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Targeting PI3K/mTOR signaling in cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192441 Year: Pages: 93 DOI: 10.3389/978-2-88919-244-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Medicine (General) --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. Rapamycin and its analogs targeting mTOR are effective in many preclinical cancer models. Although rapalogs are approved for the treatment of some cancers, their efficacy in clinical trials remains the subject of debate. Due to the complexity of the PI3K/mTOR signaling pathway, developing an effective anti-cancer therapy remains a challenge. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments.

Essential Pathways and Circuits of Autism Pathogenesis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199051 Year: Pages: 181 DOI: 10.3389/978-2-88919-905-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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The Centers for Disease Control and Prevention estimate that 1 in 68 children in the United states is afflicted with autism spectrum disorders (ASD), yet at this time, there is no cure for the disease. Autism is characterized by delays in the development of many basic skills, most notably the ability to socialize and adapt to novelty. The condition is typically identified in children around 3 years of age, however the high heritability of autism suggests that the disease process begins at conception. The identification of over 500 ASD risk genes, has enabled the molecular genetic dissection of the pathogenesis of the disease in model organisms such as mice. Despite the genetic heterogeneity of ASD etiology, converging evidence suggests that these disparate genetic lesions may result in the disruption of a limited number of key biochemical pathways or circuits. Classification of patients into groups by pathogenic rather than etiological categories, will likely aid future therapeutic development and clinical trials. In this set of papers, we explore the existing evidence supporting this view. Specifically, we focus on biochemical cascades such as mTOR and ERK signaling, the mRNA network bound by FMRP and UBE3A, dorsal and ventral striatal circuits, cerebellar circuits, hypothalamic projections, as well as prefrontal and anterior cingulate cortical circuits. Special attention will be given to studies that demonstrate the necessity and/or sufficiency of genetic disruptions (e.g. by molecular deletion and/or replacement) in these pathways and circuits for producing characteristic behavioral features of autism. Necessarily these papers will be heavily weighted towards basic mechanisms elucidated in animal models, but may also include investigations in patients.

mTOR in Human Diseases

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ISBN: 9783039210602 9783039210619 Year: Pages: 480 DOI: 10.3390/books978-3-03921-061-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 08:44:06
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The mechanistic target of rapamycin (mTOR) is a major signaling intermediary that coordinates favorable environmental conditions with cell growth. Indeed, as part of two functionally distinct protein complexes, named mTORC1 and mTORC2, mTOR regulates a variety of cellular processes, including protein, lipid, and nucleotide synthesis, as well as autophagy. Over the last two decades, major molecular advances have been made in mTOR signaling and have revealed the complexity of the events implicated in mTOR function and regulation. In parallel, the role of mTOR in diverse pathological conditions has also been identified, including in cancer, hamartoma, neurological, and metabolic diseases. Through a series of articles, this book focuses on the role played by mTOR in cellular processes, metabolism in particular, and highlights a panel of human diseases for which mTOR inhibition provides or might provide benefits. It also addresses future studies needed to further characterize the role of mTOR in selected disorders, which will help design novel therapeutic approaches. It is therefore intended for everyone who has an interest in mTOR biology and its application in human pathologies.

Keywords

acute myeloid leukemia --- metabolism --- mTOR --- PI3K --- phosphorylation --- epithelial to mesenchymal transition --- mTOR inhibitor --- pulmonary fibrosis --- transcriptomics --- miRNome --- everolimus --- mTOR --- thyroid cancer --- sodium iodide symporter (NIS)/SLC5A5 --- dopamine receptor --- autophagy --- AKT --- mTOR --- AMPK --- mTOR --- Medulloblastoma --- MBSCs --- mTOR --- T-cell acute lymphoblastic leukemia --- targeted therapy --- combination therapy --- mTOR --- metabolic diseases --- glucose and lipid metabolism --- anesthesia --- neurotoxicity --- synapse --- mTOR --- neurodevelopment --- mTOR --- rapamycin --- autophagy --- protein aggregation --- methamphetamine --- schizophrenia --- tumour cachexia --- mTOR --- signalling --- metabolism --- proteolysis --- lipolysis --- mTOR --- mTORC1 --- mTORC2 --- rapamycin --- rapalogues --- rapalogs --- mTOR inhibitors --- senescence --- ageing --- aging --- cancer --- neurodegeneration --- immunosenescence --- senolytics --- biomarkers --- leukemia --- cell signaling --- metabolism --- apoptosis --- miRNA --- mTOR inhibitors --- mTOR --- tumor microenvironment --- angiogenesis --- immunotherapy --- fluid shear stress --- melatonin --- chloral hydrate --- nocodazole --- MC3T3-E1 cells --- primary cilia --- mTOR complex --- metabolic reprogramming --- cancer --- microenvironment --- nutrient sensor --- oral cavity squamous cell carcinoma (OSCC) --- NVP-BEZ235 --- mTOR --- p70S6K --- mTOR --- advanced biliary tract cancers --- mTOR --- NGS --- illumina --- IonTorrent --- eIFs --- mTOR --- autophagy --- Parkinson’s disease --- mTOR --- PI3K --- cancer --- inhibitor --- therapy --- mTOR --- laminopathies --- lamin A/C --- Emery-Dreifuss muscular dystrophy (EDMD) --- Hutchinson-Gilford progeria syndrome (HGPS) --- autophagy --- cellular signaling --- metabolism --- bone remodeling --- ageing --- mTOR --- fructose --- glucose --- liver --- lipid metabolism --- gluconeogenesis --- Alzheimer’s disease --- autophagy --- mTOR signal pathway --- physical activity --- microRNA --- mTOR --- spermatogenesis --- male fertility --- Sertoli cells --- n/a

PI3K signalling

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194193 Year: Pages: 139 DOI: 10.3389/978-2-88919-419-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-10 11:59:06
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The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.

Pleiotropic Action of Selenium in the Prevention and Treatment of Cancer, and Related Diseases

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ISBN: 9783038976929 Year: Pages: 166 DOI: 10.3390/books978-3-03897-693-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology --- Science (General)
Added to DOAB on : 2019-04-05 11:07:22
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This book will cover topics related to the preparation and use of heterogeneous catalytic systems for the transformation of renewable sources, as well as of materials deriving from agro-industrial wastes and by-products. At the same time, the ever-increasing importance of bioproducts, due to the acceptance and request of consumers, makes the upgrade of biomass into chemicals and materials not only an environmental issue, but also an economical advantage.

Cancer Metabolomics 2018

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ISBN: 9783039213450 9783039213467 Year: Pages: 184 DOI: 10.3390/books978-3-03921-346-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2019-12-09 11:49:15
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The metabolomics approach, defined as the study of all endogenously-produced low-molecular-weight compounds, appeared as a promising strategy to define new cancer biomarkers. Information obtained from metabolomic data can help to highlight disrupted cellular pathways and, consequently, contribute to the development of new-targeted therapies and the optimization of therapeutics. Therefore, metabolomic research may be more clinically translatable than other omics approaches, since metabolites are closely related to the phenotype and the metabolome is sensitive to many factors. Metabolomics seems promising to identify key metabolic pathways characterizing features of pathological and physiological states. Thus, knowing that tumor metabolism markedly differs from the metabolism of normal cells, the use of metabolomics is ideally suited for biomarker research. Some works have already focused on the application of metabolomic approaches to different cancers, namely lung, breast and liver, using urine, exhaled breath and blood. In this Special Issue we contribute to a more complete understanding of cancer disease using metabolomics approaches.

Curcumin in Health and Disease

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ISBN: 9783039214495 9783039214501 Year: Pages: 274 DOI: 10.3390/books978-3-03921-450-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-12-09 11:49:15
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The plant-derived polyphenol curcumin has been used in promoting health and combating disease for thousands of years. Its therapeutic effects have been successfully utilized in Ayurvedic and Traditional Chinese Medicine in order to treat inflammatory diseases. Current results from modern biomolecular research reveal the modulatory effects of curcumin on a variety of signal transduction pathways associated with inflammation and cancer. In this context, curcumin’s antioxidant, anti-inflammatory, anti-tumorigenic, and even anti-metastatic activities are discussed. On the cellular level, the reduced activity of several transcription factors (such as NFkB or AP-1) and the suppression of inflammatory cytokines, matrix degrading enzymes, metastasis related genes and even microRNAs are reported. On functional levels, these molecular effects translate into reduced proliferative, invasive, and metastatic capacity, as well as induced tumor cell apoptosis. All these effects have been observed not only in vitro but also in animal models. In combination with anti-neoplastic drugs like Taxol, kinase inhibitors, and radiation therapy, curcumin potentiates the drugs’ therapeutic power and can protect against undesired side effects. Natural plant-derived compounds like curcumin have one significant advantage: They do not usually cause side effects. This feature qualifies curcumin for primary prevention in healthy persons with a predisposition to cancer, arteriosclerosis, or chronic inflammatory diseases. Nonetheless, curcumin is considered safe, although potential toxic effects stemming from high dosages, long-term intake, and pharmacological interactions with other compounds have yet to be assessed. This Special Issue examines in detail and updates current research on the molecular targets, protective effects, and modes of action of natural plant-derived compounds and their roles in the prevention and treatment of human diseases.

Keywords

brain ischemia --- curcumin --- Alzheimer’s disease --- neurodegeneration --- amyloid --- tau protein --- autophagy --- mitophagy --- apoptosis --- genes --- glioblastoma multiforme --- autophagy --- mitophagy --- curcumin --- chaperone-mediated autophagy --- Akt/mTOR signaling --- transmission electron microscopy --- Curcuma longa --- turmeric tuber --- Zingiberaceae --- TLC bioautography --- antimicrobial agents --- ImageJ --- TLC-MS --- hydrostatic counter-current chromatography --- centrifugal partition chromatography --- curcumin --- death receptor --- apoptosis --- curcumin --- anticancer --- structure activity relationship --- cellular pathway --- mechanism of action --- delivery system --- wound --- wound healing --- diet --- nutrition --- micronutrients --- macronutrients --- curcumin --- amino-acids --- vitamins --- minerals --- curcumin --- oxidative metabolites --- inflamm-aging --- cancer --- metabolic reprogramming --- direct protein binding --- IL-17 --- STAT3 --- SHMT2 --- ageing --- anti-cancer --- autophagy --- microbiota --- senescence --- senolytics --- curcumin --- transthyretin --- amyloidosis --- protein aggregation --- protein misfolding --- drug discovery --- curcumin --- renal cell cancer --- tumor growth --- tumor proliferation --- cell cycling --- curcumin --- reflux esophagitis --- gastroprotection --- gastric ulcer --- Helicobacter pylori --- gastric cancer --- curcumin --- complementary medicine --- cancer treatment --- supportive care --- antioxidants --- anti-inflamation --- ulcerative colitis --- Crohn’s disease --- necrotizing enterocolitis --- curcumin --- inflammatory bowel disease --- curcumin --- silica --- chitosan --- nanoparticles --- anti-tumor --- antioxidant activity --- n/a

AMP-Activated Protein Kinase Signalling

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ISBN: 9783038976622 Year: Pages: 452 DOI: 10.3390/books978-3-03897-663-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-03-21 14:08:22
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Starting from a kinase of interest, AMP-activated protein kinase (AMPK) has gone far beyond an average biomolecule. Being expressed in all mammalian cell types and probably having a counterpart in every eukaryotic cell, AMPK has attracted interest in virtually all areas of biological research. Structural and biophysical insights have greatly contributed to a molecular understanding of this kinase. From good old protein biochemistry to modern approaches, such as systems biology and advanced microscopy, all disciplines have provided important information. Thus, multiple links to cellular events and subcellular localizations have been established. Moreover, the crucial involvement of AMPK in human health and disease has been evidenced. AMPK accordingly has moved from an interesting enzyme to a pharmacological target. However, despite our extensive current knowledge about AMPK, the growing community is busier than ever. This book provides a snapshot of recent and current AMPK research with an emphasis on work providing molecular insight, including but not limited to novel physiological and pathological functions, or regulatory mechanisms. Up-to-date reviews and research articles are included.

Keywords

exercise --- glucose uptake --- AMP-activated protein kinase --- TBC1D4 --- AS160 --- AMP-activated protein kinase --- developmental origins of health and disease (DOHaD) --- hypertension --- kidney disease --- nutrient-sensing signals --- oxidative stress --- renin-angiotensin system --- AMPK --- autophagy --- co-expression --- microarrays --- 3T3-L1 --- adipocyte --- differentiation --- AMPK --- tight junctions --- epithelial cells --- ZO-1 --- par complex --- MDCK --- nectin-afadin --- adherent junctions --- TAK1 --- AMPK --- phosphorylation --- AMPK kinase --- endothelial nitric-oxide synthase --- vasodilation --- phenylephrine --- vasoconstriction --- endothelial cells --- ionomycin --- AMPK --- liver --- lipid metabolism --- fatty acid oxidation --- indirect calorimetry --- atrophy --- regrowth --- sirtuin 1 (SIRT1) --- peroxisome proliferator-activated receptor gamma coactivator 1-? (PGC1?) --- heat shock protein --- fiber-type --- AMPK --- monocytes --- macrophages --- differentiation --- autophagy --- AML --- MDS --- CML --- CMML --- pregnancy --- catechol-O-methyltransferase --- 2-methoxyestradiol --- preeclampsia --- gestational diabetes mellitus --- AMPK --- IL-1? --- NLRP3 --- nutrition --- dietary fatty acids --- metabolic-inflammation --- nutrigenomics --- AMPK --- LKB1 --- autophagy --- proteasome --- hypertrophy --- atrophy --- skeletal muscle --- AICAR --- mTOR --- protein synthesis --- AMPK --- epigenetics --- chromatin remodeling --- histone modification --- DNA methylation --- medulloblastoma --- sonic hedgehog --- AMPK --- AMP-activated protein kinase (AMPK) --- spermatozoa --- motility --- mitochondria --- membranes --- signaling --- stress --- assisted reproduction techniques --- AMP-activated protein kinase --- epigenetics --- protein acetylation --- KATs --- HDACs --- acetyl-CoA --- NAD+ --- AMP-activated protein kinase --- glycogen --- exercise --- metabolism --- cellular energy sensing --- energy utilization --- liver --- skeletal muscle --- metabolic disease --- glycogen storage disease --- resveratrol --- AMPK --- hepatocyte --- liver --- steatosis --- transporter --- carrier --- pump --- membrane --- energy deficiency --- AMPK --- infection --- mycobacteria --- host defense --- energy metabolism --- AMPK --- activation loop --- AID --- ?-linker --- ?-linker --- CBS --- LKB1 --- CaMKK2 --- ?RIM --- hypothalamus --- adenosine monophosphate-activated protein kinase --- adipose tissue --- food intake --- adaptive thermogenesis --- beiging --- AMPK --- HDAC4/5 --- p70S6K --- MyHC I(?), motor endplate remodeling --- soleus muscle --- mechanical unloading --- hindlimb suspension --- AMPK --- synaptic activation --- PKA --- CREB --- soluble Adenylyl cyclase --- Immediate early genes --- transcription --- AMPK --- autophagy --- metabolism --- mTOR --- ULK --- AMP-activated protein kinase --- protein kinase B --- Akt --- insulin signalling --- A769662 --- endothelial function --- n/a

Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential

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ISBN: 9783039215324 9783039215331 Year: Pages: 442 DOI: 10.3390/books978-3-03921-533-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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Abstract

This Special Issue Book, “Marine Bioactive Peptides: Structure, Function, andTherapeutic Potential"" includes up-to-date information regarding bioactivepeptides isolated from marine organisms. Marine peptides have been found invarious phyla, and their numbers have grown in recent years. These peptidesare diverse in structure and possess broad-spectrum activities that have greatpotential for medical applications. Various marine peptides are evolutionaryancient molecular factors of innate immunity that play a key role in host defense.A plethora of biological activities, including antibacterial, antifungal, antiviral,anticancer, anticoagulant, endotoxin-binding, immune-modulating, etc., makemarine peptides an attractive molecular basis for drug design. This Special IssueBook presents new results in the isolation, structural elucidation, functionalcharacterization, and therapeutic potential evaluation of peptides found inmarine organisms. Chemical synthesis and biotechnological production of marinepeptides and their mimetics is also a focus of this Special Issue Book.

Keywords

sea cucumber --- ACE-inhibitory peptide --- molecular docking --- structure-activity relationship --- plastein reaction --- Gracilariopsis lemaneiformis --- ACE-inhibitory activity --- peptide --- molecular docking --- SHRs --- prostate cancer --- Anthopleura anjunae oligopeptide --- DU-145 cells --- PI3K/AKT/mTOR signaling pathway --- cod skin --- NA-inhibitory peptide --- influenza virus --- neuraminidase --- molecular docking --- adsorption --- host defense peptide --- antimicrobial peptide --- anti-LPS factor --- host?microbe relationship --- functional diversity --- invertebrate immunity --- crustacean --- antimicrobial activity --- antimicrobial peptide --- polychaeta --- innate immunity --- BRICHOS domain --- recombinant peptide --- ?-helix --- Rana-box --- nuclear magnetic resonance (NMR) --- antimicrobial peptide --- cytotoxicity --- ?-hairpin --- polyphemusins --- tachyplesins --- cell death --- signaling pathways --- Neptunea arthritica cumingii --- multi-functional peptides --- antioxidant activity --- ACE-inhibitory activity --- anti-diabetic activity --- Arenicola marina --- antimicrobial peptides --- arenicin --- complement --- C3a --- acid-sensing ion channel --- animal models --- pain relief --- toxin --- Ugr 9-1 --- APETx2 --- hairtail (Trichiurus japonicas) --- muscle --- peptide --- antioxidant activity --- half-fin anchovy hydrolysates --- Maillard reaction products --- antibacterial peptide --- identification --- self-production of hydrogen peroxide --- membrane damage --- Perinereis aibuhitensis --- decapeptide --- lung cancer --- cell proliferation --- apoptosis --- conotoxins --- conopeptides --- computational studies --- molecular dynamics --- machine learning --- docking --- review --- drug design --- ion channels --- Conus --- conotoxin --- transcriptome sequencing --- phylogeny --- venom duct --- abalone --- peptide --- vasculogenic mimicry --- metastasis --- MMPs --- HIF-1? --- dexamethasone --- myotube atrophy --- protein synthesis --- proteolytic system --- Pyropia yezoensis peptide --- PYP15 --- QAGLSPVR --- antihypertensive effect --- Caco-2 cell monolayer --- transport routes --- oyster zinc-binding peptide --- peptide-zinc complex --- caco-2 cells --- intestinal absorption --- zinc bioavailability --- Chlorella pyrenoidosa protein hydrolysate (CPPH) --- Chlorella pyrenoidosa protein hydrolysate-calcium chelate (CPPH-Ca) --- calcium absorption --- gene expression --- gut microbiota --- cone snails --- conotoxins --- ion channels --- function --- structure --- marine peptides --- arenicin-1 --- molecular symmetry --- structure–activity relationship --- antibacterial --- cytotoxic --- chemical synthesis --- molecular dynamics --- tilapia --- HUVEC --- angiotensin II --- NF-?B --- Nrf2 --- endothelial dysfunction --- conotoxin --- cone snail --- Conus --- Conus ateralbus --- Kalloconus --- n/a

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