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umar111

Computer Science: Computer hardware - 0 views

computersciencetopper.blogspot.com/...computer-hardware.html

Best computer computer computer Science it blog

shared by umar111 on 26 Apr 23 - No Cached
  • umar111 on 26 Apr 23
     
    Computer Science Tuesday, April 25, 2023 Computer hardware Computer hardware is the physical components that make up a computer system. It includes everything from the central processing unit (CPU) to the monitor, keyboard, and mouse. Understanding the different types of hardware and how they work together is essential for anyone who works with computers. In this article, we will explore the various components of computer hardware, including internal and external components, and the peripherals that connect to them. We will also discuss the importance of hardware maintenance, the latest advancements in computer technology, and factors to consider when choosing the right hardware for your needs. Whether you are a computer technician, a gamer, or simply someone who uses a computer for everyday tasks, this article will help you better understand the world of computer hardware. Introduction to Computer Hardware Computer hardware refers to the physical components that make up a computer system. It includes everything from the processor and memory to input/output devices such as the keyboard and monitor. In this article, we will explore the different types of computer hardware and their functions. What is Computer Hardware Computer hardware refers to the physical components of a computer system. It includes all the components that can be touched, seen, and used to interact with a computer, such as the monitor, keyboard, and mouse. Hardware is different from computer software, which refers to the programs and applications that run on a computer system. History of Computer Hardware The history of computer hardware dates back to the 1820s when Charles Babbage, an English mathematician, and inventor, designed the first analytical engine, which was considered to be the first mechanical computer. With time, more complex electronic computers were developed, including the first Intel microprocessor in 1971. Since then, computer hardware has continued to evolve, becoming
Nathan Goodyear

BMC Cancer | Full text | Activity and expression of progesterone metabolizing... - 0 views

www.biomedcentral.com/...9

breast cancer progesterone metabolites progesterone metabolites hormone hormones

shared by Nathan Goodyear on 18 Jun 14 - No Cached
  • Nathan Goodyear on 18 Jun 14
     
    Might the enzymes be more important than the hormones themselves?  The number is important i.e. progesterone, but how the number came to be is more important as it points to the underlying etiology.  Here, the balance of enzymes are found to direct cell line tumor potential.  The enzyme 5alpha-reductase increased production of the 5alpha-pregnanes which increased tumor potential.  In contrast, the enzymes 20alpha-hydrosteroid oxidoreductase and 3alpha-hydroxysteroid oxidoreductase increase production of the 4alpha-pregnanes, which decreased tumor potential.
Nathan Goodyear

Stuck at the bench: Potential natural neuroprotective compounds for concussion - 0 views

www.ncbi.nlm.nih.gov/...PMC3205506

concussions concussion natural therapies brain curcumin omega 3 resveratrol green tea EGCG EPA DHA vitamin E vitamin c vitamin D

shared by Nathan Goodyear on 20 Feb 16 - No Cached
  • Long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are highly enriched in neuronal synaptosomal plasma membranes and vesicles
  • The predominant CNS polyunsaturated fatty acid is DHA
  • effective supplementation and/or increased ingestion of dietary sources rich in EPA and DHA, such as cold-water fish species and fish oil, may help improve a multitude of neuronal functions, including long-term potentiation and cognition.
  • ...45 more annotations...
  • multiple preclinical studies have suggested that DHA and/or EPA supplementation may have potential benefit through a multitude of diverse, but complementary mechanisms
  • pre-injury dietary supplementation with fish oil effectively reduces post-traumatic elevations in protein oxidation
  • The benefits of pre-traumatic DHA supplementation have not only been independently confirmed,[150] but DHA supplementation has been shown to significantly reduce the number of swollen, disconnected and injured axons when administered following traumatic brain injury.
  • DHA has provided neuroprotection in experimental models of both focal and diffuse traumatic brain injury
  • potential mechanisms of neuroprotection, in addition to DHA and EPA's well-established anti-oxidant and anti-inflammatory properties
  • Despite abundant laboratory evidence supporting its neuroprotective effects in experimental models, the role of dietary DHA and/or EPA supplementation in human neurological diseases remains uncertain
  • Several population-based, observational studies have suggested that increased dietary fish and/or omega-3 polyunsaturated fatty acid consumption may reduce risk for ischemic stroke in several populations
  • Randomized control trials have also demonstrated significant reductions in ischemic stroke recurrence,[217] relative risk for ischemic stroke,[2] and reduced incidence of both symptomatic vasospasm and mortality following subarachnoid hemorrhage
  • Clinical trials in Alzheimer's disease have also been largely ineffective
  • The clinical evidence thus far appears equivocal
  • curcumin has gained much attention from Western researchers for its potential therapeutic benefits in large part due to its potent anti-oxidant[128,194,236] and anti-inflammatory properties
  • Curcumin is highly lipophilic and crosses the blood-brain barrier enabling it to exert a multitude of different established neuroprotective effects
  • in the context of TBI, a series of preclinical studies have suggested that pre-traumatic and post-traumatic curcumin supplementation may bolster the brain's resilience to injury and serve as a valuable therapeutic option
  • Curcumin may confer significant neuroprotection because of its ability to act on multiple deleterious post-traumatic, molecular cascades
  • studies demonstrated that both pre- and post-traumatic curcumin administration resulted in a significant reduction of neuroinflammation via inhibition of the pro-inflammatory molecules interleukin 1β and nuclear factor kappa B (NFκB)
  • no human studies have been conducted with respect to the effects of curcumin administration on the treatment of TBI, subarachnoid or intracranial hemorrhage, epilepsy or stroke
  • studies have demonstrated that resveratrol treatment reduces brain edema and lesion volume, as well as improves neurobehavioral functional performance following TBI
  • green tea consumption or supplementation with its derivatives may bolster cognitive function acutely and may slow cognitive decline
  • At least one population based study, though, did demonstrate that increased green tea consumption was associated with a reduced risk for Parkinson's disease independent of total caffeine intake
  • a randomized, placebo-controlled trial demonstrated that administration of green tea extract and L-theanine, over 16 weeks of treatment, improved indices of memory and brain theta wave activity on electroencephalography, suggesting greater cognitive alertness
  • Other animal studies have also demonstrated that theanine, another important component of green tea extract, exerts a multitude of neuroprotective benefits in experimental models of ischemic stroke,[63,97] Alzheimer's disease,[109] and Parkinson's disease
  • Theanine, like EGCG, contains multiple mechanisms of neuroprotective action including protection from excitotoxic injury[97] and inhibition of inflammation
  • potent anti-oxidant EGCG which is capable of crossing the blood-nerve and blood-brain barrier,
  • Epigallocatechin-3-gallate also displays neuroprotective properties
  • More recent research has suggested that vitamin D supplementation and the prevention of vitamin D deficiency may serve valuable roles in the treatment of TBI and may represents an important and necessary neuroprotective adjuvant for post-TBI progesterone therapy
  • Progesterone is one of the few agents to demonstrate significant reductions in mortality following TBI in human patients in preliminary trials
  • in vitro and in vivo studies have suggested that vitamin D supplementation with progesterone administration may significantly enhance neuroprotection
  • Vitamin D deficiency may increase inflammatory damage and behavioral impairment following experimental injury and attenuate the protective effects of post-traumatic progesterone treatment.[37]
  • emerging evidence has suggested that daily intravenous administration of vitamin E following TBI significantly decreases mortality and improves patient outcomes
  • high dose vitamin C administration following injury stabilized or reduced peri-lesional edema and infarction in the majority of patients receiving post-injury treatment
  • it has been speculated that combined vitamin C and E therapy may potentiate CNS anti-oxidation and act synergistically with regards to neuroprotection
  • one prospective human study has found that combined intake of vitamin C and E displays significant treatment interaction and reduces the risk of stroke
  • Pycnogenol has demonstrated the ability to slow or reduce the pathological processes associated with Alzheimer's disease
  • Pcynogenol administration, in a clinical study of elderly patients, led to improved cognition and reductions in markers of lipid peroxidase
  • One other point of consideration is that in neurodegenerative disease states like Alzheimer's disease and Parkinson's disease, where there are high levels of reactive oxygen species generation, vitamin E can tend to become oxidized itself. For maximal effectiveness and to maintain its anti-oxidant capacity, vitamin E must be given in conjunction with other anti-oxidants like vitamin C or flavonoids
  • These various factors might account for the null effects of alpha-tocopherol supplementation in patients with MCI and Alzheimer's disease
  • preliminary results obtained in a pediatric population have suggested that post-traumatic oral creatine administration (0.4 g/kg) given within four hours of traumatic brain injury and then daily thereafter, may improve both acute and long-term outcomes
  • Acutely, post-traumatic creatine administration seemed to reduce duration of post-traumatic amnesia, length of time spent in the intensive care unit, and duration of intubation
  • At three and six months post-injury, subjects in the creatine treatment group demonstrated improvement on indices of self care, communication abilities, locomotion, sociability, personality or behavior and cognitive function when compared to untreated controls
  • patients in the creatine-treatment group were less likely to experience headaches, dizziness and fatigue over six months of follow-up
  • CNS creatine is derived from both its local biosynthesis from the essential amino acids methionine, glycine and arginine
  • Studies of patients with CNS creatine deficiency and/or murine models with genetic ablation of creatine kinase have consistently demonstrated significant neurological impairment in the absence of proper creatine, phosphocreatine, or creatine kinase function; thus highlighting its functional importance
  • chronic dosing may partially reverse neurological impairments in human CNS creatine deficiency syndromes
  • Several studies have suggested that creatine supplementation may also reduce oxidative DNA damage and brain glutamate levels in Huntington disease patients
  • Another study highlighted that creatine supplementation marginally improved indices of mood and reduced the need for increased dopaminergic therapy in patients with Parkinson's disease
  • Nathan Goodyear on 20 Feb 16
     
    great review of natural therapies in the treatment of concussions
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

Membrane 5α-pregnane-3,20-dione (5αP) receptors in MCF-7 and MCF-10A breast c... - 0 views

www.sciencedirect.com/...S0960076005003420

breast cancer progesterone metabolites progesterone metabolites hormone hormones

shared by Nathan Goodyear on 18 Jun 14 - No Cached
  • Nathan Goodyear on 18 Jun 14
     
    Very interesting study.  In ER/PR + breast cancer cells, Estradiol and 5alpha-dihydroprogestorone increase the membrane expression of 5alpha-dihydroprogesterone receptors.  This has a pro-growth, pro-metastatic potential.  In contrast, the metabolites 3alpha-dihdroprogesterone and 20alpha-HP inhibit the same membrane receptor expression thus giving an antigrowth, anti-metastatic potential.
Nathan Goodyear

Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically Inhibits Tumo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6064950

cancer vitamin C ascorbic acid colorectal cancer

shared by Nathan Goodyear on 26 Mar 22 - No Cached
  • therapeutic potential has been supported by a large and consistent body of evidences from in vitro
  • Ascorbic acid might act as a way to deliver hydrogen peroxide (H2O2) to the tissues
  • pharmacological concentrations of AA were capable of inducing anti-proliferative, cytotoxic and genotoxic effects
  • ...12 more annotations...
  • chemosensitizing
  • pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect
  • synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.
  • chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer
  • intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients
  • AA reinforced the anti-proliferative activity of 5-FU
  • Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect
  • cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.
  • association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions
  • AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm
    • Nathan Goodyear
      Nathan Goodyear on 26 Mar 22
       
      Apoptosis -> decrease in mitochondrial membrane potential
  • Previous results obtained by our group showed that AA mediates reactive oxygen species (ROS) formation capable of irreparably damaging DNA
  • oxidative role of AA may be a key factor on the synergistic anti-cancer mechanism
Nathan Goodyear

The telomerase activator TA-65 elongates short telomeres and increases health span of a... - 0 views

www.ncbi.nlm.nih.gov/...PMC3627294

TA-65 telomere Telomerase telomerase activator aging natural wellness health

shared by Nathan Goodyear on 16 May 16 - No Cached
  • studies have demonstrated that the shortest telomeres are causal of reduced cell viability
  • a stable and enforced expression of telomerase leads to an improved health-span, accompanied by an extension of lifespan
  • TA-65 influences the percentage of cellular short telomeres through the activation of telomerase
  • ...17 more annotations...
  • TA-65 administration during 4 months significantly improved the capacity to uptake glucose after a glucose pulse
  • liver protective action of TA-65
  • A disadvantage of mTERT potentiation could be associated to its capacity to favor proliferation of cancerous cells in murine models
  • TA-65 treated mice presented a similar incidence of malignant cancers at time of death, with a tendency to show decreased sarcomas and slightly increased lymphomas
  • We demonstrate here that TA-65 leads to a significant rescue of short telomeres through telomerase activation
  • TA-65 treatment increases proliferation and mobilization potential of mouse keratinocytes in vitro, a situation mimicking telomerase overexpression
  • TAT2, a similar molecule, have beneficial effects in the activation of CD8+ T lymphocytes from HIV-infected patients where they observe an increase of the proliferative potential and enhancement of cytokine/chemokine production
  • TA-65 resulted in a similar rescue of short telomeres in leukocytes post-treatment as observed with humans, most likely through an activation of telomerase
  • we observe that TA-65 lead to 10 fold increase of telomerase RNA levels in the liver of treated mice comparing to the non-treated same-age cohorts
  • TA-65 regulates telomerase at the transcription level, probably through the regulation of the MAPK pathway
  • TA-65 dependent telomerase activation results in a better organ fitness as demonstrated by the improved scores at the glucose tolerance test and insulin levels at fasting
  • TA-65 supplemented mice also present modest enhancement of the subcutaneous and epidermal thickness, as well as higher bone density, representative of an overall fitness status improvemen
  • TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts
  • improved health-span of TA-65 treated mice is not accompanied by increased cancer incidence, which may be related to the fact that TERT levels are very modestly increased in all tissues tested except for the liver
  • systemic telomerase overexpression from the germline leads to protection from aging associated pathologies
  • similar situation could be mimicked expressing telomerase late in life in a telomerase deficient background
  • we observed a higher proliferation rate and a partial protection from cell death in some tissues of TA65 treated mice
  • Nathan Goodyear on 16 May 16
     
    TA-65 shown to increase telomerase activity, and thus telomere length of short telomeres, in mouse study.  
Nathan Goodyear

Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among P... - 0 views

cancerres.aacrjournals.org/...696.full

estrogen metabolites estrogen metabolism ER estrogen receptors ROS hormones cancer breast cancer

shared by Nathan Goodyear on 07 Oct 15 - No Cached
  • both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
  • 2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
  • While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
  • ...15 more annotations...
  • 4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
  • In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
  • Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
  • a significant inverse association with the ratio of parent estrogens to estrogen metabolites
  • several potentially estrogenic and genotoxic mechanisms
  • Estrogen metabolites also can be genotoxic
  • Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
  • the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
  • 2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
  • act independently from the ER
  • 16α-Hydroxyestrone also may be genotoxic
  • While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
  • The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
  • the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
  • Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
  • Nathan Goodyear on 07 Oct 15
     
    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

Estrogenic Potential of Progestins in Oral Contraceptives to Stimulate Human Breast Can... - 0 views

cancerres.aacrjournals.org/...6539.full.pdf+html

progestins birth controls hormones oral contraceptives

shared by Nathan Goodyear on 04 Nov 10 - No Cached
  • Nathan Goodyear on 04 Nov 10
     
    Estrogenic Potential of Progestins in Oral Contraceptives to Stimulate Human Breast Cancer Cell Proliferation1
Nathan Goodyear

Obesity, Inflammation, and the Potential Application of Pharmaconutrition - 0 views

ncp.sagepub.com/...16.short

obesity inflammation pharmaconutrition

shared by Nathan Goodyear on 06 Jun 11 - No Cached
  • Obesity creates a low-grade systemic inflammatory response syndrome (SIRS) that is similar (but on a much smaller scale) to gram-negative sepsis.
  • Nathan Goodyear on 06 Jun 11
     
    Obesity, Inflammation, and the Potential Application of Pharmaconutrition
Nathan Goodyear

Letrozole Significantly Improves Growth Potential in a Pubertal Boy With Growth Hormone... - 0 views

pediatrics.aappublications.org/...e245.full

Letrozole HGH deficiency growth plate aromatase inhibition stature

shared by Nathan Goodyear on 13 Sep 11 - No Cached
  • Nathan Goodyear on 13 Sep 11
     
    Letrazole improves growth potential in boys with HGH deficiency through aromatase inhibition and delayed closure of the growth plates
Nathan Goodyear

Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorou... - 0 views

journals.sagepub.com/...1010428317702901

IPT insulin potentiated therapy cancer

shared by Nathan Goodyear on 02 Oct 18 - No Cached
  • Nathan Goodyear on 02 Oct 18
     
    Study finds that insulin potentiates chemo cytotoxic therapy in MCF-7 breast cancer cell lines.
Nathan Goodyear

Non-toxic potentiation of cancer chemotherapy b... [Int J Cancer. 1987] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...3666992

IV vitamin C IV vitamin K3 vitamin C K K3 chemotherapy vitamin C vitamin K3

shared by Nathan Goodyear on 16 Oct 13 - No Cached
  • Nathan Goodyear on 16 Oct 13
     
    IV vitamin C and K3 induces cancer cell death through production of H2O2 in catalase deficient cancer cells.  Pretreament shown to potentiate traditional chemotherapy.
Nathan Goodyear

Anticancer Effects of Niclosamide in Human Glioblastoma | Clinical Cancer Research - 0 views

clincancerres.aacrjournals.org/...4124.long

Niclosamide cancer Glioblastoma glioblastoma multiforme NOTCH mTOR Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • glioblastoma remains a fatal disease with a median overall survival time of only 15 months
  • inter- and intrapatient tumor heterogeneity
  • cellular and genetic diversity that characterizes glioblastoma
  • ...5 more annotations...
  • This broad effect could be a result of niclosamide's pleiotropic activity, similarly affecting signaling pathways that are known to be overly active in human malignant cells (i.e., mTOR, NOTCH, WNT/CTNNB1; refs. 44–46)
  • It is a salicylanilide that was introduced as a molluscide in 1959
  • Studies in animals suggested no mutagenic, oncogenic, or embryotoxic activity and no cumulative effects
  • its rate of absorption from the intestinal tract was estimated at only 33%
  • the potential mechanism of synergy between temozolomide and niclosamide as a “natural inducer” of NFKBIA
  • Nathan Goodyear on 16 Apr 18
     
    Niclosamide pilot animal study useful in the treatment of Glioblastoma.  Found to inhibit NOTCH, mTOR, and WNT and cancer signaling. Also found to reduce the malignant potential through cytostatic, cytotoxic and antimigratory effects of niclosamide on GBM
Nathan Goodyear

Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views

www.oncotarget.com/index.php

vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural

shared by Nathan Goodyear on 08 Dec 17 - No Cached
  • Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs
  • Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
  • ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
  • ...26 more annotations...
  • mitochondrial biogenesis may be a key driver of the CSC phenotype
  • Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
  • high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
  • CSCs may be strictly dependent on NAD(P)H to maintain their enhanced mitochondrial function
  • an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
  • Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
  • we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
  • silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
  • caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
  • Propolis has a strong history of medicinal use, dating back more than 2,000 years
  • Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
  • CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
  • CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
  • CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
  • Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
  • We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
  • high NADH is a property that is conserved between normal and cancerous stem cells
  • Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
  • CSCs may be strictly dependent on NADH to maintain their enhanced mitochondrial function
  • The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
  • Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
  • Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
  • Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
  • Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
  • CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
  • we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
  • Nathan Goodyear on 08 Dec 17
     
    The future of cancer therapy is cancer stem cells.  Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells.  Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs.  The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.
Nathan Goodyear

Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence - 0 views

www.ncbi.nlm.nih.gov/...PMC6037948

vitamin C epigenetics GLUT HIF-1alpha cancer IV vitamin C SVCT

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    Great review of the many different potential mechanisms of action of vitamin C in the the treatment of cancer.
Nathan Goodyear

The Potential Role of Hypoxia Inducible Factor 1α in Tumor Progression after ... - 0 views

cancerres.aacrjournals.org/...5496.long

cancer cisplatin hypoxia HIF-1alpha metastasis

shared by Nathan Goodyear on 08 Jul 20 - No Cached
  • Nathan Goodyear on 08 Jul 20
     
    Cisplatin increases HIF-1alpha VEGF which increases metastatic potential.
Nathan Goodyear

Low-Dose Chemotherapy with Insulin (Insulin Potentiation Therapy) in Combination with H... - 0 views

www.ncbi.nlm.nih.gov/...PMC3357525

prostate cancer IPTLD low-dose chemotherapy cancer chemotherapy insulin potentiation therapy LDMC low-dose metronomic chemotherapy IPT

shared by Nathan Goodyear on 25 Jan 18 - No Cached
  • The method of insulin potentiation therapy was empirically invented in 1930 from Mexican doctor D. Perez Garsia
  • increases the permeability of cell membrane
  • influences the metabolic processes in human body with the increase of the regenerating processes
  • ...9 more annotations...
  • facilitates the transport of intra and extra cellular liquids which helps the organism to eliminate the toxic products
  • The increased number of insulin receptors on the tumor cell, in comparison to the normal one, allows the before mentioned 2 factors to act predominantly
  • Increased permeability after the insulin effect on the cellular membrane results in increased intracellular quantity of antitumor agents
  • have other endocrine effects: directly stimulates suprarenal gland to produce epinephrine and glucocorticoid hormones and stimulates ACTH secretion. These endocrine effects also have a positive influence on the regenerating processes
  • Insulin influences the intracellular metabolism of the tumor cell, which leads to increase of the number of cells in phase S, where they are with highly sensitive to specific chemotherapeutics.
  • After the first 6 IPT applications overall (groups A and B) response to treatment on PSA criteria shows partial effect and stabilization in 12 of 16 (75%) patients
  • After the 10th IPTLD application or 3 months after starting treatment, complete response, partial response, and stabilization were observed in 4 of 9 (66.6%), while in 3 of 9 (33.3%) was registered complete effect
  • the advanced stage of disease in patients treated
  • Quality of life after the second IPTLD application is significantly improved
  • Nathan Goodyear on 25 Jan 18
     
    IPT found to be effextive in treated castrate-resistant prostate cancer.
Nathan Goodyear

Low-dose naltrexone (LDN): Tricking the body to heal itself - 0 views

www.sciencedaily.com/...110902133047.htm

low dose naltrexone LND opioid growth factor OGF inflammation cancer low dose naltrexone opioid growth factor

shared by Nathan Goodyear on 27 Nov 12 - No Cached
  • Nathan Goodyear on 27 Nov 12
     
    synopsis of a previously posted article on LDN and OGF in the potential use in cancer.
Nathan Goodyear

A role for estrogen receptor β in the regulation of growth of the ventral pro... - 0 views

www.ncbi.nlm.nih.gov/...PMC33468

estrogen receptor estrogen receptor ER-beta beta prostate cancer BPH

shared by Nathan Goodyear on 23 Nov 12 - No Cached
  • Nathan Goodyear on 23 Nov 12
     
    Estrogen receptor beta shown to be a potential site of application of therapy to treat BPH and prostate cancer.  
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