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Exploring Cancer Metabolic Reprogramming Through Molecular Imaging

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452347 Year: Pages: 242 DOI: 10.3389/978-2-88945-234-7 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2017-10-13 14:57:01
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The inclusion of oncogene-driven reprogramming of energy metabolism within the list of cancer hallmarks (Hanahan and Weinberg, Cell 2000, 2011) has provided major impetus to further investigate the existence of a much wider metabolic rewiring in cancer cells, which not only includes deregulated cellular bioenergetics, but also encompasses multiple links with a more comprehensive network of altered biochemical pathways. This network is currently held responsible for redirecting carbon and phosphorus fluxes through the biosynthesis of nucleotides, amino acids, lipids and phospholipids and for the production of second messengers essential to cancer cells growth, survival and invasiveness in the hostile tumor environment. The capability to develop such a concerted rewiring of biochemical pathways is a versatile tool adopted by cancer cells to counteract the host defense and eventually resist the attack of anticancer treatments. Integrated efforts elucidating key mechanisms underlying this complex cancer metabolic reprogramming have led to the identification of new signatures of malignancy that are providing a strong foundation for improving cancer diagnosis and monitoring tumor response to therapy using appropriate molecular imaging approaches. In particular, the recent evolution of positron emission tomography (PET), magnetic resonance spectroscopy (MRS), spectroscopic imaging (MRSI), functional MR imaging (fMRI) and optical imaging technologies, combined with complementary cellular imaging approaches, have created new ways to explore and monitor the effects of metabolic reprogramming in cancer at clinical and preclinical levels. Thus, the progress of high-tech engineering and molecular imaging technologies, combined with new generation genomic, proteomic and phosphoproteomic methods, can significantly improve the clinical effectiveness of image-based interventions in cancer and provide novel insights to design and validate new targeted therapies. The Frontiers in Oncology Research Topic “Exploring Cancer Metabolic Reprogramming Through Molecular Imaging” focusses on current achievements, challenges and needs in the application of molecular imaging methods to explore cancer metabolic reprogramming, and evaluate its potential impact on clinical decisions and patient outcome. A series of reviews and perspective articles, along with original research contributions on humans and on preclinical models have been concertedly included in the Topic to build an open forum on perspectives, present needs and future challenges of this cutting-edge research area.

Biomarkers in Drug Hypersensitivity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452262 Year: Pages: 104 DOI: 10.3389/978-2-88945-226-2 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Biomarkers, especially those based on pharmacogenomics testing, have proved to be extremely useful for type A adverse drug reactions. Clinical practice guidelines based on biomarker testing are presently being developed and updated for type A adverse drug reactions. In contrast, little attention has been paid to the potential use of biomarkers in type B adverse reactions, characterized by the occurrence of reactions not directly related to the pharmacological properties of the drug. Drug-induced hypersensitivity belongs to those type B reactions. Drug-induced hypersensitivity reactions involve complex mechanisms that include, among others, the metabolic activation and haptenization of drug metabolites. Hence, factors that influence the pharmacokinetics of drug and metabolites may contribute to the development of some drug-induced hypersensitivity reactions. This implies that processes such as ADME (absorption, distribution, metabolism and excretion) that are typically involved in type A adverse drug reactions, may have a role in hypersensitivity reactions too. In addition to metabolic activation, several signal transduction pathways participate and modulate the development and the clinical presentation of drug hypersensitivity. The diverse mechanisms underlying such drug-hypersensitivity reactions lead to four major groups of reactions according to the Gell and Coombs classification: immediate, cytotoxic, immune complex and delayed. The enormous complexity of drug-hypersensitivity reactions is a consequence of the variety of mechanisms involved, which may be related, among others, to drug metabolism, generation of antigenic signals, stimulation and maturation of dendritic cells, presentation of haptens and mechanisms of cytotoxicity. In addition, a plethora of possible clinical presentations exists, including urticaria, angioedema, anaphylaxis, cytopenias, nephritis, serum sickness, vasculitis, contact dermatitis, drug rash, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. The rapid progress in the field in recent years indicates that the combination of several disciplines is essential to understand the mechanisms involved in this particular, and not completely understood, type of adverse drug reactions. The objective of this Research Topic is to present insights obtained from both basic and clinical scientists, which may include studies related to the identification, validation, refinement and clinical implementation of biomarkers for drug-induced hypersensitivity. The Topic aims to include recent findings related, but not limited to, potential phenomic, genomic, proteomic, metabolomic and signal transduction biomarkers. These biomarkers could eventually be used in clinical practice and/or these might contribute, as a proof of concept, to our understanding of the complex events leading to drug hypersensitivity reactions. In addition the Topic will cover recent developments and methodological advances in the diagnosis, prevention and therapeutic management of drug-induced hypersensitivity.

Systems Biology and the Challenge of Deciphering the Metabolic Mechanisms Underlying Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453337 Year: Pages: 142 DOI: 10.3389/978-2-88945-333-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology --- Biology
Added to DOAB on : 2018-11-16 17:17:57
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Since the discovery of the Warburg effect in the 1920s cancer has been tightly associated with the genetic and metabolic state of the cell. One of the hallmarks of cancer is the alteration of the cellular metabolism in order to promote proliferation and undermine cellular defense mechanisms such as apoptosis or detection by the immune system. However, the strategies by which this is achieved in different cancers and sometimes even in different patients of the same cancer is very heterogeneous, which hinders the design of general treatment options.Recently, there has been an ongoing effort to study this phenomenon on a genomic scale in order to understand the causality underlying the disease. Hence, current “omics” technologies have contributed to identify and monitor different biological pieces at different biological levels, such as genes, proteins or metabolites. These technological capacities have provided us with vast amounts of clinical data where a single patient may often give rise to various tissue samples, each of them being characterized in detail by genomescale data on the sequence, expression, proteome and metabolome level. Data with such detail poses the imminent problem of extracting meaningful interpretations and translating them into specific treatment options. To this purpose, Systems Biology provides a set of promising computational tools in order to decipher the mechanisms driving a healthy cell’s metabolism into a cancerous one. However, this enterprise requires bridging the gap between large data resources, mathematical analysis and modeling specifically designed to work with the available data. This is by no means trivial and requires high levels of communication and adaptation between the experimental and theoretical side of research.

Mitochondria in Skeletal Muscle Health, Aging and Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450732 Year: Pages: 142 DOI: 10.3389/978-2-88945-073-2 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Skeletal muscle is the most abudant tissue of the human body, making up to 40 to 50% of the human body mass. While the importance of optimal muscle function is well recognized in the athletic field, its significance for general health is often underappreciated. In fact, the evidence that muscle mass, strength and metabolism are essential for our overall health is overwhelming. As the largest protein reservoir in the human body, muscles are essential in the acute response to critical illness such as sepsis, advanced cancer, and traumatic injury. Loss of skeletal muscle mass has also been associated with weakness, fatigue, insulin resistance, falls, fractures, frailty, disability, several chronic diseases and death. As a consequence, maintaining skeletal muscle mass, strength and metabolism throughout the lifespan is critical to the maintenance of whole body health. Mitochondria are fascinating organelles regulating many critical cellular processes for skeletal muscle physiology, including for instance energy supply, reactive oxygen species production, calcium homeostasis and the regulation of apoptosis. It is therefore not surprising that mitochondrial dysfunction has been implicated in a large number of adverse events/conditions and pathologies affecting skeletal muscle health. While the importance of normal mitochondrial function is well recognized for muscle physiology, there are important aspects of mitochondrial biology that are still poorly understood. These include mitochondrial dynamics (fusion and fission processes), morphology and processes involved in mitochondrial quality control (mitophagy). Defining the mechanisms regulating these different aspects of mitochondrial biology, their importance for muscle physiology, as well as the interrelations will be critical for expanding understanding of the role played by mitochondria in skeletal muscle physiology and health. The present research topic provides readers with novel experimental approaches, knowledge, hypotheses and findings related to all aspects of mitochondrial biology in healthy and diseased muscle cells.Skeletal muscle is the most abudant tissue of the human body, making up to 40 to 50% of the human body mass. While the importance of optimal muscle function is well recognized in the athletic field, its significance for general health is often underappreciated. In fact, the evidence that muscle mass, strength and metabolism are essential for our overall health is overwhelming. As the largest protein reservoir in the human body, muscles are essential in the acute response to critical illness such as sepsis, advanced cancer, and traumatic injury. Loss of skeletal muscle mass has also been associated with weakness, fatigue, insulin resistance, falls, fractures, frailty, disability, several chronic diseases and death. As a consequence, maintaining skeletal muscle mass, strength and metabolism throughout the lifespan is critical to the maintenance of whole body health. Mitochondria are fascinating organelles regulating many critical cellular processes for skeletal muscle physiology, including for instance energy supply, reactive oxygen species production, calcium homeostasis and the regulation of apoptosis. It is therefore not surprising that mitochondrial dysfunction has been implicated in a large number of adverse events/conditions and pathologies affecting skeletal muscle health. While the importance of normal mitochondrial function is well recognized for muscle physiology, there are important aspects of mitochondrial biology that are still poorly understood. These include mitochondrial dynamics (fusion and fission processes), morphology and processes involved in mitochondrial quality control (mitophagy). Defining the mechanisms regulating these different aspects of mitochondrial biology, their importance for muscle physiology, as well as the interrelations will be critical for expanding understanding of the role played by mitochondria in skeletal muscle physiology and health. The present research topic provides readers with novel experimental approaches, knowledge, hypotheses and findings related to all aspects of mitochondrial biology in healthy and diseased muscle cells.

Fungal Jewels: Secondary Metabolites

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451364 Year: Pages: 203 DOI: 10.3389/978-2-88945-136-4 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Fungal natural products are friends and foes of humans such as deleterious mycotoxins, cytotoxic, carcinogenic compounds or beneficial compounds such as antibiotics, fungicides, insecticides, antiviral and antitumor metabolites. Understanding fungal diversity and estimation of fungal species on our planet poses a great challenge to researchers. This complexity is further multiplied by secondary metabolite diversity of fungi, which requires interdisciplinary studies. It is extremely important to understand the fungal secondary metabolism to stop human, animal and plant diseases caused by fungi and harvest their valuable metabolites. Furthermore, many secondary metabolite gene clusters are silenced under laboratory conditions. It is vital to develop effective methods to activate those clusters in order to discover novel potent metabolites. This e-book is a compilation of original review articles contributed by leading fungal secondary metabolite researchers with a wide range of expertise. Important aspects of fungal secondary metabolism, including regulation, genome mining, evolution, synthetic biology and novel methods have been discussed. This book will be a great source to those people, who are interested in understanding overall structure, diversity and regulation of production of these tiny but precious chemicals.

The Metabolic-Inflammatory Axis in Brain Aging and Neurodegeneration

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452538 Year: Pages: 161 DOI: 10.3389/978-2-88945-253-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Impairment of energy metabolism is a hallmark of brain aging and several neurodegenerative diseases, such as the Alzheimer’s disease (AD). Age- and disease-related hypometabolism is commonly associated with oxidative stress and they are both regarded as major contributors to the decline in synaptic plasticity and cognition. Neuroinflammatory changes, entailing microglial activation and elevated expression of inflammatory cytokines, also correlate with age-related cognitive decline. It is still under debate whether the mitochondrial dysfunction-induced metabolic deficits or the microglia activation-mediated neuroinflammation is the initiator of the cognitive changes in aging and AD. Nevertheless, multiple lines of evidence support the notion that mitochondrial dysfunction and chronic inflammation exacerbate each other, and these mechanistic diversities have cellular redox dysregulation as a common denominator. This research topic focuses on the role of a metabolic-inflammatory axis encompassing the bioenergetic activity, brain inflammatory responses and their redox regulation in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems are reviewed in terms of their causative or in-tandem occurrence and how the systemic environment, –e.g., insulin resistance, diabetes, and systemic inflammation–, impacts on brain function.

Metabolic Control of Brain Homeostasis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452866 Year: Pages: 204 DOI: 10.3389/978-2-88945-286-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Brain function is under metabolic control, which in turn determines the equilibrium of homeostatic systems that affect neuronal and glial networks on the molecular, cellular, and systems levels. The collection of articles ranges from molecules and mechanisms involved in regulating homeostasis and neuronal excitability to therapeutic mechanisms tailored to restore homeostatic function. It also features neurological diseases and novel treatment approaches that are based on metabolic and homeostatic interventions. Together, the collection of articles outlines novel strategies to restore brain function in neurology and highlights limitations of conventional pharmacological approaches. We suggest that restoration of molecular and biochemical networks could lead to a new era of therapeutic opportunities.

Cancer Metabolism: Molecular Targeting and Implications for Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453221 Year: Pages: 114 DOI: 10.3389/978-2-88945-322-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-02-27 16:16:45
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Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists. “Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies.

Microbial Role in the Carbon Cycle in Tropical Inland Aquatic Ecosystems

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451272 Year: Pages: 144 DOI: 10.3389/978-2-88945-127-2 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Aquatic microorganisms are tidily related to the carbon cycle in aquatic systems, especially in respect to its accumulation and emission to atmosphere. In one hand, the autotrophs are responsible for the carbon input to the ecosystems and trophic chain. On the other hand, the heterotrophs traditionally play a role in the carbon mineralization and, since microbial loop theory, may play a role to carbon flow through the organisms. However, it is not yet clear how the heterotrophs contribute to carbon retention and emission especially from tropical aquatic ecosystems. Most of the studies evaluating the role of microbes to carbon cycle in inland waters were performed in high latitudes and only a few studies in the tropical area. In the prospective of global changes where the warm tropical lakes and rivers become even warmer, it is important to understand how microorganisms behave and interact with carbon cycle in the Earth region with highest temperature and light availability. This research topic documented microbial responses to natural latitudinal gradients, spatial within and between ecosystems gradients, temporal approaches and temperature and nutrient manipulations in the water and in the sediment.

Advances in Polyhydroxyalkanoate (PHA) Production

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ISBN: 9783038426370 9783038426363 Year: Pages: X, 245 DOI: 10.3390/books978-3-03842-636-3 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biotechnology
Added to DOAB on : 2017-12-22 11:01:59
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Currently, we are witnessing highly dynamic research efforts related to the exciting field of novel biodegradable plastic-like materials. These activities originate from a growing public awareness of prevailing ecological problems associated to, e.g., rising piles of plastic waste, increasing greenhouse gas emissions, and ongoing depletion of such fossil resources usually used for the synthesis of “full carbon backbone” plastics. Polyhydroxyalkanoate (PHA) biopolyesters, a family of versatile plastic-like materials produced by living microbes, are a future-oriented alternative to traditional plastics. If accomplished in an optimized way, production and the entire lifecycle of PHA are embedded into nature´s closed carbon cycle, which is underlined by PHA´s main benefits of being “biobased”, “biosynthesized”, “biocompatible”, and “biodegradable”.Sustainable and economically feasible PHA synthesis, especially on an industrially relevant scale, requires all production steps to be understood and improved. Among other aspects, this calls for new powerful production strains to be screened; knowledge about the proteome and genome of PHA accumulating organisms to be consolidated; the kinetics of the bioprocesses to be thoroughly understood; abundantly available inexpensive raw materials to be tested; the monomer composition of PHA to be adapted; (bio)chemical engineering to be optimized; and novel PHA recovery strategies to be developed in order to reduce energy and chemical inventory.The present book provides a comprehensive compilation of articles addressing all these different aspects; the individual chapters were composed by globally recognized front running experts from special niches of PHA research. We are convinced that this book will be of major benefit to the growing scientific community active in biopolymer research.

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