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Nathan Goodyear

Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances th... - 0 views

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    reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 is a key molecular feature that determines the tumor-initiating capacity of breast cancer stem-like cellular states->non-genomic signaling upregulates ER-alpha and genomic signaling.
Nathan Goodyear

Communication between genomic and non-genomic signaling events coordinate steroid hormo... - 0 views

  • steroid hormones typically interact with their cognate receptor in the cytoplasm for AR, glucocorticoid receptor (GR) and PR, but may also bind receptor in the nucleus as appears to often be the case for ERα and ERβ
  • This ligand binding results in a conformational change in the cytoplasmic NRs that leads to the dissociation of HSPs, translocation of the ligand-bound receptor to the nucleus
  • In the nucleus, the ligand-bound receptor dimerizes and then binds to DNA at specific HREs to regulate gene transcription
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  • some steroid hormone-induced nuclear events can occur in minutes
  • the genomic effects of steroid hormones take longer, with changes in gene expression occurring on the timescale of hours
  • Classical steroid hormone signaling occurs when hormone binds nuclear receptors (NR) in the cytoplasm, setting off a chain of genomic events that results in, among other changes, dimerization and translocation to the nucleus where the ligand-bound receptor forms a complex with coregulators to modulate gene transcription through direct interactions with a hormone response element (HRE)
  • NRs have been found at the plasma membrane of cells, where they can propagate signal transduction often through kinase pathways
  • Membrane-localized ER, PR and AR have been reported to modulate the activity of MAPK/ERK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), nitric oxide (NO), PKC, calcium flux and increase inositol triphosphate (IP3) levels to promote cell processes including autophagy, proliferation, apoptosis, survival, differentiation, and vasodilation
  • ERα36, a 36kDa truncated form of ERα that lacks the transcriptional activation domains of the full-length protein. Membrane-localized ERα36 can activate pathways including protein kinase C (PKC) and/or mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to promote the progression of various cancers
  • G protein-coupled receptor 30 (GPR30), also referred to as G protein-coupled estrogen receptor (GPER), is a membrane-localized receptor that has been observed to respond to estrogen to activate rapid signaling
  • hormone-responsive G protein coupled receptor is Zip9, which androgens can activate
  • GPRC6A is another G protein-coupled membrane receptor that is responsive to androgen
  • androgen-mediated non-genomic signaling through this GPCR can modulate male fertility, hormone secretion and prostate cancer progression
  • non-NR proteins located at the cell surface can bind to steroid hormones and respond by eliciting rapid signaling events
  • Estrogens have been shown to induce rapid (i.e. seconds) calcium flux via membrane-localized ER (mER)
  • ER-calcium dynamics lead to activation of kinase pathways such as MAPK/ERK which can result in cellular effects like migration and proliferation
  • 17β-estradiol (E2) has been reported to promote angiogenesis through the activation of GPER
  • Membrane NRs may also mediate rapid signaling through crosstalk with growth factor receptors (GFR)
  • A similar crosstalk occurs between the receptor tyrosine kinase insulin-related growth factor-1 receptor (IGF-IR) and ERα. Not only does IGF-IR activate ERα, but inhibition of IGF-IR downregulates estrogen-mediated ERα activity, suggesting that IGF-IR is essential for maximal ERα signaling
    • Nathan Goodyear
       
      This is a bombshell that shatters the current right brain approach to ER. It completely shatters the concept of eat sugar, whatever you want, with cancer treatment in ER+ or hormonally responsive cancer!
  • Further, ER activates IGF-IR pathways including MAPK
  • GPER is involved in the transactivation of the EGFR independent of classical ER
  • tight interconnection between genomic and non-genomic effects of NRs.
  • non-genomic pathways can also lead to genomic effects
  • androgen-bound AR associates with the kinase Src at the plasma membrane, activating Src which then leads to a signaling cascade through MAPK/ERK
  • However, Src can also increase the expression of AR target genes by the ligand-independent transactivation of AR
  • extranuclear steroid hormone actions can potentially reprogram nuclear NR events
  • estrogen modulated the expression of several genes including endothelial nitric oxide synthase (eNOS) via rapid signaling pathways
  • epigenetic changes can then mediate genomic events in uterine tissue and breast cancer cells
Nathan Goodyear

PLOS ONE: Alternate Estrogen Receptors Promote Invasion of Inflammatory Breast Cancer C... - 0 views

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    This study looked at estrogen receptors and inflammatory breast cancer.  ER-alpha36 varian and ER-beta were found to be present in non-genomic signaling in this disease.  ER-alpha is regular absent in this disease.  There is both genomic and non-genomic pathways with regards to signaling with ER
Rahul Sharma

PTFE Syringe Filters Sterile and Non Sterile - Axiva - 0 views

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    PTFE syringe filters is used for the filtration of antagonistic chemicals, including acids and non-aqueous solvents. Axiva provides both sterile and non sterile PTFE syringe filters to our clients.
Nathan Goodyear

Bisphenol-A acts as a potent estrogen vi... [Mol Cell Endocrinol. 2012] - PubMed - NCBI - 0 views

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    Bisphenol A acts via non-classical genomic signaling and more through weaker non-classical membrane receptors and their secondary messengers.
Nathan Goodyear

Non-Celiac Gluten Sensitivity | Molina-Infante | OmniaScience Monographs - 0 views

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    Only abstract available here.  Non-celiac gluten sensitivity review.  NCGS is an innate immune response rather than a humoral or autoimmune response.
Nathan Goodyear

American Journal of Gastroenterology - Abstract of article: Non-Celiac Wheat Sensitivit... - 0 views

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    Non-celiac gluten sensitivity.  Only abstract available here.
Nathan Goodyear

AroER Tri-Screen™ is a Biologically Relevant Assay for Endocrine Disrupting C... - 0 views

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    Paxil is estrogen receptor agonist.  What is interesting about this is that the FDA just approved this as a non-hormonal way to reduce hot flashes--but it is paxil under a different name.  It is non-hormonal--yeah right.  The organization making the approval doesn't know what they are doing at worse, or like the IOM stated are not up with the latest scientific knowledge.
Nathan Goodyear

Fructose Consumption as a Risk Factor for Non-alcoholic Fatty Liver Disease - 0 views

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    Fructose upregulates fructokinase activity and this increase liver triglyceride production increasing non-alcoholic fatty liver disease also known as NAFLD.
Dr. Jennifer Martinick

Dr Jennifer Martinick offers Non-Surgical Hair Restoration Solutions at her clinics - 0 views

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    Dr Jennifer Martinick is a highly skilled hair transplant surgeon and offers various effective hair restoration solutions. Here you can read a review on Non-Surgical Hair Restoration Solutions provided by Jennifer Martinick and her skilled team of technicians.
nucosmeticclinic

PRP Therapy - Non Surgical Hair Loss Treatment for Men and Women - 0 views

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    PRP Therapy or Platelet Rich Plasma Therapy is an effective non-surgical hair loss treatment for men and women. PRP Therapy makes efficient utilization of a growth enhancing blood constituent called platelets, which when combined together with plasma, results in an unprecedented increase in the hair follicles across the treated areas.
Nathan Goodyear

Normalization of testosterone level is associated with reduced incidence of myocardial ... - 0 views

  • Normalized-TRT group had significantly fewer deaths than no-TRT
  • Mortality was also significantly lower in the non-normalized-TRT group compared with those in no-TRT group
  • the normalized-TRT group was associated with significantly increased all-cause mortality-free survival (log-rank, P < 0.05) compared with the non-normalized-TRT or no-TRT groups
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  • normalized-TRT group showed lower risk of MI than non-normalized-TRT (HR: 0.82, CI 0.71–0.95, P = 0.008) and no-TRT
  • normalized-TRT group had significantly lower stroke events compared with non-normalized-TRT (HR: 0.70, CI 0.51–0.96, P = 0.028) and no-TRT
  • study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes
  • retrospective study
  • the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the TT levels
  • Patients who failed to achieve the therapeutic range after TRT did not see a reduction in MI or stroke and had significantly less benefit on mortality
  • selected patients without any previous history of MI or stroke prior to initiation of TRT to reduce bias related to CV outcomes
  • currently only half of the men on TRT had been diagnosed with hypogonadism.
  • 25% of users did not have their T concentrations tested prior to initiating therapy, and 21% of those prescribed TRT did not have their levels tested at any time during treatment.
  • men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
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    Testosterone therapy in men with low T found to reduce all cause mortality, stroke and MI.
Nathan Goodyear

Re: Plasma Sex Steroid Hormone Levels and Risk of Breast Cancer in Postmenopausal Women... - 0 views

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    non-SHBG bound serum estradiol, testosterone and DHEA reveal increase breast cancer risk; other studies show saliva testing equal to serum non-bound SHBG hormones
Nathan Goodyear

Epidemiology of non-alcoholic fatty liver disease. [Dig Dis. 2010] - PubMed result - 0 views

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    non-alcoholic fatty liver disease the result of Metabolic syndrome.  New epidemic associated with obesity. Scary statistics about the children of America.
Nathan Goodyear

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders - 0 views

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    good discussion on non-Celiac gluten sensitivity.  The incidence sits at roughly 6% of the general population.  As research builds, our understanding will also increase.
Nathan Goodyear

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders - 0 views

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    great review of Gluten sensitivity or Non-Celiac Gluten sensitivity.
wheelchairindia9

Soma SM 150-3 - 0 views

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    Soma SM 150.3: The SM-150.3 is an aluminum alloy standard wheelchair that is economic, solid, and durable. Soma SM 150.3 Wheelchair Features: Elliptical frame The unique and stylish elliptical frame ensures that the chair is both rigid and robust. Integrated seating system For intensive wheelchair users, we provide seating system that can be free from hammock effect. The innovative and durable seating system makes it easy for you to detach seat upholstery for cleaning purpose. Secure non-slip footplate A non-slip and ergonomic footplate provides you with a stable and comfortable base for placing feet. Energy-saving tipping lever The ergonomic design allows caregivers to operate the lever without much effort so the casters can overcome obstacles such as thresholds and curbs. Item Code:WCI-201 MRP: Rs 12000 Our Price:Rs 9950 Net Price:Rs 9751 ( Apply Coupon Code 'MSW2365' Get 2% Discount ) Soma SM 150.3 Wheelchair Measurements: Seat Width(cm):43 Seat Depth(cm):42 Caster Size(inch):7
wheelchairindia9

Soma SM 100.3 - 0 views

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    Soma SM 100.3 The SM-100.3 is an aluminum alloy standard wheelchair that is economic, solid, and durable. Soma SM 100.3 Wheelchair Features: Elliptical frame The unique and stylish elliptical frame ensures that the chair is both rigid and robust. Integrated seating system For intensive wheelchair users, we provide seating system that can be free from hammock effect. The innovative and durable seating system makes it easy for you to detach seat upholstery for cleaning purpose. Secure non-slip footplate A non-slip and ergonomic footplate provides you with a stable and comfortable base for placing feet. Energy-saving tipping lever The ergonomic design allows caregivers to operate the lever without much effort so the casters can overcome obstacles such as thresholds and curbs. Soma SM 100.3 Wheelchair Measurements: Seat Width(cm):43 Seat Depth(cm):42 Caster Size(inch):7 Rear Wheel Size(Inch/QR) 16F/22F
Rahul Sharma

PVDF Syringe Filters Sterile and Non Sterile - Axiva - 0 views

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    Axiva Sichem Pvt Ltd offers a wide range of PVDF Syringe Filters in sterile and non sterile category. This syringe filters intended for aqueous and organic solution samples.
Nathan Goodyear

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - 0 views

  • The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis
  • The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour.
  • Because GO is far more efficient in generating ATP compared with GLY (producing 36 vs 2 ATP per glucose
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  • molecule), cancer cells upregulate glucose receptors and significantly increase glucose uptake in an attempt to ‘catch up
  • early carcinogenesis often occurs in a hypoxic microenvironment, the transformed cells have to rely on anaerobic GLY for energy production.
  • Hypoxia-inducible factor (HIF) is activated in hypoxic conditions
  • evidence suggests that transformation to a glycolytic phenotype offers resistance to apoptosis
  • non-small cell lung cancer, breast cancer and glioblastoma
  • Dichloroacetate activated the pyruvate dehydrogenase, which resulted in increased delivery of pyruvate into the mitochondria
  • DCA increased GO and depolarised the mitochondria, returning the membrane potential towards the levels of the non-cancer cells, without affecting the mitochondria of non-cancerous cells
  • induction of apoptosis by DCA in non-small cell lung cancer, breast cancer and glioblastoma cell lines
  • DCA was shown to induce apoptosis in endometrial (Wong et al, 2008) and prostate (Cao et al, 2008) cancer cells
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    DCA as targeted therapy in cancer.
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