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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

Frontiers | Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic M... - 0 views

www.frontiersin.org/...full

press-pulse therapy hyperbaric ketogenic metabolic therapy cancer ketogenic diet Glioblastoma glioblastoma multiforme HBOT nutrition

shared by Nathan Goodyear on 01 Apr 18 - No Cached
  • The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
  • the greatest therapeutic benefit for patients (near 1.0)
  • The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
  • ...30 more annotations...
  • Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
  • Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
  • The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
  • A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
  • Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
  • therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
  • we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
  • EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
  • Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
  • HBOT to increase oxidative stress in the tumor cells
  • As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
  • Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
  • Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
  • KD (increased to 1,500 kcal/day at day 22
  • the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
  • Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
  • This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
  • Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
  • less than 20% of younger adults generally survive beyond 24 months
  • glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
  • Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
  • The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
  • Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
  • The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
  • These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
  • dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
    • Nathan Goodyear
      Nathan Goodyear on 21 May 18
       
      use mannitol instead
  • Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
  • Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
  • hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
  • The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism
  • Nathan Goodyear on 01 Apr 18
     
    Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.
Nathan Goodyear

Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic The... - 0 views

www.ncbi.nlm.nih.gov/...PMC5884883

glioblastoma glioblastoma multiforme "brain cancer" cancer ketogenic diet

shared by Nathan Goodyear on 23 Dec 18 - No Cached
  • Nathan Goodyear on 23 Dec 18
     
    Great case study of Glioblastoma
Nathan Goodyear

Corticosteroids compromise survival in glioblastoma in part through their elevation of ... - 0 views

academic.oup.com/...2715227

glioblastoma glioblastoma multiforme "brain cancer" cancer glucose

shared by Nathan Goodyear on 23 Dec 18 - No Cached
  • Nathan Goodyear on 23 Dec 18
     
    Corticosteroids elevate glucose in patients with glioblastomas, compromising treatment and shortening survival.
Nathan Goodyear

The anti‐hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ... - 0 views

embomolmed.embopress.org/...511

Glioblastoma glioblastoma multiforme hypertension prazosin cancer

shared by Nathan Goodyear on 14 May 18 - No Cached
  • glioblastoma‐initiating cells (GICs)
  • Nathan Goodyear on 14 May 18
     
    prazosin promotes apoptosis of gliobastoma-initiating cells in mouse model via Akt pathway.
Nathan Goodyear

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid... - 0 views

pubmed.ncbi.nlm.nih.gov/31600167

myeloid-derived suppressor cells glioblastoma multiforme metronomic chemotherapy low-dose chemotherapy MDSC glioblastoma

shared by Nathan Goodyear on 08 Nov 20 - No Cached
  • Nathan Goodyear on 08 Nov 20
     
    Low-dose, metronomic chemotherapy induces suppression of MDSCs in the TME in glioblastoma.
Nathan Goodyear

(PDF) Determination of the anti-glioblastoma effect of artesunate and its potential tar... - 0 views

www.researchgate.net/..._through_RNA-seq_data_analysis

Cancer glioblastoma artesunate N-acetylcysteine ar glioblastoma multiforme NAC

shared by Nathan Goodyear on 08 Jun 23 - No Cached
  • Nathan Goodyear on 08 Jun 23
     
    Interesting study here with positive effects in the treatment of glioblastoma with Artesunate. Interesting, the cytotoxic effects were countered by the administration of NAC.
Nathan Goodyear

Increasing incidence of glioblastoma multiforme and meningioma, and decreasing incidenc... - 0 views

www.ncbi.nlm.nih.gov/...PMC3263004

brain tumor tumors brain tumor meningioma glioblastoma multiforme Schwannoma australian study

shared by Nathan Goodyear on 05 Feb 13 - No Cached
  • Nathan Goodyear on 05 Feb 13
     
    Granted, this is an Australian study, but they found an increasing incidence of certain tumors: significant increase in glioblastoma multiforme in both men and women and increasing trends of meningioma's in men.  The good news, is they found a decreasing incidence of Schwannoma in women.
Nathan Goodyear

Glioblastoma Cells Require Glutamate Dehydrogenase to Survive Impairments of Glucose Me... - 0 views

cancerres.aacrjournals.org/...7986.full.pdf

cancer Glioblastoma EGCG glutamine glucose

shared by Nathan Goodyear on 29 Jun 13 - No Cached
  • Nathan Goodyear on 29 Jun 13
     
    This article describes how important glutamine is as an alternative energy source in Glioblastoma. Cancer is a substrate-level dependent energy production disease. If one disrupts glycolysis as a source of energy, then many cancers will use glutamine through glutaminolysis. The cancer cells will do this through glutamate dehydrogenase and glutamate production. This will increase alpha-ketoglutarate which will then feed the substrate-level phosphorylation through the TCA cycle. This study mentioned that EGCG is a way to naturally inhibit glutamate dehydrogenase.
Nathan Goodyear

Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibit... - 0 views

www.ncbi.nlm.nih.gov/...PMC5341871

Cancer artesunate temodar glioblastoma glioblastoma multiforme

shared by Nathan Goodyear on 19 Dec 18 - No Cached
  • Nathan Goodyear on 19 Dec 18
     
    Artesunate augments Temodar in animal model of glioblastoma.
Nathan Goodyear

Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human... - 0 views

jem.rupress.org/313

Hexokinase "hexokinase 2" "hexokinase II" glioblastoma cancer

shared by Nathan Goodyear on 19 Jan 19 - No Cached
  • Nathan Goodyear on 19 Jan 19
     
    to be read: hexokinase II and glioblastoma
Nathan Goodyear

Could Metabolic Therapy Become a Viable Alternative to the Standard of Care for Managin... - 0 views

www.touchoncology.com/...ard-care-managing-glioblastoma

cancer alternative cancer treatment cancer therapy cancer treatment

shared by Nathan Goodyear on 08 Feb 18 - No Cached
mamdouh_hfz liked it
  • Nathan Goodyear on 08 Feb 18
     
    review of the metabolic therapy of cancer as an alternative in the treatment of Glioblastoma.
Nathan Goodyear

Curcumin decreases malignant characteristics of glioblastoma stem cells via induction o... - 0 views

bmccancer.biomedcentral.com/...s12885-017-3058-2

STAT3 ROS MAPK curcumin glioblastoma multiforme

shared by Nathan Goodyear on 17 Apr 21 - No Cached
  • Nathan Goodyear on 17 Apr 21
     
    Curcumin increases ROS in glioblastoma.
Nathan Goodyear

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive ... - 0 views

www.pnas.org/...11105.full

IV vitamin C vitamin C ovarian cancer pancreatic cancer glioblastoma cancer

shared by Nathan Goodyear on 26 May 13 - Cached
  • Nathan Goodyear on 26 May 13
     
    high dose IV vitamin C shown to be treatment option in Cancer.  Granted in a mouse study, but high dose IV vitamin C shown to decrease growth rates of ovarian, pancreatic, and glioblastoma cancers.
Nathan Goodyear

Metabolic management of glioblastoma multiforme using standard therapy together with a ... - 0 views

www.ncbi.nlm.nih.gov/...PMC2874558

ketogenic ketogenic diet cancer ketones ketone bodies

shared by Nathan Goodyear on 17 Nov 16 - No Cached
  • Nathan Goodyear on 17 Nov 16
     
    case study highlights the use of a calorie restricted, ketogenic diet to augment glioblastoma multiforme.  In incomplete resection, at 2 months no brain tumor was visualized via PET and MRI.
Nathan Goodyear

Glutamate release promotes growth of malignant gli... [Nat Med. 2001] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...11533703

glutamate glutamic acid MSG cancer glioblastoma multiforme

shared by Nathan Goodyear on 10 Feb 11 - No Cached
  • Nathan Goodyear on 10 Feb 11
     
    some tumors, glioblastoma multiforme, secrete glutamate, which increases aggressive nature of cancer
Nathan Goodyear

British Journal of Cancer - A pilot clinical study of [Delta]9-tetrahydrocannabinol in ... - 0 views

www.nature.com/...6603236a.html

THC cannabinoids cancer Tetrahydrocannabinol CBD

shared by Nathan Goodyear on 15 Dec 14 - No Cached
  • Nathan Goodyear on 15 Dec 14
     
    Pilot study of THC for advanced, recurrent glioblastoma multiforme.  The infused THC appeared to be safe and provide some anti proliferative activity, but all patients died within 1 year.
Nathan Goodyear

A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma | Molecu... - 0 views

mct.aacrjournals.org/...90.long

cancer THC medical marijuana glioblastoma CBD

shared by Nathan Goodyear on 18 Sep 18 - No Cached
  • Δ9-Tetrahydrocannabinol (THC; Supplementary Fig. 1), the main active component of the hemp plant Cannabis sativa
  • CB1, abundantly expressed in the brain and at many peripheral sites
  • CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells
  • ...3 more annotations...
  • antitumoral agents
  • Aside from THC, C. sativa produces approximately 70 other cannabinoids, although, unlike THC, many of them exhibit little affinity for CB receptors (10, 20). Of interest, at least one of these components, namely, cannabinol (CBD; Supplementary Fig. 1), has been shown to reduce the growth of different types of tumor xenografts including gliomas
  • the combined administration of THC and CBD is being therapeutically explored (10, 20, 26), although its effects on the proliferation and survival of cancer cells have only been analyzed in vitro
  • Nathan Goodyear on 18 Sep 18
     
    THC found to augment chemotherapy in the glioblastoma cell culture study.
Nathan Goodyear

Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9771884

THC cancer glioblastoma medical marijuana

shared by Nathan Goodyear on 18 Sep 18 - No Cached
  • Nathan Goodyear on 18 Sep 18
     
    THC induces apoptosis of glioblastoma cells via CB1 receptor signaling.
Nathan Goodyear

https://www.spandidos-publications.com/ol/16/5/5813/download - 0 views

www.spandidos-publications.com/...download

Ozone cancer glioblastoma

shared by Nathan Goodyear on 02 Nov 18 - No Cached
  • Nathan Goodyear on 02 Nov 18
     
    Study finds that O2-O3 therapy can be useful as adjunct therapy in the treatment of Glioblastoma.
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