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Harnessing oncolytic virus-mediated immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194506 Year: Pages: 110 DOI: 10.3389/978-2-88919-450-6 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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Oncolytic viruses (OVs) have emerged as a promising anticancer treatment. OVs selectively infect, replicate in, and kill tumor cells. Oncolytic viral therapy occurs in two phases: an initial phase where the virus mediates direct oncolysis of tumor cells, and a second phase where an induced post-oncolytic immune response continues to mediate tumor destruction and retards progression of the disease. For a long time, the therapeutic efficacy was thought to depend mainly on the direct viral oncolysis based on their tumor selective replication and killing activities. But the post-oncolytic anti-tumor activity induced by the OV therapy is also a key factor for an efficient therapeutic activity. The topic adresses various strategies how to optimize OVs anti-tumor activity.

NK Cell Subsets in Health and Disease: New Developments

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453504 Year: Pages: 243 DOI: 10.3389/978-2-88945-350-4 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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Natural Killer (NK) cells were discovered ca 1975, as the first group of lymphoid cells that were neither T cells nor B cells. Since then, the dissection of the biology of NK cells has been growing exponentially with many seminal discoveries from the identification of MHC class I-specific inhibitory receptors to the discovery of receptor-ligand pairs involved in NK cell activation and to the manipulation of NK cells in cancer. In this research topic, we asked a group of thought leaders in NK cell biology to review recent advances in their origins and biology, and their roles in cancer, infection and inflammation. Together, these 25 articles provide a timely survey of NK cells as critical immunologic components of health and disease. They will hopefully prompt further dialogue and developments in basic and translational immunology.

Interaction of Nanomaterials with the Immune System: Role in Nanosafety and Nanomedicinenanomedicine

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453870 Year: Pages: 177 DOI: 10.3389/978-2-88945-387-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tiles and masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.

Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454228 Year: Pages: 111 DOI: 10.3389/978-2-88945-422-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-11-16 17:17:57
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Macroautophagy, the major lysosomal pathway for recycling intracellular components including whole organelles, has emerged as a key process modulating tumorigenesis, tumor–stroma interactions, and cancer therapy. An impressive number of studies over the past decade have unraveled the plastic role of autophagy during tumor development and dissemination. The discoveries that autophagy may either support or repress neoplastic growth and contextually favor or weaken resistance and impact antitumor immunity have spurred efforts from many laboratories trying to conceptualize the complex role of autophagy in cancer using cellular and preclinical models. This complexity is further accentuated by recent findings highlighting that various autophagy-related genes have roles beyond this catabolic mechanism and interface with oncogenic pathways, other trafficking and degradation mechanisms and the cell death machinery. From a therapeutic perspective, knowledge of how autophagy modulates the tumor microenvironment is crucial to devise autophagy-targeting strategies using smart combination of drugs or anticancer modalities. This eBook contains a collection of reviews by autophagy researchers and provides a background to the state-of-the-art in the field of autophagy in cancer, focusing on various aspects of autophagy regulation ranging from its molecular components to its cell autonomous role, e.g. in cell division and oncogenesis, miRNAs regulation, cross-talk with cell death pathways as well as cell non-autonomous role, e.g. in secretion, interface with tumor stroma and clinical prospects of autophagy-based biomarkers and autophagy modulators in anticancer therapy. This eBook is part of the TransAutophagy initiative to better understand the clinical implications of autophagy in cancer.

Molecular mechanisms regulating cytotoxic lymphocyte development and function, and their associations to human diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192793 Year: Pages: 163 DOI: 10.3389/978-2-88919-279-3 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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Cytotoxic lymphocytes, comprised of NK cells and cytotoxic T cells, play a pivotal role in immune defense. By directed release of perforin-containing lytic granules, NK and cytotoxic T cells can eradicate pathogen-infected, tumorigenic, and otherwise stressed cells. By the virtue of cytokine and chemokine secretion, they can influence other cells of the immune system. Through these processes, cytotoxic lymphocytes also contribute to the maintenance of immune homeostasis. In recent years, much progress has been made with respect to the mechanisms by which cytotoxic lymphocytes develop, differentiate, and exert their effector functions. In a clinical perspective, a wide variety of mutations impairing cytotoxic lymphocyte development and/or function have been associated with immunodeficiency and severe diseases in humans. Aberrant activity of cytotoxic T cells and/or NK cells has been linked to an increased susceptibility to viral infections, persistent inflammation, cancer and autoimmunity. In addition, lymphocyte cytotoxic activity may be harnessed therapeutically to target tumor cells in different adoptive cellular therapy regimes, or through the use of recombinant antibodies. Still, a number of questions remain in regards to how cytotoxic lymphocytes develop, their relationships and plasticity, as well as the mechanisms dictating target cell discrimination, lytic granule release and induction of target cell death. In this Research Topic we encourage submission of research articles, reviews, perspectives, or methods on cytotoxic lymphocyte development and function, their relation to the pathogenesis or treatment of different diseases, as well as comparison between similarities and/or differences in their effector functions. Considering the clinical significance of NK cells and cytotoxic T cells, we aim to provide a range of articles summarizing the current knowledge on the identification and elucidation of the mechanisms governing cytotoxic lymphocyte activity.

Evolution of NK-mediated target recognition under the pressure of physiologic or pathologic stimuli

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194520 Year: Pages: 190 DOI: 10.3389/978-2-88919-452-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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Since their discovery NK cells have come out as potential tools to fight cancer and viruses. This finding early urged different groups to study the mechanisms governing NK cell function. The identification of the MHC-I-specific inhibitory receptors (i.e. KIRs, NKG2A and certain Ly49 molecules) allowed defining rather rapidly how NK cells could avoid self-aggression and how they could be directed towards targets that were forced, by viral infection or tumor transformation, to down-regulate MHC-I expression. In a second time, also the repertoire of surface activating receptors addressing NK cytotoxicity towards tumors and pathogens was mostly defined. In spite of the first findings, however, most recent studies may suggest that NK cells and their receptors might not have been evolved to kill tumor targets and, perhaps, they might have been only partially influenced, in their evolution, by the need of recognizing viruses. Indeed certain NK receptors known to activate NK cell cytotoxicity (NKp30, DNAM-1, NKp80) can also participate at regulatory interactions occurring between NK and myeloid cells. In addition, a peculiar NK cell subset which intensively populate decidua during the first trimester of pregnancy, through the engagement of specific receptors and the interaction with decidual DC, produce chemokines and pro-angiogenic cytokines, and induce Tregs. Thus, in this context, NK cells favor decidua vascularization and development of the (semiallogeneic) foetus in a tolerant environment. Viruses have nevertheless played an important role in shaping the NK cell receptor repertoire. Several studies have unveiled clues of the evolutionary struggle between these pathogens and NK cells. Different NK receptors, including NKp46, NKp30, NKp44, NKG2D, NKG2C, Ly49, and certain KIRs have been demonstrated to recognize virus-encoded or virus-induced ligands. The expression of TLR specifically recognizing microbial products, together with the unexpected role of KIR3DL2 in shuttling these products to TLR-containing endosomes have also been documented in NK cells. On the other side, different viral immune evasion molecules have been shown to interfere with the expression of ligands for T or NK cell activating receptors. In addition, viral infections can occur in the reproductive stage of life cycle, and may represent a serious threat for the species propagation. Thus the control of viruses, together with the maintenance of foetus during pregnancy, should represent major evolutionary forces in shaping NK-receptors. Along this line, the NK-mediated control of tumors should not be under the same evolutionary pressure, as tumors mostly appear later in the life cycle, and the recognition of tumor-encoded ligands may be less efficient (as the NK cell receptors might have not been selected for such aim). This may be the reason why, although displaying strong antitumor activity in vitro, NK cells could hardly contain tumor burden in vivo. In addition the pathogen-driven evolution of NK cell function may also favor the role of NK cells in the insurgence of immune-mediated diseases. This research topic will collect contributions that may clarify the relationships between the evolution of the NK receptors and their role in an efficient recognition of viruses and tumor cells or in immune-mediated diseases.

Is the Recent Burst of Therapeutic Anti-Tumor Antibodies the Tip of an Iceberg?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454624 Year: Pages: 305 DOI: 10.3389/978-2-88945-462-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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The high effectiveness of antibodies as anti-tumor therapeutic agents has led to a burst of research aiming to increase their therapeutic applications by the use of antibodies against new targets, new antibody formats or new combinations. In this e-book we present relevant research depicting the current efforts in the field.

Immunogenic Cell Death in Cancer: From Benchside Research to Bedside

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198382 Year: Pages: 145 DOI: 10.3389/978-2-88919-838-2 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Oncology
Added to DOAB on : 2017-02-07 16:12:31
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Classically, anti-cancer therapies have always been applied with the primary aim of tumor debulking achieved through widespread induction of cancer cell death. While the role of host immune system is frequently considered as host protective in various (antigen-bearing) pathologies or infections yet in case of cancer overtime it was proposed that the host immune system either plays no role in therapeutic efficacy or plays a limited role that is therapeutically unemployable. The concept that the immune system is dispensable for the efficacy of anticancer therapies lingered on for a substantial amount of time; not only because evidence supporting the claim that anti-cancer immunity played a role were mainly contradictory, but also largely because it was considered acceptable (and sometimes still is) to test anticancer therapies in immunodeficient mice (i.e. SCID/athymic mice lacking adaptive immune system). This latter practice played a detrimental role in appreciating the role of anticancer immunity in cancer therapy. This scenario is epitomized by the fact that for a long time the very existence of cancer-associated antigens or cancer-associated ‘danger signaling’ remained controversial. However, over last several years this dogmatic view has been considerably modified. The existence of cancer-associated antigens and ‘danger signaling’ has been proven to be incontrovertible. These developments have together paved way for the establishment of the attractive concept of “immunogenic cell death” (ICD). It has been established that a restricted class of chemotherapeutics/targeted therapeutics, radiotherapy, photodynamic therapy and certain oncolytic viruses can induce a form of cancer cell death called ICD which is accompanied by spatiotemporally defined emission of danger signals. These danger signals along with other factors help cancer cells undergoing ICD to activate host innate immune cells, which in turn activate T cell-based immunity that helps eradicate live (or residual) surviving cancer cells. The emergence of ICD has been marred by some controversy. ICD has been criticized to be either experimental model or setting-specific or mostly a concept based on rodent studies that may have very limited implications for clinical application. However, in recent times it has emerged (through mainly retrospective or prognostic studies) that ICD can work in various human clinical settings hinting towards clinical applicability of ICD. However a widespread consensus on this issue is still transitional. In the current Research Topic we aimed to organize and intensify a discussion that strives to bring together the academic and clinical research community in order to provide a background to the current state-of-the-art in ICD associated bench-side research and to initiate fruitful discussions on present and future prospects of ICD translating towards the clinical, bedside reality.

Smart Nanovesicles for Drug Targeting and Delivery

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ISBN: 9783038978947 / 9783038978954 Year: Pages: 198 DOI: 10.3390/books978-3-03897-895-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-06-26 08:44:06
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Nanovesicles are highly-promising systems for the delivery and/or targeting of drugs, biomolecules and contrast agents. Despite the fact that initial studies in this area were performed on phospholipid vesicles, there is an ever-increasing interest in the use of other molecules to obtain smart vesicular carriers focusing on strategies for targeted delivery. These systems can be obtained using newly synthesized smart molecules, or by intelligent design of opportune carriers to achieve specific delivery to the site of action.

Curcumin in Health and Disease

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ISBN: 9783039214495 / 9783039214501 Year: Pages: 274 DOI: 10.3390/books978-3-03921-450-1 Language: eng
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

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