Skip to main content

Home/ Dr. Goodyear/ Group items matching "adhesion" in title, tags, annotations or url

Group items matching
in title, tags, annotations or url

Sort By: Relevance | Date Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Androgen Exposure Increases Human Monocyte Adhesion to Vascular Endothelium and Endothelial Cell Expression of Vascular Cell Adhesion Molecule-1 - 0 views

circ.ahajournals.org/...2317.long

DHT VCAM-1

shared by Nathan Goodyear on 06 Nov 13 - No Cached
  • Nathan Goodyear on 06 Nov 13
     
    DHT shown to increase VCAM-1 adhesion to endothelial cells.  This was a cell culture study of human umbilical vein endothelial cells exposed to postmenopausal female serum and then DHT.  Not exactly physiologic.
wheelchairindia9

Leg Traction Brace - 0 views

www.wheelchairindia.com/...Tynor-Leg-Traction-Brace

Tynor Leg Traction Brace Leg Traction Brace Leg Traction Braces Leg Traction Brace Online Leg Traction Brace Online India Leg Traction Brace Price Buy Leg Traction Brace

shared by wheelchairindia9 on 31 Mar 16 - No Cached
  • wheelchairindia9 on 31 Mar 16
     
    Tynor Leg Traction Brace is basically designed to provide traction to the leg. It works well even on the weak or geriatric skin. It ensures proper compression of the leg and provides traction. It is made of three layered polyurethane fabric which makes it soft and comfortable to use. The innermost layer gives the required friction for faster recovery. It is augmented with hook and loop closures to make it convenient to put on and remove. It does not require any adhesion. It provides cushion like support to the leg and relieves it from pain. It also prevents the bone from getting fractured and any muscle pull. It does not cause any peeling of skin and any rash or allergy on skin. It distributes the pressure exerted on the leg evenly. Tynor Leg Traction Brace Leg traction brace is a traction halter applied to the leg for below knee traction. It offers a distinct advantage of a very large holding surface area, ease of application and removal, reuse and patient comfort. Easy application & removal. Can be used for geriatric/ weak skin. Ideal for sensitive skins. Easy monitoring. Distributes pressure evenly. Tynor Leg Traction Brace Features Three-layered PU bonded fabric offers: Soft feel and plush looks through the top layer. Comfortable cushioning through the middle Polyurethane layer. Inner layer provides good frictional characteristics. Multiple hook loop closures Ensure controlled compression. Easy application and removal No loosening, less monitoring Large skin contact area Ensures no vaso-constriction. Eliminates need of an adhesive. Convenient and quick to apply Ensures no skin peeling. Ideal for weak or geriatric skins Tynor Rib Belt Rib belt is applied to the thoracic and upper abdominal region to compress and bind the rib cage during rib fractures and postoperative care, while allowing sufficient flexibility for comfortable breathing. Extra porous. With splinting pad. No buckling or rolling over. Controlled compression
Nathan Goodyear

The endogenous progesterone metabolite, 5α-pregnane-3,20-dione, decreases cell-substrate attachment, adhesion plaques, vinculin expression, and polymerized F-actin in MCF-7 breast cancer cells | SpringerLink - 0 views

link.springer.com/...ENDO:16:1:07

hormones progesterone progesterone metabolites 5alpha-pregnane breast cancer cancer

shared by Nathan Goodyear on 07 Oct 16 - No Cached
  • Nathan Goodyear on 07 Oct 16
     
    The progesterone metabolite, 5alpha-pregnanes, likely involved in the genesis of breast cancer through increased proliferation and decreased cell adhesion.
Nathan Goodyear

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol - 0 views

erc.endocrinology-journals.org/...731.long

3-beta androstanediol DHT Testosterone androgens prostate cancer ER beta ER-beta receptors ER men male hormone hormones

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • In the prostate, ERβ is highly expressed in the epithelial compartment, where it is the prevailing isoform
  • In the gland, DHT may be either reversibly 3α- or irreversibly 3β-hydroxylated by the different 3α- and 3β-hydroxysteroid dehydrogenases respectively (Steckelbroeck et al. 2004); these transformations generate two metabolites respectively 3α-diol and 3β-Adiol, which are both unable to bind the AR. Instead, 3β-Adiol displays a high affinity for ERβ (Kuiper et al. 1998, Nilsson et al. 2001), and it has been proposed that this metabolite may play a key role in prostate development
  • ERβ signaling, in contrast to ERα, seems to act as a suppressor of prostate growth, and may be positively involved in breast cancer
  • ...4 more annotations...
  • 3β-Adiol counteracts PC cell proliferation in vitro
  • 3β-Adiol counteracts the biological actions of its androgenic precursors testosterone and DHT
  • functional antagonism of 3β-Adiol appears to be molecularly independent from the activation of the androgenic pathway
  • the action of 3β-Adiol is mediated, at the molecular levels, by the estrogenic pathway.
  • Nathan Goodyear on 21 Jan 14
     
    another awesome article dealing with hormone metabolites. Physicians that don't understand metabolites and receptors may be doing more harm than good.   One of the mainstays of the treatment of metastatic prostate disease is androgen deprivation therapy.  This article requires a reassessment of this due to the DHT metabolite 3-beta androstanediol.  This metabolite is produced from DHT production via the enzyme 3beta HSD.  This metabolite binds to ER beta, an estrogen receptor, and inhibits proliferation, migration, promotes adhesion (limits spreading), and stimulates apoptosis.  This is contrast to 3-alpha androstanediol.  Androgen deprivation therapy will decrease 3-beta androstanediol.  This is the likely reason for the increased aggressive prostate cancer found in those men using 5 alpha reductase inhibitors.
Nathan Goodyear

Effects of Polyunsaturated Fatty Acids in Growth Medium on Lipid Composition and on Physicochemical Surface Properties of Lactobacilli - 0 views

www.ncbi.nlm.nih.gov/...PMC321255

PUFA poly unsaturated fatty acids GI dysbiosis bacteria microbiota

shared by Nathan Goodyear on 01 May 12 - No Cached
  • Nathan Goodyear on 01 May 12
     
    PUFA shown to effect GI bacterial balance.  Altering adhesion of lactobacillus to intestinal surface.  Also, lactobacilli species shown to alter PUFA metabolism in GI.  This article reveals the effect that diet can have on GI bacterial balance.
Nathan Goodyear

Progesterone metabolites in breast cancer - 1 views

erc.endocrinology-journals.org/...717.full

progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase

shared by Nathan Goodyear on 20 Feb 12 - No Cached
  • P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
  • these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
  • only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
  • ...30 more annotations...
  • P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
  • 5α-pregnane, 5β-pregnane, and 4-pregnene metabolites of P
  • These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
  • Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
  • The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
  • the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
  • In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
  • The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
  • he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
  • The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
  • altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
  • In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
  • Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
  • The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
  • 3αHP inhibited whereas 5αP-stimulated proliferation
  • Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
  • Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
  • αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
  • The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
  • he effects on proliferation and adhesion were not due to P, but due to the 5α-reduced metabolites
  • The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
  • separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
  • The studies thus provided the first demonstration of the existence of specific P metabolite receptors
  • the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
  • Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
  • In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
  • The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
  • current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
  • both testosterone and DHT inhibit cell growth more or less to the same extent
  • Note that 5α-reductase reaction is not reversible
  • Nathan Goodyear on 20 Feb 12
     
    Fantastic read on the effects of progesterone metabolism on tumor and cancer growth.  Tumorigenesis is not just about the hormone, hormone balance, but about the metabolism of hormones.  This is why premarin is so carcinogenic: it is primarily metabolized by the 4-OH estrone pathway.
Nathan Goodyear

Nutrition Journal | Full text | Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: The pleiotropic effects of folate supplementation - 0 views

www.nutritionj.com/4

homocysteine atherogenesis CVD metabolic syndrome metabolic syndrome

shared by Nathan Goodyear on 23 Jul 12 - No Cached
  • Nathan Goodyear on 23 Jul 12
     
    homocysteine contributes to atherogenesis and CVD via: increased ROS, induces endothelial dysfunction, increases platelete adhesion and thrombosis, increases smooth muscle cell proliferation, endothelial cell cytotoxicity, increases LDL oxidation, vasoconstriction, increased MCP-1 and IL-8, and induces endothelial HMG CoA reductase.
Nathan Goodyear

High Glucose-Induced Expression of Proinflammatory Cytokine and Chemokine Genes in Monocytic Cells - 0 views

diabetes.diabetesjournals.org/...1256.abstract

glucose diabetes IR insulin resistance inflammation TNF-alpha MCP-1 IL-1B

shared by Nathan Goodyear on 11 Jun 12 - No Cached
  • HG significantly increased the expression of monocyte chemoattractant protein-1 (MCP-1), TNF-α, β2-integrin, interleukin-1β, and others. HG treatment increased transcription of the MCP-1 gene, MCP-1 protein levels, and adhesion of THP-1 cells to endothelial cells. HG-induced MCP-1 mRNA expression and monocyte adhesion were blocked by specific inhibitors of oxidant stress, protein kinase C, ERK1/2, and p38 mitogen-activated protein kinases
  • Nathan Goodyear on 11 Jun 12
     
    High glucose associated with significant increase in inflammatory signaling.
Nathan Goodyear

Differential regulation of endothelium behavior by progesterone and medroxyprogesterone acetate - 0 views

joe.endocrinology-journals.org/...179.abstract

progesterone medroxyprogesterone acetate medroxyprogesterone hormone hormones women cardiovascular disease HRT

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Nathan Goodyear on 04 Feb 14
     
    No surprise that progesterone and the synthetic progestin medroxyprogesterone acetate (MPA) have different effects on the vascular endothelium. MPA inhibits NO production, whereas Progesterone maintains NO production.  MPA promoted platelet adhesion whereas Progesterone did not--significant implication in plaque formation.
Nathan Goodyear

http://ar.iiarjournals.org/content/28/4B/2129.full.pdf - 0 views

ar.iiarjournals.org/...2129.full.pdf

breast cancer progesterone metabolite metabolites 4-pregnene aromatase

shared by Nathan Goodyear on 23 Jan 14 - No Cached
  • Nathan Goodyear on 23 Jan 14
     
    20alpha dihydroprogesterone, a 4 pregnene, has been shown to inhibit breast cancer cell proliferation, decrease mets through increased cell adhesion, and increased apoptosis.  Here, it has been shown to inhibit aromatase activity.  No longer are hormone metabolites to be viewed as waste.  They are biological as active if not more so in many cases.
wheelchairindia9

Tynor PUF Liner Skin Traction Set - 0 views

www.wheelchairindia.com/...or-PUF-Liner-Skin-Traction-Set

Tynor PUF Liner Skin Traction Set skin traction set PUF Liner Skin Traction Set skin traction set (puf liner) tynor skin traction set tynor skin traction skin traction set puf liner

shared by wheelchairindia9 on 22 Mar 16 - No Cached
  • wheelchairindia9 on 22 Mar 16
     
    Tynor PUF Liner Skin Traction Set Skin traction Set (PUF liner) is used for providing indirect traction to leg or the arm to reduce fractures, skeletal deformities, muscle contractures, muscle spasms, pressure on nerves or regain normal length and alignment of involved bone. Hypoallergenic. Extra porous. Controlled adhesion and friction. Extra comfortable. Tynor PUF Liner Skin Traction Set Features Available as Complete Kit Convenient for emergencies Cost effective High performance Inbuilt cord, Quick to apply Foam liner and Bandage High performance crepe bandage for extra security Enhanced skin friction of the foam liner Easy application and removal Measure distance from knee to foot. Cut Liners for accurate use
Nathan Goodyear

microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Comparative Analysis | Scientific Reports - 0 views

www.nature.com/...s41598-017-16978-y

genetics cancer epigenetics breast cancer

shared by Nathan Goodyear on 06 Feb 18 - No Cached
mamdouh_hfz liked it
  • dysregulated miRNA could be involved in tumor cell proliferation and growth as well as cell cycle progression
  • under-expression of miR-497, 376c and 1271 in Lebanese breast cancer tissues
  • The upregulated miR-183 in our samples was predicted to be responsible for the decrease in expression of the BTG1 mRNA whose protein is involved in cell cycle arrest and apoptosis in breast cancer cells18.
  • ...9 more annotations...
  • nother molecule related to cell proliferation that was over-expressed in our data and suggested as a target of downregulated miR-376c is AURKA
  • the over-expression of miR-183 and miR-21 in Lebanese breast cancer tissues is consistent with downregulation of two important tumor suppressor predicted targets: AKAP12 whose protein regulates cellular adhesion dynamics by controlling cytoskeletal architecture, cell migration, and mitogenic signaling20; and LATS2 whose protein causes cell cycle arrest
  • dysregulation in cancer particularly in breast cancer highlights their importance in tumor development
  • mRNA-miRNA integration analysis of early breast cancer revealed a potential role of miRNA in increasing cellular proliferation and progression, and decreasing invasion and migration
  • most of the miRNA dysregulated in Lebanese breast cancer patients are similar to those dysregulated in American patients, differences in miRNA expression exist and could be attributed either to the patients’ age at diagnosis or to ethnic variation in miRNA epigenetic regulation and sequence variation of pre-miRNA
  • the number one cancer killer of women worldwide
  • microRNA (miRNA) are small non-coding 18–25 nucleotide RNA molecules currently being studied as potential diagnostic, prognostic and therapeutic biomarkers for cancer and other diseases
  • Extensive research on these post-transcriptional modulators has proven that they are deregulated in breast cancerous tissues and even in biological fluids from breast cancer patients
  • five candidate miRNAs (miR-10b, miR-148b, miR-221, miR-21, and miR-155)
  • Nathan Goodyear on 06 Feb 18
     
    Epigenetics plays a role, via disregulated miRNA, in increased cell growth, progression, and invasion in Lebanese women with breast cancer.  It is not just genetics that play a role, but epigenetics.
Nathan Goodyear

Galectin-3 in cancer - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/24530298

cancer Galectin-3

shared by Nathan Goodyear on 02 Feb 21 - No Cached
  • Nathan Goodyear on 02 Feb 21
     
    New biomarker for cancer: proliferation, angiogenesis, apoptosis, differentiation, and adhesion.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

joe.endocrinology-journals.org/...R47.full

testosterone hormone health disease hormones men male cardiovascular disease CVD

shared by Nathan Goodyear on 13 May 13 - No Cached
  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
  • ...54 more annotations...
  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
  • bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
  • Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
  • It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with CAD
  • Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
  • Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
  • the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
  • Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
  • Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
  • TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly reduced by a pre-incubation with 3β-Adiol in HUVECs
  • 3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
  • There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
  • The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
  • trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
  • Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
  • Nathan Goodyear on 13 May 13
     
    Good deep look into the testosterone and CVD link.
Nathan Goodyear

The 4-Pregnene and 5α-Pregnane Progesterone Metabolites Formed in Nontumorous and Tumorous Breast Tissue Have Opposite Effects on Breast Cell Proliferation and Adhesion - 0 views

cancerres.aacrjournals.org/...936.full

progesterone metabolism cancer risk 4-pregnene 5alpha-pregnane

shared by Nathan Goodyear on 17 Feb 12 - No Cached
  • We report here the first evidence that tumorous breast tissue exhibits elevated 5α-reductase activity, which promotes significant increases in 5α-pregnanes, especially 5αP,4 whereas the normal (nontumorous) breast tissue produces more 4-pregnenes, especially 3αHP
  • 3αHP and other 4-pregnenes inhibit, whereas 5αP and other 5α-pregnanes stimulate, breast cell proliferation and detachment
  • it is evident that breast tissue can convert progesterone into two classes of metabolites: the δ-4-pregnenes (which retain the C4–5 double bond), and the 5α-reduced 21-carbon steroids (5α-pregnanes)
  • ...12 more annotations...
  • irreversible action of 5α-reductase
  • in normal (nontumorous) breast tissue, the 4-pregnene metabolites of progesterone greatly exceeded the 5α-pregnanes, whereas in tumorous tissue, 5α-pregnanes exceeded 4-pregnenes.
  • These differences in 5α-pregnane and 4-pregnene amounts were largely attributable to differences in 5αP and 3αHP production in tumorous and nontumorous tissues
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
  • These findings suggest greatly elevated 5α-reductase activity in tumorous, as compared with nontumorous, breast tissue.
  • progesterone metabolites that retain the C-4 double bond (i.e., the 4-pregnenes) exert an antiproliferative effect in the three cell lines that were tested, whereas the 5α-pregnanes stimulate breast cell line proliferation.
  • the degree of mitogenicity would be determined by the ratio of 5α-pregnanes:4-pregnenes. Tissues with a high 4-pregnene:5α-pregnane ratio would maintain a higher degree of normalcy, whereas those with a high 5α-pregnane:4-pregnene ratio would tend toward tumorigenicity
  • The observations that progesterone metabolites affect both ER-positive and ER-negative cells as well as tumorigenic (MCF-7) and nontumorigenic (MCF-10A) cells strengthen the argument that these factors may be endocrinologically relevant for all forms of breast cancer.
  • progesterone metabolites as the active endocrine/paracrine/autocrine factors
  • Estrogen-based therapies elicit responses in only one-third of all breast cancer patients, and most of these show relapse.
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      Interesting that the effect of progesterone metabolites were found to be independent from ER status, age, and pre/post menopause
  • Nathan Goodyear on 17 Feb 12
     
    Different progesterone metabolites shown to have different tumor effects.  Implications are that, just as estrogen metabolism effects cancer risk, so does progesterone metabolism.
Nathan Goodyear

Adipose Tissue Inflammation in Obesity and Metabolic Syndrome - - Satoshi Nishimura - Discovery Medicine - 0 views

www.discoverymedicine.com/...obesity-and-metabolic-syndrome

inflammation obesity metabolic syndrome fat adipose tissue innate immune system humoral

shared by Nathan Goodyear on 21 Dec 11 - No Cached
  • Activation of inflammatory pathways in adipocytes impairs triglyceride storage and increases release of free fatty acids, an excess of which is known to induce insulin resistance in muscle and liver
  • recent studies have shown that large numbers of macrophages infiltrate obese adipose tissue,
  • It has been postulated that a paracrine loop involving free fatty acids and inflammatory cytokines establishes a vicious cycle between adipocytes and macrophages that propagates the inflammation
  • ...5 more annotations...
  • not only does interrupting the accumulation of macrophages within obese adipose tissue suppresses adipose inflammation in various animal models, it also ameliorates systemic insulin resistance and metabolic abnormalities, suggesting macrophages are key effector cells involved in adipose inflammation
  • Thus, obese visceral adipose tissue is clearly a site of chronic inflammation
  • activation of the leukocyte adhesion cascade, a hallmark of inflammation
  • CD8+ T cells within obese adipose tissue induce activation and migration of monocytes/macrophages, and in cooperation with the adipose tissue, they also induce macrophage differentiation. At the same time, obese adipose tissue activates CD8+ T cells, creating a vicious cycle involving CD8+ T cells, macrophages, and obese adipose tissue that propagates local inflammation
  • In obese adipose tissue there is a shift to dominance of CD8+ and TH1 T cells, which appears to propagate inflammation
  • Nathan Goodyear on 21 Dec 11
     
    fascinating read how the immune system and resultant inflammation results in obesity.
Nathan Goodyear

The 4-Pregnene and 5α-Pregnane Progesterone Metabolites Formed in Nontumorous and Tumorous Breast Tissue Have Opposite Effects on Breast Cell Proliferation and Adhesion - 0 views

cancerres.aacrjournals.org/...936.long

progesterone metabolite metabolites hormone hormones 5-alpha pregnene 5-alpha pregnenes 3-alpha pregnene 3-alpha pregnenes breast cancer

shared by Nathan Goodyear on 28 Jan 14 - No Cached
  • Nathan Goodyear on 28 Jan 14
     
    Good discussion of the different effects of progesterone metabolites in breast cancer cell lines (in vitro).  This article focused on the biochemical balance of 5alpha pregnane: 3alpha HP.  The increase in this ration promoted proliferation and metastasis, where a decreased ratio did the opposite
Nathan Goodyear

Progesterone metabolites regulate induction, growth, and suppression of estrogen- and progesterone receptor-negative human breast cell tumors - 0 views

www.ncbi.nlm.nih.gov/...PMC3706910

progesterone metabolites metabolite 5-alpha pregnene 5-alpha pregnenes 5alpha-dihydroprogesterone 4-pregnene 4-pregnenes 3alpha-dihydroprogesterone breast cancer ER PR hormone hormones receptors estrogen

shared by Nathan Goodyear on 28 Jan 14 - No Cached
  • in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines
  • Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP
  • When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa
  • ...31 more annotations...
  • Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors
  • Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions
  • The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress
  • hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions.
  • a large proportion (about 30% to 60%) of breast tumors are ER and/or PR negative
  • about 90% of normal proliferating breast epithelial cells are receptor negative
  • Our previous in vitro studies had shown that breast tissues and cell lines readily convert progesterone to 5α-pregnanes, such as 5αP, and delta-4-pregnenes, such as 3αHP (Figure ​(Figure1),1), and that tumorous breast tissues [15] and tumorigenic breast cell lines [16] produce higher levels of 5αP and lower levels of 3αHP than do normal breast tissues and nontumorigenic cell lines
  • The progesterone metabolism studies suggested that increases in 5αP and decreases in 3αHP production accompany the shift toward breast cell neoplasia and tumorigenicity
  • In vitro studies on five different human breast cell lines showed that cell proliferation and detachment are significantly increased by 5αP and decreased by 3αHP
  • the prevailing theory of hormonal regulation of breast cancer, as well as hormone-based therapies, revolves around estrogen and/or progesterone and ER/PR-positive breast cells and tumors.
  • Not only do these "receptor-negative" breast cancers fail to benefit from current hormonal therapies, but they also generally exhibit more-aggressive biologic behaviors and poorer prognosis than the receptor-positive ones
  • The results of the studies reported here show for the first time that the progesterone metabolites, 5αP and 3αHP, act as hormones that regulate ER/PR-negative breast tumor formation, growth, and regression
  • The onset of the ER/PR-negative human breast cell tumors in mice was considerably accelerated, and the growth significantly stimulated, by just one or two applications of 5αP
  • In contrast, 3αHP retarded onset of tumor formation, suppressed tumor growth, and inhibited or regressed existing 5αP-induced tumors
  • When both hormones were administered simultaneously, the effects of one were abrogated by the effects of the other.
  • The 5αPR and 3αHPR (which are associated with the plasma membranes of both ER/PR-positive [19] and ER/PR-negative [29] cells) are distinct from each other and from known ER, PR, androgen, and corticosteroid receptors, and lack affinity for other steroids, such as progesterone, estrogen, androgens, corticosteroids, and other progesterone metabolites
  • Levels of 5αPR are upregulated by 5αP itself and estradiol, and downregulated by 3αHP in both ER/PR-positive and -negative cells
  • ndications are that 5αP acts via the surface receptor-linked mitogen-activated protein kinase (MAPK; Erk1/2) pathway; 5αP significantly stimulates activation of Erk1/2 [30], increases the Bcl-2/Bax expression ratio [18] and actin depolymerization [31], and decreases expression of actin and adhesion plaque-associated vinculin [31], resulting in decreased apoptosis and increased mitosis and cell detachment
  • 3αHP appears to suppress protein kinase C (PKC), phospholipase C (PLC), Ca2+ mobilization (unpublished observations), and the Bcl-2/Bax expression ratio [18], and increases expression of the cell-cycle inhibitor p21 [18], resulting in increased apoptosis and decreased proliferation and detachment of breast cell lines.
  • serum from mice with tumors had significantly more 5αP than 3αHP
  • the tumors, which on average had about threefold higher concentrations of 5αP than the respective sera, and >10-fold higher 5αP than 3αHP levels
  • Previous in vitro metabolism studies showed that human breast tumor tissues convert significantly more progesterone to 5α-pregnanes like 5αP and less to 4-pregnenes like 3αHP than do paired normal (nontumorous) tissues
  • Similar differences in progesterone metabolism and enzyme gene expressions were observed between tumorigenic and nontumorigenic breast cell lines
  • breast carcinomas are able to synthesize progesterone
  • The current findings, along with the previous in vitro studies, suggest that the relative concentrations of 5αP and 3αHP in the breast microenvironment constitute important autocrine/paracrine determinants not only for tumorigenesis but also for potential regression of tumors and the maintenance of normalcy of ER/PR-negative breast cells/tissues.
  • Evidence presented here shows that a high concentration of 5αP, relative to 3αHP in the microenvironment, promotes initiation and growth of tumors, whereas a higher concentration of 3αHP, relative to 5αP, suppresses tumorigenesis and promotes normalcy
  • 5α-reductase and 5αPR levels are upregulated by 5αP
  • in the 3αHP-treated mice, the elevated 3αHP levels, relative to 5αP, in the microenvironment could have opposed progression to xenograft neoplasia by its inherent anticancer actions and the suppression of 5αP synthesis and 5αPR expression
  • the opposing actions of the progesterone metabolites also appear to exert some control over the estrogen-regulated effects on breast cancer by their ability to modulate ER numbers in ER-positive cells
  • because both ER/PR-negative and ER/PR-positive, as well as normal and tumorigenic human breast cell lines, have been shown to respond to 5αP and 3αHP in vitro, it is suggested that these endogenously produced progesterone metabolites may also play regulatory hormonal roles in ER/PR-positive breast cancers, as well as in the maintenance of normalcy in nontumorous breast tissues.
  • The in vivo data provide further evidence that progesterone metabolites, such as 5αP and 3αHP, deserve to be considered as active hormones in their own right, rather than inactive waste products
  • Nathan Goodyear on 28 Jan 14
     
    Progesterone metabolites and breast cancer
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydroxysteroid oxidoreductase and 3α(β)-hydroxysteroid oxidoreductases in tumorigenic (MCF-7, MDA-MB-231, T-47D) and nontumorigenic (MCF-10A) human breast cancer cells - 0 views

www.ncbi.nlm.nih.gov/...PMC154104

progesterone metabolites breast cancer 5alpha-reductase 5-alpha pregnene 5-alpha pregnenes 4-pregnene 4-pregnenes

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • Exposure of human breast cell lines (MCF-7, MCF-10A, and ZR-75-1) to 5α-pregnanes results in changes associated with neoplasia, including increased proliferation and decreased attachment [1], depolymerization of F-actin [2] and decreases in adhesion plaque-associated vinculin
  • Exposure to 4-pregnenes results, in general, in opposite (anti-cancer-like) effects
  • 5αR1 has been detected in various androgen-independent organs, such as the liver and brain
  • ...10 more annotations...
  • 5αR2 has been found predominantly in androgen-dependent organs, such as epididymis and prostate
  • The 5α-pregnanes:4-pregnenes ratio was about 8-fold higher in tumorous than in nontumorous breast tissue after an 8-hour incubation with [14C]progesterone
  • Studies with breast cell lines, showing that 5α-pregnanes stimulate proliferation and decrease attachment of cells
  • both tissue and breast cell line studies suggest that an elevated level of progesterone 5α-reductase activity may be an indicator of breast tumorigenesis, regardless of presence or absence of ER and/or PR
  • 5αR1 is the main isoform expressed in human breast carcinomas [29] and that 5αR2 may not be associated with risk of breast cancer
  • the differences in 5α-pregnane production between the cells is due primarily to a difference in 5αR1 expression
  • As in the case of 5α-reductase activity, the presence or absence of ER and PR do not appear to be related to 5α-reductase expression.
  • the conversion of progesterone to the cancer promoting 5α-pregnanes is significantly higher in the human tumorigenic breast cell lines
  • lthough both 5αR1 and 5αR2 are expressed by these cells, the elevated 5α-reductase activity appears to be the result of significantly greater expression of 5αR1
  • Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for promoting breast cancer progression due to increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes
  • Nathan Goodyear on 30 Jan 14
     
    balance of enzyme production between 5alpha-reductase and 20alpha-hydroxysteroid oxidoreductase and 3alpha(beta)-hydroxysteroid oxidoreductase play role in carcinogenesis and proliferation in the balance of production of progesterone metabolites. The 5alpha pregnenes are pro carcinogenic  and the 4-pregnenes are anti carcinogenic.
1 - 20 of 35 Next ›
Showing 20▼ items per page