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Brain Tumors and the Lynch Syndrome (Book chapter)

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ISBN: 9789533076461 Year: DOI: 10.5772/21293 Language: English
Publisher: IntechOpen Grant: FP7 Ideas: European Research Council - 232635
Subject: Science (General)
Added to DOAB on : 2019-01-17 11:47:59
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Lynch syndrome (LS) (MIM No. 120435-6), previously known as hereditary nonpolyposis colorectal cancer (HNPCC) (Boland, 2005), is an autosomal dominant disorder caused by

germline mutation in one of the DNA mismatch repair (MMR) genes. LS is among the most

prevalent cancer syndromes in man and is estimated to account for 1-6% of all colorectal

cancers (Lynch & de la Chapelle, 2003).

Personalized Medicine and Neurosurgery

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453368 Year: Pages: 133 DOI: 10.3389/978-2-88945-336-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Surgery
Added to DOAB on : 2018-02-27 16:16:45
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The Precision Medicine Initiative, which was instituted by President Barack Obama on January 20, 2015, highlighted the importance that advances in genomics and related “-omic” approaches have made to science and medicine, and it set the stage for their federally funded and mandated integration into the delivery of health care. Whether these advances comprise large-scale approaches, such as The Cancer Genome Atlas, which provides a modern classification of cancers based on molecular profiles, or genealogy initiatives, which seek to trace the movement of our early ancestors out of Africa, genomic technology has taken us closer to developing targeted therapies and a refined understanding of our evolutionary journey. It is against this backdrop that we summarized some of the recent advances in the field of precision medicine, or personalized medicine, as they pertain to neurosurgery. In this e-Book collection provided by Frontiers in Surgery: Neurosurgery, we present a collection of articles by leaders in the field of neurosurgery that highlight domains using a personalized approach for the treatment of patients or avenues when personalization is possible and when it will likely alter the care of patients with neurological diseases.

ACTH Action in the Adrenal Cortex: From Molecular Biology to Pathophysiology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452323 Year: Pages: 421 DOI: 10.3389/978-2-88945-232-3 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2017-10-13 14:57:01
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By stimulating adrenal gland and corticosteroid synthesis, the adrenocorticotropic hormone (ACTH) plays a central role in response to stress. In this Research Topic, a particular attention has been given to the recent developments on adrenocortical zonation; the growth-promoting activities of ACTH; the various steps involved in acute and chronic regulation of steroid secretion by ACTH, including the effect of ACTH on circadian rhythms of glucocorticoid secretion. The Research Topic also reviews progress and challenges surrounding the properties of ACTH binding to the MC2 receptor (MC2R), including the importance of melanocortin-2 receptor accessory protein (MRAP) in MC2R expression and function, the various intracellular signaling cascades, which involve not only protein kinase A, the key mediator of ACTH action, but also phosphatases, phosphodiesterases, ion channels and the cytoskeleton. The importance of the proteins involved in the cell detoxification is also considered, in particular the effect that ACTH has on protection against reactive oxygen species generated during steroidogenesis. The impact of the cellular microenvironment, including local production of ACTH is discussed, both as an important factor in the maintenance of homeostasis, but also in pathological situations, such as severe inflammation. Finally, the Research Topic reviews the role that the pituitary-adrenal axis may have in the development of metabolic disorders. In addition to mutations or alterations of expression of genes encoding components of the steroidogenesis and signaling pathways, chronic stress and sleep disturbance are both associated with hyperactivity of the adrenal gland. A resulting effect is increased glucocorticoid secretion inducing food intake and weight gain, which, in turn, leads to insulin and leptin resistance. These aspects are described in detail in this Research Topic by key investigators in the field. Many of the aspects addressed in this Research Topic still represent a stimulus for future studies, their outcome aimed at providing evidence of the central position occupied by the adrenal cortex in many metabolic functions when its homeostasis is disrupted. An in-depth investigation of the mechanisms underlying these pathways will be invaluable in developing new therapeutic tools and strategies.

Roles of NF-κB in Cancer and Their Therapeutic Approaches

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ISBN: 9783038971177 9783038971184 Year: Pages: X, 330 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Oncology --- Biology
Added to DOAB on : 2018-08-15 10:52:09
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Although mortality rates have declined in recent years, the majority of cancers are still difficult to treat and the medical need for better cancer treatment is evident. The current anticancer armamentarium includes many active agents that are applied across tumor types. However, most of these broadly-active anticancer drugs have a small therapeutic index and barely discriminate between malignant and normal cells. In recent years the focus has shifted to the development of rationally designed, molecularly-targeted therapy for the treatment of a specific cancer, therefore offering the promise of greater specificity coupled with reduced systemic toxicity. NF-kB transcription factor family as emerged as such a promising target for cancer therapy. This Special Issue will explore the routes from NF-kB basic research, cancer research and oncogenomics into the development of NF-kB-based cancer therapeutics and biomarkers.We invite research and review papers in any area of the NF-kB field that are related, but not limited to, fundamental understanding of NF-kB signaling pathways, gene expression profiling, epigenetic regulation, diagnostic, prognostic and pharmacogenomic biomarkers, molecular targets driving the progression of human cancers, cancer drug development on these targets, clinical trial with new agents, and validation in animal models.We hope that this Special Issue reflects the exciting era that we are living in with respect to the field of NF-kB and its applications in cancer research.

Carbonic Anhydrases and Metabolism

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ISBN: 9783038978008 9783038978015 Year: Pages: 184 DOI: 10.3390/books978-3-03897-801-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-04-25 16:37:17
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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.

Sex Hormone Receptor Signals in Human Malignancies

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ISBN: 9783039211739 / 9783039211746 Year: Pages: 152 DOI: 10.3390/books978-3-03921-174-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Sex steroids, including androgens, estrogens, and progestogens, are knownto have widespread physiological actions beyond the reproductive systemvia binding to the sex hormone receptors. Meanwhile, emerging evidence hasindicated that sex hormone receptor signals are involved in the outgrowth ofsome malignancies, such as prostate and breast carcinomas, as well as othersthat have not traditionally been considered as endocrine-related neoplasms. ThisSpecial Issue “Sex Hormone Receptor Signals in Human Malignancies” coversvarious aspects of the potential role of sex hormone receptors and related signalsin prostate cancer, breast cancer, and other neoplastic conditions by depictingpromising findings derived from in vitro and in vivo experiments as well as theanalyses of surgical specimens. The current observations described may thusprovide a unique insight into novel or known functions of sex hormone receptorsand related molecules.

Cancer Biomarkers and Targets in Digestive Organs

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ISBN: 9783039214631 / 9783039214648 Year: Pages: 146 DOI: 10.3390/books978-3-03921-464-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-12-09 11:49:15
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Identification and development of cancer biomarkers and targets have greatly accelerated progress towards precision medicine in oncology. Studies of tumor biology have not only provided insights into the mechanisms underlying carcinogenesis, but also led to discovery of molecules that have been developed into cancer biomarkers and targets. Multi-platforms for molecular characterization of tumors using next-generation genomic sequencing, immunohistochemistry, in situ hybridization, and blood-based biopsies have greatly expanded the portfolio of potential biomarkers and targets. These cancer biomarkers have been developed for diagnosis, early detection, prognosis, and prediction of treatment response. The molecular targets have been exploited for anti-cancer therapy and delivery of therapeutic agents. This Special Issue of Biomedicines focuses on recent advances in the discovery, characterization, translation, and clinical application of cancer biomarkers and targets in malignant diseases of the digestive system. The goal is to stimulate basic and translational research and clinical collaboration in this exciting field with the hope of developing strategies for prevention and early detection/diagnosis of cancer in digestive organs, and improving therapeutic and psychosocial outcomes in patients with these malignant diseases.

Keywords

colorectal cancer --- intestinal disorder --- intestinal tumors --- zebrafish --- stereotactic body radiation therapy --- immunotherapy --- biomarkers --- Asian Cancer Research Group (ACRG) --- gastric carcinoma --- molecular profiling --- precision therapy --- pembrolizumab --- predictive biomarkers --- ramucirumab --- The Cancer Genome Atlas (TCGA) --- therapeutic targets --- trastuzumab --- biliary tract carcinoma --- chemotherapy --- clinical trial --- colorectal carcinoma --- gastric carcinoma --- gastrointestinal oncology --- hepatocellular carcinoma --- immunotherapy --- pancreatic carcinoma --- targeted therapy --- Liver transplantation --- liver graft injury --- intragraft gene expression profiles --- cell adhesion molecules --- CD274 --- HFE --- hepatocellular carcinoma --- immunohistochemistry --- molecular profiling --- next-generation sequencing --- precision medicine --- predictive biomarkers --- gastrointestinal oncology --- pancreatic carcinoma --- hepatocellular carcinoma --- biliary tract carcinoma --- gastric carcinoma --- colorectal carcinoma --- stereotactic body radiation therapy --- liver transplant --- targeted therapy --- psychosocial support --- G protein–coupled receptors --- cholecystokinin --- gastrin --- gastrin-releasing peptide --- bombesin --- neurokinin --- neurotensin --- somatostatin --- circulating tumor cells --- colorectal carcinoma --- CAM invasion assay --- phenotypic mosaics --- tumor progenitor --- biomarker --- gastrointestinal malignancies --- immunotherapy --- n/a

Biotechnological Applications of Phage and Phage-Derived Proteins

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ISBN: 9783039214419 / 9783039214426 Year: Pages: 236 DOI: 10.3390/books978-3-03921-442-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- General and Civil Engineering
Added to DOAB on : 2019-12-09 11:49:15
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Phages have shown a high biotechnological potential with numerous applications. The advent of high-resolution microscopy techniques aligned with omic and molecular tools have revealed innovative phage features and enabled new processes that can be further exploited for biotechnological applications in a wide variety of fields. The high-quality original articles and reviews presented in this Special Issue demonstrate the incredible potential of phages and their derived proteins in a wide range of biotechnological applications for human benefit. Considering the emergence of amazing new available bioengineering tools and the high abundance of phages and the multitude of phage proteins yet to be discovered and studied, we believe that the upcoming years will present us with many more fascinating and new previously unimagined phage-based biotechnological applications.

Keywords

gene expression regulation --- molecular probe --- macromolecular interactions --- phage-host interaction --- bacteriophage --- endolysin --- Clostridium perfringens --- alpha-sheet --- cancerous tumors --- capsid dynamics --- drug delivery vehicles --- native gel electrophoresis --- neurodegenerative disease --- pathogenic viruses --- phage display --- landscape phage --- major coat protein --- nanomedicine --- diagnostics --- biosensors --- M13 bacteriophage --- biofilm --- porous structure --- filters --- self-assembly --- T7phage library --- sarcoidosis --- tuberculosis --- microarray --- immunoscreening --- R-type pyocin --- bacteriocin --- contractile injection systems --- Pseudomonas aeruginosa --- X-ray crystallography --- receptor-binding protein --- Shigella flexneri --- bacteriophage --- tailspike proteins --- O-antigen --- serotyping --- microtiter plate assay --- fluorescence sensor --- bacteriophages --- encapsulation --- niosomes --- transfersomes --- liposomes --- Staphylococcus aureus --- phage --- Enterococcus faecalis --- Streptococcus agalactiae --- culture enrichment --- bacteriophage --- diagnostics --- Listeria monocytogenes --- endolysin --- magnetic separation --- reporter phage --- endolysin --- Pal --- Cpl-1 --- safety --- toxicity --- immune response --- Streptococcus pneumoniae --- self-assembly --- nanotubular structures --- tail sheath protein --- bacteriophage vB_EcoM_FV3 --- Appelmans --- bacteriophage evolution --- bacteriophage recombination --- phage therapy --- Pseudomonas aeruginosa --- antibiotic resistance --- bacteriophages --- Myoviridae --- bacteriophage-derived lytic enzyme --- enzybiotics --- endolysin --- in vitro activity --- ESKAPE --- n/a

Transmucosal Absorption Enhancers in the Drug Delivery Field

Authors: --- ---
ISBN: 9783039218486 / 9783039218493 Year: Pages: 406 DOI: 10.3390/books978-3-03921-849-3 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2020-01-30 16:39:46
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Development of strategies to assist the movement of poorly permeable molecules across biological barriers has long been the goal of drug delivery science. In the last three decades, there has been an exponential increase in advanced drug delivery systems that aim to address this issue. However, most proprietary delivery technologies that have progressed to clinical development are based on permeation enhancers (PEs) that have a history of safe use in man. This Special Issue entitled “Transmucosal Absorption Enhancers in the Drug Delivery Field” aims to present the current state-of-the-art in the application of PEs to improve drug absorption. Emphasis is placed on identification of novel permeation enhancers, mechanisms of barrier alteration, physicochemical properties of PEs that contribute to optimal enhancement action, new delivery models to assess PEs, studies assessing safety of PEs, approaches to assist translation of PEs into effective oral, nasal, ocular and vaginal dosage forms and combining PEs with other delivery strategies.

Keywords

absorption enhancers --- sugar-based surfactants --- biocompatibility studies --- transmucosal drug delivery --- intestinal permeation enhancers --- sodium cholate (NaC) --- N-dodecyl-?-D-maltoside (DDM) --- small intestine --- enterocyte --- brush border --- tryptophan --- oral delivery --- insulin --- GLP-1 --- intestinal absorption --- amino acid --- cell-penetrating peptide --- combined microsphere --- chitosan --- cyclodextrin --- nasal delivery --- nose to brain transport --- penetration enhancer --- nasal formulation --- in vivo studies --- nose to brain delivery --- antiepileptic drug --- drug delivery --- block copolymers --- thermogel system --- chitosan derivatives --- amphiphilic polymers --- polymeric micelles --- quaternization --- curcumin --- intestinal delivery --- mucoadhesiveness --- cervicovaginal tumors --- cationic functionalization --- imatinib --- nanocrystals --- in situ hydrogel --- bioenhancer --- cytochrome P450 --- drug absorption enhancer --- efflux --- metabolism --- P-glycoprotein --- pharmacokinetic interaction --- tight junction --- Aloe vera --- gel --- whole leaf --- absorption enhancement --- Caco-2 --- confocal laser scanning microscopy --- F-actin --- FITC-dextran --- tight junctions --- transepithelial electrical resistance --- permeation enhancer --- oral delivery --- formulation --- permeability --- safety --- simulated intestinal fluid --- hydrophobization --- epithelium --- compound 48/80 --- chitosan --- nanoparticles --- mast cell activator --- vaccine adjuvant --- nasal vaccination --- absorption enhancer --- antimicrobial peptide --- Caco-2 --- claudin --- cell-penetrating peptide (CPP) --- drug delivery --- intestinal epithelial cells --- KLAL --- PN159 --- tight junction modulator --- oral macromolecule delivery --- oral peptides --- sodium caprate --- salcaprozate sodium --- epithelial permeability --- epithelial transport --- nasal permeability --- nose-to-brain --- simvastatin --- nanocapsules --- mucoadhesion --- CNS disorders --- chitosan --- nasal --- pulmonary --- drug administration --- absorption enhancers --- nanoparticle --- and liposome --- absorption enhancer --- gemini surfactant --- intestinal absorption --- poorly absorbed drug --- Caco-2 cells --- PTH 1-34 --- teriparatide --- nasal delivery --- pharmacokinetics --- osteoporosis --- man --- sheep --- clinical trial --- preclinical --- Caco-2 --- intestinal absorption --- nanomedicine --- nanoparticle --- oral delivery --- transferrin --- ocular drug delivery --- cornea --- penetration enhancers --- ocular conditions --- ophthalmology --- permeation enhancers --- absorption modifying excipients --- oral delivery --- nasal delivery --- ocular delivery --- vaginal delivery --- transmucosal permeation

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