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Semen quality, infertility and mortality in the USA - 0 views

humrep.oxfordjournals.org/...humrep.deu106 infertility semen sperm mortality men male men's health health wellness
shared by Nathan Goodyear on 20 May 14 - No Cached
  • Nathan Goodyear on 20 May 14
     
    Men with infertility associated with 2.3 fold higher risk of death. The factors evaluated were semen volume, sperm concentration, sperm motility, total sperm count, total motile sperm count.  Those that have 2 or more positive parameters were associated with increased death compared to those with normal semen analysis.
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Influence of increasing body mass index on semen and reproductive hormonal parameters i... - 0 views

www.fertstert.org/...fulltext BMI male obesity male hormones hormones Testosterone Testosterone:Estradiol Estradiol sperm sperm concentration sperm count sperm motility fertility
shared by Nathan Goodyear on 30 Nov 16 - No Cached
  • Nathan Goodyear on 30 Nov 16
     
    retrospective cohort finds mild but significant relationships b/t BMI and total Testosterone, Testosterone:Estradiol and Estradiol alone.  BMI was inversely correlated with Testosterone and the T:E2 ratio; but directly correlated with E2 alone. There was also a negative correlation with sperm concentration, motility and morphology.
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Influence of tumor necrosis factor α inhibitors on testicular function and se... - 0 views

www.fertstert.org/...abstract TNF-alpha sperm motility low T Testosterone LH FSH autoimmune disease inflammation male men hormone hormones
shared by Nathan Goodyear on 18 Feb 14 - No Cached
  • Nathan Goodyear on 18 Feb 14
     
    Cause and effect cannot be taken from this study.  However, TNF-alpha is known to disrupt testicular function, in this case the study found decreased sperm motility, lower Testosterone levels, and increased LH and FSH at baseline.  Improvement was seen after anti-TNF-alpha therapy. The point of this study should be why the elevated TNF-alpha and attack there.
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The impact of male overweight on semen quality and outcome of assisted reproduction Tho... - 0 views

www.ajandrology.com/article.asp infertility BMI sperm count sperm concentration sperm motility
shared by Nathan Goodyear on 23 Sep 14 - No Cached
  • Nathan Goodyear on 23 Sep 14
     
    Abstract only. Study in men seeking reproductive assistance found that increasing BMI had no negative impact on sperm concentration, sperm count, motility and seminal volume. 
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Leptin Level and Oxidative Stress Contribute to Obesity-Induced Low Testosterone in Mur... - 0 views

www.hindawi.com/...190945 low T low Testosterone oxidative stress leptin hormone hormones obesity sperm count sperm motility
shared by Nathan Goodyear on 22 Oct 14 - No Cached
  • Nathan Goodyear on 22 Oct 14
     
    mouse study finds that increased oxidative stress and high leptin levels in obese mice led to decreased sperm count, decreased sperm motility, and low T.
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Effect of Cordyceps militaris supplementation ... [Am J Chin Med. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19051352 Cordyceps Cordyceps sinensis Testosterone Estradiol sperm
shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • Nathan Goodyear on 27 Jan 14
     
    Cordyceps increased Testosterone, Estradiol, sperm count and motility in mouse model.
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Obestatin partially affects ghrelin stimulatio... [Endocrinology. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17204551 obestatin overweight obesity weight loss
shared by Nathan Goodyear on 02 Nov 11 - No Cached
  • Nathan Goodyear on 02 Nov 11
     
    obestatin inhibits food intake and slow GI motility.  THis is the opposite of ghrelin, which increases appetite
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Functional Importance of 1α,25(OH)2-Vitamin D3 and the Identification of Its ... - 0 views

www.hindawi.com/...808906 vitamin D Testis testicles Testosterone sperm fertility infertility
shared by Nathan Goodyear on 29 Jul 14 - No Cached
  • Nathan Goodyear on 29 Jul 14
     
    Vitamin D plays role in healthy Testes function.  This signaling occurs through genomic and non-genomic signaling pathways.  Testosterone production is influenced, sperm motility and spermatogenesis is influenced.  
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http://gut.bmj.com/content/23/7/608.full.pdf - 0 views

gut.bmj.com/...608.full.pdf celiac disease celiac disease hypogonadism low T Testosterone sperm infertility men male hormone hormones
shared by Nathan Goodyear on 28 Jul 14 - No Cached
  • Nathan Goodyear on 28 Jul 14
     
    low Testosterone and abnormal sperm morphology and motility found to be associated with Celiac disease with men in small study.  
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Reversible infertility in male coeliac patients. - 0 views

www.ncbi.nlm.nih.gov/...PMC1681902 infertility male men hormone hormones celiac disease celiac disease gluten
shared by Nathan Goodyear on 28 Jul 14 - No Cached
  • Nathan Goodyear on 28 Jul 14
     
    Small study of 40 men with Celiac disease found to have improved sperm count and motility following elimination of gluten 
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Inhibition of breast cancer cell migration by activation of cAMP signaling - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/26022351 phosphodiesterase inhibitors breast cancer phosphodiesterase 5 inhibitors cyclic AMP PDE5 inhibitors cAMP
shared by Nathan Goodyear on 08 Mar 21 - No Cached
  • Nathan Goodyear on 08 Mar 21
     
    Increase in cAMP found to inhibit breast cancer motility and migration. Here, they used cAMP analogs, forskolin and PDE inhibitors.
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Vitamin D is associated with testosterone and hypogonadism in Chinese men: Results from... - 0 views

www.ncbi.nlm.nih.gov/...PMC4504177 vitamin d male hormones low T low Testosterone Testosterone
shared by Nathan Goodyear on 09 Jan 17 - No Cached
  • lower 25(OH)D level was significantly associated with lower total T, E2, SHBG, LH and FSH levels after adjusting for age, residence area, economic status and current smoker
  • association between 25(OH)D status and hypogonadism in Chinese men and confirms that this relationship is present in a large population
  • VDR knockout mutant mice showed gonadal insufficiencies
  • ...6 more annotations...
  • High LH and FSH levels in the male mice indicated hypergonadotropic hypogonadism
  • Another mouse study reported a tendency towards low testosterone/LH ratio and Leydig cell hyperplasia in VDR null mice
  • The serum testosterone levels could increase to normal values in vitamin D-deficient rats replete with vitamin D
  • VDR knockout mice had decreased sperm count, reduced sperm motility, and histological abnormality of the testis
  • vitamin D supplementation increases testosterone levels in non-diabetic subjects
  • The data from the European Male Ageing Study [9] indicated that 25(OH)D is positively associated with total T
  • Nathan Goodyear on 09 Jan 17
     
    Study of 713 Chinese men finds a correlation between low vitamin D and low total Testosterone.
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Electronic Wheel chair - 0 views

www.wheelchairindia.com/...POWER-WHEELCHAIR Shower Wheelchair Can Dramatically Improve Lives Electronic Wheel chair electric propulsion by motors a joy stick or push buttons shower wheelchair lightweight and portable for travel accessible seat frame
shared by wheelchairindia9 on 16 Apr 15 - No Cached
  • wheelchairindia9 on 16 Apr 15
     
    Golden Technologies takes all the worry out of purchasing a power wheelchair. Designers blend the most technologically advanced components with superior designs to provide with the almost in quality, comfort and style. Motorized wheelchairs to enter bike lanes if a sidewalk isn't available or passable by wheelchair. Wheelchair users would be required to yield the right-of-way to bikers. The proposal also adds motorized wheelchairs to current law affecting vehicles and bicycles on the road, including the required three foot law between bikers and drivers. Supporters bill would help wheelchair users get around quickly and that areas without sidewalks are often difficult to navigate. It's the standard chair, with the main frame attaches to the front. This isn't a futuristic design as such, but a very good way of maintaining or building strength in those who are bound to a wheelchair, and may hope to walk again in their future. Personally, this bike is pretty cool. It's got a front frame similar to a chopper, with the added comfort of a chair appose to a saddle. A new module is set to transform electric powered wheelchairs into communication hubs. An powerchair is more compact and has a better turning radius than an electric scooter; making it is easier to navigate narrow doorways and tight turns. Another advantage of the powerwheelchair is that its armchair joystick does not require an upright posture like an electric scooter's handlebars. Most power wheelchairs can also be taken apart and stowed, while scooters usually can't. Powerwheelchairs are also usually less expensive than scooters. For many disabled people, the only way to move around is by using a wheelchair. Those who cannot powered wheelchairs propel themselves with their arms, which often leads to fatigue, pain, and even permanent damage to arms and shoulders. BENEFITS: Activates circulation system and improves cardio-pulmonary function. Helps prevent decubitus sores. Improves bowel regu
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Reduced anxiety-like behavior and central neurochemical change in germ-free mice - Neuf... - 0 views

onlinelibrary.wiley.com/...abstract anxiety mood Gut bacteria intestinal microbial balance dysbiosis
shared by Nathan Goodyear on 12 Apr 11 - No Cached
  • Nathan Goodyear on 12 Apr 11
     
    Gut health linked to brain health
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Improvement in semen quality associated with decreasing occupational lead exposure - Vi... - 0 views

onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0274(199903)35:3<257::AID-AJIM5>3.0.CO;2-#/abstract lead exposure
shared by Nathan Goodyear on 05 Jul 11 - No Cached
  • These results support the notion that occupational lead exposure at currently acceptable levels has a small adverse effect on sperm quality, especially sperm motility, and that this effect is at least partially reversible
  • Nathan Goodyear on 05 Jul 11
     
    Reducing lead exposure levels partially reverses male sperm quality
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Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocri... - 0 views

www.fasebj.org/...439.full appetite orexigenic anorexigenic gherkin leptin
shared by Nathan Goodyear on 25 Oct 14 - No Cached
  • Nathan Goodyear on 25 Oct 14
     
    orexigenic versus anorexigenic signaling and control of appetite at the level of the hypothalamus.
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Therapeutic hyperthermia: The old, the new, and the upcoming - Critical Reviews in Onco... - 1 views

www.croh-online.com/...fulltext hyperthermia hyperthermic therapy cancer oncology
shared by Nathan Goodyear on 30 Aug 18 - No Cached
  • not well understood, but it is felt to be a combination of both heat-induced necrosis and of protein inactivation (e.g., repair enzymes) as opposed to DNA damage
  • alterations in tumor cytoskeletal and membrane structures, which disrupt cell motility and intracellular signal transduction
  • A common explanation for HT-enhancement of RT and CT involves inhibition of homologous recombination repair of double-strand DNA breaks, preventing cells from repairing sub-lethal damage
  • ...15 more annotations...
  • it does appear to inhibit rejoining of RT-induced DNA breaks more than is commonly observed after RT alone
  • HT damages cells and enhances RT and CT sensitivity as a function of both temperature and duration of treatment
  • as temperature or duration increase, the rate of cell killing also increases
  • At temperatures above 42 °C, tumor vasculature is damaged, resulting in decreased blood flow
  • Cancer cells are particularly vulnerable to heating; in vivo studies have shown that temperatures in the range of 40–44 °C cause more selective damage to tumor cells
  • cancerous blood vessels are chaotic, leaky, and inefficient
  • selective cytotoxic effect on tumor cells include inhibition of key cancer cell-signaling pathways such as AKT, inducing apoptosis, suppression of cancer stem cell proliferation, and others
  • increase in immunological attacks against tumors after HT, which were believed to be achieved through activation of HSPs and subsequent modulation of the innate and adaptive immune responses against tumor cells
  • HT does lead to activation of the immune system and HSP-induced cell death through modification of the tumor cell surface
  • These HSPs and tumor antigens are taken up by dendritic cells and macrophages and go on to induce specific anti-tumor immunity
  • In vivo studies demonstrate HT-enhancement of NK cell activity, and HT has been shown to increase neutrophilic granulocytes with anti-tumor activity
  • it has become increasingly clear that HT results in immune stimulation, through both direct heat-mediated cell killing as well as innate and adaptive immune system modulation
  • The term hyperthermia is used in this review to refer to heating within the clinically accepted range of 40–45 °C
  • temperatures above 42.5–43 °C the exposure time can be halved with each 1 °C increase while maintaining equivalent cell killing
  • gradual heating at 43 °C for 1 h worked through an apoptotic pathway
  • Nathan Goodyear on 30 Aug 18
     
    Comprehensive review of hyperthemic therapy.
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Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer... - 0 views

www.ncbi.nlm.nih.gov/...PMC5282724 EMT TME metastasis cancer stem cells cancer MMP2 Notch MMP-9 MMP-2 radioresistance Hedgehog CSC MMP9 Snail HIF-1alpha tumor microenvironment epithelial to mesenchymal transition TGF-beta radiation
shared by Nathan Goodyear on 09 Feb 21 - No Cached
  • More than half of cancer patients are treated with IR at some point during their treatment
  • fractionation schedule is the delivery of 1.8–2.0&nbsp;Gy per day, five days per week
  • Nuclear DNA is the primary target of IR; it causes DNA damage (genotoxic stress) by direct DNA ionization
  • ...121 more annotations...
  • IR also indirectly induces DNA damage by stimulating reactive oxygen species (ROS) production
  • IR is known to induce EMT in vitro
  • p53 is activated in response to IR-induced DNA damage
  • IR paradoxically also promotes tumour recurrence and metastasis
  • DNA double-strand breaks (DSBs)
  • cancer cells undergoing EMT acquire invasive and metastatic properties
  • changes in the tumour microenvironment (TME)
  • IR seems to induce EMT and CSC phenotypes by regulating cellular metabolism
  • EMT, stemness, and oncogenic metabolism are known to be associated with resistance to radiotherapy and chemotherapy
  • Hanahan and Weinberg proposed ten hallmarks of cancer that alter cell physiology to enhance malignant growth: 1) sustained proliferation, 2) evasion of growth suppression, 3) cell death resistance, 4) replicative immortality, 5) evasion of immune destruction, 6) tumour-promoting inflammation, 7) activation of invasion and metastasis, 8) induction of angiogenesis, 9) genome instability, and 10) alteration of metabolism
  • EMT is a developmental process that plays critical roles in embryogenesis, wound healing, and organ fibrosis
  • IR is known to induce stemness and metabolic alterations in cancer cells
  • transforming growth factor-β [TGF-β], epidermal growth factor [EGF]) and their associated signalling proteins (Wnt, Notch, Hedgehog, nuclear-factor kappa B [NF-κB], extracellular signal-regulated kinase [ERK], and phosphatidylinositol 3-kinase [PI3K]/Akt
  • activate EMT-inducing transcription factors, including Snail/Slug, ZEB1/δEF1, ZEB2/SIP1, Twist1/2, and E12/E47
  • Loss of E-cadherin is considered a hallmark of EMT
  • IR has been shown to induce EMT to enhance the motility and invasiveness of several cancer cells, including those of breast, lung, and liver cancer, and glioma cells
  • IR may increase metastasis in both the primary tumour site and in normal tissues under some circumstance
  • sublethal doses of IR have been shown to enhance the migratory and invasive behaviours of glioma cells
  • ROS are known to play an important role in IR-induced EMT
  • High levels of ROS trigger cell death by causing irreversible damage to cellular components such as proteins, nucleic acids, and lipids, whereas low levels of ROS have been shown to promote tumour progression—including tumour growth, invasion, and metastasis
  • hypoxia-inducible factor-1 (HIF-1) is involved in IR-induced EMT
  • Treatment with the N-acetylcysteine (NAC), a general ROS scavenger, prevents IR-induced EMT, adhesive affinity, and invasion of breast cancer cells
    • Nathan Goodyear
      Nathan Goodyear on 09 Feb 21
       
      NAC for all patients receiving radiation therapy
  • Snail has been shown to play a crucial role in IR-induced EMT, migration, and invasion
  • IR activates the p38 MAPK pathway, which contributes to the induction of Snail expression to promote EMT and invasion
  • NF-κB signalling that promotes cell migration
  • ROS promote EMT to allow cancer cells to avoid hostile environments
  • HIF-1 is a heterodimer composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit.
  • Under normoxia, HIF-1α is rapidly degraded, whereas hypoxia induces stabilisation and accumulation of HIF-1α
  • levels of HIF-1α mRNA are enhanced by activation of the PI3K/Akt/mammalian target of rapamycin (mTOR)
  • IR is known to increase stabilisation and nuclear accumulation of HIF-1α, since hypoxia is a major condition for HIF-1 activation
  • IR induces vascular damage that causes hypoxia
  • ROS is implicated in IR-induced HIF-1 activation
  • IR causes the reoxygenation of hypoxic cancer cells to increase ROS production, which leads to the stabilisation and nuclear accumulation of HIF-1
  • IR increases glucose availability under reoxygenated conditions that promote HIF-1α translation by activating the Akt/mTOR pathway
  • The stabilised HIF-1α then translocates to the nucleus, dimerizes with HIF-1β, and increases gene expression— including the expression of essential EMT regulators such as Snail—to induce EMT, migration, and invasion
  • TGF-β signalling has been shown to play a crucial role in IR-induced EMT
  • AP-1 transcription factor is involved in IR-induced TGF-β1 expression
  • Wnt/β-catenin signalling is also implicated in IR-induced EMT
  • Notch signalling is known to be involved in IR-induced EMT
  • IR also increases Notch-1 expression [99]. Notch-1 is known to induce EMT by upregulating Snail
  • PAI-1 signalling is also implicated in IR-induced Akt activation that increases Snail levels to induce EMT
  • EGFR activation is known to be associated with IR-induced EMT, cell migration, and invasion by activating two downstream pathways: PI3K/Akt and Raf/MEK/ERK
  • ROS and RNS are also implicated in IR-induced EGFR activation
  • IR has also been shown to activate Hedgehog (Hh) signalling to induce EMT
  • IR has been shown to induce Akt activation through several signalling pathways (EGFR, C-X-C chemokine receptor type 4 [CXCR4]/C-X-C motif chemokine 12 [CXCL12], plasminogen activator inhibitor 1 [PAI-1]) and upstream regulators (Bmi1, PTEN) that promote EMT and invasion
  • CSCs possess a capacity for self-renewal, and they can persistently proliferate to initiate tumours upon serial transplantation, thus enabling them to maintain the whole tumour
  • Conventional cancer treatments kill most cancer cells, but CSCs survive due to their resistance to therapy, eventually leading to tumour relapse and metastasis
  • identification of CSCs, three types of markers are utilised: cell surface molecules, transcription factors, and signalling pathway molecules
  • CSCs express distinct and specific surface markers; commonly used ones are CD24, CD34, CD38, CD44, CD90, CD133, and ALDH
  • Transcription factors, including Oct4, Sox2, Nanog, c-Myc, and Klf4,
  • signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, platelet-derived growth factor receptor (PDGFR), and JAK/STAT
  • microRNAs (miRNAs), including let-7, miR-22, miR-34a, miR-128, the miR-200 family, and miR-451
  • Non-CSCs can be reprogrammed to become CSCs by epigenetic and genetic changes
  • EMT-inducing transcription factors, such as Snail, ZEB1, and Twist1, are known to confer CSC properties
  • Signalling pathways involved in EMT, including those of TGF-β, Wnt, and Notch, have been shown to play important roles in inducing the CSC phenotype
  • TGF-β1 not only increases EMT markers (Slug, Twist1, β-catenin, N-cadherin), but also upregulates CSC markers (Oct4, Sox2, Nanog, Klf4) in breast and lung cancer cells
  • some CSC subpopulations arise independently of EMT
  • IR has been shown to induce the CSC phenotype in many cancers, including breast, lung, and prostate cancers, as well as melanoma
  • Genotoxic stress due to IR or chemotherapy promotes a CSC-like phenotype by increasing ROS production
  • IR has been shown to induce reprogramming of differentiated cancer cells into CSCs
  • In prostate cancer patients, radiotherapy increases the CD44+ cell population that exhibit CSC properties
  • IR also induces the re-expression of stem cell regulators, such as Sox2, Oct4, Nanog, and Klf4, to promote stemness in cancer cells
  • EMT-inducing transcription factors and signalling pathways, including Snail, STAT3, Notch signalling, the PI3K/Akt pathway, and the MAPK cascade, have been shown to play important roles in IR-induced CSC properties
  • STAT3 directly binds to the Snail promoter and increases Snail transcription, which induces the EMT and CSC phenotypes, in cisplatin-selected resistant cells
  • Other oncogenic metabolic pathways, including glutamine metabolism, the pentose phosphate pathway (PPP), and synthesis of fatty acids and cholesterol, are also enhanced in many cancers
  • metabolic reprogramming
  • HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
  • metabolic reprogramming
  • tumour cells exhibit high mitochondrial metabolism as well as aerobic glycolysis
  • occurring within the same tumour
  • CSCs can be highly glycolytic-dependent or oxidative phosphorylation (OXPHOS)-dependen
  • mitochondrial function is crucial for maintaining CSC functionality
  • cancer cells depend on mitochondrial metabolism and increase mitochondrial production of ROS that cause pseudo-hypoxia
  • HIF-1 then enhances glycolysis
  • CAFs have defective mitochondria that lead to the cells exhibiting the Warburg effect; the cells take up glucose, and then secrete lactate to 'feed' adjacent cancer cells
  • lactate transporter, monocarboxylate transporter (MCT)
  • nutrient microenvironment
  • Epithelial cancer cells express MCT1, while CAFs express MCT4. MCT4-positive, hypoxic CAFs secrete lactate by aerobic glycolysis, and MCT1-expressing epithelial cancer cells then uptake and use that lactate as a substrate for the tricarboxylic acid (TCA) cycle
  • MCT4-positive cancer cells depend on glycolysis and then efflux lactate, while MCT1-positive cells uptake lactate and rely on OXPHOS
  • metabolic heterogeneity induces a lactate shuttle between hypoxic/glycolytic cells and oxidative/aerobic tumour cells
  • bulk tumour cells exhibit a glycolytic phenotype, with increased conversion of glucose to lactate (and enhanced lactate efflux through MCT4), CSC subsets depend on oxidative phosphorylation; most of the glucose entering the cells is converted to pyruvate to fuel the TCA cycle and the electron transport chain (ETC), thereby increasing mitochondrial ROS production
  • the major fraction of glucose is directed into the pentose phosphate pathway, to produce redox power through the generation of NADPH and ROS scavengers
  • HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
  • regulatory molecules involved in EMT and CSCs, including Snail, Dlx-2, HIF-1, STAT3, TGF-β, Wnt, and Akt, are implicated in the metabolic reprogramming of cancer cells
  • HIF-1 induces the expression of glycolytic enzymes, including the glucose transporter GLUT, hexokinase, lactate dehydrogenase (LDH), and MCT, resulting in the glycolytic switch
  • HIF-1 represses the expression of pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), thereby inhibiting mitochondrial activity
  • STAT3 has been implicated in EMT-induced metabolic changes as well
  • TGF-β and Wnt play important roles in the metabolic alteration of cancer cells
  • Akt is also implicated in the glycolytic switch and in promoting cancer cell invasiveness
  • EMT, invasion, metastasis, and stemness
  • pyruvate kinase M2 (PKM2), LDH, and pyruvate carboxylase (PC), are implicated in the induction of the EMT and CSC phenotypes
  • decreased activity of PKM2 is known to promote an overall shift in metabolism to aerobic glycolysis
  • LDH catalyses the bidirectional conversion of lactate to pyruvate
  • High levels of LDHA are positively correlated with the expression of EMT and CSC markers
  • IR has been shown to induce metabolic changes in cancer cells
  • IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
  • IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
  • IR also elevates MCT1 expression that exports lactate into the extracellular environment, leading to acidification of the tumour microenvironment
  • IR increases intracellular glucose, glucose 6-phosphate, fructose, and products of pyruvate (lactate and alanine), suggesting a role for IR in the upregulation of cytosolic aerobic glycolysis
  • Lactate can activate latent TGF-
  • lactate stimulates cell migration and enhances secretion of hyaluronan from CAF that promote tumour metastasis
  • promote tumour survival, growth, invasion, and metastasis; enhance the stiffness of the ECM; contribute to angiogenesis; and induce inflammation by releasing several growth factors and cytokines (TGF-β, VEGF, hepatocyte growth factor [HGF], PDGF, and stromal cell-derived factor 1 [SDF1]), as well as MMP
  • tumours recruit the host tissue’s blood vessel network to perform four mechanisms: angiogenesis (formation of new vessels), vasculogenesis (de novo formation of blood vessels from endothelial precursor cells), co-option, and modification of existing vessels within tissues.
  • immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
  • immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
  • intrinsic immunogenicity or induce tolerance
  • cancer immunoediting’
  • three phases: 1) elimination, 2) equilibrium, and 3) escape.
  • The third phase, tumour escape, is mediated by antigen loss, immunosuppressive cells (TAM, MDSCs, and regulatory T cells), and immunosuppressive cytokines (TGF-β and IL-10).
  • IR can elicit various changes in the TME, such as CAF activity-mediated ECM remodelling and fibrosis, cycling hypoxia, and an inflammatory response
  • IR activates CAFs to promote the release of growth factors and ECM modulators, including TGF-β and MMP
  • TGF-β directly influences tumour cells and CAFs, promotes tumour immune escape, and activates HIF-1 signalling
    • Nathan Goodyear
      Nathan Goodyear on 09 Feb 21
       
      And now the receipts
  • MMPs degrade ECM that facilitates angiogenesis, tumour cell invasion, and metastasis
    • Nathan Goodyear
      Nathan Goodyear on 09 Feb 21
       
      Receipts and mechanisms
  • IR also promotes MMP-2/9 activation in cancer cells to promote EMT, invasion, and metastasis
  • IR-induced Snail increases MMP-2 expression to promote EMT
  • Radiotherapy has the paradoxical side-effect of increasing tumour aggressiveness
  • IR promotes ROS production in cancer cells, which may induce the activation of oncogenes and the inactivation of tumour suppressors, which further promote oncogenic metabolism
  • Metabolic alterations
  • oncogenic metabolism
  • elicit various changes in the TME
  • Although IR activates an antitumour immune response, this signalling is frequently suppressed by tumour escape mechanisms
  • Nathan Goodyear on 09 Feb 21
     
    Important review article.
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