Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
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shared by Nathan Goodyear on 30 Jan 18
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Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views
www.nature.com/...s41698-017-0044-8
cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology
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Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
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differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
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high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
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The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
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Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
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Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
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Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
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we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
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Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
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In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
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Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
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Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
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As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
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we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
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we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
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as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
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In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
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we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
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Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
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Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
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several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
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high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
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these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
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pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
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The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
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These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
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qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
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Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine | PNAS - 0 views
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Vitamin C alone at concentrations up to 57 μM had little effect on cell growth but was toxic at 228 μM (SI Appendix, Fig. S1B), in line with recent studies of high vitamin C concentrations (125–2,000 μM)
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In our combination approach, vitamin C increased the effects of low doses of 5-aza-CdR, with 57 μM vitamin C almost doubling the growth inhibition
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Using the Chou–Talalay method (28), we found that the two compounds indeed acted synergistically, rather than additively, to inhibit cancer cell growth over the physiological ranges of vitamin C in healthy individuals (26–84 μM)
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These results show that targeting the cancer DNA methylome by combining low-dose 5-aza-CdR and vitamin C stimulates the expression of ERVs, the induction of a cell-autonomous immune activation response, and increased apoptosis of cancer cells
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The addition of vitamin C to treatment protocols therefore may be a straightforward way to increase the clinical efficacy of such drugs in MDS and leukemia patients
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Vitamin C deficiency has been seen previously in patients with multiple types of cancer, including hematological malignancies (35⇓–37). We predict that these patients might receive the most benefits from the combination treatment.
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We therefore measured plasma concentrations of vitamin C in a small number of patients with miscellaneous hematologic malignancies. Strikingly, 58% of patients with hematological neoplasia who were not taking vitamin C supplements had severe vitamin C deficiency (serum concentration <11.4 μM, at which clinical features of scurvy may be manifested) (34), and 33% had vitamin C levels below the normal range
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Oral administration of vitamin C should be sufficient for the therapeutic strategy, because the concentrations reported in this study would not require i.v. administration.
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Vitamin C is an essential nutrient for humans and has been reported to increase IFN levels in human cells upon virus infection
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daily treatment with vitamin C alone at physiological concentrations enhanced the expression of viral-defense genes relative to untreated cells
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When combined with low-dose 5-aza-CdR, physiological concentrations of vitamin C synergistically inhibited cancer-cell growth and induced apoptosis. Such synergy was associated with increased ERV expression and dsRNA in treated cells. The mechanism of action differs from that of vitamin C at higher doses, which involves its pro-oxidant activity, including GSH inhibition, to generate reactive oxygen species
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This activity has been shown to induce DNA damage and to enhance the sensitivities of myeloid malignancies, multiple myeloma, and cutaneous T-cell lymphoma to arsenic trioxide (41⇓⇓–44). It also can increase chemosensitivity of ovarian cancer cells (27) and selectively kill KRAS or BRAF mutant colorectal cancer cells by inhibiting GAPDH
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91% of patients with hematologic malignancies have vitamin C levels that are either low or severly deficient. This study found that vitamin C plus low dose DNA methyltransferase inhibitors have synergistic inhibition of cancer cell proliferation and increased apoptosis. Unfortunately, the authors claimed that oral vitamin C would be sufficient which indicates an incredible lack of understanding of vitamin C pharmacokinetics.
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Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations - 0 views
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Among the most encouraging mAb is trastuzumab, which targets the human epidermal growth factor receptor 2 and is indicated in the treatment of breast cancer
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bevacizumab, which inhibits vascular endothelial growth factor and is indicated in the treatment of a range of diseases, including colorectal, lung, and ovarian cancer3; and cetuximab, which blocks the epidermal growth factor receptor and is indicated in the treatment of colorectal and lung cancer
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Viscum album L (VA or European mistletoe) preparations are widely used as additive cancer therapy in Europe, especially in German-speaking countries, and have been associated with a reduction in chemotherapy-related adverse drug reactions and increased HRQL
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A multivariable GEE model indicated that the odds for patients experiencing an AE following mAb therapy were nearly 5 times higher compared with that for mAb plus VA
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VA preparations (Iscador Ltd) did not inhibit chemotherapy-induced cytostasis or cytotoxicity and showed an additive inhibitory effect at higher concentrations of VA.
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previous in vitro investigations have shown that VA preparations have either no or minor effects on a range of CYPs, suggesting that VA-drug interactions based on drug metabolism are unlikely
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Chronic kidney disease and erectile dysfunction - 0 views
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shared by Nathan Goodyear on 03 May 17
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Long term gluten consumption in adults without celiac disease and risk of coronary hear... - 0 views
www.bmj.com/bmj.j1892
gluten gluten sensitivity nutrition gluten-free heart disease health CHD CVD coronary heart disease
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Prospective study finds that gluten free diets for some may limit healthy whole grains, which may increase CVD. This increase was 75 cases per 100 000 persons. However, the study did find that it appears that an elimination of the whole grains likely is the culprit. An elimination of refined processed grains and not whole grains is beneficial. A gluten free diet is not and should not be a dietary fad. If testing reveals gluten free nutrition is required, only then should this be pursued with the additions of certain, whole-grain foods.
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shared by Nathan Goodyear on 13 Sep 17
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Age and BMI Adjusted Comparison of Reproductive Hormones in PCOS - 0 views
www.ncbi.nlm.nih.gov/...PMC3893977
PCOS polycystic ovarian syndrome LH FSH SHBG Testosterone progesterone hormones bmi
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shared by Nathan Goodyear on 04 Oct 17
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Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macropha... - 0 views
www.ncbi.nlm.nih.gov/...22698256
quercetin resveratrol pterostilbene iNOS LPS lipopolysaccharides inflammation
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shared by Nathan Goodyear on 08 Dec 17
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Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views
www.oncotarget.com/index.php
vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural
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Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
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ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
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Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
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high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
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an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
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Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
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we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
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silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
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caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
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Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
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CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
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CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
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CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
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Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
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We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
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Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
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The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
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Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
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Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
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Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
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Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
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CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
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we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
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The future of cancer therapy is cancer stem cells. Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells. Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs. The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.
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shared by Nathan Goodyear on 20 Dec 17
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Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use | Annals of Inter... - 0 views
annals.org/...lications-oral-intravenous-use
vitamin C IV vitamin C cancer hypertension blood pressure NO nitric oxide
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IV vitamin C found to significantly increased serum levels beyond that of oral. IV vitamin C is the only route that should be administered for patients with cancer. IVC at 50 grams showed peak C concentration at 13,400 micromol/L. Levels of at least 400-600 are required for tumorcidal effects. In addition, IV vitamin C increased NO release and decreases b/p
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shared by Nathan Goodyear on 01 Apr 21
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Effects of Transferrin Receptor Blockade on Cancer Cell Proliferation and Hypoxia-Induc... - 0 views
cancerres.aacrjournals.org/...2749.long
HIF-1alpha cancer HIF-1 vitamin C Hypoxia-inducible Factor 1 hypoxia
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shared by Nathan Goodyear on 02 Apr 21
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Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreas... - 0 views
www.ncbi.nlm.nih.gov/...PMC3912592
hypoxia HIF-1 IV vitamin C VEGF Hypoxia-inducible Factor 1 vitamin C HIF-1alpha cancer
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Enough said: "There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation and tumor size. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery with additional disease-free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated with decreased HIF-1 activation."
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Abstract GS2-06: Phase Ib/II study evaluating safety and efficacy of pembrolizumab and ... - 0 views
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Vitamin C - A new player in regulation of the cancer epigenome. - PubMed - 0 views
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Effect of hyperthemia in combination with vitamin E and cyclic amp on neuroblastoma cel... - 0 views
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Manipulating the Immunological Tumor Microenvironment | Frontiers Research Topic - 0 views
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Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review) - 0 views
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shared by pharmacybiz on 11 Jan 22
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Avacta Halts Sale Of Covid-19 Rapid Antigen LFT - 0 views
www.pharmacy.biz/t-to-boost-omicron-sensitivity
Avacta pharmacy-business Do-lateral-flow-tests-detect-omicron rapid-antigen-LFT-AffiDX Rapid-antigen-test Can-lateral-flow-tests-detect-omicron
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Britain's biotech firm Avacta Group on Monday (January 10) announced halting sales of its Covid-19 rapid antigen lateral flow test AffiDX to replace antibodies in the device and increase its ability to diagnose the Omicron variant. The company stated that AffiDX is capable of detecting Omicron when the virus is present in high numbers in samples, but the sensitivity of the test reduces at lower viral loads. The performance of all rapid antigen tests came under scanner in wake of a large number of mutations in the Omicron variant. AffiDX contains both a proprietary Affimer reagent and a commercially available antibody. The Affimer reagent detects the Omicron variant with the same sensitivity as the Delta variant, and performance of the antibody is paired with the Affimer reagent in the test. This has been affected by the additional Omicron mutations, the firm said. Alastair Smith, chief executive of Avacta Group, said: "Our determination to only provide high quality, high performance diagnostic tests has led us to the correct decision to pause all marketing of the AffiDX® lateral flow antigen test. We have, of course, been unable to market the product in the UK since October 2021, as the product continues to await approval under the new CTDA regulatory process.
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shared by indiacardiacsurg on 01 Dec 21
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Child Heart Surgeon in India Will Create a Healthy Tomorrow for Children and Their Fami... - 0 views
ny.biznet-us.com/12244992
Child Heart Surgeon in India Cost of pediatric cardiac surgery in India Pediatric cardiac surgery in India low cost pediatric cardiac surgery
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The cost of pediatric cardiac surgery in India remains low even when additional prices which include boarding, hotel charges, and length of stay at the hospital are taken into account. Since the cost of getting the best price for child heart surgery in India is less, hundreds of people from all around the world travel to India each year with the hope to get treated without any financial burden. Get Fast Track Query Reply just call us at +91-9370586696 or Email us: enquiry@indiacardiacsurgerysite.com
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Cheap Flights, Airline Tickets & Airfares - Find Deals on Flights at WayAway.io - 0 views
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Here's some additional information about the specific hotels and brand offers available through our platform: Hotels: Our handpicked selection of hotels caters to a variety of tastes and preferences. Whether you're seeking a tranquil beachfront retreat, a vibrant city center stay, or a cozy countryside escape, we have partnered with top-notch establishments to ensure a memorable experience. Each hotel offers unique amenities, luxurious accommodations, and exceptional service, ensuring your stay is nothing short of extraordinary. Tickets: Our ticket offerings encompass a wide range of events and attractions. From sports games and concerts to theater performances and cultural exhibitions, we provide access to sought-after experiences. With our ticket deals, you can secure coveted seats, enjoy VIP access, and immerse yourself in the excitement of live entertainment. Enhance your travel itinerary with unforgettable memories. Brand Offers: We have collaborated with renowned brands to bring you exclusive offers and promotions across various industries. From fashion and beauty to technology and lifestyle, our brand partners have crafted special deals tailored to our community. Enjoy discounts, unique packages, and access to limited-edition products, elevating your everyday life with exceptional quality and value. By going straight to the product page, our platform ensures a streamlined and user-friendly experience. This allows you to explore the details, features, and pricing of each hotel, ticket, or brand offer directly, increasing the convenience and efficiency of your purchase process. Discover extraordinary accommodations, secure tickets to unforgettable events, and indulge in exclusive brand offers through our platform. Begin your journey and unlock remarkable experiences today! VISIT THIS BY CLICKING HERE: https://sharecta.com/l/40x4cx4xarc44