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Nathan Goodyear

Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among Premenopausal Women - 0 views

cancerres.aacrjournals.org/...696.full

estrogen metabolites estrogen metabolism ER estrogen receptors ROS hormones cancer breast cancer

shared by Nathan Goodyear on 07 Oct 15 - No Cached
  • both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
  • 2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
  • While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
  • ...15 more annotations...
  • 4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
  • In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
  • Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
  • a significant inverse association with the ratio of parent estrogens to estrogen metabolites
  • several potentially estrogenic and genotoxic mechanisms
  • Estrogen metabolites also can be genotoxic
  • Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
  • the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
  • 2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
  • act independently from the ER
  • 16α-Hydroxyestrone also may be genotoxic
  • While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
  • The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
  • the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
  • Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
  • Nathan Goodyear on 07 Oct 15
     
    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

Therapeutic hyperthermia: The old, the new, and the upcoming - Critical Reviews in Oncology / Hematology - 1 views

www.croh-online.com/...fulltext

hyperthermia hyperthermic therapy cancer oncology

shared by Nathan Goodyear on 30 Aug 18 - No Cached
  • not well understood, but it is felt to be a combination of both heat-induced necrosis and of protein inactivation (e.g., repair enzymes) as opposed to DNA damage
  • alterations in tumor cytoskeletal and membrane structures, which disrupt cell motility and intracellular signal transduction
  • A common explanation for HT-enhancement of RT and CT involves inhibition of homologous recombination repair of double-strand DNA breaks, preventing cells from repairing sub-lethal damage
  • ...15 more annotations...
  • it does appear to inhibit rejoining of RT-induced DNA breaks more than is commonly observed after RT alone
  • HT damages cells and enhances RT and CT sensitivity as a function of both temperature and duration of treatment
  • as temperature or duration increase, the rate of cell killing also increases
  • At temperatures above 42 °C, tumor vasculature is damaged, resulting in decreased blood flow
  • Cancer cells are particularly vulnerable to heating; in vivo studies have shown that temperatures in the range of 40–44 °C cause more selective damage to tumor cells
  • cancerous blood vessels are chaotic, leaky, and inefficient
  • selective cytotoxic effect on tumor cells include inhibition of key cancer cell-signaling pathways such as AKT, inducing apoptosis, suppression of cancer stem cell proliferation, and others
  • increase in immunological attacks against tumors after HT, which were believed to be achieved through activation of HSPs and subsequent modulation of the innate and adaptive immune responses against tumor cells
  • HT does lead to activation of the immune system and HSP-induced cell death through modification of the tumor cell surface
  • These HSPs and tumor antigens are taken up by dendritic cells and macrophages and go on to induce specific anti-tumor immunity
  • In vivo studies demonstrate HT-enhancement of NK cell activity, and HT has been shown to increase neutrophilic granulocytes with anti-tumor activity
  • it has become increasingly clear that HT results in immune stimulation, through both direct heat-mediated cell killing as well as innate and adaptive immune system modulation
  • The term hyperthermia is used in this review to refer to heating within the clinically accepted range of 40–45 °C
  • temperatures above 42.5–43 °C the exposure time can be halved with each 1 °C increase while maintaining equivalent cell killing
  • gradual heating at 43 °C for 1 h worked through an apoptotic pathway
  • Nathan Goodyear on 30 Aug 18
     
    Comprehensive review of hyperthemic therapy.
Nathan Goodyear

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial - The Lancet - 0 views

www.thelancet.com/...fulltext

obesity type 2 diabetes type II diabetes calorie restriction nutrition weight loss diet

shared by Nathan Goodyear on 11 Dec 17 - No Cached
  • Nathan Goodyear on 11 Dec 17
     
    study finds very low calorie diet reversed diabetes. The greatest weight loss was associated with greatest remission of diabetes at 86% with >15 kg weight loss.
Nathan Goodyear

The Androgen Derivative 5α-Androstane-3β,17β-Diol Inhibits Prostate Cancer Cell Migration Through Activation of the Estrogen Receptor β Subtype - 0 views

cancerres.aacrjournals.org/...5445.full

prostate cancer 3-beta androstanediol DHT metabolite E-cadherin ER beta ER-beta male hormone hormones men

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • In the early stages, prostate cancer growth is dependent on circulating androgens
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      This is in contrast to studies that show poor prognosis with Lower T at time of diagnosis of prostate cancer
  • 5α-reductase not only provides a potent amplification of the androgenic signal ( 4– 6), but it also prevents estrogen formation by subtracting testosterone from the action of aromatase ( 7, 8), thus blocking activation of the estrogen receptor subtypes (ERα and ERβ; refs. 9, 10)
  • ERβ is the prevailing subtype ( 11), and a growing body of evidence points to the protective role of this receptor in prostate cancer
  • ...3 more annotations...
  • It has been shown that the transformation of the dihydrotestosterone to 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-Adiol), generates two metabolites unable to bind the androgen receptor, but possessing a very high affinity for the estrogen receptors
  • the effects of testosterone may result from the balance between the androgenic and the estrogenic molecules originating from its catabolism.
  • Recent data have been published postulating a direct estrogenic role of the 3β-hydroxylated derivatives of dihydrotestosterone in the prostate development and homeostasis
  • Nathan Goodyear on 27 Jan 14
     
    Here is the full article.
Nathan Goodyear

Low-T3 Syndrome - 0 views

circ.ahajournals.org/...708.long

T3 low T3 cardiac heart disease CVD cardiovascular thyroid hormone hormones hypothyroid hypothyroidism

shared by Nathan Goodyear on 03 Jul 12 - No Cached
  • More than 80% of the biologically active hormone triiodothyronine (T3) derives from peripheral conversion of prohormone thyroxine (T4) secreted by the thyroid gland
  • Low thyroid hormone concentrations, in particular low serum T3 concentrations, are a common finding in patients with nonthyroidal illnesses, including cardiac disorders
  • a direct relationship between low circulating levels of T3 and adverse prognosis of cardiac patients
  • ...4 more annotations...
  • The present study clearly shows the existence of a strong association between the reduction of biologically active T3 and mortality in a large population of cardiac hospitalized patients
  • highly significant increase in the incidence of cardiac and cumulative deaths in patients with low T3 compared with patients with normal T3 levels
  • the relevance of the low T3 state as a strong, independent predictor of mortality in cardiac patients
  • low T3 concentrations are a strong independent predictive marker of poor prognosis in cardiac patients
  • Nathan Goodyear on 03 Jul 12
     
    low T3 associated with poor prognosis in cardiac patients.   Poor prognosis = death.  T3 is important in cardiac remodeling, which is inherently important with cardiac disease.
Nathan Goodyear

Testosterone: More Than Having the Guts to Win the Tour de France - 0 views

www.sciencedirect.com/...S1074761313003439

Testosterone gut flora gut microbiome gut microbiota autoimmune disease diabetes

shared by Nathan Goodyear on 30 Apr 15 - No Cached
  • female adult mice have microbiomes similar to those of prepubescent mice of both sexes;
  • the commensal microbial community in adult male mice significantly deviates from this shared initial pool.
  • A minimum level of testosterone and specific male-enriched microbes working together upregulate M2 macrophage and IFN-γ producing T cells in pancreatic lymph nodes. Microarray data show that both the IFN-γ and IL-1β pathways are also stimulated.
  • ...10 more annotations...
  • The incidence of T1D in these mice is positively correlated with the “femaleness” of the microbiota
  • These results support the hypothesis that the host androgen level is influential in determining the composition of the microbiota, which in turn affects T1D initiation and progression
  • a high testosterone level enriches the microbiota for specific organisms such as segmented filamentous bacteria (SFB) and Escherichia coli or Shigella–like (SECS) strains.
  • the microbiome in castrated adult males clearly shifts away from that of normal adult males and is closer to the microbiome of females
  • These microbes also upregulate host testosterone
  • In four independent experiments, the authors found no universal unique “male microbiome”
  • they did find that four distinct combinations of microbial groupings (with an interesting lack of overlap at the individual family level in the four experiments) were enhanced by androgen
  • one species consists of the segmented filamentous bacteria (SFB) and belongs to the Firmicutes, whereas the other is an Escherichia coli or Shigella–like (SECS) strain belonging to the Proteobacteria
  • colonization with protective microbiomes—e.g., SPF microbiota, SFB, and SECS—is positively correlated with high blood testosterone levels in male mice
  • A direct implication of this study is that probiotic administration or fecal transplantation is a theoretically possible approach to protection against T1D
  • Nathan Goodyear on 30 Apr 15
     
    nice summary of article on the relationship between Testosteorne and gut microbiome in autoimmune disease.
Nathan Goodyear

Assessment of bioavailability of oral micronized p... [Gynecol Endocrinol. 1993] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...8213223

saliva salivary hormone testing hormones progesterone bioidentical

shared by Nathan Goodyear on 16 Nov 10 - No Cached
  • The use of non-invasive salivary sampling and a cost-effective, direct enzymeimmunoassay showed a considerable advantage in the present study, compared with previous ones.
  • Nathan Goodyear on 16 Nov 10
     
    saliva testing verified as cost effective and with considerable advantage
Nathan Goodyear

Therapeutic Testosterone Administration Preserves Excitatory Synaptic Transmission in the Hippocampus during Autoimmune Demyelinating Disease - 0 views

www.jneurosci.org/...12312.long

Testosterone polyneuropathy MS multiple Sclerosis Estriol hormones autoimmune disease

shared by Nathan Goodyear on 17 Mar 15 - No Cached
  • direct androgen receptor activation is not a mutually exclusive requirement of testosterone-mediated neuroprotection.
  • Testosterone treatment after EAE induction restores synaptic transmission and corresponding synaptic protein levels within the hippocampus during EAE
  • A growing body of evidence suggests that testosterone enhances hippocampal synaptogenesis
  • ...7 more annotations...
  • This study demonstrates that testosterone treatment either before or after EAE disease induction partially restores deficits in synaptic transmission, preserves presynaptic and postsynaptic integrity, and prevents hippocampal pathology.
  • treatment with a pregnancy estrogen, estriol, can prevent deficits in excitatory synaptic transmission in the hippocampus during EAE
  • testosterone is important to the maintenance of normal synaptic spine density in the hippocampus
  • estriol treatment was also capable of preserving levels of synaptic proteins that are known to orchestrate functional synaptic transmission within the hippocampus.
  • Estriol is a therapeutic candidate in MS because it has widespread effects on the immune system and the CNS
  • MS patients have significantly decreased relapse rates during the third trimester of pregnancy, when estriol levels are most elevated, and relapse rates rebound during the postpartum period coinciding with an abrupt decline in serum estriol levels
  • In nonpregnant MS patients, estriol treatment has been shown to significantly reduce gadolinium-enhancing lesion number and volumes measured by MRI
  • Nathan Goodyear on 17 Mar 15
     
    Testosterone restores/preserves nerve synapsis within the hippocampus in autoimmune demyelinating disease.  Testosterone appears to have neuroprotection.  The authors conclude that the majority of the protective effect was through aromatase activity.
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