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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.
  • the microbiome in castrated adult males clearly shifts away from that of normal adult males and is closer to the microbiome of females
  • ...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.
  • 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.
  • 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

The gut flora as a forgotten organ - 0 views

www.ncbi.nlm.nih.gov/...PMC1500832

gut flora gut microbiome gut microbiota

shared by Nathan Goodyear on 24 Aug 15 - No Cached
  • Nathan Goodyear on 24 Aug 15
     
    To be read
wheelchairindia9

Ergonomic Lightweight Wheelchair - 0 views

disabilityproduct.in/...ERGONOMIC-WHEELCHAIR

Compact Design Ergo Lite 2501 Wheelchair strength and durability Ergonomic Lightweight Wheelchair strong and safe folding seat and backrest Karma Ergolite Km-2501 wheels and footrest removed

shared by wheelchairindia9 on 08 Aug 15 - No Cached
  • wheelchairindia9 on 08 Aug 15
     
    Pediatric wheelchairs enable child or teen to participate in all types of daily activities. Pediatric wheelchairs are lightweight, portable, and convenient for use at school, day programs, doctor visits, and recreation with family and friends. Pediatric wheelchairs comes in wide range of sizes and vibrant colors for every lightweight wheelchair. A variety of positioning options are also available. Pediatric wheelchairs are manufactured with unsurpassed quality and style, specializing in compact-folding, lightweight wheelchairs for children of all ages - from toddlers to teens! Custom built to child's specific needs, mobility aids offer rehabilitative benefits for physical disabilities from Cerebral Palsy to Autism. Pediatric, or child wheelchairs, are mobile aids designed for and used by children. Children require the use of a wheelchair for many different reasons, some may have suffered head injuries, some have muscular dystrophy or cerebral palsy, some are amputees, and others only have an occasional use of their wheelchairs in lieu of a walking device or crutches. Certain types of pediatric wheelchairs are built to expand in size to accommodate increased bulk and weight by altering a cross balance on the bottom of the chair. The front frames for the legs can be lengthened as child's legs grow longer. For a pediatrician seeking to prescribe a Pediatric Wheelchair, must be sure that the patient has the proper upper body strength to use one. If the patient is too weak for self movement, the practitioner would be better to consider a powered wheelchair for mobility. While Pediatric Wheelchairs are smaller and can be just as manuverable as scooters, that depends upon the patient's own abilities in steering the chair. These are factors that the doctor must think about before recommending what type of wheelchair a patient should get. Pediatric Wheelchair with a body contouring S-Shaped seat frame and contoured armrests provides the user with all day comfort an
Nathan Goodyear

Saliva--a diagnostic window to the body, both in h... [J Med Life. 2009 Apr-Jun] - PubM... - 0 views

www.ncbi.nlm.nih.gov/...20108531

saliva testing salivary diagnostic

shared by Nathan Goodyear on 19 Jan 11 - No Cached
  • Saliva includes a large number of inorganic and organic compounds, which act as a "mirror of the body's health."
  • Nathan Goodyear on 19 Jan 11
     
    saliva testing is broad in its diagnostic potential
Nathan Goodyear

Mechanism of Human SIRT1 Activation by Resveratrol - 0 views

www.jbc.org/...17187.short

Resveratrol SIRT1

shared by Nathan Goodyear on 18 Mar 11 - No Cached
  • The NAD+-dependent protein deacetylase family, Sir2 (or sirtuins), is important for many cellular processes including gene silencing, regulation of p53, fatty acid metabolism, cell cycle regulation, and life span extension
  • resveratrol was shown to increase life span in three model organisms through a Sir2-dependent pathway.
  • Nathan Goodyear on 18 Mar 11
     
    Resveratrol potentially increases life span through SIRT1 activation
Nathan Goodyear

The intestine and its microflora are partners for the protection of the host: report on... - 0 views

www.ajcn.org/...675.abstract

microflora probiotics probiotic gut bacteria immune system health intesting

shared by Nathan Goodyear on 07 Sep 11 - No Cached
  • The intestine is the primary immune organ of the body represented by the gut-associated lymphoid tissue through innate and acquired immunity
  • Nathan Goodyear on 07 Sep 11
     
    The balance of our gut bacteria are critical to the health of our immune system and thus the health of the whole body
Nathan Goodyear

Exposure to volatile organic compounds and loss of pulmonary function in the elderly - 0 views

erj.ersjournals.com/...1270.abstract

volatile solvents benzene xylene toluene

shared by Nathan Goodyear on 14 Apr 11 - No Cached
  • is study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.
  • Nathan Goodyear on 14 Apr 11
     
    volatile solvents and lung damage
Nathan Goodyear

The multitude and diversity of environmental carci... [Environ Res. 2007] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...17692309

environmental carcinogens

shared by Nathan Goodyear on 28 Mar 11 - No Cached
  • Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved
  • Nathan Goodyear on 28 Mar 11
     
    diversity of environmental carcinogens
Nathan Goodyear

1210_article_14 - 0 views

jpp.krakow.pl/...14_article.html

neurotoxic thimerosal vaccinations

shared by Nathan Goodyear on 03 Apr 11 - No Cached
  • These modulatory effects - which most likely involve binding with functional thiol residues - are interwoven with neurotoxic actions of both mercurials.
  • THIM is metabolized in the body to ethyl mercury (EtHg) and subsequently to inorganic mercury forms, which accumulate in tissues of vital organs, including the brain (22). Information about neurochemical and neurotoxic effects of THIM is still limited, but the existing data indicate that in pharmacodynamics and toxicity THIM/EtHg does not differ significantly from methyl mercury (MeHg), which has been studied more extensively, although these compounds differ somewhat in pharmacokinetics (8).
  • Several studies documented that the neurotoxic effects of mercurials involve glutamate-mediated excitotoxicty, due to their ability to inhibit uptake of glutamate in astrocytes, resulting in an increase of the extracellular level of this excitatory amino acid
  • Nathan Goodyear on 03 Apr 11
     
    neurotoxic effects of thimerosal
Nathan Goodyear

Chemical toxins: a hypothesis to explain the globa... [J Altern Complement Med. 2002] -... - 0 views

www.ncbi.nlm.nih.gov/...12006126

chemical toxins obesity overweight

shared by Nathan Goodyear on 06 Apr 11 - No Cached
  • Because the obesity epidemic occurred relatively quickly, it has been suggested that environmental causes instead of genetic factors maybe largely responsible
  • exponential production and usage of synthetic organic and inorganic chemicals. Many of these chemicals are better known for causing weight loss at high levels of exposure but much lower concentrations of these same chemicals have powerful weight-promoting actions.
  • his paper presents a hypothesis that the current level of human exposure to these chemicals may have damaged many of the body's natural weight-control mechanisms. Furthermore, it is posited here that these effects, together with a wide range of additional, possibly synergistic, factors may play a significant role in the worldwide obesity epidemic.
  • Nathan Goodyear on 06 Apr 11
     
    Toxins as chemical cause of obesity problem?
Nathan Goodyear

Biological and health implications of toxic heavy ... [Prog Food Nutr Sci. 1987] - PubM... - 0 views

www.ncbi.nlm.nih.gov/...3303135

heavy metal toxicity

shared by Nathan Goodyear on 19 Apr 11 - No Cached
  • hey are cumulative poison, and are toxic even at low dose
  • These metals serve no biological function and their presence in tissues reflects contact of the organism with its environment
  • heavy metals cadmium, lead, and mercury are specially prevalent in nature due to their high industrial use
  • Nathan Goodyear on 19 Apr 11
     
    implications of heavy metal toxicity
Nathan Goodyear

Parent bisphenol A accumulation in the human mater... [Environ Health Perspect. 2002] -... - 0 views

www.ncbi.nlm.nih.gov/...12417499

BPA endocrine disurptor

shared by Nathan Goodyear on 01 Jul 11 - No Cached
  • Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring
  • BPA blood concentrations were higher in male than in female fetuses
  • Nathan Goodyear on 01 Jul 11
     
    Mother's exposure to toxic BPA passed to her child
tom cruze

Clinical Trial Data Management Ensuring regulation and accuracy of clinical trial data | - 0 views

blog.worksure.org/clinical-trial-data-management

Clinical Trial Data Management

shared by tom cruze on 25 Feb 15 - No Cached
  • tom cruze on 25 Feb 15
     
    The data management of a clinical trial is a crucial step for the firms that are undergoing research studies in the hospitals. Maintaining the quality and integrity of clinical data is yet another daring task to perform. Many of recent studies showed numerous troubles with data management system (DMS) in clinical trials performed at academic organizations.
Nathan Goodyear

PLOS ONE: Persistent Organic Pollutants and Early Menopause in U.S. Women - 0 views

journals.plos.org/...article

EDC endocrine disrupting chemicals women hormone hormones female xenoestrogens endocrine disruptors menopause

shared by Nathan Goodyear on 30 Jan 15 - No Cached
  • Nathan Goodyear on 30 Jan 15
     
    study identifies 15 Endocrine Disrupting Chemicals that lead to earlier Menopause.  Maybe we should change it to Chemopause.
Nathan Goodyear

Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocri... - 0 views

www.fasebj.org/...439.full

appetite orexigenic anorexigenic gherkin leptin

shared by Nathan Goodyear on 25 Oct 14 - No Cached
  • Nathan Goodyear on 25 Oct 14
     
    orexigenic versus anorexigenic signaling and control of appetite at the level of the hypothalamus.
Nathan Goodyear

High Prevalence of Chronic Pituitary and Target-Organ Hormone Abnormalities after Blast... - 0 views

www.ncbi.nlm.nih.gov/...PMC3273706

brain injury TBI traumatic brain injury PTHP post traumatic hypopituitarism low Testosterone T Testosterone hormones

shared by Nathan Goodyear on 20 Jan 16 - No Cached
  • Nathan Goodyear on 20 Jan 16
     
    The prevalence of post traumatic hypopituitarism post TBI sits at around 35%.  
Nathan Goodyear

The current state and future perspectives of cannabinoids in cancer biology - 0 views

www.ncbi.nlm.nih.gov/...PMC5852356

Cancer CBD THC cannabinoids

shared by Nathan Goodyear on 19 Sep 18 - No Cached
hoangkimchi liked it
  • The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
  • phytocannabinoids, endocannabinoids, and synthetic cannabinoids
  • Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
  • ...8 more annotations...
  • The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
  • concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
  • CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
  • endocannabinoid‐degrading enzymes are upregulated in cancer cell lines and in human tumors
  • Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
  • Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
  • CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity
  • process of autophagy is upstream of apoptosis in mechanism of cell death induced by cannabinoids
Nathan Goodyear

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4287931

ivermectin cancer WTF Selamectin

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • WNT signaling
  • early colon cancers commonly display loss of function of the tumor suppressor Adenomatous polyposis coli (APC), a key component of the β-CATENIN destruction complex
  • Other cancers also show an active canonical WNT pathway; these include carcinomas of the lung, stomach, cervix, endometrium, and lung as well as melanomas and gliomas
  • ...31 more annotations...
  • In normal embryogenesis and homeostasis, the canonical WNT pathway is activated by secreted WNT ligands produced in highly controlled context-dependent manners and in precise amounts. WNT activity is transduced in the cytoplasm, inactivates the APC destruction complex, and results in the translocation of activate β-CATENIN to the nucleus, where it cooperates with DNA-binding TCF/LEF factors to regulate WNT-TCF targets and the ensuing genomic response
  • beyond the loss of activity of the APC destruction complex, for instance throughAPC mutation, phosphorylation of β-CATENIN at C-terminal sites is required for the full activation of WNT-TCF signaling and the ensuing WNT-TCF responses in cancer.
  • The WNT-TCF response blockade that we describe for low doses of Ivermectin suggests an action independent to the deregulation of chloride channels
  • involve the repression of the levels of C-terminally phosphorylated β-CATENIN forms and of CYCLIN D1, a critical target that is an oncogene and positive cell cycle regulator.
  • the Avermectin single-molecule derivative Selamectin, a drug widely used in veterinarian medicine (Nolan & Lok, 2012), is ten times more potent acting in the nanomolar range
  • Ivermectin also diminished the protein levels of CYCLIN D1, a direct TCF target and oncogene, in both HT29 and H358 tumor cells
  • Activated Caspase3 was used as a marker of apoptosis by immunohistochemistry 48 h after drug treatment. Selamectin and Ivermectin induced up to a sevenfold increase in the number of activated Caspase3+ cells in two primary (CC14 and CC36) and two cell line (DLD1 and Ls174T) colon cancer cell types (Fig​(Fig2C).2C). All changes were significative
  • The strong downregulation of the expression of the intestinal stem cell genesASCL2 andLGR5 (van der Flieret al, 2009; Scheperset al, 2012; Zhuet al, 2012b) by Ivermectin and Selamectin (Fig​(Fig2D)2D) raised the possibility that these drugs could affect WNT-TCF-dependent colon cancer stem cell behavior
  • Pre-established H358 tumors responded to Ivermectin showing a ˜ 50% repression of growth
  • Ivermectin hasin vivo efficacy against human colon cancer xenografts sensitive to TCF inhibition with no discernable side effects
  • Ivermectin (Campbellet al, 1983), an off-patent drug approved for human use, and related macrocyclic lactones, have WNT-TCF pathway response blocking and anti-cancer activities
  • these drugs block WNT-TCF pathway responses, likely acting at the level of β-CATENIN/TCF function, affecting β-CATENIN phosphorylation status.
  • anti-WNT-TCF activities of Ivermectin and Selamectin
  • Ivermectin has a well-known anti-parasitic activity mediated via the deregulation of chloride channels, leading to paralysis and death (Hibbs & Gouaux, 2011; Lynagh & Lynch, 2012). The same mode of action has been suggested to underlie the toxicity of Ivermectin for liquid tumor cells and the potentiation or sensitization effect of Avermectin B1 on classical chemotherapeutics
  • the specificity of the blockade of WNT-TCF responses we document, at low micromolar doses for Ivermectin and low nanomolar doses for Selamectin, indicate that the blockade of WNT-TCF responses and chloride channel deregulation are distinct modes of action
  • What is key then is to find a dose and a context where the use of Ivermectin has beneficial effects in patients, paralleling our results with xenografts in mice.
  • Cell toxicity appears at doses greater (> 10 μM for 12 h or longer or > 5 μM for 48 h or longer for Ivermectin) than those required to block TCF responses and induce apoptosis.
  • Our data point to a repression of WNT-β-CATENIN/TCF transcriptional responses by Ivermectin, Selamectin and related macrocylic lactones.
  • (i) The ability of Avermectin B1 to inhibit the activation of WNT-TCF reporter activity by N-terminal mutant (APC-insensitive) β-CATENIN as detected in our screen
  • (ii) The ability of Avermectin B1, Ivermectin, Doramectin, Moxidectin and Selamectin to parallel the modulation of WNT-TCF targets by dnTCF
  • (iii) The finding that the specific WNT-TCF response blockade by low doses of Ivermectin and Selamectin is reversed by constitutively active TCF
  • (iv) The repression of key C-terminal phospho-isoforms of β-CATENIN resulting in the repression of the TCF target and positive cell cycle regulator CYCLIN D1 by Ivermectin and Selamectin
  • (v) The specific inhibition ofin-vivo-TCF-dependent, but notin-vivo-TCF-independent cancer cells by Ivermectin in xenografts.
  • These results together with the reduction of the expression of the colon cancer stem cell markersASCL2 andLGR5 (e.g., Hirschet al, 2013; Ziskinet al, 2013) raise the possibility of an inhibitory effect of Ivermectin, Selamectin and related macrocyclic lactones on TCF-dependent cancer stem cells.
  • the capacity of cancer cells to form 3D spheroids in culture, as well as the growth of these, is also WNT-TCF-dependent (Kanwaret al, 2010) and they were also affected by Ivermectin treatment
  • If Ivermectin is specific, it should only block TCF-dependent tumor growth. Indeed, the sensitivity and insensitivity of DLD1 and CC14 xenografts to Ivermectin treatment, respectively, together with the desensitization to Ivermectin actionin vivo by constitutively active TCF provide evidence of the specificity of this drug to block an activated WNT-TCF pathway in human cancer.
  • Ivermectin has a good safety profile since onlyin-vivo-dnTCF-sensitive cancer xenografts are responsive to Ivermectin treatment, and we have not detected side effects in Ivermectin-treated mice at the doses used
  • previous work has shown that side effects from systemic treatments with clinically relevant doses in humans are rare (Yang, 2012), that birth defects were not observed after exposure of pregnant mothers (Pacquéet al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet al, 2001; Orzechowskiet al, 2012)
  • Indications may include treatment for incurable β-CATENIN/TCF-dependent advanced and metastatic human tumors of the lung, colon, endometrium, and other organs.
  • Ivermectin, Selamectin, or related macrocyclic lactones could also serve as topical agents for WNT-TCF-dependent skin lesions and tumors such as basal cell carcinomas
  • they might also be useful as routine prophylactic agents, for instance against nascent TCF-dependent intestinal tumors in patients with familial polyposis and against nascent sporadic colon tumors in the general aging population
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin, a common anti-parasitic, found to inhibit WTF-TCF pathway and decrease c-terminal phosophorylaiton of Beta-CATENIN all resulting in increased aptosis and inhibition of cancer growth in colon cancer cell lines and lung cancer cell lines.
Nathan Goodyear

Growth Inhibition of Ovarian Tumor-Initiating Cells by Niclosamide | Molecular Cancer T... - 0 views

mct.aacrjournals.org/...1703.long

Niclosamide Tumor-initiation cells TIC ovarian cancer cancer CSC cancer stem cells

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Ovarian cancer is the most lethal gynecologic malignancy and the fifth-most cause of overall cancer death of women in developed countries
  • An increasingly accepted cancer stem cell hypothesis regards tumors as caricatures of normal organs, possessing a hierarchy of cell types, at various stages of aberrant differentiation, descended from precursor tumor-initiating cells (TIC) cells that are highly resistant to conventional cytotoxics
  • Significant changes of gene expression in 2,928 genes were identified after niclosamide treatment for different time periods
  • ...14 more annotations...
  • uncoupling of mitochondrial oxidative phosphorylation is believed to be its anti-helminthic mechanism of action
  • we hypothesized that niclosamides antagonistic effects on OTICs could, in part, be due to its disruption of metabolism
  • Our results showed that genes participating in protein complexes of oxidative phosphorylation were downregulated
  • niclosamide treatment resulted in a more than 20% increase in reactive oxygen species (ROS) in cultured OTICs
  • niclosamide, which has proved to be safe and effective for the past 2 decades against numerous parasites, inhibited OTIC growth both in vitro and in vivo
  • niclosamide represses metabolic enzymes responsible for bioenergetics, biosynthesis, and redox regulation specifically in OTICs, presumably leading to mitochondrial intrinsic apoptosis pathways, loss of tumor stemness, and growth inhibition
  • Niclosamide is believed to inhibit mitochondrial oxidative phosphorylation
  • Niclosamide was reported to inactivate NF-κB, causing mitochondrial damage and the generation of ROS, leading to apoptosis of leukemic stem cells
  • niclosamide were identified in a screen for mTOR-signaling inhibitors
  • mTOR was reported to maintain stemness properties of HSCs by inhibiting mitochondrial biogenesis and ROS levels (39), implying that mTOR inhibitors (such as niclosamide) may interfere with mitochondria and various metabolic pathways in TICs via disruption of antioxidant responses
  • We observed Wnt hyperactivity in OTICs, in agreement with previous hypotheses of Wnt inhibitor effectiveness as an ovarian cancer therapy
  • niclosamide has now been independently identified in screens for Wnt inhibitors
  • downregulation of the Wnt/β-catenin target oncogenes survivin and c-Myc
  • ovarian carcinogenesis, the cell-to-cell signaling pathway Notch (8), were also suppressed by niclosamide (data not shown). These results agree with another recent niclosamide study in leukemia (49), and it has been widely hypothesized that disruption of Notch signaling may represent a highly effective therapy for ovarian and other solid tumors, via its essentiality to maintaining TIC stemness
  • Nathan Goodyear on 16 Apr 18
     
    Niclosamide, common anti-parasitic medication, inhibits cellular metabolism and increases ROS; both of which provide powerful anti-proliferative, anti-cancer treatment mechanism in TICs. Powerful target therapy for cancer stem cells. Also shown to inhibit Wnt stimulated oncogenes survivin and c-Myc, disrupts Notch signaling, inactivates NF-kappaBeta, and inhibits mTOR-signaling.  This has been found in in vitro and in vivo studies.
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.
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