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Nathan Goodyear

Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androg... - 0 views

www.nature.com/...srep01528.html

prostate cancer 3-alpha androstanediol 3-beta androstanediol DHT metabolite metabolites

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • PSA levels in media were increased by 3α-diol
  • Similarly to 3α-diol, 3β-diol also increased PSA levels in media in a concentration-dependent manner
  • intracellular DHT is synthesized from inactive androgen 3α- and 3β-diol via different pathways in prostate cancer cells
  • ...12 more annotations...
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      error in statement: DHT metabolites are not inactive, they just don't activate AR.
  • 3β-diol can be a precursor of DHT in prostate cancer cells.
  • serum 3α-diol G levels reflect the androgen milieu in localized prostate cancer patients receiving ADT
  • A few studies reported that 3β-diol is a potential ligand of estrogen receptor β (ERβ) and has an antiproliferative effect
  • our results revealed that 3β-diol is potentially a precursor of DHT in prostate cancer cells
  • Bauman et al. showed that 3α-diol is inactive at AR, but induces prostate growth
  • Prostate cancer cells promoted synthesis from the DHT metabolite 3α-diol during the long duration of ADT
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      the authors highlight the suggestion is that 3alpha-diol's activity is via 3alpha-HSD, but fail to mention that it is known that 3alpha-diol interacts with the ER-alpha in the prostate.
  • verified the synthesis of DHT from 3α- or 3β-diol via different pathways in prostate cancer cells in this study
  • HSD17B6 expression levels in prostate cancer can be useful for the diagnosis of high-risk prostate cancer
  • serum 3α-diol G levels reflect the adrenal androgen milieu in localized prostate cancer patients
  • 3α- and 3β-diol has a much more significant role in intratumoral androgen metabolism during ADT
  • Nathan Goodyear on 27 Jan 14
     
    DHT metabolites play an important role of intra-prostate DHT synthesis in those following ADT.  This is a proposed mechanism for the failure rate and aggressive nature of prostate cancer that fails ADT.   3-alpha androstanediol is converted via 3 alpha HSD back to DHT.  In contrast, 3-beta androstanediol cannot.
Nathan Goodyear

The anti-malarial drug artesunate causes cell cycle arrest and apoptosis of triple-nega... - 0 views

www.ncbi.nlm.nih.gov/...30660598

breast cancer cancer artesunate

shared by Nathan Goodyear on 01 Jul 19 - No Cached
  • Nathan Goodyear on 01 Jul 19
     
    ART inhibited breast cancer cell proliferation via a reactive oxygen species (ROS)-dependent G2/M arrest and ROS-independent G1 arrest. ART-treated MDA-MB-468 and SK-BR-3 cells also experienced apoptotic cell death, which was both ROS- and iron-dependent. ART-induced oxidative stress caused the loss of mitochondrial outer membrane integrity and damage to the cellular DNA of MDA-MB-468 and SK-BR-3 cells. Only abstract available...I will post full article once available.
Nathan Goodyear

European Journal of Clinical Nutrition - Effect of maternal n-3 long-chain polyunsatura... - 0 views

www.nature.com/...ejcn2014158a.html

nutrition n-3 omega 3 omega-3 fish oil pregnancy childhood obesity

shared by Nathan Goodyear on 22 Dec 14 - No Cached
  • It is estimated that approximately 30% of children and adolescents in the United States and about 15–30% of those in Europe can be classified as overweight or obese
  • An increasing body of evidence now suggests that the nutritional environment encountered in utero and the early postnatal life may elicit permanent alterations in adipose tissue structure or function and, thereby, programme the individual’s propensity to later obesity
  • The composition of fatty acids in the Western diets has shifted toward an increasing dominance of n-6 relative to n-3 LCPUFAs over the past decades.9,10 This shift is also reflected in the fatty acid composition of breast milk
  • ...8 more annotations...
  • Evidence from animal studies suggests that the n-6 LCPUFA arachidonic acid promotes adipose tissue deposition, whereas the n-3 LCPUFAs eicosapentaenoic acid and docosahexaenoic acid seem to exert an opposite effect
  • Overall, no effect of supplementation was found on BMI in preschool (<5 years) and school-aged (6–12 years) children
  • increased adiposity, once established in childhood, tends to track into adulthood
  • Many studies have shown that even children <2 years with a high BMI are at increased risk of developing obesity later in life
  • The acquisition of fat cells early in life appears to be an irreversible process
  • Evidence from cell culture and animal studies suggests that early exposure to n-3 LCPUFAs has the potential to limit adipose tissue deposition mainly by attenuating the production of the arachidonic acid metabolite prostacyclin, which has been shown to enhance adipogenesis
  • In conclusion, there is currently no evidence to support that maternal n-3 LCPUFA supplementation during pregnancy and/or lactation exerts a favourable programming effect on adiposity status in childhood
  • our systematic review highlights that most of the trials reviewed were prone to methodological limitations
  • Nathan Goodyear on 22 Dec 14
     
    Literature review finds limited data (9 studies, only 6 RCTs) of omega-3 during pregnancy.  No data was found that supported reduced obesity in children by mothers taking n-3 during pregnancy.  No harm was found either.  Data was sparse.   Take home: not enough data, no harm to pregnancy, children, thus if indications are present for mother, then recommend n-3.  At this point not studies have pointed to reduced obesity in children.
Nathan Goodyear

International Journal of Impotence Research - Obesity, low testosterone levels and erec... - 0 views

www.nature.com/...ijir200842a.html

low T low Testosterone men male hormone hormones ED erectile dysfunction Testosterone diabetes metabolic syndrome obesity

shared by Nathan Goodyear on 27 Jan 15 - No Cached
  • Studies have shown that ED may be an early biomarker of general endothelial dysfunction, atherosclerosis and CVD
  • testosterone treatment of hypogonadal young and older men improves sexual function, increases lean mass and decreases fat mass
  • In men with low serum testosterone (for example, <8 or 230 nmol l−1) with obesity, metabolic syndrome and diabetes mellitus, treatment with testosterone is warranted
  • ...12 more annotations...
  • In obese middle-aged men, testosterone treatment reduced visceral adipocity, insulin resistance, serum cholesterol and glucose levels
  • testosterone replacement has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure in hypogonadal men with the metabolic syndrome as well as type 2 diabetes mellitus
  • Testosterone significantly inhibits lipoprotein lipase activity, which reduces triglycerides uptake into adipocytes in the abdominal adipose tissue
  • testosterone treatment decreased endogenous inflammatory cytokines (tumor necrosis factor-α and IL-1β) and lipids (total cholesterol) and increased IL-10 in hypogonadal men
  • Testosterone treatment reduced leptin and adiponectin levels in hypogonadal type 2 diabetic men after 3 months of testosterone replacement
  • available data clearly show a relationship between obesity, low testosterone levels and ED
  • Obesity adversely affects endothelial function and lowers serum testosterone levels through the development of insulin resistance and metabolic syndrome
  • Metabolic disturbances as well as production of cytokines and adipokines by inflamed fat cells may be causal factors in the development of ED
  • The onset of ED and the associated risk of CVD may be delayed through lifestyle modifications that affect obesity, such as diet and exercise
  • Very low testosterone levels contribute to the development of ED in obesity, metabolic syndrome and type 2 diabetes mellitus
  • Obesity is associated with low total testosterone levels that can be explained at least partially by lower sex hormone-binding globulin (SHBG) in obese men
  • epidemiological studies have shown a negative correlation between BMI and total testosterone and to a lesser extent with free and bioavailable (biologically active) testosterone levels
  • Nathan Goodyear on 27 Jan 15
     
    Obesity is associated with low Testosterone and ED in men.
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

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 0 views

www.researchgate.net/...10A)_human_breast_cancer_cells

progesterone metabolites breast cancer 5-alpha-pregnanediol 4-pregnenediol

shared by Nathan Goodyear on 23 Jan 14 - No Cached
  • Nathan Goodyear on 23 Jan 14
     
    Intra mammary progesterone metabolism and its associated metabolites found to be associated with tumorigenic activity in cell lines.  This was independent from ER PR status.  5 alpha-pregnanes were found to be pro-tumor and 4-pregnanes were anti-tumor.
Nathan Goodyear

Abstract 2958: Evaluating the therapeutic effects of methylene blue against prostate ca... - 0 views

aacrjournals.org/...uating-the-therapeutic-effects

p53 prostate cancer Bax TRAIL methylene blue

shared by Nathan Goodyear on 16 Nov 22 - No Cached
  • Nathan Goodyear on 16 Nov 22
     
    Bax, TRAIL R2/D5, and phospho p53 (Serine 15, Serine 46, Serine 392) were robustly upregulated in LNCaP cells following MB treatment.
Nathan Goodyear

Lipoproteins - 0 views

www.rpi.edu/...lipoprot.htm

cholesterol lipoproteins apolipoproteins VLDL HDL LDL IDL chylomicrons biochemistry

shared by Nathan Goodyear on 21 May 13 - Cached
  • Nathan Goodyear on 21 May 13
     
    Good review of the biochemistry and truth behind cholesterol.  The read here is tedious but important.  Cholesterol is about apolipoproteins, not cholesterol.
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 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.
Nathan Goodyear

BMC Cancer | Full text | Activity and expression of progesterone metabolizing... - 0 views

www.biomedcentral.com/...9

breast cancer progesterone metabolites progesterone metabolites hormone hormones

shared by Nathan Goodyear on 18 Jun 14 - No Cached
  • Nathan Goodyear on 18 Jun 14
     
    Might the enzymes be more important than the hormones themselves?  The number is important i.e. progesterone, but how the number came to be is more important as it points to the underlying etiology.  Here, the balance of enzymes are found to direct cell line tumor potential.  The enzyme 5alpha-reductase increased production of the 5alpha-pregnanes which increased tumor potential.  In contrast, the enzymes 20alpha-hydrosteroid oxidoreductase and 3alpha-hydroxysteroid oxidoreductase increase production of the 4alpha-pregnanes, which decreased tumor potential.
Nathan Goodyear

Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk... - 0 views

www.carcinogenesis.com/article.asp

Cadmium heavy metals pregnancy endocrine disrupting chemicals endocrine disruptors hormones puberty

shared by Nathan Goodyear on 20 Jul 14 - No Cached
  • Nathan Goodyear on 20 Jul 14
     
    Animal study finds that Cadmium is estrogenic.  This study found that not only was Cadmium an endocrine disruptor for the pregnant animals, but was also estrogenic in the mammary glands of the offspring.
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 0 views

bmccancer.biomedcentral.com/...1471-2407-3-9

hormones progesterone progesterone metabolites cancer breast cancer 5alpha reductase 5alpha-pregnane 4-pregnene

shared by Nathan Goodyear on 07 Oct 16 - No Cached
  • Nathan Goodyear on 07 Oct 16
     
    cell culture study finds that increased 5alpha reductase activity and resultant 5alpha-pregnanes are associated with breast cancer cell lines.  This is in contrast to the 4-pregnenes.  In fact, decreased 4-pregnenes are found in the same breast cancer cell lines; this suggests decreased 20alpha-HSO and 3alpha-HSO activity.
Nathan Goodyear

Cross-kingdom inhibition of breast cancer growth by plant miR159 - 0 views

www.ncbi.nlm.nih.gov/...PMC4746606

cancer epigenetics nutrigenomics nutrition diet

shared by Nathan Goodyear on 11 Dec 17 - No Cached
  • MicroRNAs (miRNAs), a major family of small RNAs, are ∼23 nt-long single strands of RNA that bind to mRNA transcripts to inhibit their translation
  • A recent study by Zhang et al. reported that plant-derived miRNAs can be found in human serum.
  • The group demonstrates that the plant miRNA miR168 may be taken up through dietary intake to inhibit the expression of its target low-density lipoprotein receptor 1 in the liver21, providing the first evidence that miRNA in food may influence gene expression in mammalian organs.
  • ...6 more annotations...
  • A more recent finding by the same group shows that a plant miRNA from honeysuckle is able to inhibit Influenza A replication22, indicating that plant miRNAs may be useful for treating human diseases.
  • We found that plant miR159 could be detected in human sera and its levels were inversely correlated with BC incidence and progression.
  • We further identified TCF7 as a mammalian target for miR159 and showed the anti-proliferative function of miR159 in BC cells using in vitro and in vivo models, demonstrating for the first time that a plant miRNA is able to influence BC cell growth.
  • certain dietary miRNAs from plants and other species may serve as highly affordable and powerful means of treatment with minimal inconvenience to patients.
  • miR159 which (using a synthetic mimic) targets TCF7 to inhibit the proliferation of cells whose growth is dependent on TCF7 such as the BC cells MDA-MB-231
  • our study using a BC model clearly indicates the anti-tumor effect of orally administered synthetic miR159 in its naturally existing form with the plant-specific 2'-O-methylation, suggesting the feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track
  • Nathan Goodyear on 11 Dec 17
     
    Plant microRNA found to exist in human serum from gut absorption to then alter genetic expression in in-vitro and in vivo studies.
Nathan Goodyear

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells - 0 views

journals.plos.org/...article

NF-KappaB breast cancer artesunate

shared by Nathan Goodyear on 13 Jun 19 - No Cached
  • Nathan Goodyear on 13 Jun 19
     
    Upregulation of NF-kappaB found to promote Artesunate resistance in breast cancer cell line.
Nathan Goodyear

Short-term beneficial effects of methylene blue on kidney damage in septic shock patien... - 0 views

www.ncbi.nlm.nih.gov/...PMC2228379

methylene blue MB sepsis renal failure renal injury

shared by Nathan Goodyear on 19 Jun 22 - No Cached
  • Nathan Goodyear on 19 Jun 22
     
    1 mg/kg improved renal function in sepsis patients
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