More than half of cancer patients are treated with IR at some point during their treatment
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Tumour-Associated Macrophages (TAMs) in Colon Cancer and How to Reeducate Them - 0 views
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Lipid-associated macrophages are induced by cancer-associated fibroblasts and mediate i... - 0 views
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cancer CAF Tumor associate macrophages TME TAMs TAM breast cancer tumor microenvironment cancer associated fibroblasts
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The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confer... - 0 views
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EMT Tumor associate macrophages epithelial to mesenchymal transition TAMs cancer
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Tumor-associated macrophages in tumor metastasis: biological roles and clinical therape... - 0 views
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metastasis Tumor associate macrophages tumor microenvironment TME TAMs cancer
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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
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Nuclear DNA is the primary target of IR; it causes DNA damage (genotoxic stress) by direct DNA ionization
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EMT, stemness, and oncogenic metabolism are known to be associated with resistance to radiotherapy and chemotherapy
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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
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EMT is a developmental process that plays critical roles in embryogenesis, wound healing, and organ fibrosis
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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
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activate EMT-inducing transcription factors, including Snail/Slug, ZEB1/δEF1, ZEB2/SIP1, Twist1/2, and E12/E47
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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
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IR may increase metastasis in both the primary tumour site and in normal tissues under some circumstance
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sublethal doses of IR have been shown to enhance the migratory and invasive behaviours of glioma cells
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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
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Treatment with the N-acetylcysteine (NAC), a general ROS scavenger, prevents IR-induced EMT, adhesive affinity, and invasion of breast cancer cells
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IR activates the p38 MAPK pathway, which contributes to the induction of Snail expression to promote EMT and invasion
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HIF-1 is a heterodimer composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit.
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Under normoxia, HIF-1α is rapidly degraded, whereas hypoxia induces stabilisation and accumulation of HIF-1α
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levels of HIF-1α mRNA are enhanced by activation of the PI3K/Akt/mammalian target of rapamycin (mTOR)
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IR is known to increase stabilisation and nuclear accumulation of HIF-1α, since hypoxia is a major condition for HIF-1 activation
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IR causes the reoxygenation of hypoxic cancer cells to increase ROS production, which leads to the stabilisation and nuclear accumulation of HIF-1
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IR increases glucose availability under reoxygenated conditions that promote HIF-1α translation by activating the Akt/mTOR pathway
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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
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PAI-1 signalling is also implicated in IR-induced Akt activation that increases Snail levels to induce EMT
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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
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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
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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
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Conventional cancer treatments kill most cancer cells, but CSCs survive due to their resistance to therapy, eventually leading to tumour relapse and metastasis
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identification of CSCs, three types of markers are utilised: cell surface molecules, transcription factors, and signalling pathway molecules
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CSCs express distinct and specific surface markers; commonly used ones are CD24, CD34, CD38, CD44, CD90, CD133, and ALDH
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signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, platelet-derived growth factor receptor (PDGFR), and JAK/STAT
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EMT-inducing transcription factors, such as Snail, ZEB1, and Twist1, are known to confer CSC properties
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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
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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
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IR has been shown to induce the CSC phenotype in many cancers, including breast, lung, and prostate cancers, as well as melanoma
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Genotoxic stress due to IR or chemotherapy promotes a CSC-like phenotype by increasing ROS production
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In prostate cancer patients, radiotherapy increases the CD44+ cell population that exhibit CSC properties
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IR also induces the re-expression of stem cell regulators, such as Sox2, Oct4, Nanog, and Klf4, to promote stemness in cancer cells
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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
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STAT3 directly binds to the Snail promoter and increases Snail transcription, which induces the EMT and CSC phenotypes, in cisplatin-selected resistant cells
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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
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cancer cells depend on mitochondrial metabolism and increase mitochondrial production of ROS that cause pseudo-hypoxia
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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
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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
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MCT4-positive cancer cells depend on glycolysis and then efflux lactate, while MCT1-positive cells uptake lactate and rely on OXPHOS
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metabolic heterogeneity induces a lactate shuttle between hypoxic/glycolytic cells and oxidative/aerobic tumour cells
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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
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the major fraction of glucose is directed into the pentose phosphate pathway, to produce redox power through the generation of NADPH and ROS scavengers
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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
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HIF-1 induces the expression of glycolytic enzymes, including the glucose transporter GLUT, hexokinase, lactate dehydrogenase (LDH), and MCT, resulting in the glycolytic switch
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HIF-1 represses the expression of pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), thereby inhibiting mitochondrial activity
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pyruvate kinase M2 (PKM2), LDH, and pyruvate carboxylase (PC), are implicated in the induction of the EMT and CSC phenotypes
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IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
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IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
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IR also elevates MCT1 expression that exports lactate into the extracellular environment, leading to acidification of the tumour microenvironment
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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
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lactate stimulates cell migration and enhances secretion of hyaluronan from CAF that promote tumour metastasis
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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
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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.
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immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
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immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
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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).
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IR can elicit various changes in the TME, such as CAF activity-mediated ECM remodelling and fibrosis, cycling hypoxia, and an inflammatory response
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IR activates CAFs to promote the release of growth factors and ECM modulators, including TGF-β and MMP
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TGF-β directly influences tumour cells and CAFs, promotes tumour immune escape, and activates HIF-1 signalling
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MMPs degrade ECM that facilitates angiogenesis, tumour cell invasion, and metastasis
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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
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Although IR activates an antitumour immune response, this signalling is frequently suppressed by tumour escape mechanisms
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Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer ... - 0 views
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Ferritin is increased as a byproduct of the inflammation, which studies suggest, are the result of TAMs. Some ferritin is also likely the result of release from cell death. L-ferritin is the most prevalent in cancer. Elevated ferritin is associated with a poor prognosis in many cancers. It also correlates with CRP, WBC in this study. 1 mg/ml of serum ferritin correlates to 8mg of stored Fe.
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The prognostic impact of traditional Chinese medicine monomers on tumor-associated macr... - 0 views
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Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and... - 0 views
www.ncbi.nlm.nih.gov/...PMC6206903
Tumor associate macrophages hydroxychloroquine M1 macrophages cancer TAMs M2 macrophages
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Frontiers | Vitamin C Inhibits Metastasis of Peritoneal Tumors By Preventing Spheroid F... - 0 views
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TME metastasis tumor microenvironment Tumor associate macrophages M2 M2 macrophages vitamin C TAM TAMs
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Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo - PMC - 0 views
www.ncbi.nlm.nih.gov/...PMC7865688
zometa Tumor associate macrophages TAM TAMs Zoledronic acid M1 macrophages
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The role of tumour-associated macrophages in bone metastasis - PMC - 0 views
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Metabolic management of brain cancer - 0 views
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Glutamine is a major metabolic fuel for both brain tumor cells and tumor-associated macrophages (TAMs)
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the malignant phenotype of brain tumor cells that survive radiotherapy is often greater than that of the cells from the original tumor.
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Conventional chemotherapy has faired little better than radiation therapy for the long-term management of malignant brain cancer
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most conventional radiation and brain cancer chemotherapies can enhance glioma energy metabolism and invasive properties, which would contribute to tumor recurrence and reduced patient survival [34].
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We contend that all cancer regardless of tissue or cellular origin is a disease of abnormal energy metabolism
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complex disease phenotypes can be managed through self-organizing networks that display system wide dynamics involving oxidative and non-oxidative (substrate level) phosphorylation
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As long as brain tumors are provided a physiological environment conducive for their energy needs they will survive; when this environment is restricted or abruptly changed they will either grow slower, growth arrest, or perish [8] and [19]
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New information also suggests that ketones are toxic to some human tumor cells and that ketones and ketogenic diets might restrict availability of glutamine to tumor cells [68], [69] and [70].
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The success in dealing with environmental stress and disease is therefore dependent on the integrated action of all cells in the organism
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Tumor cells survive in hypoxic environments not because they have inherited genes making them more fit or adaptable than normal cells, but because they have damaged mitochondria and have thus acquired the ability to derive energy largely through substrate level phosphorylation
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Cancer cells survive and multiply only in physiological environments that provide fuels (mostly glucose and glutamine) subserving their requirement for substrate level phosphorylation
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Integrity of the inner mitochondrial membrane is necessary for ketone body metabolism since β-hydroxybutyrate dehydrogenase, which catalyzes the first step in the metabolism of β-OHB to acetoacetate, interacts with cardiolipin and other phospholipids in the inner membrane
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Any genetic or environmental alteration in the content or composition of cardiolipin will compromise energy production through oxidative phosphorylation
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the Crabtree effect can be reversible, the Warburg effect is largely irreversible because its origin is with permanently damaged mitochondria
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The continued production of lactic acid in the presence of oxygen is the metabolic hallmark of most cancers and is referred to as aerobic glycolysis or the Warburg effect
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We recently described how the retrograde signaling system could induce changes in oncogenes and tumor suppressor genes to facilitate tumor cell survival following mitochondrial damage [48].
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In addition to glycolysis, glutamine can also increase ATP production under hypoxic conditions through substrate level phosphorylation in the TCA cycle after its metabolism to α-ketoglutarate
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mitochondrial lipid abnormalities, which alter electron transport activities, can account in large part for the Warburg effect
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targeting both glucose and glutamine metabolism could be effective for managing most cancers including brain cancer
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The bulk of experimental evidence indicates that mitochondria are dysfunctional in tumors and incapable of generating sufficient ATP through oxidative phosphorylation
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Cardiolipin defects in tumor cells are also associated with reduced activities of several enzymes of the mitochondrial electron transport chain making it unlikely that tumor cells with cardiolipin abnormalities can generate adequate energy through oxidative phosphorylation
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TCA cycle substrate level phosphorylation could therefore become another source of ATP production in tumor cells with impairments in oxidative phosphorylation
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Caloric restriction, which lowers glucose and elevates ketone bodies [63] and [64], improves mitochondrial respiratory function and glutathione redox state in normal cells
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DR naturally inhibits glycolysis and tumor growth by lowering circulating glucose levels, while at the same time, enhancing the health and vitality of normal cells and tissues through ketone body metabolism
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We suggest that apoptosis resistance arises largely from enhanced substrate level phosphorylation of tumor cells and to the genes associated with elevated glycolysis and glutaminolysis, e.g., c-Myc, Hif-1a, etc, which inhibit apoptosis
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Modern medicine has not looked favorably on diet therapies for managing complex diseases especially when well-established procedures for acceptable clinical practice are available, regardless of how ineffective these procedures might be in managing the disease
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More than 60 years of clinical research indicates that such approaches are largely ineffective in extending survival or improving quality of life
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The process is rooted in the well-established scientific principle that tumor cells are largely dependent on substrate level phosphorylation for their survival and growth
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targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia
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Blood glucose ranges between 3.0 and 3.5 mM (55–65 mg/dl) and β-OHB ranges between 4 and 7 mM should be effective for tumor management
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Informa Healthcare - The Aging Male - 5(2):98 - Summary - 0 views
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Impact Of Unimaginable Harms Of Chickens Chicken Prevention - Men's Health Clinic - 1 views
trungtamnamkhoa.com/c-hai-cua-benh-sui-mao-ga.html
hormones cancer hormone Testosterone Men inflammation Disease Male HPV Viruss
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The harmful effects of chicken papilloma disease not only stop at physical health but also the spirit of patients is seriously affected. Patients may be depressed, mentally in crisis when they know that they can follow them all their lives. Chicken ridge is considered the undeniable obsession of men. Referring to this disease, many boys are bored, because once they get sick, the chicken's neck often hangs and leaves many harms. Dr. Vo Duy Tam said, "The chicken's crest is a sexually transmitted disease caused by HPV (Human Papilloma Virus) - The virus causes human papilloma. Currently there are more than 130 HPV types that have been discovered, among them, the ones that often cause genital warts are types 6, 11, 16, and 18.
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Tumour infiltrating host cells and their significance for hyperthermia: International J... - 0 views
www.tandfonline.com/...02656730903413375
TAMs cancer M2 macrophages Tumor associate macrophages M1 macrophages
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Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising syne... - 0 views
www.sciencedirect.com/...S0168365917301189
cancer M1 macrophages Tumor associate macrophages TAMs M2 macrophages
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Targeting Tumor Microenvironment for Cancer Therapy - 0 views
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Effect of artesunate on apoptosis and autophagy in tamoxifen resistant breast cancer ce... - 0 views
"Re-educating" tumor-associated macrophages by targeting NF-κB - 0 views
www.ncbi.nlm.nih.gov/...PMC2413024
TME cancer TAM Tumor associate macrophages NF-KappaB inflammation tumor microenvironment
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