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Nathan Goodyear

A novel mechanism of lung cancer inhibition by methionine enkephalin through remodeling the immune status of the tumor microenvironment | Request PDF - 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

CD40 may be key to activating immune response in pancreatic cancer - 0 views

www.healio.com/...-response-in-pancreatic-cancer

immunology immunotherapy cancer immune immuneCD40 immune system check point inhibitors

shared by Nathan Goodyear on 30 Jul 23 - No Cached
  • Nathan Goodyear on 30 Jul 23
     
    "…it seems most patients who respond do so by reactivation of a previously existing immune response that was perhaps exhausted or subverted by the cancer. If you block these brakes that slow an immune response, you can resume immune activity and achieve a remarkable regression in many cases." "…data shows that CD40 is an important switch for converting a tumor from cold to hot."
Nathan Goodyear

Melatonin inhibits both ER alpha activation and... [J Pineal Res. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16635015

Cadmium CD estrogen receptor alpha estrogen receptor estrogen receptor melatonin hormones ER alpha

shared by Nathan Goodyear on 19 Jan 13 - No Cached
  • Nathan Goodyear on 19 Jan 13
     
    Several interesting points about this article.  Cadmium is a non-carcinogen.  Cadmium acts through estrogen receptors.  Cd acts as an estrogen.  Second, melatonin inhibits ER alpha, which promotes inflammation and growth signaling.
Nathan Goodyear

Gender and sex hormones in multiple sclerosis pathology and therapy - 0 views

www.ncbi.nlm.nih.gov/...PMC2689399

hormones MS multiple Sclerosis Estriol progesterone

shared by Nathan Goodyear on 11 Jan 17 - No Cached
  • It is now well recognized that the disease manifestation is reduced in pregnant women with relapsing-remitting MS
  • This occurs particularly during the third trimester when levels of estrogens (estradiol and estriol) and progesterone (see Table 2) are elevated up to about 20 times
  • This seems well correlated with a decrease in active white matter lesions detected by MRI
  • ...12 more annotations...
  • This clinical improvement is however followed by temporary rebound exacerbations at post-partum, when the hormone levels decline
  • a shift from Th1 to Th2 immune response, expansion of suppressive regulatory T lymphocytes and decrease in the number of circulating CD16+ natural killer (NK)-cells
  • Th1 lymphocytes secrete proinflammatory cytokines (e.g. IL-2, IFNgamma, lymphotoxin) while Th2 cells secrete anti-inflammatory cytokines (e.g. IL-4, IL-5, IL-10), which favor humoral-mediated responses
  • Th2 cytokines are associated with down-regulation of Th1 cytokines and this Th2 shift is believed to provide protection from allograft rejection during pregnancy as well as from Th1-mediated autoimmune disease
  • it is worth noting that the levels of other hormones with anti-inflammatory activity (1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase by 2 to 4 times during late pregnancy
  • 1,25-dihydroxy vitamin D3 induces regulatory T-cell function important for development of self-tolerance
  • breast-feeding does not alter the relapse rate in women with MS
  • Leptin is a pleiotropic hormone produced primarily by adipocytes but also by T lymphocytes and neurons
  • Several lines of evidence indicate that leptin contributes to EAE/MS pathogenesis, influencing its onset and clinical severity, by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg) anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma) and reduced Th2 (IL-4) cytokine production
  • circulating leptin levels are increased in relapsing-remitting MS patients (men and women analyzed together) while the CD4+CD25+Treg population decreases
  • As the leptin plasma concentrations are proportional to the amount of fat tissue, obese/overweight individuals produce higher levels of leptin
  • Nielsen et al found that estradiol and progesterone exert neuroprotection against glutamate neurotoxicity, while MPA antagonizes the neuroprotective effect of estradiol and exacerbated neuron death induced by glutamate excitotoxicity
  • Nathan Goodyear on 11 Jan 17
     
    very good review of the differences in MS and hormones between the sexes.
Nathan Goodyear

Natural Killer Cell Counts Are Not Different between Patients with Post-Lyme Disease Syndrome and Controls - 0 views

www.ncbi.nlm.nih.gov/...PMC2725528

lyme CD57 chronic PLDS post lyme disease syndrome

shared by Nathan Goodyear on 21 Nov 13 - No Cached
  • Nathan Goodyear on 21 Nov 13
     
    small study finds no difference in CD57 levels in people with post lyme and "normal" people
Nathan Goodyear

Journal of Clinical Investigation -- A peripheral circulating compartment of natural naive CD4+ Tregs - 0 views

www.jci.org/23963

T reg cells CD4 CD25 immune system

shared by Nathan Goodyear on 01 Jul 11 - No Cached
  • Nathan Goodyear on 01 Jul 11
     
    in depth discussion of Treg cells. Treg cells help keep T cells, of the immune system, in check
Nathan Goodyear

https://www.nature.com/articles/6601943.pdf?origin=ppub - 0 views

www.nature.com/...6601943.pdf

prostate cancer cancer CD4

shared by Nathan Goodyear on 24 Dec 18 - No Cached
  • Nathan Goodyear on 24 Dec 18
     
    CD4 tumor infiltrates of the tumor microenvironment is associated with worse overall survival in prostate cancer patients.
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

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid - EBioMedicine - 0 views

www.ebiomedicine.com/...fulltext

multiple myeloma vitamin C IV vitamin C smoldering myeloma cancer

shared by Nathan Goodyear on 25 Sep 17 - No Cached
  • Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
  • The generation of ascorbyl- and H2O2 radicals by PAA increases ROS stress in cancer cells
  • In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008Chen et al., 2008), in xenograft MM mice
  • ...33 more annotations...
  • These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
  • These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
  • These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
  • A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
  • RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
  • the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
  • Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
  • our pilot study also suggested that PAA could overcome drug resistance to bortezomib in MM cells
  • Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
  • combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
  • Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
  • These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
  • if creatinine clearance is <30 mL/min, high dose ascorbic acid should be not administrated.
  • In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
  • Multiple myeloma (MM) is a plasma cell neoplasm.
  • Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
  • pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
  • In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
  • the labile iron pool (LIP) is significantly elevated in MM cells
  • The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
  • In contrast, no significant change of cell viability was observed in CD138− BM cells from the same patients
  • The same effect of PAA was also observed in the SMM patients
  • no response to PAA was detected in CD138+ cells from the 2 MGUS patients
  • the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
  • Both catalase and NAC protect cells from oxidative damage
  • cells pretreated with NAC and catalase became resistant to PAA even at high doses
  • adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
  • iron is essential for PAA to achieve its anti-cancer activity
  • PAA induced early necrosis (Fig. 3Fig. 3A, 60 min) followed by late apoptosis
  • results further indicated that PAA induced mitochondria-mediated apoptosis
  • PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
  • ROS and H2O2 are well known factors mediating PAA-induced cancer cell death
  • PAA was sensitive to all 9 MMs and 2 SMMs
  • Nathan Goodyear on 25 Sep 17
     
    animal study finds high-dose, pharmacologic vitamin C found to kill multiple myeloma cells via pro-oxidant effect found in similar studies in dealing with different cancers.
Nathan Goodyear

Thus, these opinions are not based on all the relevant research that is available and are, therefore incomplete and biased - 0 views

Thus, these opinions are not based on all the relevant research that is available and are, therefore incomplete and biased

CD57 cancer metastasis NK cells NK immune system immunotherapy

shared by Nathan Goodyear on 05 Feb 19 - No Cached
  • Nathan Goodyear on 05 Feb 19
     
    CD 57 cells infiltrating solid tumor microenvironment yields positive prognosis. Inverse relationship for Mets.
Nathan Goodyear

IL-2: The First Effective Immunotherapy for Human Cancer | The Journal of Immunology - 0 views

www.jimmunol.org/...5451

cancer IL-2 Treg immune system immunology

shared by Nathan Goodyear on 17 Apr 18 - No Cached
  • IL-2 is a 15.5-kDa cytokine secreted predominately by Ag-simulated CD4+ T cells, but it can also be produced by CD8+ cells, NK cells, and activated dendritic cells
  • IL-2 is the predominant factor responsible for the maintenance of CD4+ regulatory T cells
  • A generalized capillary leak syndrome was induced by IL-2 in vivo that resulted in interstitial pulmonary infiltrates and substantial weight gain in patients
  • ...4 more annotations...
  • The side effects were transient and returned to baseline following treatment
  • Tumors do not express IL-2 receptors and thus the antitumor activity was the result of IL-2 stimulation of immune cell
  • Patients with metastatic melanoma or metastatic renal cell cancer were uniquely responsive to high-dose IL-2 administration, and except for patients with advanced non-Hodgkin’s lymphomas (35) only rare responses were seen in patients with other tumor types
  • The underlying toxicity of IL-2 results from a capillary leak that leads to fluid extravasation into visceral organs that can compromise their function
  • Nathan Goodyear on 17 Apr 18
     
    Great review of the history of IL-2 in the treatment of cancer.  IL-2 stimulates the immune system to attack cancer.  Don't reinvent the wheel; use what is already present and available.
Nathan Goodyear

Changes in the immune system during menopause and aging. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...20515802

menopause disease NK cells natural killer cells CD4 aging

shared by Nathan Goodyear on 05 Oct 16 - No Cached
  • Nathan Goodyear on 05 Oct 16
     
    Menopause is associated with a decline in CD4 T and B cells and well as a decrease in NK cells.  This is a set up for disease, particularly cancer.
Nathan Goodyear

First Study of Oral Artenimol-R in Advanced Cervical Cancer: Clinical Benefit, Tolerability and Tumor Markers - 0 views

ar.iiarjournals.org/...4417.long

artemisinin EGFR artesunate Ki67 p53 CD31 cervical cancer

shared by Nathan Goodyear on 13 Jun 19 - No Cached
  • Nathan Goodyear on 13 Jun 19
     
    Results show a clear down-regulation of p53, EGFR, Ki-67 and CD31 in cervical cancer cells.
Nathan Goodyear

Methionine Enkephalin | SpringerLink - 0 views

link.springer.com/...978-1-4899-0059-3_19

cancer NK cells MET-enkephalin CD8 MET-5

shared by Nathan Goodyear on 15 Aug 21 - No Cached
  • Nathan Goodyear on 15 Aug 21
     
    MET-enkephalin similar to IL-2 in its NK cell and CD8 stimulation.
Benton Smith

Printinginn - 0 views

www.printinginn.com

Booklets Bookmarks Box Printing Brochures Business Cards Calendars CD Jackets Flyers Labels Letterheads Post Posters Rack Stickers Tickets.

shared by Benton Smith on 30 Oct 12 - No Cached
  • Benton Smith on 30 Oct 12
     
    Printinginn.com is a one-stop solution for all your printing needs. Printinginn provides full color printing in different styles, sizes and shapes using materials of your choice. We are specialized in Booklets, Bookmarks, Box Printing, Brochures, Business Cards, CD Jackets, Flyers, Labels, Letterheads, Post Cards, Posters, Rack Cards, Stickers and many more. We use the best printing methods to achieve best printing results and thus can print your jobs using a vast number of custom options.
Nathan Goodyear

Telomerase at the intersection of cancer and aging - 0 views

www.ncbi.nlm.nih.gov/...PMC3896987

telomere telomeres telomerase telomerase activator aging disease cancer

shared by Nathan Goodyear on 18 May 16 - No Cached
  • The anti-aging role of telomerase has been demonstrated to be largely mediated by its canonical role in elongating telomeres, which prevents the accumulation of critically short telomeres and loss of tissue homeostasis
  • Short telomeres, and subsequent DDR activation, could occur both in cancer and aging
  • increased abundance of short telomeres correlates with higher genomic instability and decreased longevity in various organisms, including mice, zebrafish, and yeast
  • ...15 more annotations...
  • mice deficient for telomerase or for telomere binding proteins are characterized by accelerated age-related defects
  • In humans, short telomeres are considered good indicators of an individual’s health status and correlate with both genetic and environmental factors
  • Although recent findings strongly support the idea that short telomeres drive several age-related diseases 38 we cannot exclude the possibility that in some situations short telomeres may be a consequence of the disease itself.
  • the current view is that telomerase deficiency may contribute to the early steps of cancer development by fueling chromosomal instability, while subsequent activation of telomerase may be necessary to allow tumor growth and tumor progression towards more malignant states
  • telomerase activation can be an early event in cancer, it is not necessary for cancer initiation
  • telomerase can stimulate tumor progression by ensuring maintenance of telomeres above a critically short length, thus preventing induction of cellular senescence or apoptosis
  • Almost all human cancers present activation of telomerase as a hallmark, most likely as a mechanism to allow unlimited cell proliferation of tumor cells
  • recent evidence demonstrated that short telomeres alone could lead to genomic instability and cancer
  • Getting rid of telomerase can also be problematic; the lack of telomerase could lead to increased chromosomal instability, which in turn could be at the basis for cancer initiation when tumor suppressor barriers are bypassed
  • telomerase activation is a potential therapeutic strategy for the treatment of age-related diseases
  • telomerase activation in adult or old mice by means of a gene therapy strategy was shown to be sufficient to improve metabolic fitness, neuromuscular capacity, and prevent bone loss, as well as significantly increase both median and maximum longevity, without increased cancer incidence
  • These studies suggest that telomerase expression could be considered a feasible approach to reverse tissue dysfunction and extend healthy lifespan without increasing cancer incidence
  • humans almost completely lose telomerase activity from somatic tissues in the adulthood
  • a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging
  • Telomerase expression in a background of high levels of tumor suppressors or in aged organisms seems to prevent its expected pro-cancer activity and yet it still functions as an anti-aging factor
  • Nathan Goodyear on 18 May 16
     
    Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging.  In contrast, telomerase activity is found to be involved in carcinogenesis.  Increased carcinogenic potential of telomerase activity has not borne out in studies.  In addition, increased CD8 cell activity as a result of telomerase activation will actually decrease carcinogenic potential via NK activation.
Nathan Goodyear

International Journal of Obesity - Obesity is associated with impaired immune response to influenza vaccination in humans - 0 views

www.nature.com/...ijo2011208a.html

obesity flu vaccine vaccinations influenza

shared by Nathan Goodyear on 10 May 16 - No Cached
  • Nathan Goodyear on 10 May 16
     
    flu vaccine not effective in obese individuals due to compromised CD8 cell activity; no surprise due to the fact that obesity is an inflammatory disease.
Nathan Goodyear

T-cell subsets (Th1 versus Th2). - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10923599

interleukins Th1 Th2 immune system autoimmune disease CD4 CD8

shared by Nathan Goodyear on 11 Jan 17 - No Cached
  • Nathan Goodyear on 11 Jan 17
     
    only abstract available: Review of the cell mediated immune system and the interleukin signaling.
Nathan Goodyear

Role of certain trace minerals in oxidative stress, inflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients - 0 views

acb.sagepub.com/...344.abstract

asthma selenium zinc copper glutathione hs-CRP TBARS FEV1 FVC catalase inflammation minerals

shared by Nathan Goodyear on 07 Jul 16 - No Cached
  • Nathan Goodyear on 07 Jul 16
     
    Asthma associated with low selenium, low zinc, high copper, low glutathione peroxidase, glutathione reductase, and catalase activity; in contrast, increased hs-CRP, and TBARS was  noted.  Interesting that FEV1 and FVC positively correlated with Se levels.
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