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Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views

edrv.endojournals.org/...44.full

natural killer cells pregnancy loss recurrent immune system miscarriage NK

shared by Nathan Goodyear on 15 Apr 12 - No Cached
  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
  • ...28 more annotations...
  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
  • Nathan Goodyear on 15 Apr 12
     
    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
Nathan Goodyear

Duration of intralipid's suppressive eff... [Am J Reprod Immunol. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18782287

intralipid therapy natural killer cells NK infertility reproduction reproductive failure

shared by Nathan Goodyear on 16 Apr 12 - No Cached
  • Nathan Goodyear on 16 Apr 12
     
    Intralipid therapy effect in treating natural killer cell overactivity in those women that have immune mediated recurrent pregnancy loss.
Nathan Goodyear

Symposium 3: Vitamin D and immune function: from pregnancy to adolescence - 0 views

www.ncbi.nlm.nih.gov/...PMC3733090

vitamin d vitamin immune function Natural killer cells invariant NKT iNKT pregnancy

shared by Nathan Goodyear on 12 Aug 13 - No Cached
  • Nathan Goodyear on 12 Aug 13
     
    Good article on the immunomodulation effect of vitamin D.  The importance of vitamin D goes back to pregnancy.   Vitamin D deficiencies during pregnancy inhibit appropriate invariant Natrual killer cells, which play important regulatory effect in autoimmune disease.  Even with restoration of vitamin D levels with replacement, the full positive effects of vitamin D are not seen due to limited iNKT potential.
Nathan Goodyear

Clinical implication of natural killer c... [Am J Reprod Immunol. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18405309

NK natural killer infertility immune endocrine

shared by Nathan Goodyear on 04 Feb 13 - No Cached
  • Nathan Goodyear on 04 Feb 13
     
    increased NK activity plays role in infertility. No surprise that the immune system interacts with the endocrine system.
Nathan Goodyear

Uterine and circulating natural killer cell... [J Reprod Immunol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21632120

RPL recurrent pregnancy loss NK immunology immune system natural killer cells preeclampsia pre-eclampsia PIH

shared by Nathan Goodyear on 19 Apr 12 - No Cached
  • Nathan Goodyear on 19 Apr 12
     
    women with RPL and preeclampsia carry same immunologic NK abnormalities.  Loss of immune tolerance, elevated maternal NK, shown to play role in both.
Nathan Goodyear

Angiogenic Factors and Natural Killer (NK) Cells in the Pathogenesis of Preeclampsia - 0 views

www.ncbi.nlm.nih.gov/...PMC2147723

natural killer cells pregnancy preeclampsia pre-eclampsia RPL

shared by Nathan Goodyear on 20 Apr 12 - No Cached
  • Nathan Goodyear on 20 Apr 12
     
    Abnormal NK cell activity in the placenta plays a likely role in the development of preeclampsia. This proposes an immunologic role in the development of preeclampsia.  This process is similar to the literatures link between maternal NK and RPL.
Nathan Goodyear

The role of decidual natural killer ce... [J Obstet Gynaecol Can. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18611298

preeclampsia pre-eclampsia NK cell natural killer RPL recurrent pregnancy loss

shared by Nathan Goodyear on 20 Apr 12 - No Cached
  • Nathan Goodyear on 20 Apr 12
     
    same NK link to RPL, linked to preeclampsia.  NK cells play important role in the development of the spiral arteries in the placenta. It has long been thought, that the placenta was the likely culprit in the development of preeclampsia
Nathan Goodyear

Androgen Deprivation Therapy, Insulin Resistance, and Cardiovascular Mortality: An Inco... - 0 views

onlinelibrary.wiley.com/...full

androgen deprivation therapy androgen male men hormone hormones deprivation therapy prostate cancer cardiovascular disease insulin resistance diabetes metabolic syndrome mortality CVD

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    Androgen deprivation therapy is associated with increased diabetes, metabolic syndrome, insulin resistance, and cardiovascular mortality.  The longer the duration of therapy, the more the progression of metabolic dysfunction.  This process seems similar to chemotherapy i.e. secondary cancer due to chemotherapy.  The treatment of one disease, prostate cancer in this case, leads to an increase in the risk of the #1 killer in men--logic seems severely flawed there.
Nathan Goodyear

CD56bright natural killer (NK) cells: an important NK cell subset - 0 views

www.ncbi.nlm.nih.gov/...PMC2673358

natural killer cells NK cells

shared by Nathan Goodyear on 28 Sep 18 - No Cached
  • Nathan Goodyear on 28 Sep 18
     
    Good review of CD16/56 cell subpopulation of NK cells.
Nathan Goodyear

High-Dose Parenteral Ascorbate Enhanced Chemosensitivity of Ovarian Cancer and Reduced ... - 0 views

stm.sciencemag.org/...222ra18

ovarian cancer IV vitamin C vitamin C intravenous vitamin C

shared by Nathan Goodyear on 06 Feb 14 - No Cached
  • Nathan Goodyear on 06 Feb 14
     
    IV vitamin C shown to augment cancer killer effect of chemotherapy.  This study looked at ovarian cancer in animal models and in humans.  The effect--a synergistic effect was found that promoted tumor destruction.  The great thing about IV vitamin C is the benefit but also the very low side effect profile.
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.
ashleyobama

Buy best painkillers online without prescripton . - 0 views

uberant.com/...rs-online-without-prescripton-

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  • ashleyobama on 22 May 20
     
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Roids Meds - 0 views

www.evernote.com/...ee11de246aed65b74fcac6dfadd372

adderall ketamine painkillers methadone therapy teherapy cancer cancerin codeine

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  • ashleyobama on 28 May 20
     
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Nathan Goodyear

VEGF receptor inhibitors block the ability of metronomically dosed cyclophosphamide to ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3294103

low-dose chemotherapy glioblastoma multiforme VEGF glioblastoma cancer metronomic chemotherapy

shared by Nathan Goodyear on 11 Nov 20 - No Cached
  • Nathan Goodyear on 11 Nov 20
     
    CPA administered on an intermittent, every 6-day metronomic schedule stimulates tumor recruitment of macrophages, natural killer (NK) cells, and dendritic cells with regression of large established tumors, as seen in several implanted glioma models; also of note, VEGF inhibition inhibited this effect.
Nathan Goodyear

A novel mechanism of lung cancer inhibition by methionine enkephalin through remodeling... - 0 views

www.researchgate.net/..._of_the_tumor_microenvironment

M2 macrophages M1 macrophages cancer MET-enkephalins TME MET-5 tumor microenvironment

shared by Nathan Goodyear on 15 Aug 21 - No Cached
  • Nathan Goodyear on 15 Aug 21
     
    MENK increased the infiltration of M1-type macrophages, natural killer cells, CD8+ T cells, CD4+ T cells, and dendritic cells into the TME, and decreased the proportion of myeloid inhibitory cells and M2-type macrophages. Plays particular role in preventing immune escape and immune dysfunction paramount to cancer metastasis
Nathan Goodyear

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in... - 0 views

www.thelancet.com/...fulltext

PURE cancer prospective urban rural epidemiology study PURE study

shared by Nathan Goodyear on 05 Sep 19 - No Cached
  • Nathan Goodyear on 05 Sep 19
     
    Latest study finds in moderate and high income countries, cancer has overtaken cardiovascular disease as the #1 killer between the ages of 35-70.
Nathan Goodyear

The impact of the microbiome in cancer: Targeting metabolism of cancer cells and host -... - 0 views

www.ncbi.nlm.nih.gov/...PMC9708872

tumor microbiome cancer gut microbiome TME metabolism

shared by Nathan Goodyear on 20 Mar 24 - No Cached
  • Nathan Goodyear on 20 Mar 24
     
    Studies have found that high-salt diet can enhance the function of natural killer (NK) cells by enriching the abundance of Bifidobacterium, thus inhibiting tumor growth (63). High dietary fiber can enrich A. muciniphila, activate innate immunity, reshape the tumor microenvironment, and exert the function of inhibiting tumor (64). Notably, Wargo et al. have confirmed that high-dietary fiber diet can enhance anti-tumor immunity and increase the infiltration of tumor-killing T cells, while commercial probiotics treatment alone does not enhance the efficacy of immunotherapy. This study suggests that probiotics intervention is strain-specific and should be put in a specific dietary environment to make sense, to some extent (65).
Nathan Goodyear

Regulatory NK-Cell Functions in Inflammation and Autoimmunity - 0 views

www.ncbi.nlm.nih.gov/...PMC2710290

NK natural killer inflammation autoimmune autoimmune disease autoimmunity

shared by Nathan Goodyear on 04 Feb 13 - No Cached
  • Nathan Goodyear on 04 Feb 13
     
    good review on NK cell role in inflammation and autoimmune disease
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