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Nathan Goodyear

An Oncolytic Virus Expressing a T-cell Engager Simultaneously Targets Cancer and Immuno... - 0 views

cancerres.aacrjournals.org/...0008-5472.CAN-18-1750

oncolytic therapy cancer"

shared by Nathan Goodyear on 10 Dec 18 - No Cached
  • Nathan Goodyear on 10 Dec 18
     
    Oncolytic adenovirus kills cancer cell and activates Tcells.
Nathan Goodyear

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor,... - 0 views

europepmc.org/...PMC2510818

GC-MAF Nagalase cancer prostate cancer immunotherapy PSA

shared by Nathan Goodyear on 08 May 18 - No Cached
  • the MAF precursor activity of prostate cancer patient Gc protein is lost or reduced, because their serum Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells
  • Administration of 100 ng of GcMAF
  • 100 ng of GcMAF was administered intramuscularly once a week
  • ...11 more annotations...
  • As GcMAF therapy progressed the MAF precursor activity of all five patients increased and their serum Nagalase activity decreased inversely
  • As GcMAF therapy progressed, the MAF precursor activity increased with a concomitant decrease in serum Nagalase activity
  • serum Nagalase is proportional to tumor burden
  • as GcMAF therapy progressed, serum Nagalase activity decreased and, concomitantly, tumor burden decreased
  • the serum Nagalase activities of all 16 patients decreased as GcMAF therapy progressed
  • annual computed tomographic scans of these patients confirmed them being tumor recurrence-free for the 7 years
  • undifferentiated cells were killed rapidly during the first few weeks, and the differentiated cells were killed slowly in the remaining GcMAF therapeutic period
  • PSA levels of prostatectomized patients decreased as serum Nagalase decreased during GcMAF therapy
  • In patients without tumor resection, however, although serum Nagalase activity decreased as GcMAF therapy progressed, their PSA values remained unchanged. The result suggests that the PSA derived from tumor-bearing prostate did not change while tumor burden decreased. Because tumor-induced inflammation in the noncancerous prostate tissues causes secretion of PSA [38], the PSA produced from these inflamed noncancerous prostate tissues cannot be changed by the decrease in tumor burden
  • Advanced cancer patients have high serum Nagalase activities, resulting in no macrophage activation and severe immunosuppression that explain why cancer patients die with overwhelming infection
  • Prognostic utility of serum α-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients
  • Nathan Goodyear on 08 May 18
     
    GC-MAF levels exist in inverse relationship to nagalase.  In this study of men with prostate cancer, weekly GCMAF injections reduced Nagalase activity to levels found in healthy controls suggesting tumor free. The dose was 100 ng/week. Nagalase is a protein that suppresses GC-MAF production and thus is immunosuppressive.
Nathan Goodyear

https://www.nature.com/articles/2401085.pdf?origin=publication_detail - 0 views

www.nature.com/...2401085.pdf

IL-2 leukemia NK cancer

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    IL-2 therapy foud to kill myeloid leukemia cells via NK activation in vitro study.
Nathan Goodyear

Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharma... - 0 views

www.ncbi.nlm.nih.gov/...9624250

hyperthermia cisplatin cancer

shared by Nathan Goodyear on 04 Aug 19 - No Cached
  • Nathan Goodyear on 04 Aug 19
     
    combination of hyperthermia and cisplatin enhanced cell killing compared with either treatment alone. The hyperthermia induced a favorable pharmacokinetics.
Nathan Goodyear

Opposing effects of low versus high concentrations of water soluble vitamins/dietary in... - 0 views

www.ncbi.nlm.nih.gov/...28755485

vitamin C cancer colorectal cancer niacin

shared by Nathan Goodyear on 18 Aug 19 - No Cached
  • Nathan Goodyear on 18 Aug 19
     
    High dose vitamin C + high dose niacin kill CSCs, but low dose stimulates CSCs.
Nathan Goodyear

Intravenously administered vitamin C as cancer therapy: three cases - 0 views

www.ncbi.nlm.nih.gov/...PMC1405876

IV vitamin C vitamin C cancer

shared by Nathan Goodyear on 24 Apr 17 - No Cached
  • peak plasma concentrations obtained intravenously are estimated to reach 14 000 μmol/L, and concentrations above 2000 μmol/L may persist for several hours
  • Emerging in vitro data show that extracellular ascorbic acid selectively kills some cancer but no normal cells by generating hydrogen peroxide
  • Death is mediated exclusively by extracellular ascorbate, at pharmacologic concentrations that can be achieved only by intravenous administration
  • ...6 more annotations...
  • Vitamin C may serve as a pro-drug for hydrogen peroxide delivery to extravascular tissues, but without the presence of hydrogen peroxide in blood
  • not all cancer cells were killed by ascorbic acid in vitro
  • Intravascular hemolysis was reported after massive vitamin C administration in people with glucose-6-phosphate dehydrogenase deficiency
  • Administration of high-dose vitamin C to patients with systemic iron overload may increase iron absorption and represents a contraindication
  • Ascorbic acid is metabolized to oxalate, and 2 cases of acute oxalate nephropathy were reported in patients with pre-existing renal insufficiency given massive intravenous doses of vitamin C
  • Rare cases of acute tumour hemorrhage and necrosis were reported in patients with advanced cancer within a few days of starting high-dose intravenous vitamin C therapy, although this was not independently verified by pathologic review
  • Nathan Goodyear on 24 Apr 17
     
    IV vitamin C associated with prolonged survival in 3 patients with different cancers.  Peak serum levels reached 14,000 micromol/L, which levels above the 1,000 micro mol/L (cancer cell cytotoxic threshold) were maintained for hours
Nathan Goodyear

Artemisinin sensitizes tumor cells to NK cell-mediated cytolysis - ScienceDirect - 0 views

www.sciencedirect.com/...S0006291X20301637

cancer artemisinin NK cells

shared by Nathan Goodyear on 22 Aug 20 - No Cached
  • Nathan Goodyear on 22 Aug 20
     
    Artemisinin increases tumor cell sensitivity to NK cell killing activity.
Nathan Goodyear

Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting G... - 0 views

www.ncbi.nlm.nih.gov/...PMC4778961

KRAS BRAF vitamin C IV vitamin C cancer

shared by Nathan Goodyear on 02 Jul 18 - No Cached
  • Nathan Goodyear on 02 Jul 18
     
    Cell culture study finds that vitamin C selectively kills colorectal cancer cells that express KRAS or BRAF mutations.
Nathan Goodyear

Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Co... - 0 views

pubmed.ncbi.nlm.nih.gov/33419797

colon cancer peptides cancer CSC PNC-27 cancer stem cells PNC27

shared by Nathan Goodyear on 14 Aug 21 - No Cached
  • Nathan Goodyear on 14 Aug 21
     
    PNC-27 selectively kills colon cancer stem cells by binding to membrane H/MDM-2. This was an in vivo study. As with other studies, the result was tumor cell necrosis and associated high LDH release.
Nathan Goodyear

Israeli Study Shows New Cannabis Treatment Kills Cancer Cells - 0 views

contenthub.gcintelligence.com/s-treatment-kills-cancer-cells

cancer medical cannabis chemotherapy

shared by Nathan Goodyear on 28 Nov 23 - No Cached
  • Nathan Goodyear on 28 Nov 23
     
    Just a PR, but worth a mention. I will track down this study if able
Nathan Goodyear

Sars-Cov-2 Kills T-Cells, Just Like HIV - by Igor Chudov - 0 views

igorchudov.substack.com/...-cov-2-kills-t-cells-just-like

ACE2 immune system T cells cancer SAR T lymphocytes COVID SARS-CoV-2

shared by Nathan Goodyear on 17 Mar 22 - No Cached
  • Nathan Goodyear on 17 Mar 22
     
    Just an article.
Nathan Goodyear

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and h... - 0 views

www.ncbi.nlm.nih.gov/...PMC1885574

vitamin C ascorbic acid Cancer

shared by Nathan Goodyear on 05 Mar 18 - No Cached
  • Proposed mechanism
  • The data show that pharmacologic ascorbate concentrations produced Asc•− selectively in extracellular fluid compared with blood and that H2O2 formation occurred when Asc•− concentrations were >100 nM in extracellular fluid.
  • These data validate the hypothesis that ascorbate is a prodrug for selective delivery of reactive species to the extravascular space
  • ...22 more annotations...
  • pharmacologic ascorbate as a prooxidant drug for therapeutic use.
  • Recently we reported that pharmacologic ascorbic acid concentrations produced H2O2 concentrations of ≥25 μM, causing cancer cell death in vitro
  • We found that H2O2 concentrations generated in vivo were those that caused cancer cell death in vitro
  • When ascorbate was given parenterally, Asc•−, the product of a loss of one electron from ascorbate, was detected preferentially in extracellular fluid compared with blood
  • Asc•− generation in extracellular fluid depended on the ascorbate dose and the resulting concentrations
  • With i.v. administration of ascorbate, Asc•− concentrations were as much as 12-fold greater in extracellular fluid compared to blood and approached 250 nM
  • In blood, such Asc•− concentrations were never produced and were always <50 nM
  • These data are all consistent with the hypothesis that pharmacologic ascorbate concentrations in vivo serve as a prodrug for selective delivery of H2O2 to the extracellular space
  • After oral ingestion, control of intracellular and extracellular ascorbate concentrations is mediated by three mechanisms: intestinal absorption, tissue transport, and renal reabsorption
  • intestinal absorption, or bioavailability, declines at doses >200 mg
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      significant limitation of gut absorption of vitamin C--at 200 mg po.
  • corresponding to plasma concentrations of ≈60 μM
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      equates to 0.06 mM.  Max blood levels found with po AA dosing has been 0.22 mM
  • at approximately this concentration, the ascorbate tissue transporter SVCT2 approaches Vmax, and tissues appear to be saturated
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      SVCT2 Rc in gut reach max binding.
  • also at ≈60 μM, renal reabsorption approaches saturation, and excess ascorbate is excreted in urine
  • Parenteral administration bypasses tight control
  • When tight control is bypassed, H2O2 forms in the extracellular space
  • in vivo validation of ascorbate as a prodrug for selective H2O2 formation
  • Temporarily bypassing tight control with parenteral administration of ascorbate allows H2O2 to form in discrete time periods only, decreasing likelihood of harm, and provides a pharmacologic basis for therapeutic use of i.v. ascorbate
  • H2O2 formation results in selective cytotoxicity
  • Tumor cells are killed with exposure to H2O2 for ≤30 min
  • In vitro, killing is mediated by H2O2 rather than Asc•−
  • In addition to cancer treatment, another potential therapeutic use is for treatment of infections. H2O2 concentrations of 25–50 μM are bacteriostatic
  • virally infected cells may also be candidates
  • Nathan Goodyear on 05 Mar 18
     
    follow up invivo study to previous study from 2005.  Here, the authors prove their hypothesis that ascorbate is a prodrug for delivery of H2O2.
Nathan Goodyear

The impact of the microbiome in cancer: Targeting metabolism of cancer cells and host -... - 0 views

www.ncbi.nlm.nih.gov/...PMC9708872

tumor microbiome cancer gut microbiome TME metabolism

shared by Nathan Goodyear on 20 Mar 24 - No Cached
  • Nathan Goodyear on 20 Mar 24
     
    Studies have found that high-salt diet can enhance the function of natural killer (NK) cells by enriching the abundance of Bifidobacterium, thus inhibiting tumor growth (63). High dietary fiber can enrich A. muciniphila, activate innate immunity, reshape the tumor microenvironment, and exert the function of inhibiting tumor (64). Notably, Wargo et al. have confirmed that high-dietary fiber diet can enhance anti-tumor immunity and increase the infiltration of tumor-killing T cells, while commercial probiotics treatment alone does not enhance the efficacy of immunotherapy. This study suggests that probiotics intervention is strain-specific and should be put in a specific dietary environment to make sense, to some extent (65).
Nathan Goodyear

Vitamin C Can Kill Multidrug-Resistant TB in the Lab - 0 views

www.lef.org/...LefDailyNews.htm

vitamin C vitamin C

shared by Nathan Goodyear on 28 May 13 - No Cached
  • Nathan Goodyear on 28 May 13
     
    Vitamin C shown to be bactericidal to multi-drug resistant TB in vitro.  Whether in vivo studies duplicate this or not remains to be seen, but I would anticipate it will.
Nathan Goodyear

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views

www.pnas.org/...13604.abstract

IV vitamin C intravenous therapy treatment cancer

shared by Nathan Goodyear on 14 Nov 11 - No Cached
  • Nathan Goodyear on 14 Nov 11
     
    IV vitamin C shown to be useful aid in cancer treatment
Nathan Goodyear

Deprive to kill: glutamine closes the gate to anti... [Autophagy. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22932475

3-bromopyruvate 3-BrPA cancer

shared by Nathan Goodyear on 11 Sep 13 - No Cached
  • Nathan Goodyear on 11 Sep 13
     
    Another reason to avoid glutamine in individuals with cancer.  Glutamine blocks the uptake of 3-Bromopyruvate via the monocarboxylate transporter.
Nathan Goodyear

The association of vitamins C and K3 kills ca... [Eur J Med Chem. 2003] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...12767595

IV vitamin C IV vitamin K3 vitamin C K K3 vitamin C vitamin K3 cancer autoschizis

shared by Nathan Goodyear on 16 Oct 13 - No Cached
  • Nathan Goodyear on 16 Oct 13
     
    IV vitamin C and K3 show synergistic cancer cell death via autoschizis.
Nathan Goodyear

Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 years later - 0 views

ivvitaminc.us/..._and_Cancer_25_Years_Later.pdf

IV vitamin C cancer intravenous vitamin C vitamin C vitamin C ascorbic acid

shared by Nathan Goodyear on 26 May 13 - No Cached
  • Nathan Goodyear on 26 May 13
     
    Great review of the literature on vitamin C and cancer. No opinion. No hear say. Just a review of the literature.
Nathan Goodyear

Branched Chain Amino Acid Supplementation for Patients with Cirrhosis | Clinical Correl... - 0 views

www.clinicalcorrelations.org/?p=3544

BCCA branched chain amino acids liver cirrhosis hepatitis amino acids

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • low level of BCAAs in patients with cirrhosis is hypothesized to be one of multiple factors responsible for development of hepatic encephalopathy
  • supplementation of BCAAs is thought to facilitate ammonia detoxification by supporting synthesis of glutamine, one of the non-branched chain amino acids, in skeletal muscle and in the brain as well as diminishing the influx of AAAs across the blood-brain barrier
  • oral BCAA supplementation is more useful in chronic encephalopathic patients than is parenteral BCAA supplementation in patients with acute encephalopathy
  • ...35 more annotations...
  • malnutrition progressing to cachexia is another common manifestation of cirrhosis
  • Malnutrition can be mitigated with BCAA supplementation
  • Studies show that administration of amino acid formulas enriched with BCAAs can reduce protein loss, support protein synthesis, and improve nutritional status of patients with chronic liver disease
  • Leucine has been shown to be the most effective of the BCAAs because it acts via multiple pathways to stimulate protein synthesis
  • BCAAs metabolites inhibit proteolysis
  • Patients with cirrhosis have both insulin deficiency and insulin resistance
  • BCAAs (particularly leucine) help to reverse the catabolic, hyperglucagonemic state of cirrhosis both by stimulating insulin release from the pancreatic β cells and by decreasing insulin resistance allowing for better glucose utilization
  • Coadministration of BCAAs and glucose has been found to be particularly useful
  • BCAA supplementation improves protein-energy malnutrition by improving utilization of glucose, thereby diminishing the drive for proteolysis, inhibiting protein breakdown, and stimulating protein synthesis
  • Cirrhotic patients have impaired immune defense, characterized by defective phagocytic activity and impaired intracellular killing activity
  • another effect of BCAA supplementation is improvement of phagocytic function of neutrophils and possibly improvement in natural killer T (NKT) cell lymphocyte activity
  • BCAA supplementation may reduce the risk of infection in patients with advanced cirrhosis not only through improvement in protein-energy malnutrition but also by directly improving the function of the immune cells themselves
  • BCAA administration has also been shown to have a positive effect on liver regeneration
  • A proposed mechanism for improved liver regeneration is the stimulatory effect of BCAAs (particularly leucine) on the secretion of hepatocyte growth factor by hepatic stellate cells
  • BCAAs activate rapamycin signaling pathways which promotes albumin synthesis in the liver as well as protein and glycogen synthesis in muscle tissue
  • Chemical improvement with BCAA treatment is demonstrated by recovery of serum albumin and lowering of serum bilirubin levels
  • long-term oral BCAA supplementation was useful in staving off malnutrition and improving survival by preventing end-stage fatal complications of cirrhosis such as hepatic failure and gastrointestinal bleeding
  • The incidence of death by any cause, development of liver cancer, rupture of esophageal varices, or progression to hepatic failure was decreased in the group that received BCAA supplementation
  • Patients receiving BCAA supplementation also have a lower average hospital admission rate, better nutritional status, and better liver function tests
  • patients taking BCAA supplementation report improved quality of life
  • BCAAs have been shown to mitigate hepatic encephalopathy, cachexia, and infection rates, complications associated with the progression of hepatic cirrhosis
  • BCAAs make up 20-25% of the protein content of most foods
  • Highest levels are found in casein whey protein of dairy products and vegetables, such as corn and mushrooms. Other sources include egg albumin, beans, peanuts and brown rice bran
  • In addition to BCAAs from diet, oral supplements of BCAAs can be used
  • Oral supplementation tends to provide a better hepatic supply of BCAAs for patients able to tolerate PO nutrition as compared with IV supplementation, especially when treating symptoms of hepatic encephalopathy
  • Coadministration of BCAAs with carnitine and zinc has also been shown to increase ammonia metabolism further reducing the encephalopathic symptoms
  • Cirrhotic patients benefit from eating frequent, small meals that prevent long fasts which place the patient in a catabolic state
  • the best time for BCAA supplementation is at bedtime to improve the catabolic state during starvation in early morning fasting
  • A late night nutritional snack reduces symptoms of weakness and fatigability, lowers postprandial hyperglycemia, increases skeletal muscle mass,[25] improves nitrogen balance, and increases serum albumin levels.[26] Nocturnal BCAAs even improve serum albumin in cirrhotic patients who show no improvement with daytime BCAAs
  • Protein-energy malnutrition (PEM), with low serum albumin and low muscle mass, occurs in 65-90% of cases of advanced cirrhosis
  • hyperglucagonemia results in a catabolic state eventually producing anorexia and cachexia
  • BCAAs are further depleted from the circulation due to increased uptake by skeletal muscles that use the BCAAs in the synthesis of glutamine, which is produced in order to clear the ammonia that is not cleared by the failing liver
  • patients with chronic liver disease, particularly cirrhosis, routinely have decreased BCAAs and increased aromatic amino acids (AAAs) in their circulation
  • Maintaining a higher serum albumin in patients with cirrhosis is associated with decreased mortality and improved quality of life
  • the serum BCAA concentration is strongly correlated with the serum albumin level
  • Nathan Goodyear on 05 Oct 15
     
    great review of cirrhosis and BCCA supplementation.
Nathan Goodyear

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views

www.ncbi.nlm.nih.gov/...PMC1224653

IV vitamin C vitamin C intravenous alternative Intravenous vitamin C vitamin C cancer H2O2 ascorbic acid

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    IV vitamin C and IV vitamin C only can deliver levels to tumor cells that induce formation of H2O2 that then induces cell death.
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