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Nathan Goodyear

The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Ac... - 0 views

cancerres.aacrjournals.org/...2677.long

pH acid tumor cancer alkaline NaHCO3

shared by Nathan Goodyear on 19 Nov 18 - No Cached
  • Nathan Goodyear on 19 Nov 18
     
    Great diagram of the pH in/around solid tumors. Cancer exists in an obvious hypoxic environment which favors the HIF-1alpha which favors lactate production which drops the pH in the tumor extracellular environment effecting chemoresistance, radioresistance, angiogenesis, invasion, aggressiveness, metastasis, immune evasion...
Nathan Goodyear

Acidic extracellular microenvironment and cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC3849184

acid tumor cancer cancer lactate "lactic acid"

shared by Nathan Goodyear on 16 Nov 18 - No Cached
hoangkimchi liked it
  • Nathan Goodyear on 16 Nov 18
     
    Cancer thrives in an acidic micro environment, which also limits penetration of the immune system and other therapies often used in the treatment of cancer.
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

High-Dose Vitamin C for Cancer Therapy - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC9231292

vitamin C cancer

shared by Nathan Goodyear on 27 Jul 22 - No Cached
  • diabetes [8], atherosclerosis [9], the common cold [10], cataracts [11], glaucoma [12], macular degeneration [13], stroke [14], heart disease [15], COVID-19 [16], and cancer.
  • 1–5% of the Vit-C inside the human cells
  • interaction between Fe(II) and H2O2 produces OH− through the Fenton reaction
  • ...35 more annotations...
  • metabolic activity, oxygen transport, and DNA synthesis
  • Iron is found in the human body in the form of haemoglobin in red blood cells and growing erythroid cells.
  • macrophages contain considerable quantities of iron
  • iron is taken up by the majority of cells in the form of a transferrin (Tf)-Fe(III) complex that binds to the cell surface receptor transferrin receptor 1 (TfR1)
  • excess iron is retained in the liver cells
  • the endosomal six transmembrane epithelial antigen of the prostate 3 (STEAP3) reduces Fe(III) (ferric ion) to Fe(II) (ferrous ion), which is subsequently transferred across the endosomal membrane by divalent metal transporter 1 (DMT1)
  • labile iron pool (LIP)
  • LIP is toxic to the cells owing to the production of massive amounts of ROS.
  • DHA is quickly converted to Vit-C within the cell, by interacting with reduced glutathione (GSH) [45,46,47]. NADPH then recycles the oxidized glutathione (glutathione disulfide (GSSG)) and converts it back into GSH
  • Fe(II) catalyzes the formation of OH• and OH− during the interaction between H2O2 and O2•− (Haber–Weiss reaction)
  • Ascorbate can efficiently reduce free iron, thus recycling the cellular Fe(II)/Fe(III) to produce more OH• from H2O2 than can be generated during the Fenton reaction, which ultimately leads to lipid, protein, and DNA oxidation
  • Vit-C-stimulated iron absorption
  • reduce cellular iron efflux
  • high-dose Vit-C may elevate cellular LIP concentrations
  • ascorbate enhanced cancer cell LIP specifically by generating H2O2
  • Vit-C produces H2O2 extracellularly, which in turn inhibits tumor cells immediately
  • tumor cells have a need for readily available Fe(II) to survive and proliferate.
  • Tf has been recognized to sequester most labile Fe(II) in vivo
  • Asc•− and H2O2 were generated in vivo upon i.v Vit-C administration of around 0.5 g/kg of body weight and that the generation was Vit-C-dose reliant
  • free irons, especially Fe(II), increase Vit-C autoxidation, leading to H2O2 production
  • iron metabolism is altered in malignancies
  • increase in the expression of various iron-intake pathways or the downregulation of iron exporter proteins and storage pathways
  • Fe(II) ion in breast cancer cells is almost double that in normal breast tissues
  • macrophages in the cancer microenvironment have been revealed to increase iron shedding
  • Advanced breast tumor patients had substantially greater Fe(II) levels in their blood than the control groups without the disease
  • increased the amount of LIP inside the cells through transferrin receptor (TfR)
  • Warburg effect, or metabolic reprogramming,
  • Warburg effect is aided by KRAS or BRAF mutations
  • Vit-C is supplied, it oxidizes to DHA, and then is readily transported by GLUT-1 in mutant cells of KRAS or BRAF competing with glucose [46]. DHA is quickly converted into ascorbate inside the cell by NADPH and GSH [46,107]. This decrease reduces the concentration of cytosolic antioxidants and raises the intracellular ROS amounts
  • increased ROS inactivates glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+ (a critical co-factor of GAPDH); thus, further reducing the GAPDH associated with a multifaceted metabolic rewiring
  • Hindering GAPDH can result in an “energy crisis”, due to the decrease in ATP production
  • high-dose Vit-C recruited metabolites and increased the enzymatic activity in the pentose phosphate pathway (PPP), blocked the tri-carboxylic acid (TCA) cycle, and increased oxygen uptake, disrupting the intracellular metabolic balance and resulting in irreversible cell death, due to an energy crisis
  • mega-dose Vit-C influences energy metabolism by producing tremendous amounts of H2O2
  • Due to its great volatility at neutral pH [76], bolus therapy with mega-dose DHA has only transitory effects on tumor cells, both in vitro and in vivo.
Nathan Goodyear

Intravenous Vitamin C and Cancer: A Syste... [Integr Cancer Ther. 2014] - PubMed - NCBI - 1 views

www.ncbi.nlm.nih.gov/...24867961

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

shared by Nathan Goodyear on 27 Aug 14 - No Cached
  • Nathan Goodyear on 27 Aug 14
     
    So help me out here:  If IV vitamin C has been shown to prolong time to cancer relapse, aid in reducing tumor size, improve survival with chemotherapy, improve quality of life, improve physical function, reduce chemo side effects, improve energy, reduce nausea, aid insomnia, reduce constipation, and improve depression in cancer patient--then why does the author say that IV vitamin C is contentious?  Add that IV vitamin C has not been implicated in any deaths in cancer therapy.  Contrast that with chemotherapy.  Why again is this contentious?  Whom is best served by this being contentious?
Nathan Goodyear

Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Bas... - 0 views

www.ncbi.nlm.nih.gov/...PMC1505597

cancer acid tumor cancer alkaline NaHCO3

shared by Nathan Goodyear on 27 Nov 18 - No Cached
  • Nathan Goodyear on 27 Nov 18
     
    alkalinization of the tumor microenvironment with NaHCO3 in mouse model improves deliver of chemotherapy to tumor.
Nathan Goodyear

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models - 0 views

www.ncbi.nlm.nih.gov/...PMC7504298

acid tumor cancer cancer acidic pH hypoxia apoptosis hyperthermia

shared by Nathan Goodyear on 14 Mar 21 - No Cached
  • Nathan Goodyear on 14 Mar 21
     
    "Cells are more responsive and sensitive to heat under oxygen-deprived and highly acidic conditions, which are common in cancer tissue due to aggressive growth and enhanced glycolysis"
Nathan Goodyear

How We Read Oncologic FDG PET/CT | Cancer Imaging | Full Text - 0 views

cancerimagingjournal.biomedcentral.com/...s40644-016-0091-3

PET_CT PET scan CT cancer

shared by Nathan Goodyear on 20 Feb 18 - No Cached
  • In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
  • We contend that SUV analysis has virtually no role in this setting.
  • tumours grow as spheres, whereas inflammatory processes are typically linear
  • ...35 more annotations...
  • Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
  • Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
  • Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
  • aerobic glycolysis
  • Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
  • The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
  • When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
  • One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
  • Many benign and inflammatory processes are also associated with high glycolytic activity
  • Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
  • The intensity of uptake in metastases usually parallels that in the primary site of disease
  • For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
  • By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
  • The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
  • Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
  • The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
  • The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
  • “metabolic signature”
  • For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
  • a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
  • Warburg effect
  • There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
  • This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
  • There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
  • Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
  • patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
  • These have intense uptake on FDG PET/CT despite often having low proliferative rate.
  • Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
  • Metabolic activity switches off rapidly following initiation of therapy
  • Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
  • It is therefore critical to perform PET staging before commencement of anti-tumour therapy
  • The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
  • Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
  • If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
  • The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
  • Nathan Goodyear on 20 Feb 18
     
    good read on the PET/CT scan reading.  They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
Nathan Goodyear

Alfa-lipoic acid controls tumor growt... [ScientificWorldJournal. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23002387

alpha lipoic acid tumor cancer

shared by Nathan Goodyear on 30 Jan 13 - No Cached
  • Nathan Goodyear on 30 Jan 13
     
    alpha lipoic acid inhibits tumor cell growth in mice model.  The dosing here was oral
Nathan Goodyear

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and in... - 0 views

pubmed.ncbi.nlm.nih.gov/23420584

tumor microenvironment TME immunosuppression cancer immunomodulation DCA lactic acid

shared by Nathan Goodyear on 13 Mar 21 - No Cached
  • Nathan Goodyear on 13 Mar 21
     
    The title tells all: Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity
Nathan Goodyear

Dietary factors and growth and metabolism in experimental tumors - 0 views

www.jnutbio.com/...abstract

omega-6 inflammation tumor cancer dietary

shared by Nathan Goodyear on 10 Feb 11 - No Cached
  • Linoleic acid (LA), an essential n-6 polyunsaturated fatty acid (PUFA), was identified as an agent in dietary fat that is responsible for an up-regulation of tumor growth in vivo
  • Nathan Goodyear on 10 Feb 11
     
    High omega-6 intake in diet increases tumor growth
Nathan Goodyear

Vitamin C and cancer revisited - 0 views

www.ncbi.nlm.nih.gov/...PMC2516245

IV vitamin C cancer vitamin C H2O2 hydrogen peroxide Fe

shared by Nathan Goodyear on 05 Mar 18 - No Cached
  • It is well known that vitamin C, or ascorbic acid, is an effective biologic antioxidant and does not act as a pro-oxidant under normal conditions (5) because it does not readily autoxidize, i.e., react with oxygen (O2) to produce reactive oxygen species, such as superoxide radicals (O2•−) or H2O2
  • However, ascorbate readily donates an electron to redox-active transition metal ions, such as cupric (Cu2+) or ferric (Fe3+) ions, reducing them to cuprous (Cu+) and ferrous (Fe2+) ions, respectively
  • Reduced transition metal ions, in contrast to ascorbic acid, readily react with O2, reducing it to superoxide radicals (Reaction 2), which in turn dismutate to form H2O2 and O2
  • ...6 more annotations...
  • The H2O2 produced this way (Reactions 1–3) seems to be key to ascorbate's antitumor effect because H2O2 causes cancer cells to undergo apoptosis, pyknosis, and necrosis
  • In contrast, normal cells are considerably less vulnerable to H2O2
  • The reason for the increased sensitivity of tumor cells to H2O2 is not clear but may be due to lower antioxidant defenses
  • In fact, a lower capacity to destroy H2O2—e.g., by catalase, peroxiredoxins, and GSH peroxidases—may cause tumor cells to grow and proliferate more rapidly than normal cells in response to low concentrations of H2O2
  • These observations, combined with the inhibitory effect on xenograft growth, provide the proof of concept that millimolar concentrations of extracellular ascorbate, achievable by i.p. injection or i.v. infusion in experimental animals and humans, respectively, exert pro-oxidant, antitumor effects in vivo.
  • They also show that the concentration of the ascorbyl radical correlates with the concentration of H2O2 in interstitial fluid, whereas no H2O2 can be detected in blood or plasma
  • Nathan Goodyear on 05 Mar 18
     
    review of the mechanism of how extracellular AA, only obtainable from parenteral dosing, can produce H2O2 extracellularly to then be cytotoxic to cancer cells.
Nathan Goodyear

Cellular pH Gradient in Tumor versus Normal Tissue: Potential Exploitation for the Trea... - 0 views

cancerres.aacrjournals.org/...1194.long

Cancer acid alkaline "pH and cancer"

shared by Nathan Goodyear on 16 Nov 18 - No Cached
  • Nathan Goodyear on 16 Nov 18
     
    Cancer has an acid bed compared to alkaline in health cell environment.
Nathan Goodyear

Frontiers | Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate ... - 0 views

www.frontiersin.org/...full

vitamin C ascorbic acid tumor surgery HIF-1alpha cancer HIF-1 HIF-1α RBC ascorbic acid

shared by Nathan Goodyear on 29 Jun 22 - No Cached
  • Nathan Goodyear on 29 Jun 22
     
    Vitamin C found to increase tumor concentration of vitamin C over control.
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

Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer c... - 0 views

www.nature.com/...s41598-018-29386-7

hermetic dose response prooxidative low dose vitamin C vitamin sodium dependent vitamin C transporter High dose IV vitamin C SVCT C high dose vitamin C

shared by Nathan Goodyear on 11 Aug 22 - No Cached
  • Nathan Goodyear on 11 Aug 22
     
    Low dose vitamin C, via SVCT, increases tumor proliferation; whereas high dose decreases tumor proliferation.
Nathan Goodyear

Enhancement of chemotherapy by manipulation of tumour pH | British Journal of Cancer - 0 views

www.nature.com/6690455

Cancer pH acid tumor cancer chemotherapy

shared by Nathan Goodyear on 19 Nov 18 - No Cached
  • Nathan Goodyear on 19 Nov 18
     
    Study from 1999 confirms the extracellular acid pH increases resistance to chemotherapy in in vivo study
Nathan Goodyear

(n-3) Fatty Acids and Cancer Therapy - J. Nutr. - 0 views

jn.nutrition.org/...3427S.abstract

Omega-3 cancer

shared by Nathan Goodyear on 11 Feb 11 - No Cached
  • Used alone, an (n-3) supplement may be a useful alternative therapy for patients who are not candidates for standard toxic cancer therapies.
  • Nathan Goodyear on 11 Feb 11
     
    Omega-3 reduce inflammation, inhibit tumor growth, inhibit angiogenesis, induce cancer cell death, and inhibit estrogen signaling
Nathan Goodyear

Boswellic Acid Suppresses Growth and Metastasis of Human Pancreatic Tumors in an Orthot... - 0 views

www.ncbi.nlm.nih.gov/...PMC3204996

Frankincense acetyl-11-keto-beta-boswellic acid AKBA cancer

shared by Nathan Goodyear on 06 Jan 15 - No Cached
  • Nathan Goodyear on 06 Jan 15
     
    Study finds that acetyl-11-keto-Beta-boswellic acid (AKBA) reduced growth of pancreatic cancer and metastasis in mouse model.  AKBA also inhibits NF-kappaB and induced apoptosis.  AKBA is found in Frankinsense. 
Nathan Goodyear

Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer... - 0 views

www.nature.com/...s41416-019-0542-2

prostate cancer tumor microenvironment TME M2 macrophages acidic pH

shared by Nathan Goodyear on 19 Apr 20 - No Cached
  • Nathan Goodyear on 19 Apr 20
     
    The acidic pH of the TME induces M2 polarization.
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