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Nathan Goodyear

Salivary 8-OHdG: a useful biomarker for predicting severe ED and hypogonadism. - PubMed... - 0 views

www.ncbi.nlm.nih.gov/...18422497

oxidative stress 8-OHdG 8-hydroxy-2-deoxyguanosine hormones Testosterone phosphodiesterase 5 inhibitors

shared by Nathan Goodyear on 15 Jun 15 - No Cached
  • Nathan Goodyear on 15 Jun 15
     
    Study finds salivary 8-OHdG is associated with increased severity of ED in men.  The study found that phosphodiesterase 5 inhibitor therapy increased total and free Testosterone as well as decreased 8-OHdG.
Nathan Goodyear

Acta Pharmacologica Sinica - Progress in studies of huperzine A, a natural cholinestera... - 0 views

www.nature.com/...aps20061a.html

Huperzine-A Huperzine Alzheimer's disease brain NMDA organophosphate organophosphates

shared by Nathan Goodyear on 04 Nov 13 - No Cached
  • Nathan Goodyear on 04 Nov 13
     
    This study found that Huperzine A improved memory deficits in elderly and those with Alzheimer's disease.  Huperzine A is an acetylcholinisterase inhibitor, thereby increasing the neurotransmitter acetylcholine.  Huperzine A has also been shown to be neuroprotective through its antagonistic action with the NMDA receptors. Huperzine A has been shown to be protective from organophosphate toxicity.
Nathan Goodyear

Selective serotonin reuptake inhibitors - PubMed Mobile - 0 views

www.ncbi.nlm.nih.gov/...11876575

SSRI CYP cytochrome P450 estrogen

shared by Nathan Goodyear on 01 Nov 13 - No Cached
  • Nathan Goodyear on 01 Nov 13
     
    SSRI's have variable inhibition of CYP.  Fluvoxamine was found to be the most potent inhibitor.  CYP3A4 and CYP2D6 were found to be the main targets of inhibition.  
Nathan Goodyear

Clinical dose ranging studies with finasteride, a type 2 5α-reductase inhibit... - 0 views

www.eblue.org/...abstract

finasteride propecia male-pattern baldness

shared by Nathan Goodyear on 31 Mar 11 - No Cached
  • Nathan Goodyear on 31 Mar 11
     
    propecia, 5-alpha reductase inhibitor, improves male pattern baldness
Nathan Goodyear

International Journal of Impotence Research - Mechanisms of action of PDE5 inhibition i... - 0 views

www.nature.com/...3901205a.html

ED PDE5 PDE5 inhibitors erectile dysfunction impotence men male NO

shared by Nathan Goodyear on 08 Sep 14 - No Cached
  • Nitric oxide (NO) is produced from oxygen and L-arginine under the control of nitric oxide synthase (NOS)
  • Cyclic GMP is the intracellular trigger for penile erection
  • PDE5 is the predominant phosphodiesterase in the corpus cavernosum
  • Nathan Goodyear on 08 Sep 14
     
    Nice review of the mechanism of action of PDE5 inhibitors and ED.
Nathan Goodyear

Oncolytic virotherapy promotes intratumoral T cell infiltration and improves Anti-PD-1... - 0 views

www.cell.com/...S0092-8674(17)30952-2

immunotherapy cancer RIGVIR oncolytic therapy PD-1 check point inhibitors

shared by Nathan Goodyear on 23 Oct 18 - No Cached
  • Nathan Goodyear on 23 Oct 18
     
    Study found that viral oncolytic therapy improved efficacy of PD-1 check point inhibitors by 62%. Increased CD8 expression, interferon-gamma...Interesting, starting CD8 levels played no role in predicting outcome.
Nathan Goodyear

How is the Immune System Suppressed by Cancer - 1 views

www.cancertutor.com/ancer-suppresses-immune-system

iNOS cancer immune system

shared by Nathan Goodyear on 23 May 18 - No Cached
  • nitric oxide (NO) released by tumor cells
  • Excellent work by Prof de Groot of Essen, indicated by adding exogenous xanthine oxidase ( XO) in hepatoma cells, hydrogen peroxide was produced to destroy the hepatoma cells
  • NO from eNOS in cancer cells can travel through membranes and over long distances in the body
  • ...43 more annotations...
  • NO also is co linked to VEGF which in turn increases the antiapoptotic gene bcl-2
  • The other important influence of NO is in its inhibition of the proapoptoic caspases cascade. This in turn protects the cells from intracellular preprogrammed death.
  • nitric oxide in immune suppression in relation to oxygen radicals is its inhibitory effect on the binding of leukocytes (PMN) at the endothelial surface
  • Inhibition of inducible Nitric Oxide Synthase (iNOS)
  • NO from the tumor cells actually suppresses the iNOS, and in addition it reduces oxygen radicals to stop the formation of peroxynitrite in these cells. But NO is not the only inhibitor of iNOS in cancer.
  • Spermine and spermidine, from the rate limiting enzyme for DNA synthases, ODC, also inhibit iNOS
  • tolerance in the immune system that decreases the immune response to antigens on the tumors
  • Freund’s adjuvant
  • increase in kinases in these cells which phosphorylate serine, and tyrosine
  • responsible for activation of many growth factors and enzymes
  • phosphorylated amino acids suppress iNOS activity
  • Hexokinase II
  • Prostaglandin E2, released from tumor cells is also an inhibitor of iNOS, as well as suppressing the immune system
  • Th-1 subset of T-cells. These cells are responsible for anti-viral and anti-cancer activities, via their cytokine production including Interleukin-2, (IL-2), and Interleukin-12 which stimulates T-killer cell replication and further activation and release of tumor fighting cytokines.
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      Th1 cells stimulate NK and other tumor fighting macrophages via IL-2 and IL-12; In contrast, Th2, which is stimulated in allergies and parasitic infections, produce IL-4 and IL-10.  IL-4 and IL-10 inhibit TH-1 activation and the histamine released from mast cell degranulation upregulates T suppressor cells to further immune suppression.
  • Th-2 subset of lymphocytes, on the other hand are activated in allergies and parasitic infections to release Interleukin-4 and Interleukin-10
  • These have respectively inhibitory effects on iNOS and lymphocyte Th-1 activation
  • Mast cells contain histamine which when released increases the T suppressor cells, to lower the immune system and also acts directly on many tumor Histamine receptors to stimulate tumor growth
  • Tumor cells release IL-10, and this is thought to be one of the important areas of Th-1 suppression in cancer patients
  • IL-10 is also increased in cancer causing viral diseases such as HIV, HBV, HCV, and EBV
  • IL-10 is also a central regulator of cyclooxygenase-2 expression and prostaglandin production in tumor cells stimulating their angiogenesis and NO production
  • nitric oxide in tumor cells even prevents the activation of caspases responsible for apoptosis
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      NO produced by cancer cells inhibits proapoptotic pathways such as the caspases.
  • early stages of carcinogenesis, which we call tumor promotion, one needs a strong immune system, and fewer oxygen radicals to prevent mutations but still enough to destroy the tumor cells should they develop
  • later stages of cancer development, the oxygen radicals are decreased around the tumors and in the tumor cells themselves, and the entire cancer fighting Th-1 cell replication and movement are suppressed. The results are a decrease in direct toxicity and apoptosis, which is prevented by NO, a suppression of the macrophage and leukocyte toxicity and finally, a suppression of the T-cell induced tumor toxicity
  • cGMP is increased by NO
  • NO in cancer is its ability to increase platelet-tumor cell aggregates, which enhances metastases
  • the greater the malignancies and the greater the metastatic potential of these tumors
  • The greater the NO production in many types of tumors,
  • gynecological
  • elevated lactic acid which neutralizes the toxicity and activity of Lymphocyte immune response and mobility
  • The lactic acid is also feeding fungi around tumors and that leads to elevated histamine which increases T-suppressor cells.  Histamine alone stimulates many tumor cells.
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      The warburg effect in cancer cells results in the increase in local lactic acid production which suppresses lymphocyte activity and toxicity as well as stimulates histamine production with further stimulates tumor cell growth.
  • T-regulatory cells (formerly,T suppressor cells) down regulate the activity of Natural killer cells
  • last but not least, the Lactic acid from tumor cells and acidic diets shifts the lymphocyte activity to reduce its efficacy against cancer cells and pathogens in addition to altering the bacteria of the intestinal tract.
  • intestinal tract bacteria in cancer cells release sterols that suppress the immune system and down regulate anticancer activity from lymphocytes.
  • In addition to the lactic acid, adenosine is also released from tumors. Through IL-10, adenosine and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state
  • Adenosine up regulates the PD1 receptor in T-1 Lymphocytes and inhibits their activity
  • Adenosine is a purine nucleoside found within the interstitial fluid of solid tumors at concentrations that are able to inhibit cell-mediated immune responses to tumor cells
  • Adenosine appears to up-regulate the PD1 receptor in T-1 Lymphocytes and inhibits the immune system further
  • Mast cells with their release of histamine lower the immune system and also stimulate tumor growth and activate the metalloproteinases involved in angiogenesis and metastases
  • COX 2 inhibitors or all trans-retinoic acid
  • Cimetidine, an antihistamine has been actually shown to increase in apoptosis in MDSC via a separate mechanism than the antihistamine effect
    • Nathan Goodyear
      Nathan Goodyear on 23 May 18
       
      cimetidine is an H2 blocker
  • interleukin-8 (IL-8), a chemokine related to invasion and angiogenesis
  • In vitro analyses revealed a striking induction of IL-8 expression in CAFs and LFs by tumor necrosis factor-alpha (TNF-alpha)
  • these data raise the possibility that the majority of CAFs in CLM originate from resident LFs. TNF-alpha-induced up-regulation of IL-8 via nuclear factor-kappaB in CAFs is an inflammatory pathway, potentially permissive for cancer invasion that may represent a novel therapeutic target
  • Nathan Goodyear on 23 May 18
     
    Great review of the immunosuppression in cancer driven by the likes of NO.
Nathan Goodyear

Immune checkpoint inhibitors: recent progress and potential biomarkers | Experimental &... - 0 views

www.nature.com/...s12276-018-0191-1

cancer immunotherapy check point inhibitors immune check point inhibitors

shared by Nathan Goodyear on 28 Feb 21 - No Cached
  • Nathan Goodyear on 28 Feb 21
     
    Evidence points to their lacking benefits
Nathan Goodyear

A Randomized Phase II Preoperative Study of Autophagy Inhibition With High-Dose Hydroxy... - 0 views

www.ncbi.nlm.nih.gov/...PMC8086597

immunomodulation hydroxychloroquine pancreatic cancer autophagy inhibitor

shared by Nathan Goodyear on 03 May 21 - No Cached
  • Nathan Goodyear on 03 May 21
     
    Preoperative hydroxychloroquine shows benefit as autophagy inhibitor in conjunction with surgery and chemotherapy
Nathan Goodyear

Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce... - 0 views

www.ncbi.nlm.nih.gov/...PMC3896521

quercetin PARP PARP inhibitor

shared by Nathan Goodyear on 19 Jan 21 - No Cached
  • Nathan Goodyear on 19 Jan 21
     
    Quercetin is a PARP inhibitor, especially in BRCA deficiencies.
Nathan Goodyear

Curcumin as tyrosine kinase inhibitor in cancer treatment - ScienceDirect - 0 views

www.sciencedirect.com/...S0223523419306361

receptor tyrosine kinase VEGF curcumin IGF-1 tyrosine kinase FGFR PDGF

shared by Nathan Goodyear on 28 Sep 20 - No Cached
  • Nathan Goodyear on 28 Sep 20
     
    Curcumin shown to be a natural TK inhibitor
Nathan Goodyear

Targeting cancer with phosphodiesterase inhibitors: Expert Opinion on Investigational D... - 1 views

www.tandfonline.com/...13543780903485642

phosphodiesterase inhibitors PDE5 inhibitors cAMP PDE PDE5 cancer

shared by Nathan Goodyear on 15 Feb 21 - No Cached
  • Nathan Goodyear on 15 Feb 21
     
    Only abstract available here, but PDE inhibition, particularly PDE5 is associated with increase in cAMP in the TME.
Nathan Goodyear

Prognostic Significance of COVID-19 Receptor ACE2 and Recommendation for Antihypertensi... - 0 views

www.hindawi.com/...2054376

SARS-CoV-2 COVID-19 COVID ACE inhibitors ACE2 COVID19 hypertension

shared by Nathan Goodyear on 13 Nov 21 - No Cached
  • Nathan Goodyear on 13 Nov 21
     
    ACE inhibitors increase ACE2
Nathan Goodyear

Progesterone Receptor Inhibits Aromatase and Inflammatory Response Pathways in Breast C... - 0 views

mend.endojournals.org/...1812.long

progesterone receptor receptors PR breast cancer anti-inflammatory

shared by Nathan Goodyear on 12 Nov 12 - No Cached
  • Nathan Goodyear on 12 Nov 12
     
    Progesterone receptor (PR) shown to provide an important anti-inflammatory role in breast cancer in this study.  PR shown to increase NF-kappaB inhibitor IkBalpha, shown to inhibit aromatase activity, shown to inhibit COX-2 expression and shown to inhibit HER-2/neu expression.
Nathan Goodyear

Estradiol, Tamoxifen, and Flaxseed A... [J Clin Endocrinol Metab. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22930784

diet estradiol flaxseed breast cancer Ca inflammation cytokines IL-1alpha IL-1Beta IL-1Ra

shared by Nathan Goodyear on 17 Nov 12 - No Cached
  • Nathan Goodyear on 17 Nov 12
     
    Tamoxifen and more importantly, flaxseed increases endogenous IL-1Ra that is a known inhibitor of the pro-inflammatory cytokines IL-1alpha and IL-1beta. These pro-inflammatory cytokines are associated with breast cancer.  Conclusion: diet modification can effect inflammatory cytokines associated with breast cancer.  This should be explored as true preventative therapies for women. This study also found a positive association with estradiol and IL-1Beta in breast tissue and SC fat; inversely associated with IL-Ra in the breast.
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