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Nathan Goodyear

Vitamin D and Acute Myeloid Leukemia | IntechOpen - 0 views

www.intechopen.com/...n-d-and-acute-myeloid-leukemia

cancer AML acute myeloid leukemia vitamin D leukemia

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    low vitamin D associated with poor outcomes in hematologic cancers. This chapter reviews several studies that highlight the link with low vitamin D and poor outcomes in AML patients.
Nathan Goodyear

Improved leukemia-free survival after postconsolidation immunotherapy with histamine di... - 0 views

www.bloodjournal.org/...88

AML acute myeloid leukemia leukemia IL-2 histamine

shared by Nathan Goodyear on 12 May 18 - No Cached
  • several independent lines of evidence suggest that cytotoxic effector cells such as T cells and natural killer (NK) cells participate in protecting patients with AML against relapse
  • A plethora of mechanisms have been proposed to account for the dysfunctional antileukemic lymphocytes in AML, including the production of T-cell- and NK-cell-inhibitory factors by AML blasts,48 a deficient expression of NK-cell receptors on leukemic cells,49 inhibition of antileukemic lymphocytes by mononuclear phagocytes,4 and an impaired stimulatory interaction between the CD28 antigen expressed by T cells and contact antigens on AML blasts
  • This trial met the primary endpoint and thus showed a significantly improved LFS for patients receiving HDC/IL-2 as compared with the current standard of care
  • ...2 more annotations...
  • T cells and NK cells with antileukemic activity can be recovered from most patients with AML in remission not receiving a transplant,
  • The present study evaluated an approach to immunotherapy in AML in which IL-2 is supplemented with histamine dihydrochloride (HDC) to enhance the function of cytotoxic antileukemic lymphocytes
  • Nathan Goodyear on 12 May 18
     
    IL-2 plus histamine in patients with AML complete remission improves leukemia free survival.
Nathan Goodyear

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation im... - 0 views

www.academia.edu/...rapy_in_acute_myeloid_leukemia

AML leukemia acute myeloid leukemia IL-2 histamine cancer NK cells

shared by Nathan Goodyear on 31 May 18 - No Cached
  • IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines
  • combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts
  • histamine improves the effects of IL-2 on T cell activation
  • ...3 more annotations...
  • principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2
  • random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions
  • HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models
  • Nathan Goodyear on 31 May 18
     
    histamine dihydrochloride enhances immune effects of NK cells in IL02 therapy; specifically in this analysis in AML, the histamin prevented inactivation of the IL-2 activated NK cells.
Nathan Goodyear

Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acut... - 0 views

www.ncbi.nlm.nih.gov/...PMC3572185

aml acute myeloid leukemia cancer leukemia curcumin NF-kappaB

shared by Nathan Goodyear on 12 May 18 - No Cached
  • In a variety of solid tumors and blood cancers, aberrant hypermethylation of CpG-rich regions (>55% CG content, 0.5-4 kb in length, the so-called “CpG islands”) in the promoters of tumor suppressor genes (TSGs) results in their transcriptional silencing
  • These agents have been reported to suppress tumor growth by reversing aberrantly hypermethylation in the promoters of inactivated TSGs (e.g. p15INK4B), allowing re-expression of TSGs, thereby restoring normal cell cycle regulation, proliferation, apoptosis, and differentiation
  • groups have reported that curcumin acts as a scavenger of free radicals [13], an inhibitor of NF-κB nuclear translocation [14], and a modulator of histone deacetylase (HDAC) and histone acetyltransferase (HAT)
  • ...9 more annotations...
  • In this study, we found that curcumin down-regulated DNMT1 expression in AML cells. This occurred, at least in part, through down-modulation of two positive regulators of DNMT1: Sp1 and the NF-κB component, p65. We also found that curcumin-mediated down-regulation of DNMT1 was associated with reactivation of TSGs and tumor suppression, both in vivo and in vitro.
  • curcumin may selectively downregulate DNMT1 expression in tumor cells, but not in normal cells
  • DNMT1 expression is positively regulated by Sp1 and the NF-κB signaling component
  • indicating that curcumin may have significant anti-tumor activity in AML
  • We found that, compared to the vehicle control, curcumin treatment reduced tumor weight by 70%
  • Surprisingly, although curcumin significantly inhibited tumor growth in these mice, we were unable to find any obvious toxicity associated with curcumin treatment
  • Consistent with our observations regarding curcumin’s ability to inhibit tumor growth in vivo (Figure 4) and down-regulate DNMT1 expression in vitro and ex vivo (Figure 1), we found that decreased levels of DNMT1 protein and mRNA were expressed by tumor cells isolated from curcumin-treated mice
  • we identified curcumin as a substance which acts as an inhibitor of DNA methyltransferase enzymatic activity and induces significant global DNA hypomethylation in AML cells
  • In this study, we first demonstrated that curcumin decreases DNMT1 mRNA and protein expression levels, most likely through inhibiting expression of positive regulators of DNMT1, such as Sp1 and the p65 component of NF-κB component, and/or altering their ability to bind to the promoter region of DNMT1
  • Nathan Goodyear on 12 May 18
     
    Curcumin beneficial in AML
Nathan Goodyear

Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acut... - 0 views

journals.plos.org/...article

aml acute myeloid leukemia curcumin cancer leukemia

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    curcumin beneficial in AML
Nathan Goodyear

Histamine and Interleukin-2 in Acute Myelogenous Leukemia: Leukemia & Lymphoma: Vol 27,... - 0 views

www.tandfonline.com/...10428199709058309

leukemia AML acute myeloid leukemia IL-2 cancer histamine

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    IL-2 + histamine to prolong remission time in AML.
Nathan Goodyear

Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine | PNAS - 0 views

www.pnas.org/10238

AML leukemia acute myeloid leukemia MDS vitamin C cancer

shared by Nathan Goodyear on 12 May 18 - No Cached
  • 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)
  • 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
  • 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)
  • ...12 more annotations...
  • 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
  • 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
  • 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.
  • induction of an innate immune response
  • 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
  • it is possible that vitamin C was oxidized to DHA before it was transported into the cells
  • 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.
    • Nathan Goodyear
      Nathan Goodyear on 12 May 18
       
      This statement lacks a basic understanding of vitamin C pharmacokinetics.
  • Vitamin C is an essential nutrient for humans and has been reported to increase IFN levels in human cells upon virus infection
  • daily treatment with vitamin C alone at physiological concentrations enhanced the expression of viral-defense genes relative to untreated cells
  • 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
  • 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
  • reactive oxygen species
  • Nathan Goodyear on 12 May 18
     
    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.
Nathan Goodyear

Evaluation of artemisinins for the treatment of acute myeloid leukemia - 0 views

www.ncbi.nlm.nih.gov/...PMC4918815

DHA AML acute myeloid leukemia artesunate artemisinins

shared by Nathan Goodyear on 29 May 20 - No Cached
  • Nathan Goodyear on 29 May 20
     
    cell study finds artesuante and DHA augment Ara-c in AML via increase in ROS.
Nathan Goodyear

L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide... - 0 views

www.ncbi.nlm.nih.gov/...15313465

vitamin c H2O2 cancer leukemia catalase

shared by Nathan Goodyear on 29 Oct 17 - No Cached
  • Nathan Goodyear on 29 Oct 17
     
    vitamin C induces apoptosis of leukemia cells via the production of H2O2 inside the cancer cell that lacks adequate catalse activity to break it down.
Nathan Goodyear

Intravenous Vitamin C Administration Improved Blood Cell Counts and Health-Related Qual... - 0 views

www.ncbi.nlm.nih.gov/...PMC6070822

acute myeloid leukemia IV vitamin C vitamin C AML

shared by Nathan Goodyear on 29 May 20 - No Cached
  • Nathan Goodyear on 29 May 20
     
    Case study of IV vitamin C twice weekly for treatment of relapse AML.
Nathan Goodyear

https://www.researchgate.net/publication/12392637_A_phase_II_study_of_neuroimmunotherap... - 0 views

www.researchgate.net/...anced_hematologic_malignancies

acute myeloid leukemia leukemia cancer melatonin IL-2 multiple myeloma

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    only abstract available here, but 20 mg melatonin plus 4 weeks of low-dose IL-2 found to provide partial response in 1 patient and stable disease in 7 other patients in 12 patients with untreatable, advanced hematologic cancers.
Nathan Goodyear

http://www.slaop.org/pdf/492132.Leucemia%20Interleukin2induced%20GraftVersusLeukemia%20... - 0 views

www.slaop.org/...Fanconi%20Anemia%20Patient.pdf

AML acute myeloid leukemia IL-2 leukemia

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    IL-2 used to stimulate GVL in patient with Fanconi anemia with AML.
Nathan Goodyear

http://www.bloodjournal.org/content/bloodjournal/84/7/2158.full.pdf?sso-checked=true - 0 views

www.bloodjournal.org/...2158.full.pdf

AML acute myeloid leukemia cancer IL-2

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    Study used high dose IL-2 to achieve CR in 57% of 14 patients with heavily pretreated advanced AML.
Nathan Goodyear

A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and L... - 0 views

www.ncbi.nlm.nih.gov/...PMC4526680

AML acute myeloid leukemia Mistletoe

shared by Nathan Goodyear on 05 Jul 22 - No Cached
  • Nathan Goodyear on 05 Jul 22
     
    Viscum album L. (Loranthaceace)
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