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Nathan Goodyear

Autoimmune (auto-inflammatory) syndrome induce... [Curr Med Chem. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23992328

Macrophagic myofasciitis vaccine vaccines vaccinations ASIA autoimmune syndromes induced by adjuvants autoimmune disease adjuvants

shared by Nathan Goodyear on 01 Oct 14 - No Cached
  • Nathan Goodyear on 01 Oct 14
     
    Animal proof of concept supports the thought that adjuvants in vaccines induce auto inflammatory diseases.
Nathan Goodyear

JNK Expression by Macrophages Promotes Obesity-induced Insulin Resistance and Inflammation - 0 views

www.ncbi.nlm.nih.gov/...PMC3835653

JNK inflammation obesity insulin resistance insulin resistance

shared by Nathan Goodyear on 06 Oct 14 - No Cached
  • Nathan Goodyear on 06 Oct 14
     
    JNK pathway plays important role in inflammation signaling.  In this article, JNK activation plays role in insulin resistance, obesity, and metabolic dysfunction.
Nathan Goodyear

Testosterone: More Than Having the Guts to Win the Tour de France - 0 views

www.sciencedirect.com/...S1074761313003439

Testosterone gut flora gut microbiome gut microbiota autoimmune disease diabetes

shared by Nathan Goodyear on 30 Apr 15 - No Cached
  • female adult mice have microbiomes similar to those of prepubescent mice of both sexes;
  • the commensal microbial community in adult male mice significantly deviates from this shared initial pool.
  • the microbiome in castrated adult males clearly shifts away from that of normal adult males and is closer to the microbiome of females
  • ...10 more annotations...
  • The incidence of T1D in these mice is positively correlated with the “femaleness” of the microbiota
  • These results support the hypothesis that the host androgen level is influential in determining the composition of the microbiota, which in turn affects T1D initiation and progression
  • a high testosterone level enriches the microbiota for specific organisms such as segmented filamentous bacteria (SFB) and Escherichia coli or Shigella–like (SECS) strains.
  • A minimum level of testosterone and specific male-enriched microbes working together upregulate M2 macrophage and IFN-γ producing T cells in pancreatic lymph nodes. Microarray data show that both the IFN-γ and IL-1β pathways are also stimulated.
  • These microbes also upregulate host testosterone
  • In four independent experiments, the authors found no universal unique “male microbiome”
  • they did find that four distinct combinations of microbial groupings (with an interesting lack of overlap at the individual family level in the four experiments) were enhanced by androgen
  • one species consists of the segmented filamentous bacteria (SFB) and belongs to the Firmicutes, whereas the other is an Escherichia coli or Shigella–like (SECS) strain belonging to the Proteobacteria
  • colonization with protective microbiomes—e.g., SPF microbiota, SFB, and SECS—is positively correlated with high blood testosterone levels in male mice
  • A direct implication of this study is that probiotic administration or fecal transplantation is a theoretically possible approach to protection against T1D
  • Nathan Goodyear on 30 Apr 15
     
    nice summary of article on the relationship between Testosteorne and gut microbiome in autoimmune disease.
Nathan Goodyear

Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Dis... - 0 views

www.ncbi.nlm.nih.gov/...PMC3448089

dysbiosis diet nutrition metabolic endotoxemia disease inflammation gut

shared by Nathan Goodyear on 27 Jul 14 - No Cached
  • The gut microbiota participates in the body’s metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders
  • Firmicutes and Bacteroidetes represent the two largest phyla in the human and mouse microbiota and a shift in the ratio of these phyla has been associated with many disease conditions, including obesity
  • In obese humans, there is decreased abundance of Bacteroidetes compared to lean individuals
  • ...21 more annotations...
  • weight loss in obese individuals results in an increase in the abundance of Bacteroidetes
  • there is conflicting evidence on the composition of the obese microbiota phenotype with regards to Bacteroidetes and Firmicutes ratios
  • Bifidobacteria spp. from the phyla Actinobacteria, has been shown to be depleted in both obese mice and human subjects
  • While it is not yet clear which specific microbes are inducing or preventing obesity, evidence suggests that the microbiota is a factor.
  • targeted manipulation of the microbiota results in divergent metabolic outcomes depending on the composition of the diet
  • The microbiota has been linked to insulin resistance or type 2 diabetes (T2D) via metabolic syndrome and indeed the microbiota of individuals with T2D is also characterized by an increased Bacteroidetes/Firmicutes ratio, as well as an increase in Bacillus and Lactobacillus spp
  • It was also observed that the ratio of Bacteriodes-Prevotella to C. coccoides-E. rectale positively correlated with glucose levels but did not correlate with body mass index [80]. This suggests that the microbiota may influence T2D in conjunction with or independently of obesity
  • In humans, high-fat Western-style diets fed to individuals over one month can induce a 71% increase in plasma levels of endotoxins, suggesting that endotoxemia may develop in individuals with GI barrier dyfunction connected to dysbiosis
  • LPS increases macrophage infiltration essential for systemic inflammation preceding insulin resistance, LPS alone does not impair glucose metabolism
  • early treatment of dysbiosis may slow down or prevent the epidemic of metabolic diseases and hence the corresponding lethal cardiovascular consequences
  • increased Firmicutes and decreased Bacteroidetes, which is the microbial profile found in lean phenotypes, along with an increase in Bifidobacteria spp. and Lactobacillus spp
  • mouse and rat models of T1D have been shown to have microbiota marked by decreased diversity and decreased Lactobacillus spp., as well as a decrease in the Firmicutes/Bacteroidetes ratio
  • microbial antigens through the innate immune system are involved in T1D progression
  • The microbiota appears to be essential in maintaining the Th17/Treg cell balance in intestinal tissues, mesenteric and pancreatic lymph nodes, and in developing insulitis, although progression to overt diabetes has not been shown to be controlled by the microbiota
  • There is evidence that dietary and microbial antigens independently influence T1D
  • Lactobacillus johnsonii N6.2 protects BB-rats from T1D by mediating intestinal barrier function and inflammation [101,102] and a combination probiotic VSL#3 has been shown to attenuate insulitis and diabetes in NOD mice
  • breast fed infants have higher levels of Bifidobacteria spp. while formula fed infants have higher levels of Bacteroides spp., as well as increased Clostridium coccoides and Lactobacillus spp
  • the composition of the gut microbiota strongly correlates with diet
  • In mice fed a diet high in fat, there are many key gut population changes, such as the absence of gut barrier-protecting Bifidobacteria spp
  • diet has a dominating role in shaping gut microbiota and changing key populations may transform healthy gut microbiota into a disease-inducing entity
  • “Western” diet, which is high in sugar and fat, causes dysbiosis which affects both host GI tract metabolism and immune homeostasis
  • Nathan Goodyear on 27 Jul 14
     
    Nice discussion of how diet, induces gut bacterial change, that leads to metabolic endotoxemia and disease.
Nathan Goodyear

Genomic and Nongenomic Signaling Induced by 1α,25(OH)2-Vitamin D3 Promotes th... - 0 views

iospress.metapress.com/...1321517j461377p2

vitamin D amyloid plaque alzheimer's disease Alzheimer's disease brain

shared by Nathan Goodyear on 01 Nov 13 - No Cached
  • Nathan Goodyear on 01 Nov 13
     
    Vitamin D3 clears amyloid plaque from the brains of those battling Alzheimer's disease.
Nathan Goodyear

Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in... - 0 views

joe.endocrinology-journals.org/...217.full.pdf

CRP testosterone inflammation men male hormones cytokines

shared by Nathan Goodyear on 18 Jun 13 - No Cached
  • Nathan Goodyear on 18 Jun 13
     
    This study finds no difference between the sexes as it relates to testosterone and inflammatory cytokines. They only found a correlation with CRP as it relates to oxidized LDL.
Nathan Goodyear

Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macropha... - 0 views

www.ncbi.nlm.nih.gov/...16115546

pomegranate oxLDL CVD cardiovascular disease natural

shared by Nathan Goodyear on 13 Oct 15 - No Cached
  • Nathan Goodyear on 13 Oct 15
     
    Pomegranate inhibited foam cell avtivity and uptake of oxLDL
Nathan Goodyear

PPARγ and human metabolic disease - 0 views

www.ncbi.nlm.nih.gov/...PMC1386124

PPAR-gamma perioxisome proliferator-activated receptor disease PPAR

shared by Nathan Goodyear on 24 Jan 13 - No Cached
  • PPARα and PPARδ appear primarily to stimulate oxidative lipid metabolism
  • PPARγ is principally involved in the cellular assimilation of lipids via anabolic pathways
  • PPARs are members of the nuclear hormone receptor superfamily
  • ...7 more annotations...
  • Expression of PPARγ is highest in adipose tissue,
  • PPARγ also plays a key role in the entraining of adipose tissue lipid metabolism to nutritional state
  • Its expression is highest postprandially
  • its activation leads to upregulation of genes that mediate FA uptake and trapping
  • PPARγ may also promote futile cycling in adipocytes between triglyceride (TG) esterification and de-esterification
  • its high expression in macrophages, which are now known to infiltrate the dysfunctional adipose tissue of obese subjects
    • Nathan Goodyear
      Nathan Goodyear on 28 Aug 14
       
      PPAR gamma is associated with adipocyte differentiation and lipid storage.
  • Nathan Goodyear on 24 Jan 13
     
    review of PPAR gamma
  • Blu Electronic Cigarettes on 03 Sep 14
     
    very informative! Thanks for sharing!
Nathan Goodyear

Mucosal Immunology - Commensal Gram-positive bacteria initiates colitis by inducing mon... - 0 views

www.nature.com/...mi201453a.html

commensal bacteria gut gut flora gut microbiome gut microbiota

shared by Nathan Goodyear on 12 Jan 16 - No Cached
  • Nathan Goodyear on 12 Jan 16
     
    good discussion of commensal bacteria interaction with immune system.
Nathan Goodyear

Transcriptional profiling of the LPS induced NF-κB response in macrophages - 0 views

www.ncbi.nlm.nih.gov/...PMC1781469

LPS lipopolysaccharides NF-kappaB apoptosis cancer inflammation

shared by Nathan Goodyear on 08 Nov 18 - No Cached
  • Nathan Goodyear on 08 Nov 18
     
    LPS increases NF-kappaB expression and inhibits apoptosis.
Nathan Goodyear

FOREIGN BODY REACTION TO BIOMATERIALS - 0 views

www.ncbi.nlm.nih.gov/...PMC2327202

mesh inflammation immune

shared by Nathan Goodyear on 31 Aug 18 - No Cached
  • We have demonstrated that biomaterial-adherent cells can undergo material-dependent apoptosis both in vitro and in vivo, thus rendering macrophages nonfunctional while the surrounding environment of the implant or biomaterial remains unaffected
  • Adherent inflammatory cell apoptosis has been described as an important mechanism for the persistence of cardiovascular device infection where apoptosis is induced by shear stress in cardiovascular devices.
  • Nathan Goodyear on 31 Aug 18
     
    mesh and inflammation
Nathan Goodyear

Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma - 0 views

www.ncbi.nlm.nih.gov/...PMC4925562

Hodgkin's lymphoma Hodgkin's disease hypercalcemia lymphoma

shared by Nathan Goodyear on 21 Aug 18 - No Cached
  • administered zoledronic acid (4 mg). Prednisolone (1 mg/kg/day) was started and simultaneously, she was administered first cycle of ABVD (Adriamycin: 25 mg/m2, Bleomycin: 10 U/m2, Vinblastine: 6 mg/m2 and Dacarbazine: 375 mg/m2), which led to normalisation of serum calcium levels over 4 days and improvement in her hemoglobin levels
  • Etiology of anemia in Hodgkin’s lymphoma is multifactorial. Anemia of chronic disease, decreased red cell survival, infiltration of bone marrow by tumor and marrow suppression by chemotherapy/radiotherapy are the common mechanisms
  • Our case had only a transient response to steroids and chemotherapy. Therefore, she was treated with Rituximab which brought hemolysis under control
  • ...7 more annotations...
  • Mechanism of hypercalcemia in HL has long been suggested to involve extra-renal activation of 1α-hydroxylase leading to production of 1, 25(OD)2 Vitamin D3 or Calcitriol, an active metabolite of Vitamin D, which leads to increased re-absorption of calcium and phosphate from intestine, increased osteoclast activation and bone resorption as well as increased phosphate re-absorption in renal tubules
  • Hypercalcemia of malignancy involves three mechanisms: 1. Humoral hypercalcemia mediated by PTHrP—seen in solid tumors like breast cancer and adult T cell leukemia/lymphoma (ATLL), 2. Direct osteoclast mediated bone resorption due to bony metastasis—seen in solid tumors and multiple myeloma, 3. Calcitriol mediated hypercalcemia—seen in Hodgkin’s and non-Hodgkin’s lymphoma as well as granulomatous disorders like tuberculosis, sarcoidosis, leprosy and disseminated Candidiasis
  • Hypercalcemia in HL is rare and its incidence has been reported as 0.9, 1.6 and 5.4 % in different series
  • The source of 1α-hydroxylase in HL has been postulated as monocytes and macrophages infiltrating the tumor akin to tuberculosis or sarcoidosis and is stimulated by IFN-γ secreted by T-lymphocytes
  • Like sarcoidosis, patients with HL exhibit increased sensitivity to Vitamin D supplements and sunlight, which have been found to precipitate hypercalcemia in these patients
  • Classical biochemical profile in Calcitriol mediated hypercalcemia include: an elevated calcium, normal/slightly elevated phosphate, normal 25(OH) Vitamin D, suppressed PTHrP and PTH, elevated Calcitriol and a normal/increased tubular reabsorption of phosphate
  • not been associated with a poorer prognosis and tends to subside after treatment of the underlying disease
  • Nathan Goodyear on 21 Aug 18
     
    great read on hypercalcemia in hodgkin's lymphoma.
Nathan Goodyear

Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5992645

Tumor associate macrophages cancer ferritin

shared by Nathan Goodyear on 18 Apr 19 - No Cached
hoangkimchi liked it
  • Nathan Goodyear on 18 Apr 19
     
    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.
Nathan Goodyear

Exploring the basic science of prolapse meshes - 0 views

www.ncbi.nlm.nih.gov/...PMC5161092

vaginal mesh mesh immune system M1 M2 macrophages

shared by Nathan Goodyear on 24 Jan 19 - No Cached
  • Nathan Goodyear on 24 Jan 19
     
    Mesh implantation, here in the vaginal area, increases both M1 and M2 maturation migration. M1 increases pro-inflammatory signaling and processes and M2 promotes remodeling/healing... Both increase, but M1 increases more than M2 proportionally. M2 can increase the bridge scaring that can occur as well as the potential for immune suppression and autoimmune/cancer implications
Nathan Goodyear

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutr... - 0 views

nutritionandmetabolism.biomedcentral.com/...s12986-017-0178-2

ketogenic diet ketogenic press-pulse hyperbaric oxygen therapy HBOTnutrition diet cancer HBOT IVC IV vitamin C DCA dichloracetic acid cancer therapy cancer treatment alternative cancer treatment

shared by Nathan Goodyear on 09 Jul 17 - No Cached
mamdouh_hfz liked it
  • A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
  • “pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
  • Neoplasia involving dysregulated cell growth is the biological endpoint of the disease
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  • Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
  • cancer is predicted to overtake heart disease as the leading cause of death in Western societies
  • cancer can also be recognized as a metabolic disease.
  • glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
  • Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
  • persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
  • Otto Warburg first proposed that all cancers arise from damage to cellular respiration
  • The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
  • the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
  • The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
  • Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
  • Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
  • all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
  • The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
  • respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
  • data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
  • Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
  • In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
  • Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
  • Glucose and glutamine act synergistically for driving rapid tumor cell growth
  • Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
  • Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
  • Hif-1α stabilization enhances aerobic fermentation
  • targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
  • Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
  • Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
  • Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
  • Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
  • Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
  • It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
  • Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
  • The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
  • According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
  • A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
  • Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
  • Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
  • The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
  • Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      reason to eliminate glutamine in cancer patients and even GSH with cancer patients
  • It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
  • Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
  • glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
  • In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
  • Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
  • Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
  • Ketone bodies and fats are non-fermentable fuels
  • Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
  • Apoptosis under energy stress is greater in tumor cells than in normal cells
  • A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
  • . This energy stress acts as a press disturbance
  • Drugs that target availability of glucose and glutamine would act as pulse disturbances
  • Hyperbaric oxygen therapy can also be considered another pulse disturbance
  • The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
  • Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
  • Protein amino acids can be metabolized to glucose through the Cori cycle
  • The fats in KDs used clinically also contain more medium chain triglycerides
  • Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
  • Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
  • GKI values of 1.0 or below are considered therapeutic
  • The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
  • It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
  • The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
  • Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
  • Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      Ketones are much more than energy adaptabilit, but actually are therapeutic.
  • ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
  • Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
  • Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
  • In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
  • Ketone supplementation has also been shown to reduce anxiety behavior in animal models
  • This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
  • lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
  • Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
  • A synergistic interaction of the KD diet plus radiation was seen
  • It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
  • Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
  • HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
  • The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
  • Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
  • Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
  • Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
  • GBM and use glutamine as a major fuel
  • Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
  • Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
  • Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
  • Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
  • Nathan Goodyear on 09 Jul 17
     
    Cancer is a mitochondrial disease? So says the well published Dr Seyfried. Glucose and glutamine drive cancer growth.
Nathan Goodyear

The psychoneuroendocrine-immunotherapy of cancer: Historical evolution and clinical res... - 0 views

www.ncbi.nlm.nih.gov/...PMC5426095

cancer melatonin immunotherapy

shared by Nathan Goodyear on 10 May 18 - No Cached
  • It is known that immune system-induced destruction of cancer cells is mainly mediated by T cytotoxic lymphocytes (CD8+) and NK cells (CD16+), respectively, through an antigen-specific and an antigen nonspecific cytotoxicity
  • NK cells are mainly stimulated by IL-2 released by T helper-1 (TH1) lymphocytes (CD4+) while T cytotoxic lymphocytes (CD8+) are namely under a stimulatory control released by IL-12 produced by the dendritic cells
  • On the other hand, the anticancer immunity is inhibited by the activation of the macrophage system through the production of suppressive cytokines, such as IL-6 and T regulatory (T reg) lymphocytes (CD4+CD25+), which counteract the anticancer immunity by producing immunosuppressive cytokines inhibiting the secretion of both IL-2 and IL-12, including TGF-beta and IL-10, or by a direct cell-cell contact
  • Nathan Goodyear on 10 May 18
     
    to be read review of melatonin in cancer treatment.
Nathan Goodyear

Ferrous iron content of intravenous iron formulations - 0 views

www.ncbi.nlm.nih.gov/...PMC4879161

M1 macrophages NK cells FE IRON M1 venofer oxidative stress

shared by Nathan Goodyear on 28 Jun 19 - No Cached
  • Nathan Goodyear on 28 Jun 19
     
    Study finds that IV venofer increases oxidative stress and immune modulation to increase M1 but decreased NK cell expression. The study found that this was related to the effects of the IV Fe2+ (ferrous) form; whereas the oral delivered Fe3+ (ferric) form. More free Fe2+ was released as a result of venofer infusion that was independent of transferrin. This was associated with increased oxidative stress.
Nathan Goodyear

Targeting Tumor Microenvironment for Cancer Therapy - 0 views

cancer TAMs Tumor associate macrophages hyperthermia TME tumor microenvironment

shared by Nathan Goodyear on 08 Aug 19 - No Cached
  • Nathan Goodyear on 08 Aug 19
     
    To be read
Nathan Goodyear

Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting ... - 0 views

www.karger.com/...489982

LPS artesunate inflammation sepsis TLR4 cytokine storm

shared by Nathan Goodyear on 04 Apr 20 - No Cached
  • Nathan Goodyear on 04 Apr 20
     
    To be read
Nathan Goodyear

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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