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Nathan Goodyear

Artesunate attenuates the growth of human colorectal carcinoma and inhibits h... - 0 views

onlinelibrary.wiley.com/...ijc.22804

artesunate cancer Wnt colorectal cancer

shared by Nathan Goodyear on 07 Aug 18 - No Cached
  • Nathan Goodyear on 07 Aug 18
     
    artesunate and colorectal cancer
Nathan Goodyear

Frontiers | Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically I... - 0 views

www.frontiersin.org/...full

vitamin C chemotherapy colorectal cancer ascorbic acid colon cancer

shared by Nathan Goodyear on 08 Nov 22 - No Cached
  • Nathan Goodyear on 08 Nov 22
     
    Vitamin C sensitizes colorectal cancer cells to chemotherapy
Nathan Goodyear

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 0 views

www.ebiomedicine.com/...fulltext

multiple myeloma vitamin C IV vitamin C smoldering myeloma cancer

shared by Nathan Goodyear on 25 Sep 17 - No Cached
  • Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
  • The generation of ascorbyl- and H2O2 radicals by PAA increases ROS stress in cancer cells
  • In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008Chen et al., 2008), in xenograft MM mice
  • ...33 more annotations...
  • These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
  • These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
  • These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
  • A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
  • RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
  • the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
  • Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
  • our pilot study also suggested that PAA could overcome drug resistance to bortezomib in MM cells
  • Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
  • combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
  • Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
  • These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
  • if creatinine clearance is <30 mL/min, high dose ascorbic acid should be not administrated.
  • In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
  • Multiple myeloma (MM) is a plasma cell neoplasm.
  • Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
  • pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
  • In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
  • the labile iron pool (LIP) is significantly elevated in MM cells
  • The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
  • In contrast, no significant change of cell viability was observed in CD138− BM cells from the same patients
  • The same effect of PAA was also observed in the SMM patients
  • no response to PAA was detected in CD138+ cells from the 2 MGUS patients
  • the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
  • Both catalase and NAC protect cells from oxidative damage
  • cells pretreated with NAC and catalase became resistant to PAA even at high doses
  • adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
  • iron is essential for PAA to achieve its anti-cancer activity
  • PAA induced early necrosis (Fig. 3Fig. 3A, 60 min) followed by late apoptosis
  • results further indicated that PAA induced mitochondria-mediated apoptosis
  • PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
  • ROS and H2O2 are well known factors mediating PAA-induced cancer cell death
  • PAA was sensitive to all 9 MMs and 2 SMMs
  • Nathan Goodyear on 25 Sep 17
     
    animal study finds high-dose, pharmacologic vitamin C found to kill multiple myeloma cells via pro-oxidant effect found in similar studies in dealing with different cancers.
Nathan Goodyear

Immunohistochemical Expression of Estrogen and Progesterone Receptors in Human Colorect... - 0 views

www.ncbi.nlm.nih.gov/...PMC3215447

estrogen progesterone ER estrogen receptor estrogen receptors ER alpha ER beta ER-alpha ER-beta PR progesterone receptor progesterone receptors

shared by Nathan Goodyear on 09 Jun 14 - No Cached
  • Nathan Goodyear on 09 Jun 14
     
    Study finds ER and PR increase along the timeline of tumor initiation.  The authors point to likely association that ER and PR expression is associated with and key to initiating colorectal transformation.  A lot to be determined from this study.  IF this were entirely true, then what to explain the 35% lower colorectal cancer risk in women vs men?  Likely ER and PR pertubance plays a significant role is likely, but the mere expression--yet to be determined.
Nathan Goodyear

Cyclooxygenase-2 Induces EP1- and HER-2/Neu-Dependent Vascular Endothelial Growth Facto... - 0 views

cancerres.aacrjournals.org/...554

COX-2 cancer HER-2 Celebrex VEGF metastasis prostate cancer lung cancer colorectal cancer

shared by Nathan Goodyear on 07 Aug 18 - No Cached
  • Nathan Goodyear on 07 Aug 18
     
    COX-2 is overexpressed in a variety of human cancers i.e. colorectal, prostate, lung adenocarcinoma.  This study hightlights the increased tumor metastatic potential via upregulation of VEGF-C via EP1 and HER-2 dependent pathways.  This upregulation was correlated with survival and mets.
Nathan Goodyear

Global patterns and trends in colorectal cancer incidence in young adults | Gut - 1 views

gut.bmj.com/...gutjnl-2019-319511

colorectal cancer

shared by Nathan Goodyear on 14 Sep 19 - No Cached
  • Nathan Goodyear on 14 Sep 19
     
    Disturbing trend shows increasing colorectal cancer in younger patients.
Nathan Goodyear

Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreas... - 0 views

pubmed.ncbi.nlm.nih.gov/24551593

HIF-1alpha Hypoxia-inducible Factor 1 vitamin C colorectal cancer

shared by Nathan Goodyear on 25 Nov 21 - No Cached
  • Nathan Goodyear on 25 Nov 21
     
    Vitamin C increases disease free survival via downregulation of HIF-1alpha activity in colorectal cancer.
Nathan Goodyear

SUNSHINE: Randomized double-blind phase II trial of vitamin D supplementation in patien... - 0 views

ascopubs.org/...JCO.2017.35.15_suppl.3506

vitamin D chemotherapy colorectal cancer

shared by Nathan Goodyear on 27 Dec 22 - No Cached
  • Nathan Goodyear on 27 Dec 22
     
    Phase II clinical trial found increased PFS in combination vitamin D and chemotherapy in advanced colorectal cancer. The problem here, again is the dose. Inadequate dosing across this type of integrative studies is rampant.
Nathan Goodyear

Assessment of Colorectal Cancer Molecular Features along Bowel Subsites Challenges the ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3345105

colorectal cancer gut microbiota gut microbiome

shared by Nathan Goodyear on 02 Apr 24 - No Cached
  • Nathan Goodyear on 02 Apr 24
     
    Clearly different cancer types between distal and proximal colorectal origin-microbiome?
Nathan Goodyear

Estrogen Receptors in Colorectal Cancer: Goalkeepers, Strikers, or Bystanders? - 0 views

cancerpreventionresearch.aacrjournals.org/...897.full

estrogen colon cancer ER beta ER-beta breast

shared by Nathan Goodyear on 19 Nov 13 - No Cached
  • one can conclude that ERβ has an overall antiproliferative effect, thereby inhibiting cancer cell proliferation and antagonizing ERα function in the breast
  • HRT with estrogen alone did not increase the risk of breast cancer in the Women's Health Initiative clinical trials program
  • colorectal normal or cancer epithelium does not coexpress ERα and ERβ
  • ...7 more annotations...
  • ERβ expression resulted in the inhibition of proliferation and G1 phase cell-cycle arrest
  • ERβ expression strongly inhibited cMyc and tumor growth in a xenograft mouse model
  • induced ERβ in CRC cells has an antiproliferative, tumor-suppressive function that is independent of ERα
  • ERs also have the ability to bind many other compounds with an estrogen-like structure, including phytoestrogens and xenoestrogens (or endocrine disruptors)
  • Phytoestrogens are a diverse class of natural compounds with structural similarity to estradiol
  • Barone et al. recently found that two ERβ-selective phytoestrogens effectively counteracted CRC tumorigenesis and surprisingly increased ERβ expression in mice with mutations of the tumor-suppressor gene adenomatous polyposis coli
  • We can conclude that estrogens are important in protecting against CRC initiation and progression, and that the protective effect most likely is mediated by ERβ
  • Nathan Goodyear on 19 Nov 13
     
    ER beta is a new potential mode of therapy in colon cancer.  ER beta stimulation has been shown to inhibit colon cancer cell growth.
Nathan Goodyear

Intravenous vitamin C as a chemotherapy age... [P R Health Sci J. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15377059

IV vitamin C IV vitamin C therapy antioxidant antioxidants cancer

shared by Nathan Goodyear on 25 Sep 13 - No Cached
  • Nathan Goodyear on 25 Sep 13
     
    IV vitamin C shown to be beneficial in treatment of renal cell cancer, colorectal cancer, pancreatic cancer, non-Hodgkin's lymphoma, and breast cancer without toxic side effects.  The doses provided here were high dose and these are patients that are very unhealthy.
Nathan Goodyear

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights ... - 0 views

cancerci.biomedcentral.com/...s12935-015-0241-x

curcumin tumeric cancer colorectal cancer colon cancer

shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    curcumin effective in inhibition of cancer and cancer stem cell activity through increasing apoptotic genes, affecting cellular signaling, altering growth factor receptors, microRNAs, tumor spheroid formation, and epithelial-mesenchymal transition; and found to be helpful in increasing chemo sensitivity to chemo and radiotherapy.
Nathan Goodyear

Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically Inhibits Tumo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6064950

cancer vitamin C ascorbic acid colorectal cancer

shared by Nathan Goodyear on 26 Mar 22 - No Cached
  • therapeutic potential has been supported by a large and consistent body of evidences from in vitro
  • Ascorbic acid might act as a way to deliver hydrogen peroxide (H2O2) to the tissues
  • pharmacological concentrations of AA were capable of inducing anti-proliferative, cytotoxic and genotoxic effects
  • ...12 more annotations...
  • chemosensitizing
  • pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect
  • synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.
  • chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer
  • intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients
  • AA reinforced the anti-proliferative activity of 5-FU
  • Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect
  • cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.
  • association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions
  • AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm
    • Nathan Goodyear
      Nathan Goodyear on 26 Mar 22
       
      Apoptosis -> decrease in mitochondrial membrane potential
  • Previous results obtained by our group showed that AA mediates reactive oxygen species (ROS) formation capable of irreparably damaging DNA
  • oxidative role of AA may be a key factor on the synergistic anti-cancer mechanism
Nathan Goodyear

Menopausal Hormone Therapy and Risk of Colorectal Cancer - 0 views

cebp.aacrjournals.org/...196.full

progesterone progestin estrogen breast cancer hormone hormones

shared by Nathan Goodyear on 19 Nov 13 - No Cached
  • Nathan Goodyear on 19 Nov 13
     
    This study looked at relative risk, but estrogen plus progestin reduces the risk of colorectal cancer.  Progestin is a poor sythetic progesterone analogue.  One wonders what additional benefit progesterone may add as studies have shown with regards to breast cancer.
Nathan Goodyear

High Fat High Calories Diet (HFD) Increase Gut Susceptibility to Carcinogens by Alterin... - 0 views

www.jcancer.org/v11p4091.htm

diet high fat diet high calorie diet excess calorie cancer nutrition colorectal cancer

shared by Nathan Goodyear on 22 Aug 21 - No Cached
  • Nathan Goodyear on 22 Aug 21
     
    High fat and high calorie diets associated with increased colorectal cancer risk through alteration of gut flora. The exact mechanism between the altered gut flora and the cancer risk is unknown, per the authors, but the inflammation is likely the connection.
Nathan Goodyear

Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorect... - 0 views

www.spectracell.com/...calciumoncolorectaladenoma.pdf

inflammation cancer colorectal vitamin D3 CRP TNF IL-6 IL-1B IL-8

shared by Nathan Goodyear on 01 Feb 12 - No Cached
  • Nathan Goodyear on 01 Feb 12
     
    Vitamin D3 shown to reduce CRP, TNF, IL-6, IL-1B, IL-8 in colorectal adenoma patients. This study supports the anti-inflammatory, anti-cancer benefits of vitamin D3.
Nathan Goodyear

Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive... - 0 views

www.ncbi.nlm.nih.gov/...17520675

artesunate Wnt colorectal cancer

shared by Nathan Goodyear on 07 May 20 - No Cached
  • Nathan Goodyear on 07 May 20
     
    artesunate inhibits colorectal cancer cells via Wnt pathway inhibition.
Nathan Goodyear

TLR4 siRNA inhibits proliferation and invasion in colorectal cancer cells by downregula... - 0 views

www.sciencedirect.com/...S0024320516302934

TLR-4 cancer TLR4 colorectal cancer

shared by Nathan Goodyear on 12 Jun 20 - No Cached
  • Nathan Goodyear on 12 Jun 20
     
    inhibition of TLR-4 expression reduces colorectal growth.
Nathan Goodyear

PLOS ONE: Microbial Dysbiosis in Colorectal Cancer (CRC) Patients - 0 views

journals.plos.org/...article

dybsiosis cancer colon cancer Bacteroidetes Prevotella IL-17

shared by Nathan Goodyear on 26 Feb 15 - No Cached
  • differences in the colon microbiota in individuals with colon cancer versus those with a normal colonoscopy
  • qPCR revealed significant elevation of the Bacteroides/Prevotella population in cancer patients that appeared to be linked with elevated IL17 producing cells in the mucosa of individuals with cancer.
  • Bacteroides genus populations and more specifically those of Bacteroides fragilis, have recently been shown to produce a metalloprotease in colon cancer patients, but not in controls [12] suggesting this species sub population might favor carcinogenesis
  • ...3 more annotations...
  • It is noteworthy that among the many mechanisms that may mediate associations between microbiota and human health [21]–[22], pro-inflammatory and immune cell activation in colon mucosa are of great importance in relation to malignancy
  • B. fragilis has been shown to induce mucosal regulatory T-cell responses in the intestine involving TH17 cell recruitment in experimental models
  • the elevations of Bacteroides in the stool and/or IL17 immunoreactive cells in the normal mucosa appear to be promising sensitive markers
  • Nathan Goodyear on 26 Feb 15
     
    A relationship between dysbiosis and colon cancer appears to be present.  Particularly an increase in Bacteroidetes and Prevotella species were found in those with colon cancer versus those without.  An inflammatory up regulation of IL-17 appears to be involved.  Whether this is a cause or effect is yet to be determined, but the presence of elevated Bacteroidetes species with increased IL17 could be used as sensitive biomarkers.
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.
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