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Multidrug resistance in Cancer: Pharmacological Strategies from Basic Research to Clinical Issues

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196159 Year: Pages: 99 DOI: 10.3389/978-2-88919-615-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology --- Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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Abstract

More than 40 years ago, the observation that doxorubicin-resistant tumor cells were cross-resistant to several structurally different anticancer agents was the first step in the discovery of P-glycoprotein (P-gp). P-gp belongs to the superfamily of ATP-binding cassette (ABC) transporters;its overexpression has become a therapeutic target for overcoming multidrug resistance in tumors. However, P-gp is also expressed in cells of normal tissues where it plays a physiological role, by protecting them from the toxic effects of xenobiotics. Also, ABCB1 gene polymorphisms may influence the response to anticancer drugs substrate of P-gp. Several strategies to overcome P-gp tumor drug resistance have been suggested. P-gp 'circumvention’ is the most explored and is based on the coadministration of anticancer agents and pump inhibitors (P-gp modulators). Despite the positive findings obtained in preclinical studies, results of clinical trials are not yet successful and clinical research is still ongoing. Other investigational approaches have been studied (e.g. P-gp targeting antibodies, use of antisense strategies or transcriptional regulators targeting ABCB1 gene expression) but their use is still circumscribed to the preclinical setting. A further approach is represented by the encapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles. This strategy has shown higher efficacy in tumor previously treated with the free drug. The reasons explaining the increased efficacy of liposomal/nanoparticle-based drugs in Pgp-overexpressing tumors include the coating with specific surfactants, the composition changes in the plasma membrane microdomains where P-gp is embedded, the direct impairment of P-gp catalytic mechanisms exerted by specific component of the liposomal shell, but are not yet fully understood. A second strategy to overcome P-gp tumor drug resistance is represented by exploiting the P-gp presence. Actually, P-gp-overexpressing cells show increased sensitivity (collateral sensitivity) to some drugs (e.g. verapamil, narcotic analgesics) and to some investigational compounds (e.g. NSC73306). P-gp-overexpressing cell are hypersensitive to reactive oxygen species, to agents perturbing the energetic metabolic pathways, changing the membrane compositions, reducing the efflux of endogenous toxic catabolites. However, the mechanisms explaining collateral sensitivity have not been fully elucidated. Another approach to exploit P-gp is represented by ABCB1 gene transfer to transform bone marrow progenitor cells into a drug resistant state which may allow conventional or higher doses of anticancer drug substrates of P-gp to be administered safely after transplantation. More recently the development and introduction in the clinics of anticancer drugs which are not substrates of P-gp (e.g. new microtubule modulators, topoisomerase inhibitors) has provided a new and promising strategy to overcome P-gp tumor drug resistance (P-gp 'evasion'). This ‘research topic’ issue aims at exploding the above mentioned matters, in particular by: -retracing the history of the first researches on P-gp - describing the physiological role of P-gp - describing the molecular basis, structural features and mechanism of action of P-gp - describing diagnostic laboratory methods useful to determine the expression of P-gp and its transporter function - describing strategies to overcome tumor drug resistance due to P-gp and other ABC transporters - indicating novel approaches to overcome P-gp multidrug resistance, ranging from basic research studies to pre-clinical/clinical studies.

Molecular Computing and Bioinformatics

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ISBN: 9783039211951 / 9783039211968 Year: Pages: 390 DOI: 10.3390/books978-3-03921-196-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- Biotechnology
Added to DOAB on : 2019-08-28 11:21:27
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Abstract

This text will provide the most recent knowledge and advances in the area of molecular computing and bioinformatics. Molecular computing and bioinformatics have a close relationship, paying attention to the same object but working towards different orientations. The articles will range from topics such as DNA computing and membrane computing to specific biomedical applications, including drug R&D and disease analysis.

Keywords

prostate cancer --- Mycoplasma hominis --- endoplasmic reticulum --- systems biology --- protein targeting --- biomedical text mining --- big data --- Tianhe-2 --- parallel computing --- load balancing --- bacterial computing --- bacteria and plasmid system --- Turing universality --- recursively enumerable function --- miRNA biogenesis --- structural patterns --- DCL1 --- protein–protein interaction (PPI) --- clustering --- protein complex --- penalized matrix decomposition --- avian influenza virus --- interspecies transmission --- amino acid mutation --- machine learning --- Bayesian causal model --- causal direction learning --- K2 --- brain storm optimization --- line graph --- Cartesian product graph --- join graph --- atom-bond connectivity index --- geometric arithmetic index --- P-glycoprotein --- efflux ratio --- in silico --- machine learning --- hierarchical support vector regression --- absorption --- distribution --- metabolism --- excretion --- toxicity --- image encryption --- chaotic map --- DNA coding --- Hamming distance --- Stenotrophomonas maltophilia --- iron acquisition systems --- iron-depleted --- RAST server --- NanoString Technologies --- siderophores --- gene fusion data --- gene susceptibility prioritization --- evaluating driver partner --- gene networks --- drug-target interaction prediction --- machine learning --- drug discovery --- microRNA --- environmental factor --- structure information --- similarity network --- bioinformatics --- identification of Chinese herbal medicines --- biochip technology --- DNA barcoding technology --- DNA strand displacement --- cascade --- 8-bit adder/subtractor --- domain label --- Alzheimer’s disease --- gene coding protein --- sequence information --- support vector machine --- classification --- adverse drug reaction prediction --- heterogeneous information network embedding --- stacking denoising auto-encoder --- meta-path-based proximity --- Panax ginseng --- oligopeptide transporter --- flowering plant --- phylogeny --- transcription factor --- multiple interaction networks --- function prediction --- multinetwork integration --- low-dimensional representation --- dihydrouridine --- nucleotide physicochemical property --- pseudo dinucleotide composition --- RNA secondary structure --- ensemble classifier --- diabetes mellitus --- hypoxia-inducible factor-1? --- angiogenesis --- bone formation --- osteogenesis --- protein transduction domain --- membrane computing --- edge detection --- enzymatic numerical P system --- resolution free --- molecular computing --- molecular learning --- DNA computing --- self-organizing systems --- pattern classification --- machine learning --- laccase --- Brassica napus --- lignification --- stress --- molecular computing --- bioinformatics --- machine learning --- protein --- DNA --- RNA --- drug --- bio-inspired

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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Abstract

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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