Skip to main content

Home/ Dr. Goodyear/ Group items tagged Lung

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Estrogen Receptor-α as a Drug Target Candidate for Preventing Lung Inflammation - 0 views

www.ncbi.nlm.nih.gov/...PMC2803150

ER-alpha ER estrogen receptor alpha inflammation

shared by Nathan Goodyear on 23 Nov 12 - No Cached
  • Nathan Goodyear on 23 Nov 12
     
    ER alpha promotes lung inflammation.  In this study, they found that ER alpha could be a potential target to reduce lung inflammation.
Nathan Goodyear

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4287931

ivermectin cancer WTF Selamectin

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • WNT signaling
  • early colon cancers commonly display loss of function of the tumor suppressor Adenomatous polyposis coli (APC), a key component of the β-CATENIN destruction complex
  • Other cancers also show an active canonical WNT pathway; these include carcinomas of the lung, stomach, cervix, endometrium, and lung as well as melanomas and gliomas
  • ...31 more annotations...
  • In normal embryogenesis and homeostasis, the canonical WNT pathway is activated by secreted WNT ligands produced in highly controlled context-dependent manners and in precise amounts. WNT activity is transduced in the cytoplasm, inactivates the APC destruction complex, and results in the translocation of activate β-CATENIN to the nucleus, where it cooperates with DNA-binding TCF/LEF factors to regulate WNT-TCF targets and the ensuing genomic response
  • beyond the loss of activity of the APC destruction complex, for instance throughAPC mutation, phosphorylation of β-CATENIN at C-terminal sites is required for the full activation of WNT-TCF signaling and the ensuing WNT-TCF responses in cancer.
  • The WNT-TCF response blockade that we describe for low doses of Ivermectin suggests an action independent to the deregulation of chloride channels
  • involve the repression of the levels of C-terminally phosphorylated β-CATENIN forms and of CYCLIN D1, a critical target that is an oncogene and positive cell cycle regulator.
  • the Avermectin single-molecule derivative Selamectin, a drug widely used in veterinarian medicine (Nolan & Lok, 2012), is ten times more potent acting in the nanomolar range
  • Ivermectin also diminished the protein levels of CYCLIN D1, a direct TCF target and oncogene, in both HT29 and H358 tumor cells
  • Activated Caspase3 was used as a marker of apoptosis by immunohistochemistry 48 h after drug treatment. Selamectin and Ivermectin induced up to a sevenfold increase in the number of activated Caspase3+ cells in two primary (CC14 and CC36) and two cell line (DLD1 and Ls174T) colon cancer cell types (Fig​(Fig2C).2C). All changes were significative
  • The strong downregulation of the expression of the intestinal stem cell genesASCL2 andLGR5 (van der Flieret al, 2009; Scheperset al, 2012; Zhuet al, 2012b) by Ivermectin and Selamectin (Fig​(Fig2D)2D) raised the possibility that these drugs could affect WNT-TCF-dependent colon cancer stem cell behavior
  • Pre-established H358 tumors responded to Ivermectin showing a ˜ 50% repression of growth
  • Ivermectin hasin vivo efficacy against human colon cancer xenografts sensitive to TCF inhibition with no discernable side effects
  • Ivermectin (Campbellet al, 1983), an off-patent drug approved for human use, and related macrocyclic lactones, have WNT-TCF pathway response blocking and anti-cancer activities
  • these drugs block WNT-TCF pathway responses, likely acting at the level of β-CATENIN/TCF function, affecting β-CATENIN phosphorylation status.
  • anti-WNT-TCF activities of Ivermectin and Selamectin
  • Ivermectin has a well-known anti-parasitic activity mediated via the deregulation of chloride channels, leading to paralysis and death (Hibbs & Gouaux, 2011; Lynagh & Lynch, 2012). The same mode of action has been suggested to underlie the toxicity of Ivermectin for liquid tumor cells and the potentiation or sensitization effect of Avermectin B1 on classical chemotherapeutics
  • the specificity of the blockade of WNT-TCF responses we document, at low micromolar doses for Ivermectin and low nanomolar doses for Selamectin, indicate that the blockade of WNT-TCF responses and chloride channel deregulation are distinct modes of action
  • What is key then is to find a dose and a context where the use of Ivermectin has beneficial effects in patients, paralleling our results with xenografts in mice.
  • Cell toxicity appears at doses greater (> 10 μM for 12 h or longer or > 5 μM for 48 h or longer for Ivermectin) than those required to block TCF responses and induce apoptosis.
  • Our data point to a repression of WNT-β-CATENIN/TCF transcriptional responses by Ivermectin, Selamectin and related macrocylic lactones.
  • (i) The ability of Avermectin B1 to inhibit the activation of WNT-TCF reporter activity by N-terminal mutant (APC-insensitive) β-CATENIN as detected in our screen
  • (ii) The ability of Avermectin B1, Ivermectin, Doramectin, Moxidectin and Selamectin to parallel the modulation of WNT-TCF targets by dnTCF
  • (iii) The finding that the specific WNT-TCF response blockade by low doses of Ivermectin and Selamectin is reversed by constitutively active TCF
  • (iv) The repression of key C-terminal phospho-isoforms of β-CATENIN resulting in the repression of the TCF target and positive cell cycle regulator CYCLIN D1 by Ivermectin and Selamectin
  • (v) The specific inhibition ofin-vivo-TCF-dependent, but notin-vivo-TCF-independent cancer cells by Ivermectin in xenografts.
  • These results together with the reduction of the expression of the colon cancer stem cell markersASCL2 andLGR5 (e.g., Hirschet al, 2013; Ziskinet al, 2013) raise the possibility of an inhibitory effect of Ivermectin, Selamectin and related macrocyclic lactones on TCF-dependent cancer stem cells.
  • the capacity of cancer cells to form 3D spheroids in culture, as well as the growth of these, is also WNT-TCF-dependent (Kanwaret al, 2010) and they were also affected by Ivermectin treatment
  • If Ivermectin is specific, it should only block TCF-dependent tumor growth. Indeed, the sensitivity and insensitivity of DLD1 and CC14 xenografts to Ivermectin treatment, respectively, together with the desensitization to Ivermectin actionin vivo by constitutively active TCF provide evidence of the specificity of this drug to block an activated WNT-TCF pathway in human cancer.
  • Ivermectin has a good safety profile since onlyin-vivo-dnTCF-sensitive cancer xenografts are responsive to Ivermectin treatment, and we have not detected side effects in Ivermectin-treated mice at the doses used
  • previous work has shown that side effects from systemic treatments with clinically relevant doses in humans are rare (Yang, 2012), that birth defects were not observed after exposure of pregnant mothers (Pacquéet al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet al, 2001; Orzechowskiet al, 2012)
  • Indications may include treatment for incurable β-CATENIN/TCF-dependent advanced and metastatic human tumors of the lung, colon, endometrium, and other organs.
  • Ivermectin, Selamectin, or related macrocyclic lactones could also serve as topical agents for WNT-TCF-dependent skin lesions and tumors such as basal cell carcinomas
  • they might also be useful as routine prophylactic agents, for instance against nascent TCF-dependent intestinal tumors in patients with familial polyposis and against nascent sporadic colon tumors in the general aging population
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin, a common anti-parasitic, found to inhibit WTF-TCF pathway and decrease c-terminal phosophorylaiton of Beta-CATENIN all resulting in increased aptosis and inhibition of cancer growth in colon cancer cell lines and lung cancer cell lines.
Nathan Goodyear

RB&E | Abstract | Levothyroxine and lung cancer in females: the importance of oxidative... - 0 views

www.rbej.com/...abstract

levothyroxine T4 lung cancer hypothyroid oxidative stress

shared by Nathan Goodyear on 22 Dec 13 - No Cached
  • Nathan Goodyear on 22 Dec 13
     
    Interesting study finds T4 therapy, levothyroxine,  linked to increased lung cancer.  The link could be through oxidative stress.
Nathan Goodyear

Levothyroxine and lung cancer in females: the importance of oxidative stress - 0 views

www.rbej.com/...1477-7827-11-75.pdf

T4 synthroid lung cancer oxidative stress ROS reactive oxygenation species

shared by Nathan Goodyear on 13 Aug 13 - No Cached
  • Nathan Goodyear on 13 Aug 13
     
    Study links synthetic T4, synthroid, to increased risk of Lung cancer. The authors acknowledge that the limitations of this study are large. Yet, the association is evident. The proposed mechanism is likely the overdosing and the resultant ROS as a result.
Nathan Goodyear

Raw Garlic Consumption as a Protective Factor for Lung Cancer, a Population-Based Case-... - 0 views

cancerpreventionresearch.aacrjournals.org/...711.abstract

raw garlic lung cancer Aillicin

shared by Nathan Goodyear on 12 Aug 13 - No Cached
  • Nathan Goodyear on 12 Aug 13
     
    Garlic intake at twice weekly reduces lung cancer rates in smokers and non-smokers.  The component that provides the benefit is Aillicin.  This study only looked at raw garlic intake.  
fnfdoc

COPD: Stages, Causes, Symptoms And Treatment - Health Blog - 0 views

fnfdoc.com/...ages-causes-symptoms-treatment

Alpha-1 Antitrypsin Deficiency COPD Causes Stages Symptoms Treatment Lung Disease

shared by fnfdoc on 16 Feb 19 - No Cached
  • fnfdoc on 16 Feb 19
     
    COPD consists of multiple lung infections and is considered incurable by most physicians. Can timely diagnosis, on the bright side, slow down its progress?
  • fnfdoc on 16 Feb 19
     
    COPD consists of multiple lung infections and is considered incurable by most physicians. Can timely diagnosis, on the bright side, slow down its progress?
Nathan Goodyear

Update on Programmed Death-1 and Programmed Death-Ligand 1 Inhibition in the Treatment ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5382272

cancer PD-1 immunotherapy programmed death-1

shared by Nathan Goodyear on 20 Apr 18 - No Cached
  • Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the first immune checkpoint receptor to be clinically targeted, is exclusively expressed on the surface of CD4+ and CD8+ T cells in lymphatic tissue and is involved in T-cell regulation, proliferation, and tolerance
  • programmed death-1 (PD-1) immune checkpoint inhibitor antibodies, which restores T-cell effector function and augments the host anti-tumor response by blocking the binding of either programmed death-ligand 1 (PD-L1) and/or PD-L2 to PD-1 receptors
  • lung cancer is the first and second cause of cancer mortality in men and women
  • ...1 more annotation...
  • Eighty-five percent of lung cancers are non-small-cell lung cancer (NSCLC)
  • Nathan Goodyear on 20 Apr 18
     
    To read update article on PD-1 and immunotherapy.
Nathan Goodyear

Artemisinin and its derivatives can significantly inhibit lung tumorigenesis ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5058767

Wnt lung cancer artesunate artemisinin

shared by Nathan Goodyear on 07 May 20 - No Cached
  • Nathan Goodyear on 07 May 20
     
    Artemisinin(s) inhibit Wnt pathway in lung cancer.
Nathan Goodyear

Crosstalk between Integrin αvβ3 and Estrogen Receptor-α Is Involved in Thyroi... - 0 views

www.ncbi.nlm.nih.gov/...PMC3222665

ER alpha thyroid hormones thyroid integrin αvβ3 cancer ER-alpha lung cancer

shared by Nathan Goodyear on 13 Apr 21 - No Cached
  • Nathan Goodyear on 13 Apr 21
     
    Integrin αvβ3 cross talk with ER-alpha + lung cancer
Nathan Goodyear

Metronomic Chemotherapy in Non-Small-Cell Lung Cancer | Request PDF - 0 views

www.researchgate.net/..._in_Non-Small-Cell_Lung_Cancer

low-dose low-dose chemotherapy metronomic chemotherapy LDMC lung cancer

shared by Nathan Goodyear on 29 Apr 21 - No Cached
  • Nathan Goodyear on 29 Apr 21
     
    LDMC effect in lung cancer via its Antiangiogenic and anti immunosuppressive effects.
Nathan Goodyear

Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Ca... - 0 views

cebp.aacrjournals.org/...1319.full

Testosterone cancer men male hormone hormones

shared by Nathan Goodyear on 19 Nov 14 - No Cached
  • Nathan Goodyear on 19 Nov 14
     
    Study finds that increased free Testosterone is associated with increased incidence of prostate cancer.  Higher Total Testosterone was associated with lung cancer and androgens were not associated with colorectal cancer incidence.  That being said, the evaluation of androgens only is a significant limiting factor of this study.  
Nathan Goodyear

Cyclooxygenase-2 Induces EP1- and HER-2/Neu-Dependent Vascular Endothelial Growth Facto... - 0 views

cancerres.aacrjournals.org/...554

COX-2 cancer HER-2 Celebrex VEGF metastasis prostate cancer lung cancer colorectal cancer

shared by Nathan Goodyear on 07 Aug 18 - No Cached
  • Nathan Goodyear on 07 Aug 18
     
    COX-2 is overexpressed in a variety of human cancers i.e. colorectal, prostate, lung adenocarcinoma.  This study hightlights the increased tumor metastatic potential via upregulation of VEGF-C via EP1 and HER-2 dependent pathways.  This upregulation was correlated with survival and mets.
Nathan Goodyear

30-day mortality after systemic anticancer treatment for breast and lung cancer in Engl... - 0 views

www.thelancet.com/...fulltext

chemotherapy cancer mortality

shared by Nathan Goodyear on 11 Jul 17 - No Cached
  • Our data also suggest that 30-day mortality might be higher than previously estimated by several clinical trials.9, 10 The 30-day mortality rate after SACT with curative intent for NSCLC reported here is high at 3% compared with published trial data for the standard treatments, which suggested that 0·8% of patients died from treatment-induced toxicity when chemotherapy was given as adjuvant treatment alongside surgery
  • findings of clinical trials in selected age cohorts cannot readily be generalised to all patients
  • Nathan Goodyear on 11 Jul 17
     
    Population study from England finds significant increase in mortality in first 30 days of chemotherapy in breast and lung cancer treatment.  The previously published trial dat was 0.8%; this study was as high as 3%.  This cast doubt as to the inference of the risk from clinical trials to the general population.
fnfdoc

Tuberculosis Pathogenesis | Your Health Our Priority - 0 views

www.fnfdoc.com/...tuberculosis-pathogenesis

tuberculosis TB Pathogenesis

shared by fnfdoc on 17 May 18 - No Cached
  • fnfdoc on 17 May 18
     
    Approximately 2 billion people suffer from Tuberculosis each year. Tuberculosis or simply TB is an infectious and highly contagious disease of the body especially lungs. It spreads mainly via Mycobacterium tuberculosis which is a tough and highly resistant microbe.
  • fnfdoc on 17 May 18
     
    Tuberculosis is a serious, infectious and often fatal disease of the lungs. It can also affect other parts of the body. But the most common type of Tuberculosis is pulmonary Tuberculosis. It is more common in women than in men. The causative agent is a Gram-positive bacterium (Mycobacterium tuberculosis).
Nathan Goodyear

Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dep... - 0 views

pubmed.ncbi.nlm.nih.gov/28648644

Snail quercetin non-small cell lung cancer lung cancer Akt

shared by Nathan Goodyear on 20 May 21 - No Cached
  • Nathan Goodyear on 20 May 21
     
    Quercetin effective in inhibiting EMT and Akt proliferation signaling.
Nathan Goodyear

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 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.
Nathan Goodyear

Glucose-6-Phosphate Dehydrogenase Is Not Essential for K-Ras-Driven Tumor Growth or Met... - 0 views

aacrjournals.org/...Dehydrogenase-Is-Not-Essential

cancer glucose 6 phosphate dehydrogenase G6PD lung seeding

shared by Nathan Goodyear on 24 Jul 22 - No Cached
  • Nathan Goodyear on 24 Jul 22
     
    Interesting point here: G6PD involved in lung seeding.
Nathan Goodyear

Core needle biopsy promotes lung metastasis of breast cancer: An experimental study - 0 views

www.spandidos-publications.com/...mco.2018.1784

TGF-beta TGF-1beta cancer epithelial to mesenchymal transition core needle biopsy metastasis EMT biopsy

shared by Nathan Goodyear on 04 May 23 - No Cached
  • Nathan Goodyear on 04 May 23
     
    "CNB was found to promote the lung metastasis of breast cancer, and the underlying mechanism may be associated with epithelial‑to‑mesenchymal transition (EMT) mediated by the TGF‑β1 signaling pathway."
Nathan Goodyear

O2⋅− and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Su... - 0 views

www.cell.com/...S1535-6108(17)30062-4

IV vitamin C cancer vitamin C alternative medicine

shared by Nathan Goodyear on 12 Apr 17 - No Cached
  • Nathan Goodyear on 12 Apr 17
     
    IV vitamin C shown to have selective cytotoxicity, no surprise, on lung cancer and glioblastoma cells via H2O2, while at the same time safe to other cells.  
Nathan Goodyear

Curcumin-induced apoptosis in scleroderma lung fibroblasts - Role of protein kinase Cep... - 0 views

eurekamag.com/...of-protein-kinase-cepsilon.php

curcumin tumeric autoimmune disease scleroderma fibrosis

shared by Nathan Goodyear on 22 Jan 14 - No Cached
  • Nathan Goodyear on 22 Jan 14
     
    Curcumin found to cause apoptosis of fibrotic pulmonary cells versus no effect on healthy pulmonary cells.
1 - 20 of 153 Next › Last »
Showing 20▼ items per page