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Nathan Goodyear

Exogenous testosterone, aggression, and mood i... [Physiol Behav. 2002] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...12062320

testosterone therapy treatment low T low testosterone mood brain men male hormone hormones aggression

shared by Nathan Goodyear on 06 Jul 12 - No Cached
  • Nathan Goodyear on 06 Jul 12
     
    study finds that supra physiological replacement of testosterone is not associated with aggressive behavior.
Nathan Goodyear

Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program fo... - 0 views

jco.ascopubs.org/...JCO.2015.62.5764.full

prostate cancer prostate cancer men

shared by Nathan Goodyear on 02 Sep 15 - No Cached
  • Nathan Goodyear on 02 Sep 15
     
    low aggressive prostate cancer followed conservatively results in low mortality rate in study.  The study is significant in that it followed 1,298 men up to 18 years and found reclassification to "lethal" grade prostate cancer to be only 5.9%.  This challenges long held dogma that the first approach to cancer is to cut it out. For those with low aggressive prostate cancer, conservative approaches i.e. observation, can be employed.
Nathan Goodyear

From the Cover: Pharmacologic doses of ascorbate act as a prooxidant and decrease growt... - 0 views

www.ncbi.nlm.nih.gov/...PMC2516281

cancer IV intravenous vitamin C IV vitamin C

shared by Nathan Goodyear on 18 Sep 13 - No Cached
  • An extensive panel of 43 tumor and 5 normal cell lines were exposed to ascorbate in vitro for ≤2 h to mimic clinical pharmacokinetics
  • effective concentration that decreased survival 50% (EC50) was determined. EC50 was <10 mM for 75% of tumor cells tested, whereas cytotoxicity was not evident in normal cells with >20 mM ascorbate
  • The addition of catalase to the medium ameliorated death of ovarian carcinoma (Ovcar5), pancreatic carcinoma (Pan02), and glioblastoma (9L) cells exposed to 10 mM ascorbate (1 h), indicating cytotoxicity was mediated by H2O2
  • ...8 more annotations...
  • A treatment dose of 4 g ascorbate/kg body weight either once or twice daily did not produce any discernible adverse effects
  • Xenograft experiments showed that parenteral ascorbate as the only treatment significantly decreased both tumor growth and weight by 41–53%
  • Peak plasma concentrations of ascorbate approached 30 mM
  • Pharmacologic concentrations of ascorbate decreased tumor volumes 41–53% in diverse cancer types known for both their aggressive growth and limited treatment options.
  • Our findings showed that pharmacologic ascorbic acid concentrations were cytotoxic to many types of cancer cells in vitro (Fig. 1A) and significantly impeded tumor progression in vivo without toxicity to normal tissues
  • The amelioration of ascorbate cytotoxicity in vitro by the addition of catalase was consistent among sensitive cancer cells (Fig. 1B) and points unambiguously to H2O2 generation in the extracellular medium
  • the current in vivo data support that pharmacologic ascorbate concentrations, which can readily be achieved in humans (Fig. 3E), diminished growth of several aggressive cancer types in mice (Fig. 2) without causing apparent adverse effects.
  • These intratumoral H2O2 concentrations of >125 μM persisted for >3 h after ascorbate administration
  • Nathan Goodyear on 18 Sep 13
     
    Tumor xenograft model in mice finds reduction in growth rates of ovarian cancer, pancreatic cancer, and glioblastoma with daily IV vitamin C.
Nathan Goodyear

UCLA's Jonsson Comprehensive Cancer Center : In the News : Radiation Treatments Generat... - 0 views

www.cancer.ucla.edu/index.aspx

radiation therapy treatment chemotherapy UCLA breast cancer stem cells

shared by Nathan Goodyear on 20 Mar 12 - No Cached
  • Nathan Goodyear on 20 Mar 12
     
    radiation therapy creates more aggressive cancer cells that are resistant to chemotherapy.  This study was done at UCLA on breast cancer cells.
Nathan Goodyear

Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate ... - 0 views

jnci.oxfordjournals.org/...815.abstract

prostate cancer estrogen receptors ER alpha ER-alpha ER beta ER-beta

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    Estrogen receptors play a role in prostate cancer.  TMPRSS2-ERG expression is associated with increased aggressive cancer phenotype--ER beta decreases TMPRSS2-ERG expression, whereas ER alpha increases it.
Nathan Goodyear

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer ce... - 0 views

mct.aacrjournals.org/...2921.long

CBD cancer "breast cancer" Id-1

shared by Nathan Goodyear on 12 Nov 18 - No Cached
  • Nathan Goodyear on 12 Nov 18
     
    CBD can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness
Nathan Goodyear

Diagnostic Pathology | Full text | Estrogen receptor beta expression in prostate adenoc... - 0 views

www.diagnosticpathology.org/...61

prostate cancer estrogen receptor estrogen receptor beta ER-beta hormone hormones receptor receptors estrogen

shared by Nathan Goodyear on 09 Jan 13 - No Cached
  • Nathan Goodyear on 09 Jan 13
     
    ER beta and prostate cancer.  More aggressive prostate cancer is found to be associated with lower ER beta expression in the prostate.  this makes sense, as other studies have shown that ER beta in the prostate can induce apoptosis (cell death), which is a powerful mechanism to regulate uncontrolled growth as found in cancer.
Nathan Goodyear

Effects of androgens on insulin actio... [Diabetes Metab Res Rev. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18615851

insulin resistance androgen testosterone DHT DHEA women PCOS hormones hormone

shared by Nathan Goodyear on 17 Oct 12 - No Cached
  • Nathan Goodyear on 17 Oct 12
     
    elevated insulin associated with insulin resistance causes elevated male hormones in women.  Whether it is in PCOS or postmenopausal over-aggressive replacement, Testosterone also turns right around and contributes to insulin resistance.  Vicious cycle.
Nathan Goodyear

Estrogen receptor β and the progression of prostate cancer: role of 5α-andros... - 0 views

erc.endocrinology-journals.org/...731.long

3-beta androstanediol DHT Testosterone androgens prostate cancer ER beta ER-beta receptors ER men male hormone hormones

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • In the prostate, ERβ is highly expressed in the epithelial compartment, where it is the prevailing isoform
  • In the gland, DHT may be either reversibly 3α- or irreversibly 3β-hydroxylated by the different 3α- and 3β-hydroxysteroid dehydrogenases respectively (Steckelbroeck et al. 2004); these transformations generate two metabolites respectively 3α-diol and 3β-Adiol, which are both unable to bind the AR. Instead, 3β-Adiol displays a high affinity for ERβ (Kuiper et al. 1998, Nilsson et al. 2001), and it has been proposed that this metabolite may play a key role in prostate development
  • ERβ signaling, in contrast to ERα, seems to act as a suppressor of prostate growth, and may be positively involved in breast cancer
  • ...4 more annotations...
  • 3β-Adiol counteracts PC cell proliferation in vitro
  • 3β-Adiol counteracts the biological actions of its androgenic precursors testosterone and DHT
  • functional antagonism of 3β-Adiol appears to be molecularly independent from the activation of the androgenic pathway
  • the action of 3β-Adiol is mediated, at the molecular levels, by the estrogenic pathway.
  • Nathan Goodyear on 21 Jan 14
     
    another awesome article dealing with hormone metabolites. Physicians that don't understand metabolites and receptors may be doing more harm than good.   One of the mainstays of the treatment of metastatic prostate disease is androgen deprivation therapy.  This article requires a reassessment of this due to the DHT metabolite 3-beta androstanediol.  This metabolite is produced from DHT production via the enzyme 3beta HSD.  This metabolite binds to ER beta, an estrogen receptor, and inhibits proliferation, migration, promotes adhesion (limits spreading), and stimulates apoptosis.  This is contrast to 3-alpha androstanediol.  Androgen deprivation therapy will decrease 3-beta androstanediol.  This is the likely reason for the increased aggressive prostate cancer found in those men using 5 alpha reductase inhibitors.
Nathan Goodyear

Testosterone and the brain. [Aging Male. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17178554

testosterone therapy treatment low T low testosterone hypogonadal men mood depression hormone hormones brain male

shared by Nathan Goodyear on 06 Jul 12 - No Cached
  • Nathan Goodyear on 06 Jul 12
     
    testosterone therapy in men with "low T" will see improvement in mood i.e.. depression, energy...aggression associated with testosterone therapy is due to supra physiologic levels.
Nathan Goodyear

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Pr... - 0 views

cancerdiscovery.aacrjournals.org/...1130.abstract

Telomere length prostate cancer

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    The longer the telomere length, the less aggressive prostate cancer appears to be.  In fact, this study found that those with the longest Telomere length had a 87% lower risk of death from prostate cancer.
Nathan Goodyear

Androgens and prostate disease Cooper LA, Page ST - Asian J Androl - 0 views

www.ajandrology.com/article.asp

prostate disease cancer Testosterone DHT 5-alpha reductase men male hormone hormones

shared by Nathan Goodyear on 15 Jan 14 - No Cached
  • intraprostatic androgens are not concomitantly increased when serum androgen levels are raised.
  • The "saturation model" proposes that the prostate is sensitive to very low concentrations of circulating androgens, but that once maximal AR binding is achieved, which occurs at relatively low concentrations of circulating T, further increases in serum T have little impact
  • men with metastatic prostate cancer given T who had been previously treated with castration had worsening of disease, whereas those without prior castration did not
  • ...3 more annotations...
  • There is little data to support the withholding of T therapy on the basis of concern for precipitating prostate cancer.
  • Both intervention data and physiology studies point to minimal effects on the prostate gland when serum T levels are increased to the mid-normal range with T therapy
  • an individualized care plan to assess the possible risks and benefits of T therapy for each patient is critical to optimizing the use of androgens in male health.
  • Nathan Goodyear on 15 Jan 14
     
    Nice review of the mixed data on Testosterone and Prostate disease. It is clear that Testosterone does not precipitate prostate cancer.  The intraprostatic hormone milieu likely is different than that present in the serum.  No surprise there.  5alpha reductase decreases prostate volume, PSA, and low-grade prostate cancer, but actually increases aggressive prostate cancer. Supraphysiologic doping in young men associated with no increase in prostate disease. PSA no longer to be followed in men < 55.  Mortality rate not changed.  PSA change of 1.4 ng/ml is appropriate for additional prostate evaluation.  Testosterone therapy on average increased 0.5 ng/ml. Still, no mention of aromatase activity in this article.  Why is it that hormone sensitive disease in men is only with regards to androgens and women estrogen.
Nathan Goodyear

Estrogen receptor β2 and β5 are associated with poor prognosis in prostate ca... - 0 views

erc.endocrinology-journals.org/...675.short

ER beta ER-beta estrogen receptor receptors prostate cancer

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    Study finds that ER beta isomer type 2 and 4 increased prostate cancer aggressiveness.
Nathan Goodyear

Clinicopathological and molecular characterizatio... [Mod Pathol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21358618

progesterone estrogen receptors papillary thyroid cancer

shared by Nathan Goodyear on 25 Nov 13 - No Cached
  • Nathan Goodyear on 25 Nov 13
     
    Though nuclear expression of estrogen and progesterone receptors were increased in papillary cancer, only progesterone receptor expression was decreased in aggressive cancer.
Nathan Goodyear

Papillary Thyroid Carcinoma: Differential Diagnosis and Prognostic Values of Its Differ... - 0 views

www.hindawi.com/...915925

papillary thyroid cancer estrogen progesterone receptors

shared by Nathan Goodyear on 25 Nov 13 - No Cached
  • Nathan Goodyear on 25 Nov 13
     
    columnar cell variant of papillary cancer associated with increased estrogen and progesterone nuclear receptor expression.  However, when you read this study, the more aggressive tumors were associated with a decrease in progesterone expression.
Nathan Goodyear

Vitamin D Deficiency Predicts Prostate Biopsy Outcomes - 0 views

clincancerres.aacrjournals.org/...2289.abstract

vitamin D vitamin d low prostate cancer

shared by Nathan Goodyear on 10 Jun 14 - No Cached
  • Nathan Goodyear on 10 Jun 14
     
    Not only was low vitamin D associated with increased diagnosis of prostate cancer at the time of diagnosis, but it was also associated with a higher Gleason grade and stage--aggressiveness.
Nathan Goodyear

Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androg... - 0 views

www.nature.com/...srep01528.html

prostate cancer 3-alpha androstanediol 3-beta androstanediol DHT metabolite metabolites

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • PSA levels in media were increased by 3α-diol
  • Similarly to 3α-diol, 3β-diol also increased PSA levels in media in a concentration-dependent manner
  • intracellular DHT is synthesized from inactive androgen 3α- and 3β-diol via different pathways in prostate cancer cells
  • ...12 more annotations...
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      error in statement: DHT metabolites are not inactive, they just don't activate AR.
  • 3β-diol can be a precursor of DHT in prostate cancer cells.
  • serum 3α-diol G levels reflect the androgen milieu in localized prostate cancer patients receiving ADT
  • A few studies reported that 3β-diol is a potential ligand of estrogen receptor β (ERβ) and has an antiproliferative effect
  • our results revealed that 3β-diol is potentially a precursor of DHT in prostate cancer cells
  • Bauman et al. showed that 3α-diol is inactive at AR, but induces prostate growth
  • Prostate cancer cells promoted synthesis from the DHT metabolite 3α-diol during the long duration of ADT
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      the authors highlight the suggestion is that 3alpha-diol's activity is via 3alpha-HSD, but fail to mention that it is known that 3alpha-diol interacts with the ER-alpha in the prostate.
  • verified the synthesis of DHT from 3α- or 3β-diol via different pathways in prostate cancer cells in this study
  • HSD17B6 expression levels in prostate cancer can be useful for the diagnosis of high-risk prostate cancer
  • serum 3α-diol G levels reflect the adrenal androgen milieu in localized prostate cancer patients
  • 3α- and 3β-diol has a much more significant role in intratumoral androgen metabolism during ADT
  • Nathan Goodyear on 27 Jan 14
     
    DHT metabolites play an important role of intra-prostate DHT synthesis in those following ADT.  This is a proposed mechanism for the failure rate and aggressive nature of prostate cancer that fails ADT.   3-alpha androstanediol is converted via 3 alpha HSD back to DHT.  In contrast, 3-beta androstanediol cannot.
Nathan Goodyear

Inhibitors of Prostaglandin Synthesis Inhibit Human Prostate Tumor Cell Invasiveness an... - 0 views

cancerres.aacrjournals.org/...4629.full

omega-3 prostaglandin inhibitors prostate cancer

shared by Nathan Goodyear on 10 Feb 11 - No Cached
  • Nathan Goodyear on 10 Feb 11
     
    omega-3 reduces aggressiveness of prostate cancer
Nathan Goodyear

Glutamate release promotes growth of malignant gli... [Nat Med. 2001] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...11533703

glutamate glutamic acid MSG cancer glioblastoma multiforme

shared by Nathan Goodyear on 10 Feb 11 - No Cached
  • Nathan Goodyear on 10 Feb 11
     
    some tumors, glioblastoma multiforme, secrete glutamate, which increases aggressive nature of cancer
Nathan Goodyear

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

www.ncbi.nlm.nih.gov/...PMC3180189

cancer reverse warburg effect warburg effect NF-kapppB HIF-1alpha Cav-1 H2O2

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
  • ...38 more annotations...
  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
  • Nathan Goodyear on 12 Nov 14
     
    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
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