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Regulation of Inflammation; Its Resolution and Therapeutic Targeting

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453597 Year: Pages: 105 DOI: 10.3389/978-2-88945-359-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:45
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Inflammation is a fundamental protective mechanism and at the same time the driving force of a variety of major diseases in humans. Indeed, acute self-resolving inflammation usually plays a positive role for the host, as exemplified by infectious diseases where its positive role is well established and testified by its perception as innate immunity. On the other hand, non-resolving inflammation and consequent chronicization is a key determinant of immunopathology and clinical manifestations of most major diseases in humans. As a consequence, it is increasing appreciated that the problem with inflammation is not how often it starts, but how often it fails to resolve. Appropriate resolution of inflammatory responses, which also drives activation of tissue damage repair mechanisms and return of local tissues to homeostasis, is a necessary process for ongoing health. Interestingly, cells sustaining these processes are also key to the proinflammatory responses, and the underlying “pro-resolving” molecular pathways are triggered as part of the pro-inflammatory response. This clearly indicates resolution of inflammation as an active process requiring functional repolarization of inflammatory cells that calls our attention on the underlying molecular mechanisms. The increasing number of anti-inflammatory drugs best-sellers in the pharma market is a clear indication of the relevance of having inflammation under check; nonetheless, there is still a great need for better acting pharmacological tools for the control of inflammation. Indeed, the remarkable success of biological drugs targeting proinflammatory cytokines has indicates that tools able to block proinflammatory mediators have promising applications, but at the same time has made clear that there are intrinsic limitations to this approach which frequently vanish undermine the activity of single targeting drugs, including the well-known redundancy of inflammatory mediators. Under self-limiting conditions inflammation spontaneously resolves in an active process. Some cellular and molecular mechanisms involved in inflammation resolution have been uncovered in the recent past, and include generation of specific cytokines, apoptosis of inflammatory leukocytes, lipid mediators, macrophage repolarization and others are likely to be revealed in the next future, since loss-of-function mutations of an increasing number of genes results in the development of spontaneous inflammation in experimental animals. We argue that “pushing for“ inflammation resolution by exploiting active naturally-occurring pro-resolving processes may have significant advantages over the attempt to simply “push back” inflammation by passive blockade of proinflammatory mediators. At present the research in the field of inflammation aims at identifying and validates new molecules involved in the resolution of inflammation as a basis for the development of innovative therapeutic strategies in chronic inflammatory and autoimmune diseases. This involves the discovery of new natural or synthetic “pro-resolving” molecules from plant and animals and the investigation of endogenous inflammation “pro-resolving” mechanisms, including atypical chemokine receptors, decoy receptors, and microRNA. An extensive effort is focused on the regulation by “pro-resolving” agents on two molecular systems of key relevance in inflammation: the chemokine system, which regulates recruitment, permanence and egress of leukocyte in tissues; and the Toll Like Receptor (TLR)/IL-1R system, which is central for the activation of infiltrating leukocytes.

Ways to improve tumor uptake and penetration of drugs into solid tumors

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193509 Year: Pages: 129 DOI: 10.3389/978-2-88919-350-9 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General) --- Therapeutics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1).

Translocator Protein (TSPO)

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ISBN: 9783038427575 9783038427582 Year: Pages: 176 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-03-16 13:21:14
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The high number of papers submitted and ultimately accepted for publication in this special issue attests the great amount of research being conducted on TSPO and its role in living cells. Thus, TSPO has become an extremely attractive subcellular biomark for the early detection of disease states overexpressing this protein and for the selective delivery to mitochondria of drugs and probes. Moreover, the effort in the design and synthesis of new, more specific and effective TSPO ligands proves to be very valuable. All these topics have been addressed in the special issue.

Interest-Rate Rules in a New Keynesian Framework with Investment

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Book Series: Schriften zur Wirtschaftstheorie und Wirtschaftspolitik ISBN: 9783631611289 Year: Pages: 162 Language: English
Publisher: Peter Lang International Academic Publishing Group
Subject: Economics --- Political Science
Added to DOAB on : 2019-01-15 13:33:00
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The last decades have witnessed major progress in both monetary policy theory and practice, with broad academic consensus on the desirability of monetary policy rules and ongoing research on their exact specification. Typically, the analysis is carried out in a New Keynesian framework with nominal rigidities and constant capital stock. The latter represents a constraint that this study seeks to overcome by introducing a model with investment and capital adjustment costs. The work assesses different interest-rate rule specifications with respect to the target variables included, based on two criteria: determinacy of rational-expectations equilibrium and convergence to steady state after a shock. The study concludes that rules with both an inflation and an output gap target ensure a unique rational-expectations equilibrium and a less distressful adjustment of the economy after the occurrence of shocks.

Geldpolitik und Beschaeftigung

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Book Series: Hohenheimer volkswirtschaftliche Schriften ISBN: 9783631538470 Year: Pages: 479 DOI: 10.3726/b13959 Language: German
Publisher: Peter Lang International Academic Publishing Group
Subject: Economics
Added to DOAB on : 2019-01-15 13:32:23
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Anfang 2006 tritt Alan Greenspan als Vorsitzender der Federal Reserve (Fed) ab. Damit endet gleichzeitig eine einschneidende Epoche der amerikanischen Geldpolitik. Das Urteil zur Greenspan-Ära fällt bisher ambivalent aus. Auf der einen Seite wird der pragmatischen und flexiblen Geldpolitik der letzten 18 Jahre ein erheblicher Anteil am Wachstums- und Beschäftigungserfolg der USA zugebilligt. Andererseits wird die einseitige Ausrichtung auf den Vorsitzenden und das Fehlen einer klaren und verständlichen Konzeption bemängelt. Diese Arbeit versucht zu klären, ob die geldpolitische Strategie der Federal Reserve in der heutigen Form ein Erfolgs- oder Auslaufmodell darstellt. Dazu wird die Fed-Strategie seit 1987 umfassend analysiert und bewertet. Die Analyse soll insbesondere Antworten darauf geben, welche Rolle Beschäftigungsziele in der Geldpolitik spielen sollten, und ob die Fed-Strategie für die Europäische Zentralbank (EZB) Vorbildcharakter besitzt.

Novel Methods and Applications for Mineral Exploration

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ISBN: 9783039289431 / 9783039289448 Year: Pages: 264 DOI: 10.3390/books978-3-03928-944-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Geology --- Earth Sciences
Added to DOAB on : 2020-06-09 16:38:57
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This special volume offers a snapshot of the latest developments in mineral exploration, in particular, geophysical, geochemical, and computational methods. It reflects the cutting-edge applications of geophysics and geochemistry, as well as novel technologies, such as in artificial intelligence and hyperspectral exploration, methods that have profoundly changed how exploration is conducted. This special volume is a representation of these cutting-edge and pioneering methods to consider and conduct exploration, and should serve both as a valuable compendium of the most innovative exploration methodologies available and as a foreshadowing of the form of future exploration. As such, this volume is of significant importance and would be useful to any exploration geologist and company

Designing Hydrogels for Controlled Drug Delivery

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ISBN: 9783039283569 9783039283576 Year: Pages: 162 DOI: 10.3390/books978-3-03928-357-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2020-04-07 23:07:08
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The aim of this book is to provide an analysis of the main characteristics and applications of hydrogels. Hydrogels are frequently used for manufacturing contact lenses, hygiene products, tissue engineering scaffolds, drug delivery systems, and wound dressings. These materials are useful in everyday life, so publicizing them in both academic and pharmaceutical fields is essential.

Anticancer Drugs

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ISBN: 9783039215867 9783039215874 Year: Pages: 214 DOI: 10.3390/books978-3-03921-587-4 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 past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody–drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.

Methods in Computational Biology

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ISBN: 9783039211630 9783039211647 Year: Pages: 214 DOI: 10.3390/books978-3-03921-164-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Computer Science
Added to DOAB on : 2019-08-28 11:21:27
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Modern biology is rapidly becoming a study of large sets of data. Understanding these data sets is a major challenge for most life sciences, including the medical, environmental, and bioprocess fields. Computational biology approaches are essential for leveraging this ongoing revolution in omics data. A primary goal of this Special Issue, entitled “Methods in Computational Biology”, is the communication of computational biology methods, which can extract biological design principles from complex data sets, described in enough detail to permit the reproduction of the results. This issue integrates interdisciplinary researchers such as biologists, computer scientists, engineers, and mathematicians to advance biological systems analysis. The Special Issue contains the following sections:•Reviews of Computational Methods•Computational Analysis of Biological Dynamics: From Molecular to Cellular to Tissue/Consortia Levels•The Interface of Biotic and Abiotic Processes•Processing of Large Data Sets for Enhanced Analysis•Parameter Optimization and Measurement

Targets, Tracers and Translation – Novel Radiopharmaceuticals Boost Nuclear Medicine

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ISBN: 9783039213139 9783039213146 Year: Pages: 214 DOI: 10.3390/books978-3-03921-314-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-12-09 11:49:15
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This is the fourth Special Issue in Pharmaceuticals within the last six years dealing with aspects of radiopharmaceutical sciences. It demonstrates the significant interest and increasing relevance to ameliorate nuclear medicine imaging with PET or SPECT, and also radiotherapeutical procedures.Numerous targets and mechanisms have been identified and have been under investigation over the previous years, covering many fields of medical and clinical research. This development is well illustrated by the articles in the present issue, including 13 original research papers and one review, covering a broad range of actual research topics in the field of radiopharmaceutical sciences.

Keywords

breast cancer --- 68Ga --- GRPR --- NPY(Y1)R --- peptide heterodimers --- PET/CT imaging --- sentinel lymph node --- dextran --- mannose --- 99mTc-radiopharmaceuticals --- glutamate --- metabotropic glutamate receptor subtype 5 --- [18F]PSS232 --- ketamine --- ceftriaxone --- positron emission tomography --- allosteric modulator --- MMPEP --- ABP688 --- pretargeting --- Fusarinine C --- rituximab --- click chemistry --- multimerization --- PET --- gallium-68 --- carbonic anhydrase IX --- girentuximab --- renal cell carcinomas --- 177Lu-radiopharmaceuticals --- radioimmunotherapy --- neuroinflammation --- microglia --- carbon-11 --- radiochemistry --- positron emission tomography --- hypoxia --- radiosensitizer --- benzotriazine-1,4-dioxide (BTDO), benzotriazine-1-monoxide (BTMO), tirapazamine (TPZ), SR 4317 --- radioiodination --- tropomyosin receptor kinase --- positron emission tomography --- neurodegeneration --- oncogenic fusions --- [11C]meta-hydroxyephedrine --- radiosynthesis --- separation --- apparent molar activity --- cholecystokinin-2 receptor --- minigastrin --- molecular imaging --- radiometals --- technetium-99m --- hydrazinonicotinic acid (HYNIC) --- PSMA-617 --- salivary gland uptake --- prostate cancer --- endoradiotherapy --- Chloramine T --- electrophilic radioiodination --- iodine-131 --- Iodo-Gen® --- oxidizing agent --- ?-CIT. --- tumor hypoxia --- PET --- small animal imaging --- azomycin nucleosides --- [18F]FMISO --- bombesin --- gastrin-releasing peptide --- gastrin-releasing peptide receptor --- tumor targeting --- 99mTc-radioligand --- metabolic stability --- neprilysin-inhibition --- phosphoramidon --- n/a --- n/a

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