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Nathan Goodyear

Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men | European Heart Journal - 0 views

eurheartj.oxfordjournals.org/...2706

low T low Testosterone Testosterone Testosterone therapy mortality MI stroke heart men male hormones

shared by Nathan Goodyear on 18 Jan 16 - No Cached
  • In this study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes.
  • retrospective study
  • significant benefit is observed only if the dose is adequate to normalize the TT levels
  • ...9 more annotations...
  • the mechanisms for these effects remain speculative
  • It can be postulated that the beneficial effect of normal T levels on adipose tissue, insulin sensitivity, and lipid profiles or by its anti-inflammatory and anticoagulant properties, as reported by other investigators, might have contributed to our findings
  • off-label use of TRT remains a concern
  • Recent FDA analyses suggest that currently only half of the men on TRT had been diagnosed with hypogonadism
  • 25% of users did not have their T concentrations tested prior to initiating therapy
  • 21% of those prescribed TRT did not have their levels tested at any time during treatment
  • two very recent meta-analyses suggested a lack of convincing evidence posed by TRT.
  • men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
  • TRT should aim for doses resulting in normalization of TT level as this was shown to be associated with reduction in adverse CV events
  • Nathan Goodyear on 18 Jan 16
     
    Testosterone therapy in men with low T to restore physiologic Testosterone levels found to reduce mortality, MI, and stroke risk.
Nathan Goodyear

Mistletoe viscotoxins increase natural killer cell‐mediated cytotoxicity - Tabiasco - 2002 - European Journal of Biochemistry - Wiley Online Library - 0 views

febs.onlinelibrary.wiley.com/...j.1432-1033.2002.02932.x

cancer mistletoe NK NK cells

shared by Nathan Goodyear on 08 Jul 18 - No Cached
  • Nathan Goodyear on 08 Jul 18
     
    Study finds that mistletoe augments NK activity not via an increase in NK numbers.
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality - 0 views

www.ncbi.nlm.nih.gov/...PMC6114970

cancer metabolism breast cancer glutamine glutamate aspartate oncogenes

shared by Nathan Goodyear on 24 Sep 18 - No Cached
  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
  • ...16 more annotations...
  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
  • Nathan Goodyear on 24 Sep 18
     
    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
Nathan Goodyear

Medical education in pharmacogenomics-results from a survey on pharmacogenetic knowledge in healthcare professionals within the European pharmacogenomics clinical implementation project Ubiquitous Pharmacogenomics (U-PGx) - 0 views

www.ncbi.nlm.nih.gov/...PMC5599468

genetics pharmacogenetics

shared by Nathan Goodyear on 17 Jan 18 - No Cached
  • Of participants, 84.3% found pharmacogenomics relevant to their current practice
  • More than two-thirds (65.7%) did not order nor recommend a pharmacogenomic test in the past year
  • pharmacogenomic testing was understood mainly for assessment of the variability of genes affecting drug disposition, metabolism and drug transport leading to individual responses to drugs
  • ...4 more annotations...
  • Pre-emptive, prospective, genotyping to make individualised drug therapy feasible is seen to contribute to personalised medicine
  • assumed to improve drug efficacy and safety
  • Potential benefits of pharmacogenomics (PGx) have been defined such as predicting intended response to medication by more accurate dosing, avoiding adverse drug reactions and therefore enhancing drug safety and reducing health care cost
  • survey among Dutch pharmacists revealed 14.7% recent users of PGx diagnostics [27], whereas in our cohort, the percentage was with 34.3% higher.
  • Nathan Goodyear on 17 Jan 18
     
    Doctors and pharmacists are slow to integrate pharmacogenetics. Good working definition of pharmacogenetics as well.
Nathan Goodyear

Abrogation of the Negative Influence of Opioids on IL-2 Immunotherapy of Renal Cell Cancer by Melatonin - Abstract - European Urology 2000, Vol. 38, No. 1 - Karger Publishers - 0 views

www.karger.com/...20263

cancer Melatonin IL-2 opiates morphine immune system

shared by Nathan Goodyear on 01 Jun 18 - No Cached
  • Nathan Goodyear on 01 Jun 18
     
    only abstract available here to general public.  Opiates suprress the immune system.  This is an important point in the fight against cancer. Cancer is, in part, the result of signficant immune imbalance.  In this study of patients with Renal Cell Cancer, melatonin + IL-2 was found to counter this immunosuppressive effect of morphine to increase partial response and to increase the 3 year survival.
Nathan Goodyear

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations - 0 views

www.ncbi.nlm.nih.gov/...PMC5950938

VAE mistletoe cancer monoclonal antibodies mAB IL-12 NK cells

shared by Nathan Goodyear on 06 Jun 18 - No Cached
  • 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
  • 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
  • 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
  • ...6 more annotations...
  • leading to enhancement of interleukin-12 secretion and natural killer cell function
  • Helixor VA preparations
  • 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
  • VA preparations (Iscador Ltd) did not inhibit chemotherapy-induced cytostasis or cytotoxicity and showed an additive inhibitory effect at higher concentrations of VA.
  • 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
  • mAb do not undergo hepatic metabolism but undergo proteolytic catabolism throughout the body
  • Nathan Goodyear on 06 Jun 18
     
    VAE therapy found to reduce adverse events in those receiving monoclonal Ab therapy.
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

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • 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
  • ...17 more annotations...
  • 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.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies | European Heart Journal | Oxford Academic - 0 views

academic.oup.com/...ehx163

HDL cholesterol cardiovascular disease mortality

shared by Nathan Goodyear on 30 Aug 17 - No Cached
  • Nathan Goodyear on 30 Aug 17
     
    High HDL found to actually increase cardiovascular risk in men and women. Peak benefit is found at 58 mg/dl and 77 mg/dl for men and women respectively. Higher levels of HDL >90 increased risk and all-cause mortality in men and women.
Nathan Goodyear

Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe extract - 0 views

www.spandidos-publications.com/...or.2012.2026

apoptosis leukemia mistletoe fraxinii

shared by Nathan Goodyear on 27 May 21 - No Cached
  • Nathan Goodyear on 27 May 21
     
    In vitro study, but a. Fraxinii found to stimulate apoptosis of leukemic cells.
Nathan Goodyear

Professional Resource: European Mistletoe - 0 views

Mistletoe

shared by Nathan Goodyear on 02 Mar 23 - No Cached
  • Nathan Goodyear on 02 Mar 23
     
    Nice summary article
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