT is thought to generate cancer stem cells (CSCs), which are generally resistant to apoptosis and to standard chemotherapeutic drugs and radiotherapy
  • IL‐6, which enhances TGF‐β‐induced EMT changes in NSCLC
  • aside from TGF‐β and Snail, several other signalling pathways including Notch, Wnt, and integrin are known to activate EMT through transcriptional repression of E‐cadherin
  • ...4 more annotations...
  • increasing evidence that treatment with chemotherapy or chemoradiotherapy can induce EMT in NSCLC which in turn is thought to generate CSCs which are generally resistant to such treatments
  • cisplatin has been shown to increase the release of Interleukin‐6 (IL‐6) and expression of transforming growth factor beta (TGF‐β)
  • EMT confers an invasive phenotype and
  • IL‐6 serves to block apoptosis in cells
  • Nathan Goodyear on 19 Apr 20
     
    Chemotherapy causes EMT.
Nathan Goodyear

A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumo... - 0 views

www.nature.com/...nature10525

cancer stem cells VEGF angiogenesis stem

shared by Nathan Goodyear on 23 Apr 21 - No Cached
  • Nathan Goodyear on 23 Apr 21
     
    Not specifically focused on CSC, but anti-angiogenic therapies via blockade of VEGF inhibit stem ness.
Nathan Goodyear

Redox Regulation in Cancer Stem Cells - 0 views

www.hindawi.com/...750798

Cancer redox cancer stem cells CSC

shared by Nathan Goodyear on 04 Dec 18 - No Cached
  • Nathan Goodyear on 04 Dec 18
     
    Redox reactions in cancer stem cells
Nathan Goodyear

MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via ... - 0 views

www.cell.com/...S1550-4131(17)30560-0

Cancer "cancer stem cells" CSC protein amino acids

shared by Nathan Goodyear on 24 Nov 18 - No Cached
  • Nathan Goodyear on 24 Nov 18
     
    Cancer stem cells found to maintain oxidative phosphorylation and increases dependence from amino acids rather than glucose
Nathan Goodyear

Home: Cell PressInhibition of Amino Acid Metabolism Selectively Targets Human Leukemia ... - 0 views

www.cell.com/...S1535-6108(18)30471-9

Cancer cancer stem cells CSC

shared by Nathan Goodyear on 24 Nov 18 - No Cached
  • Nathan Goodyear on 24 Nov 18
     
    Cancer Stem cells are not tied to the Warburg effect.
Nathan Goodyear

BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent... - 0 views

www.ncbi.nlm.nih.gov/...PMC3595363

CSC cancer stem cells leukemia oxidative phosphorylation cancer

shared by Nathan Goodyear on 28 Nov 18 - No Cached
  • Nathan Goodyear on 28 Nov 18
     
    Leukemia stem cells use oxidative phosphorylation metabolism via upregulation of bcl-2 gene.
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

Cancers | Free Full-Text | A Second WNT for Old Drugs: Drug Repositioning against WNT-D... - 0 views

www.mdpi.com/htm

cancer Niclosamide ivermectin Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • To date nearly half of known human tumors show a dysregulation of the WNT signaling pathway
  • It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics
  • The intestine seems to be the most vulnerable in this regard
  • ...8 more annotations...
  • Ivermectin inhibits proliferation of human colon cancer and lung cancer cells both in vitro and in vivo
  • The anti-proliferative action, affecting both the bulk tumor cells and CSCs, was linked in this study to inhibition of WNT signaling
  • the anti-WNT IC50 of ivermectin is 5–10 times (~1–2 µM vs. 10 µM) lower than that of its toxic effect against chloride channels
  • oral bioavailability of the drug, as for other antiparasitic drugs discussed in this section, is very low
  • Toxicity studies in vivo have also demonstrated a wide therapeutic index for ivermectin
  • Its anti-proliferative activity has been demonstrated in a wide array of cancer cell lines representative of WNT-dependent cancers: non-small lung carcinoma [96], multiple myeloma [97], hepatoma [98], adrenocortical carcinoma [99], ovarian cancer [100] and glioblastoma
  • Niclosamide inhibits the canonical WNT pathway
  • In addition to inhibiting the canonical WNT pathway, niclosamide may mediate its anticancer activities through several other signaling pathways such as NOTCH [107], MTOR [108], NF-κB [97] and STAT3 [96]
  • Nathan Goodyear on 16 Apr 18
     
    review article highlights older medications that have anti-Wnt pathway effects in cancer.  Roughly, 50% of cancer involve upregulated Wnt pathway activity. Other drugs of note: metformin
Nathan Goodyear

PO-238 Dichloroacetate (DCA) treatment affects mitochondrial activity and ste... - 0 views

esmoopen.bmj.com/...A113.1

cancer" DCA CSC pancreatic cancer stem cells cancer dichloracetic acid dichloroacetate

shared by Nathan Goodyear on 27 Nov 18 - No Cached
  • Nathan Goodyear on 27 Nov 18
     
    DCA shown to decrease tumor size in mouse model of pancreatic cancer stem cells.
Nathan Goodyear

Salinomycin: A Novel Anti-Cancer Agent with Known Anti-Coccidial Activities - 0 views

www.ncbi.nlm.nih.gov/...PMC4102832

CSC cancer cancer stem cells salinomycin

shared by Nathan Goodyear on 27 Apr 21 - No Cached
  • Nathan Goodyear on 27 Apr 21
     
    To be read
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