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Nathan Goodyear

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial | Blood Journal - 0 views

  • 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
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    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 immunotherapy in acute myeloid leukemia | Fredrik Thorén - Academia.edu - 0 views

  • 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
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    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.
Rahul Sharma

Air Monitoring Filters | Membrane Filters for Air Monitoring | Axiva - 0 views

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    Axiva PM 2.5 PTFE membrane filters are specially designed for PM 2.5 ambient air monitoring. These air monitoring membrane filters have low tare mass for accurate gravimetric determination.
Nathan Goodyear

PO-238 Dichloroacetate (DCA) treatment affects mitochondrial activity and stemness in pancreatic cancer (PC) cell lines | Esmo Open - 0 views

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    DCA shown to decrease tumor size in mouse model of pancreatic cancer stem cells.
Nathan Goodyear

Overall survival of cancer patients with serum lactate dehydrogenase greater than 1000 IU/L - 0 views

  • catalyzes the interconversion of pyruvate and lactate during glycolysis and gluconeogenesis
  • It has long been known that many human cancers have higher LDH levels than normal tissues
  • It has long been appreciated that LDH is a prognostic factor for survival
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  • The serum level of LDH correlated with tumor burden and was thought to reflect the tumor’s growth and invasive potential
  • the majority of patients with advanced or metastatic disease could be detected to have extremely high serum level of LDH
  • strong evidence to support effective chemotherapy of full dose even in patients with high LDH level
  • LDH is a key enzyme in the process of energy production in cancer cells, it catalyzes the conversion of pyruvate to lactate in hypoxic conditions
  • its function in anaerobic metabolism, cancer cells grow even after their rapid proliferation that leads to low-oxygen conditions in the tumor microenvironment
  • LDH plays an important role in tumor progression and maintenance
  • inhibition of LDH inhibits tumor progression and has been considered for the therapeutic target of cancer energy metabolism
  • LDH levels are increased in response to tissue injury or during disease states
  • LDH could be a marker of tumor burden for advanced cancer patients
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    High LDH, defined as >1,000, found to be maker for very poor overall survival in retrospective study.
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menhealthvn - Slashdot User - 1 views

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    Male health is an important issue that directly affects the well-being of families and labor productivity in the whole society. Today, with the negative changes of the environment and work pressures, many diverse and complex male pathologies have arisen. However, while gynecological examinations are performed periodically by women, male medical examination is often not respected by men because of the subjectivity as well as reservations about psychology.
Nathan Goodyear

Ascorbic acid: Chemistry, biology and the treatment of cancer - 0 views

  • iron and ascorbate has long been used as an oxidizing system; the combination of these two reagents is referred to as the Udenfriend system
  • ascorbate serves as a reducing cofactor for many enzymes
  • uptake of ascorbate from the intestinal tract is very tightly controlled
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  • pharmacokinetic data indicate that intravenous administration of ascorbate can bypass this tight control resulting in highly elevated plasma levels
  • ascorbate readily oxidizes to produce H2O2, pharmacological ascorbate has been proposed as a prodrug for the delivery of H2O2 to tumors
  • Ascorbate is an excellent reducing agent and readily undergoes two consecutive, one-electron oxidations to form ascorbate radical (Asc•−) and dehydroascorbic acid (DHA)
  • Ascorbate oxidizes readily. The rate of oxidation is dependent on pH and is accelerated by catalytic metals
  • In near-neutral buffers with contaminating metals, the oxidation and subsequent loss of ascorbate can be very rapid
  • Ascorbate is required for maintaining iron in the ferrous state
  • In the presence of catalytic metal ions, ascorbate can also exert pro-oxidant effects
  • Ascorbate is an excellent one-electron reducing agent that can reduce ferric (Fe3+) to ferrous (Fe2+) iron, while being oxidized to ascorbate radical
  • In a classic Fenton reaction, Fe2+ reacts with H2O2 to generate Fe3+ and the very oxidizing hydroxyl radical
  • e presence of ascorbate can allow the recycling of Fe3+ back to Fe2+, which in turn will catalyze the formation of highly reactive oxidants from H2O2
  • Depending on concentrations, the effects of ascorbate on models of lipid peroxidation can be pro- or antioxidant
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    ferritin released enhanced pharmacologic ascorbate induced-cytotoxicity, indicating that ferritin with high iron-saturation could be a source of catalytic iron. Consistent with this, ascorbate has also been shown to be capable of releasing iron from cellular ferritin
Nathan Goodyear

renal dosing of antibiotics - 0 views

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    Renal dosing of antibiotics
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Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated Her2 / neu‐positive breast cancer cells - Carson - 2001 - European Journal of Immunology - Wiley Online Library - 1 views

  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
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  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
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    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - 0 views

  • The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis
  • The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour.
  • Because GO is far more efficient in generating ATP compared with GLY (producing 36 vs 2 ATP per glucose
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  • molecule), cancer cells upregulate glucose receptors and significantly increase glucose uptake in an attempt to ‘catch up
  • early carcinogenesis often occurs in a hypoxic microenvironment, the transformed cells have to rely on anaerobic GLY for energy production.
  • Hypoxia-inducible factor (HIF) is activated in hypoxic conditions
  • evidence suggests that transformation to a glycolytic phenotype offers resistance to apoptosis
  • non-small cell lung cancer, breast cancer and glioblastoma
  • Dichloroacetate activated the pyruvate dehydrogenase, which resulted in increased delivery of pyruvate into the mitochondria
  • DCA increased GO and depolarised the mitochondria, returning the membrane potential towards the levels of the non-cancer cells, without affecting the mitochondria of non-cancerous cells
  • induction of apoptosis by DCA in non-small cell lung cancer, breast cancer and glioblastoma cell lines
  • DCA was shown to induce apoptosis in endometrial (Wong et al, 2008) and prostate (Cao et al, 2008) cancer cells
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    DCA as targeted therapy in cancer.
Phiten Singapore

Thank You Attendees! - 0 views

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    Thank you to all the participants who join our roadshow which was at Waterway Point. Your participation makes the event more enjoyable and memorable. Go through the link: https://www.facebook.com/PhitenSGOfficial/videos/1476136799064785/
Nathan Goodyear

Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting "stemness" - 0 views

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    Vitamin C outperforms experimental drug in stopping cancer stem cell activity.
Nathan Goodyear

Hyperbaric oxygen therapy promotes neurogenesis: where do we stand? - 0 views

  • Numerous in vivo and in vitro studies confirm that HBOT induces neurogenesis
  • HIF-1α is the principal mediator of cellular hypoxia adaptations
  • activated by hypoxia, HIF-1α causes the transcription of its regulated downstream genes, including erythropoietin (EPO) and VEGF which are known to promote neurogenesis
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  • The safety of HBOT was also evaluated and it was pointed out that, if given at proper paradigms, like 1.5 ATA for 60 minutes, HBOT will not cause oxygen toxicity
  • Rockswold et al., on the other hand, found that HBOT might be potentially beneficial for severe TBI patients
  • McDonagh et al., concluded that there was insufficient evidence to establish the effectiveness of HBOT in the treatment of TBI
  • The first multicenter, randomized, double-blind, controlled trial in 2009 found that 40-hour HBOT of 24% oxygen at 1.3 ATM produced significant improvement in children's overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to those received slightly pressurized room air
  • Another study in 2010 on 16 autism patients, adopting a similar treatment paradigm, showed no effect on a wide array of behavioral evaluations
  • To date, there is little evidence that HBOT causes malignant growth or metastasis. A history of malignancy should therefore not be considered as a contraindication for HBOT
  • HBOT enhances the production of reactive oxygen species (ROS) and causes oxidative stress in body tissues
  • Excessive accumulation of oxidative stress may contribute to neurodegenerative processes and cell death in the brain, as seen in diseases like Alzheimer's disease (AD) and Parkinson's disease (PD)
  • Hormesis
  • process that results in a functional improvement of cellular stress resistance, survival, and longevity in response to sub-lethal levels of stress
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    great review of hbot, brain injury, neuroplasticity and neurogenesis.
Nathan Goodyear

Effects of transdermal application of DHEA on the levels of steroids, gonadotropins and lipids in men. - PubMed - NCBI - 0 views

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    topical DHEA found to significantly decrease LH.
Nathan Goodyear

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle: Cell Metabolism - 0 views

  • our results provide evidence to suggest that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle
  • Our results suggest that DNA methylation is a component of the exercise-induced effect on expression of these genes.
  • Caffeine exposure decreased promoter methylation of Pgc-1α, Tfam, Mef2a, Cs, and Pdk4
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  • the effect of exercise on DNA methylation in human skeletal muscle and provide evidence that acute exercise alters promoter methylation of exercise-responsive genes in a dose-dependent manner
  • DNA methylation was unaltered 48 hr after a 3-week exercise training program, whereas RNA expression of PGC-1α and TFAM promoters was elevated (data not shown), further suggesting that DNA hypomethylation is a transient mechanism involved in mRNA synthesis
  • Our findings that ionomycin, AICAR, or ROS production increased mRNA expression without altering promoter methylation may support the notion that DNA methylation does not exclusively control exercise-induced gene expression
  • acute exercise leads to transient changes in DNA methylation in adult skeletal muscle
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    Small study finds acute exercise is associated with epigenetic alteration of muscle through methylation.  This study found a hypomethylation of the genes PGC-1alpha, PDK4, and PPAR-delta with a respondent increase in expression.  The methylation activity was in the promoter region of these genes.
Nathan Goodyear

Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1β (IL-1β) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages - 0 views

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    Metformin inhibits LPS induced IL-1beta stimulation.  Interesting that metformin is a inhibitor of complex I in the electron transport chain.
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