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Nathan Goodyear

Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasi... - 0 views

www.cell.com/...S1550-4131(17)30570-3

cancer breast cancer epigenetics obesity menopause

shared by Nathan Goodyear on 25 Oct 17 - No Cached
  • Nathan Goodyear on 25 Oct 17
     
    Just abstract available here.  Obesity in menopause is associated with 20-40% increased risk of breast cancer. Obesity also increases risk of metastasis and recurrence.  This new study suggests, one mechanism is via the phosphorylation of the acetyl-CoA carboxylase enzyme.  In part, epigenetics plays a role.
Nathan Goodyear

Influence of complications following immediate breast reconstruction on breast cancer r... - 0 views

www.ncbi.nlm.nih.gov/...26891211

breast cancer infection cancer

shared by Nathan Goodyear on 08 Mar 19 - No Cached
hoangkimchi liked it
  • Nathan Goodyear on 08 Mar 19
     
    Wound complications and infection increase breast cancer recurrence by 4.6 and 6.15 times respectively.
Nathan Goodyear

Oncotarget | Vitamin C and Doxycycline: A synthetic lethal combination therapy targetin... - 0 views

www.impactjournals.com/...index.php

cancer doxycycline IV vitamin C vitamin C

shared by Nathan Goodyear on 14 Jun 17 - No Cached
  • These eight distinct cancer types included: DCIS, breast (ER(+) and ER(-)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma. Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease (isolated from ascites fluid and/or pleural effusions)
  • Doxycycline behaves as a strong radio-sensitizer, successfully overcoming radio-resistance in breast CSCs
  • cancer cells can indeed escape the effects of Doxycycline, by reverting to a purely glycolytic phenotype. Fortunately, the metabolic inflexibility conferred by this escape mechanism allows Doxycycline-resistant (DoxyR) CSCs to be more effectively targeted with many other metabolic inhibitors, including Vitamin C, which functionally blocks aerobic glycolysis
  • ...36 more annotations...
  • Vitamin C inhibits GAPDH (a glycolytic enzyme) and depletes the cellular pool of glutathione, resulting in high ROS production and oxidative stress
  • DoxyR CSCs are between 4- to 10-fold more susceptible to the effects of Vitamin C
  • Doxycycline and Vitamin C may represent a new synthetic lethal drug combination for eradicating CSCs, by ultimately targeting both mitochondrial and glycolytic metabolism
  • inhibiting their propagation in the range of 100 to 250 µM
  • metabolic flexibility in cancer cells allows them to escape therapeutic eradication, leading to chemo- and radio-resistance
  • used doxycycline to pharmacologically induce metabolic inflexibility in CSCs, by chronically inhibiting mitochondrial biogenesis
  • This treatment resulted in a purely glycolytic population of surviving cancer cells
  • DoxyR cells are mainly glycolytic
  • MCF7 cells survive and develop Doxycycline-resistance, by adopting a purely glycolytic phenotype
  • Cancer stem cells (CSCs) are thought to be the “root cause” of tumor recurrence, distant metastasis and therapy-resistance
  • the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics inhibit mitochondrial protein translation, as an off-target side-effect
  • Vitamin C was more potent than 2-DG; it inhibited DoxyR CSC propagation by > 90% at 250 µM and 100% at 500 µM
  • IC-50
  • DoxyR CSCs are between 4- to 10-fold more sensitive to Vitamin C than control MCF7 CSCs
  • Berberine, which is a naturally occurring antibiotic that also behaves as an OXPHOS inhibitor
  • treatment with Berberine effectively inhibited the propagation of the DoxyR CSCs by > 50% at 1 µM and > 80% at 10 µM.
  • Doxycycline, a clinically approved antibiotic, induces metabolic stress in cancer cells. This allows the remaining cancer cells to be synchronized towards a purely glycolytic phenotype, driving a form of metabolic inflexibility
  • Doxycycline-driven aerobic glycolysis
  • new synthetic lethal strategy for eradicating CSCs, by employing i) Doxycycline (to target mitochondria) and ii) Vitamin C (to target glycolysis)
  • Doxycycline inhibits mitochondrial biogenesis and OXPHOS,
  • hibits glycolytic metabolism by targeting and inhibiting the enzyme GAPDH
  • CSCs act as the main promoter of tumor recurrence and patient relapse
  • a metabolic shift from oxidative to glycolytic metabolism represents an escape mechanism for breast cancer cells chronically-treated with a mitochondrial stressor like Doxycycline, as mitochondrial dys-function leads to a stronger dependence on glucose
  • Vitamin C has been demonstrated to selectively kill cancer cells in vitro and to inhibit tumor growth in experimental mouse models
  • many of these actions have been attributed to the ability of Vitamin C to act as a glycolysis inhibitor, by targeting GAPDH and depleting the NAD pool
  • here we show that DoxyR CSCs are more vulnerable to the inhibitory effects of Vitamin C, at 4- to 10-fold lower concentrations, between 100 to 250 μM
  • concurrent use of Vitamin C, with standard chemotherapy, reduces tumor recurrence and patient mortality
  • after oral administration, Vitamin C plasma levels reach concentrations of ~70-220 μM
  • intravenous administration results in 30- to 70- fold higher plasma concentrations of Vitamin C
  • pro-oxidant activity results from Vitamin C’s action on metal ions, which generates free radicals and hydrogen peroxide, and is associated with cell toxicity
  • it has been shown that high-dose Vitamin C is more cytotoxic to cancer cells than to normal cells
  • This selectivity appears to be due to the higher catalase content observed in normal cells (~10-100 fold greater), as compared to tumor cells. Hence, Vitamin C may be regarded as a safe agent that selectively targets cancer cells
  • the concurrent use of Doxycycline and Vitamin C, in the context of this infectious disease, appeared to be highly synergistic in patients
  • Goc et al., 2016, showed that Doxycycline is synergistic in vitro with certain phytochemicals and micronutrients, including Vitamin C, in the in vitro killing of the vegetative spirochete form of Borrelia spp., the causative agent underlying Lyme disease
  • Doxycycline, an FDA-approved antibiotic, behaves as an inhibitor of mitochondrial protein translation
  • CSCs successfully escape from the anti-mitochondrial effects of Doxycycline, by assuming a purely glycolytic phenotype. Therefore, DoxyR CSCs are then more susceptible to other metabolic perturbations, because of their metabolic inflexibility
  • Nathan Goodyear on 14 Jun 17
     
    Not especially new, but IV vitamin C + daily doxycycline found to kill cancer stem cells.
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

Paradoxical effects of chemotherapy on tumor relapse and metastasis promotion - Science... - 0 views

www.sciencedirect.com/...S1044579X19301749

circulating tumor cells cancer metastasis recurrence CTC chemotherapy

shared by Nathan Goodyear on 05 Apr 21 - No Cached
  • Nathan Goodyear on 05 Apr 21
     
    Not just the what, but the how of chemotherapy causing metastasis and recurrence.
Nathan Goodyear

Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain relief... - 0 views

pubmed.ncbi.nlm.nih.gov/16423749

hyperthermia pain

shared by Nathan Goodyear on 25 Jan 21 - No Cached
  • Nathan Goodyear on 25 Jan 21
     
    Radiotherapy hyperthermia found to reduce pain in colorectal cancer recurrence. This was regional/local hyperthermia.
Nathan Goodyear

Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosi... - 0 views

pubmed.ncbi.nlm.nih.gov/15741161

metastasis local recurrence surgery

shared by Nathan Goodyear on 13 Aug 20 - No Cached
  • Nathan Goodyear on 13 Aug 20
     
    Again, surgical upregulation of PI3k stimulates local recurrence via anti-apoptosis and induction of chemoresistance.
Nathan Goodyear

Molecular Control of Immune/Inflammatory Responses: Interactions Between Nucl... - 0 views

edrv.endojournals.org/...435.long

progesterone NK macrophage T cell activity inflammation immune system

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    Benefits of progesterone, are in part, due to its function on the immune system.  Progesterone shown to decrease T cell activity, macrophage activity and NK cell activity.  Aside, NK cell activity has been found to be increased in those with recurrent first trimester miscarriages and progesterone defects.  So, low progesterone allows for a rise in NK cell activity and inflammation that is detrimental to a developing pregnancy.  If that is the case in pregnancy, what about the rest of the body?
Nathan Goodyear

Relationship Between Healthy Diet and Risk of Cardiovascular Disease Among Patients on ... - 0 views

circ.ahajournals.org/...2705

cardiovascular disease CVD diet health healthy

shared by Nathan Goodyear on 06 Dec 12 - No Cached
  • Nathan Goodyear on 06 Dec 12
     
    This study proves that the foundation of our current health problem is our diet.  Eat better!  In this study, individuals with CVD, had a significant reduction in recurrent CVD events with a simple change in diet.  The amazing thing it was above and beyond that of medications.
Nathan Goodyear

JAMA Network | JAMA | Effect of Disodium EDTA Chelation Regimen on Cardiovascular Event... - 0 views

jama.jamanetwork.com/article.aspx

TACT TACT study EDTA chelation cardiovascular events CVD

shared by Nathan Goodyear on 10 Jun 13 - No Cached
  • Nathan Goodyear on 10 Jun 13
     
    This study looked at those with previous MIs.  This study found a reduction in recurrent events in those receiving EDTA chelation versus placebo.  The authors of this study looked at the Hazard ratio, which was reduced in every end point that this study was designed to evaluate.
Nathan Goodyear

Testosterone replacement therapy after primary treatm... [J Urol. 2005] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15643240

prostate cancer prostate Testosterone therapy cancer testosterone hormone hormones men replacement therapy

shared by Nathan Goodyear on 05 Jul 12 - No Cached
  • Nathan Goodyear on 05 Jul 12
     
    Testosterone therapy in men with history of prostate cancer not found to increase risk of recurrence.
wheelchairindia9

Tynor Ankle Splint - 0 views

www.wheelchairindia.com/...Tynor-Ankle-Splint

Tynor Ankle Splint Ankle Splint ankle splints ankle support splints Ankle Splint braces ankle support splint ankle brace splint tynor ankle support splint

shared by wheelchairindia9 on 17 Mar 16 - No Cached
  • wheelchairindia9 on 17 Mar 16
     
    Ankle Splint Ankle Splint is designed to immobilize, support and stabilize the ankle joint in injury, or offer protection to people prone to ankle injuries. Rigid exoskeleton shell design gives better protection and control of the inversion or aversion of the ankle. Rigid immobilization Foam cushioning One size, that fits all Anatomical Easy to clean. Ankle Splint Features Unique figure of eight gripping Effective control on inversion & eversion movement of ankle Most effective gripping around ankle. Enhances comfort and walking pleasure Large enough room for ankle Unconventional, swollen or distorted ankles can be accommodated No compression hot spots on the ankle , so enhances comfort to injured ankle Reduces chances of sports related injuries in recurrent ankle problems Quick healing and better recovery of the fully immobilized ankle Molded Ethafoam Foam Pad Provides optimal compression and pressure Good cushioning , enhances comfort Skin friendly Ergonomic design Light in weight - enhance compliance Bilateral symmetry - can be used for either ankle Neoprene sleeves - good cushioning ,reduce pressure of gripping straps One size fits all Molded splint with perfect anatomy Pleasing aesthetics Sleek can be used inside the shoe Effective immobilization. Ankle Splint Measurements Measure circumference approx 2 inches above the ankle joint. Size Chart - Size Inches CM Universal 7.2-12 18-30
wheelchairindia9

Tynor Foot Drop Splint Right-Left - 0 views

www.wheelchairindia.com/...or-Foot-Drop-Splint-Right-Left

Ankle Splint and Foot Drop Splint Stabilize Ankle Joint uphold the ankle joint easily fits into the feet foot drop splint flexible reduces the pressure on the ankle proper cushioning to the ankles Enhances comfort and walking pleasure

shared by wheelchairindia9 on 17 Mar 16 - No Cached
  • wheelchairindia9 on 17 Mar 16
     
    Tynor Foot Drop Splint Right/Left Applications Prevention and correction of foot drop. Peripheral nerve paralysis. Nerve/Muscle damage. Ankle or Plantar flexion contracture. Functional Alignment of the foot. Post operative care. Burn patients. Tynor Foot Drop Splint Right/Left Features Effective foot lift. Strong leaf spring action. Customizable. Thin walled, worn in a shoe. Tynor Foot Drop Splint Right/Left Measurements Measure shoe size Size Chart - Sizes European American Small 34-36 2.8-4.4 Medium 37-39 5.3-6.8 Large 40-42 7.5-9.0
Nathan Goodyear

Pregnancy Outcome After Intralipid Infusion Among Women Experiencing Recurrent Pregnanc... - 0 views

www.fertstert.org/...fulltext

intralipid therapy treatment recurrent pregnancy loss miscarriage

shared by Nathan Goodyear on 16 Apr 12 - No Cached
  • Nathan Goodyear on 16 Apr 12
     
    no abstract, but intralipid therapy was shown to improve pregnancy rate.
Nathan Goodyear

Duration of intralipid's suppressive eff... [Am J Reprod Immunol. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18782287

intralipid therapy natural killer cells NK infertility reproduction reproductive failure

shared by Nathan Goodyear on 16 Apr 12 - No Cached
  • Nathan Goodyear on 16 Apr 12
     
    Intralipid therapy effect in treating natural killer cell overactivity in those women that have immune mediated recurrent pregnancy loss.
Nathan Goodyear

Coffee and tea consumption in relation... [Cancer Causes Control. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23907772

coffee tea prostate cancer

shared by Nathan Goodyear on 04 Sep 13 - No Cached
  • Nathan Goodyear on 04 Sep 13
     
    daily tea and coffee decrease the risk of prostate cancer recurrence and progression.
Nathan Goodyear

An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Fa... - 0 views

circ.ahajournals.org/...ULATIONAHA.113.003602.abstract

PPI proton pump inhibitors PPI's cardiovascular disease events PPIs

shared by Nathan Goodyear on 16 Jul 13 - No Cached
  • Nathan Goodyear on 16 Jul 13
     
    Not only do PPIs increase risk of recurrent cardiovascular events in those with prior history, but they increase risk in those individuals with no preexisting history
Nathan Goodyear

Long-Acting Octreotide for the Treatment and Symptomatic Relief of Bowel Obstruction in... - 0 views

www.sciencedirect.com/...S0885392405005397

octreotide cancer

shared by Nathan Goodyear on 11 Sep 13 - No Cached
  • Nathan Goodyear on 11 Sep 13
     
    Long term octreotide well tolerated in patients with recurrent ovarian cancer.  
Nathan Goodyear

Blood levels of vitamin D and early ... [Breast Cancer Res Treat. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24104883

vitamin d vitamin D breast cancer

shared by Nathan Goodyear on 15 Oct 13 - No Cached
  • Nathan Goodyear on 15 Oct 13
     
    low vitamin D associated with breast cancer recurrence and mortality.
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