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Nathan Goodyear

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 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.
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

www.blogroll.net/article.php

Easy Handicap Life By Heavy Duty Wheelchair types of medical wheelchairs folding frame adjustable backrest adjustable rear wheel position Axle Plate Adjustments Double cross-brace

shared by wheelchairindia9 on 24 Apr 15 - No Cached
  • wheelchairindia9 on 24 Apr 15
     
    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

www.apsense.com/...-by-heavy-duty-wheelchair.html

Easy Handicap Life By Heavy Duty Wheelchair types of medical wheelchairs folding frame adjustable backrest adjustable rear wheel position Axle Plate Adjustments Double cross-brace

shared by wheelchairindia9 on 19 Apr 15 - No Cached
  • wheelchairindia9 on 19 Apr 15
     
    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
wheelchairindia9

Easy Handicap Life By Heavy Duty Wheelchair - 0 views

www.articlepoint.org/...-by-heavy-duty-wheelchair.aspx

Easy Handicap Life By Heavy Duty Wheelchair types of medical wheelchairs folding frame adjustable backrest adjustable rear wheel position Axle Plate Adjustments Double cross-brace

shared by wheelchairindia9 on 19 Apr 15 - No Cached
  • wheelchairindia9 on 19 Apr 15
     
    Mobility is an important part of human life. When an affordable wheelchair becomes necessary, for whatever reason, the circumstances are often not ideal. Purchasing an affordable wheelchair starts with knowing the patient and researching the types of wheelchairs available. It is a great resource on many different types of medical wheelchairs. Bariatric wheelchair, designed for users between 18 and 26 stone. It has a padded sling and backrest to ensure the comfort of the user, and the armrests can be removed to allow easy transfer into and out of the wheelchair. The Heavy User Wheelchair is self-propelled, giving the option to either push it, or have the user move themselves. The large rear wheels make the wheelchair well-suited to outdoor use, and allow the user to change the direction they face when in social situations. It has folding frame, so it is easy for storage and transport. Interchangeable frame components allow to grow and change the chairs width and depth. There are custom frame specifications available. Maximum option choices allow chair to be built to the individual's specifications. It has folding "lockout" cross-brace. Cross-brace locks to limit flex in the frame for more efficient propelling. Double cross-brace. Allows more strength and enables greater weight capacity. Wheelchair Bariatric has Adjustable back height. Ensures optimal positioning of backrest for stability and scapular movement. Stabilizer bar to minimize flex and provides a more efficient ride. Multiple footplate options ensure optimal positioning of lower extremities. Quick-release axle allows quick removal of rear wheels for easy transport. Adjustable Axle Plate Adjustments help to maximize stability and propulsion of the chair. Allows center of gravity adjustment for more efficient ride. Also makes it possible to adjust the rear frame height when it's necessary to change the caster wheels. Description: Attendant cable brake. 14" rear wheels. Detachable and washable cu
Nathan Goodyear

Smoldering multiple myeloma - 0 views

www.ncbi.nlm.nih.gov/...PMC4432003

smoldering myeloma multiple myeloma cancer

shared by Nathan Goodyear on 13 Mar 18 - No Cached
  • Nathan Goodyear on 13 Mar 18
     
    good review of smoldering multiple myeloma
Nathan Goodyear

Artesunate overcomes drug resistance in multiple myeloma by inducing mitochondrial stre... - 0 views

www.ncbi.nlm.nih.gov/...PMC4147310

multiple myeloma artesunate

shared by Nathan Goodyear on 31 Mar 20 - No Cached
  • Nathan Goodyear on 31 Mar 20
     
    Artesunate effective at stand alone therapy and adjunctive with chemotherapy in multiple myeloma. Intracellular Ferrous is required for effect. This was a cell culture study.
Nathan Goodyear

Estrogen Treatment in Multiple Sclerosis - 0 views

www.ncbi.nlm.nih.gov/...PMC2760629

Estriol estrogen MS multiple Sclerosis multiple sclerosis hormone hormones

shared by Nathan Goodyear on 19 Mar 14 - No Cached
  • Nathan Goodyear on 19 Mar 14
     
    Good review of the pathogenesis of MS and estrogen therapies effects on MS.  Particularly are the benefits seen with Estriol.
Nathan Goodyear

Immunomodulatory effects of Vitamin D in multiple sclerosis - 0 views

brain.oxfordjournals.org/...1146.long

Vitamin D MS multiple Sclerosis multiple sclerosis Th17 T reg T-reg

shared by Nathan Goodyear on 12 Aug 13 - No Cached
  • Nathan Goodyear on 12 Aug 13
     
    Vitamin D has an important immunomodulating role in MS.  Vitamin D increases Treg cells and decreases IL-6, but more importantly IL-17.
Nathan Goodyear

Understanding the Roles of the Kynurenine Pathway in Multiple Sclerosis Progression - 0 views

www.ncbi.nlm.nih.gov/...PMC3195238

kynurenate disordered tryptophan metabolism multiple Sclerosis multiple sclerosis MS

shared by Nathan Goodyear on 07 Jan 14 - No Cached
  • Nathan Goodyear on 07 Jan 14
     
    disordered tryptophan metabolism and MS
Nathan Goodyear

Treatment of multiple sclerosis with the pregnanc... [Ann Neurol. 2002] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...12325070

MS multiple sclerosis Estriol hormone hormones women multiple sclerosis

shared by Nathan Goodyear on 07 Jan 14 - No Cached
  • Nathan Goodyear on 07 Jan 14
     
    Estriol, the dominant estrogen in pregnancy shown to decrease MS symptoms.  When Estriol was stopped, MS lesions relapsed.  Estriol binds to ERbeta at a rate of 5:1 compared to ER alpha.
Nathan Goodyear

Sex hormones modulate brain damage in multiple sclerosis: MRI evidence - 0 views

www.ncbi.nlm.nih.gov/...PMC1739476

brain MS multiple sclerosis multiple sclerosis hormone hormones

shared by Nathan Goodyear on 07 Jan 14 - No Cached
  • Nathan Goodyear on 07 Jan 14
     
    Nice article that discusses the interaction between hormones, the immune system and MS in both women and men. Men with the highest aromatase activity shown to have the highest incidence of neurodamage.
Nathan Goodyear

Steroid hormones in multiple sclerosis. [J Neurol Sci. 2005] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15878598

MS multiple sclerosis multiple sclerosis hormone hormones pregnancy women Estriol E3 progesterone

shared by Nathan Goodyear on 07 Jan 14 - No Cached
  • Nathan Goodyear on 07 Jan 14
     
    Pregnancy has a positive effect on MS patients, especially during the 3rd trimester.  Rebound of MS increases in the postpartum period.  Estriol is the dominant pregnancy estrogen.  Progesterone is also produced at high levels.  The withdrawal of these hormones in the postpartum period are likely to lead to this rebound in MS.
Nathan Goodyear

Multiple sclerosis and pregnancy. [Neurol Clin. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15474765

multiple sclerosis multiple sclerosis pregnancy hormone hormones estriol E3 women

shared by Nathan Goodyear on 07 Jan 14 - No Cached
  • Nathan Goodyear on 07 Jan 14
     
    Pregnancy has a neutral to likely positive effect during pregnancy.  This is due to the high E3 production.
Nathan Goodyear

CORONARY ARTERY CALCIUM SCORE VERSUS A MULTIPLE BIOMARKER APPROACH FOR CORONARY HEART D... - 0 views

www.sciencedirect.com/...S0735109713608128

coronary artery calcium CAD CVD cardiovascular disease heart health risk homocysteine BNP

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Coronary artery calcium is positively associated with CAD risk.  It compares to multiple biomarker assessment, BNP, and homocysteine assessment.
Nathan Goodyear

Hypopituitarism After Multiple Concussions: A Retrospective Case Study in an Adolescent... - 0 views

www.ncbi.nlm.nih.gov/...PMC1978466

concussions concussion head trauma men male hypopituitarism hormone hormones

shared by Nathan Goodyear on 30 Jul 14 - No Cached
  • Nathan Goodyear on 30 Jul 14
     
    multiple concussions result in hypopituitarism in 14 year old young man.
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
fnfdoc

COPD: Stages, Causes, Symptoms And Treatment - Health Blog - 0 views

fnfdoc.com/...ages-causes-symptoms-treatment

Alpha-1 Antitrypsin Deficiency COPD Causes Stages Symptoms Treatment Lung Disease

shared by fnfdoc on 16 Feb 19 - No Cached
  • fnfdoc on 16 Feb 19
     
    COPD consists of multiple lung infections and is considered incurable by most physicians. Can timely diagnosis, on the bright side, slow down its progress?
  • fnfdoc on 16 Feb 19
     
    COPD consists of multiple lung infections and is considered incurable by most physicians. Can timely diagnosis, on the bright side, slow down its progress?
Nathan Goodyear

Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expec... - 0 views

www.nature.com/ja201711

Ivermectin cancer

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • The avermectins are known to possess pronounced antitumor activity
  • Over the past few years, there have been steadily increasing reports that ivermectin may have varying uses as an anti-cancer agent, as it has been shown to exhibit both anti-cancer and anti-cancer stem cell properties
  • In human ovarian cancer and NF2 tumor cell lines, high-dose ivermectin inactivates protein kinase PAK1 and blocks PAK1-dependent growth
  • ...13 more annotations...
  • PAK1 is essential for the growth of more than 70% of all human cancers, including breast, prostate, pancreatic, colon, gastric, lung, cervical and thyroid cancers, as well as hepatoma, glioma, melanoma, multiple myeloma and for neurofibromatosis tumors
  • Ivermectin suppresses breast cancer by activating cytostatic autophagy, disrupting cellular signaling in the process, probably by reducing PAK1 expression
  • Cancer stem cells are a key factor in cancer cells developing resistance to chemotherapies and these results indicate that a combination of chemotherapy agents plus ivermectin could potentially target and kill cancer stem cells, a paramount goal in overcoming cancer
  • Triple-negative breast cancers, which lack estrogen, progesterone and HER2 receptors, account for 10–20% of breast cancers and are associated with poor prognosis
  • Ivermectin addition led to transcriptional modulation of genes associated with epithelial–mesenchymal transition and maintenance of a cancer stem cell phenotype in triple-negative breast cancers cells, resulting in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo
  • ivermectin synergizes with the chemotherapy agents cytarabine and daunorubicin to induce cell death in leukemia cells
  • Ivermectin-induced cytostatic autophagy also leads to suppression of tumor growth in breast cancer xenografts, causing researchers to believe there is scope for using ivermectin to inhibit breast cancer cell proliferation and that the drug is a potential treatment for breast cancer
  • Ivermectin inhibits proliferation and increases apoptosis of various human cancers
  • Activation of WNT-TCF signaling is implicated in multiple diseases, including cancers of the lungs and intestine,
  • A new screening system has found that ivermectin inhibits the expression of WNT-TCF targets
  • It represses the levels of C-terminal β-catenin phosphoforms and of cyclin D1 in an okadaic acid-sensitive manner, indicating its action involves protein phosphatases
  • In vivo, ivermectin selectively inhibits TCF-dependent, but not TCF-independent, xenograft growth without side effects
  • ivermectin has an exemplary safety record, it could swiftly become a useful tool as a WNT-TCF pathway response blocker to treat WNT-TCF-dependent diseases, encompassing multiple cancers.117
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin shows promise and usefullness in several cancer types.  This is a review article.
Nathan Goodyear

Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking m... - 0 views

www.ncbi.nlm.nih.gov/...PMC3777479

Niclosamide cancer NF-kappaB Wnt ROS mTOR

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Accumulating evidence suggests that niclosamide targets multiple signaling pathways such as nuclear factor-kappaB (NF-kB), Wnt/β-catenin, and Notch, most of which are closely involved with cancer stem cell proliferation
  • The transcription factor NF-κB has been demonstrated to promote cancer growth, angiogenesis, escape from apoptosis, and tumorigenesis
  • NF-κB is sequestered in the cytosol of resting cells through binding the inhibitory subunit IκBα
  • ...13 more annotations...
  • Niclosamide blocked TNFα-induced IκBα phosphorylation, translocation of p65, and the expression of NF-κB-regulated genes
  • Niclosamide also inhibited the DNA binding of NF-κB to the promoter of its target genes
  • niclosamide has two independent effects: NF-kB activation and ROS elevation
  • The Wnt signaling pathway plays fundamental roles in directing tissue patterning in embryonic development, in maintaining tissue homeostasis in differentiated tissue, and in tumorigenesis
  • niclosamide is a potent inhibitor of the Wnt/β-catenin pathway
  • The Notch signaling pathway plays important roles in a variety of cellular processes such as proliferation, differentiation, apoptosis, cell fate decisions, and maintenance of stem cells
  • niclosamide potently suppresses the luciferase activity of a CBF-1-dependent reporter gene in both a dose-dependent and a time-dependent manners in K562 leukemia cells
  • niclosamide treatment abrogated the epidermal growth factor (EGF)-stimulated dimerization and nuclear translocation and transcriptional activity of Stat3, and induced cell growth inhibition and apoptosis in several types of cancer cells (e.g. Du145, Hela, A549) that exhibit relatively higher levels of Stat3 constitutive activation
  • niclosamide can rapidly increase autophagosome formation
  • niclosamide induced autophagy and inhibited mammalian target of rapamycin complex 1 (mTORC1)
  • Niclosamide has low toxicity in mammals (oral median lethal dose in rats >5000 mg/kg
  • Niclosamide is active against cancer cells such as AML and colorectal cancer cells, not only as a monotherapy but also as part of combination therapy, in which it has been found to be synergistic with frontline chemotherapeutic agents (e.g., oxaliplatin, cytarabine, etoposide, and daunorubicin)
  • Because niclosamide targets multiple signaling pathways (e.g., NF-κB, Wnt/β-catenin, and Notch), most of which are closely involved with cancer stem cells, it holds promise in eradicating cancer stem cells
  • Nathan Goodyear on 16 Apr 18
     
    Review article: common anti-parasitic medication, niclosamide, provides anti-proliferative effect in cancer stem cells (CSC), via inhibition of NF-kappaBeta, Wnt/B-catenin, Notch, ROS, mTORC1, and STAT2 pathways.
Nathan Goodyear

Discovering the Meaning of Monoclonal Gammopathy of Undetermined Significance: Current ... - 0 views

www.ncbi.nlm.nih.gov/...PMC4000459

MGUS monoclonal gammopathy of undetermined significance multiple myeloma smoldering myeloma

shared by Nathan Goodyear on 25 Sep 17 - No Cached
  • Nathan Goodyear on 25 Sep 17
     
    Good, up to date, review of the MGUS and the timeline to multiple myeloma.  
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