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Drug Discovery Today

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https://www.readbyqxmd.com/read/28435062/recent-advances-in-activatable-fluorescence-imaging-probes-for-tumor-imaging
#1
REVIEW
Jing Zhao, Guorui Jin, Guojun Weng, Jianjun Li, Jian Zhu, Junwu Zhao
Fluorescence imaging is superior in sensitivity and resolution compared with other imaging modalities; however, its application is hindered by high background noise. Tissue-selective strategies, such as passive, active, and activatable targeting, hold great promise in accelerating clinical translation by significantly improving the tumor:background ratio (TBR) and, in turn, the sensitivity and contrast of fluorescence imaging. Compared with the 'always on' contrast agents, activatable probes, which remain nonfluorescent until being activated by tumor-specific molecular targets, further enhance TBR and at the same time provide additional molecular information that can be related to tumor staging and therapy response...
April 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28435061/nanomedicine-mediated-drug-targeting-of-cancer-stem-cells
#2
REVIEW
Deepika Singh, Aliva Prity Minz, Sanjeeb Kumar Sahoo
Tumors are heterogeneous and contain a small population of cells that has a crucial role in tumor progression, metastasis, drug resistance, and relapse as a result of their self-renewal, proliferation, and differentiation properties. These cells are known as cancer stem cells (CSCs) and accumulating evidence suggests that they show significant resistance to conventional chemotherapy. Thus, various antitumor strategies have been developed to eliminate therapeutic-resistant CSCs by targeting the molecular differences between CSCs and bulk cancer cells...
April 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28435060/the-multiple-therapeutic-applications-of-mirnas-for-bone-regenerative-medicine
#3
REVIEW
J C Scimeca, Elise Verron
With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to have in bone tissue physiopathology, exploring their potential has recently garnered increased interest. In this review, we first describe the involvement of miRNAs in bone metabolism, and then focus on their potential therapeutic applications (as bone biomarkers and molecular targets)...
April 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28435059/in-vivo-cancer-research-using-aggregation-induced-emission-organic-nanoparticles
#4
REVIEW
Xiaoyong Yi, Jun Li, Zhipeng Zhu, Qian Liu, Qiang Xue, Dan Ding
Exploration of a nanoplatform that benefits precise cancer diagnosis and treatment in vivo is particularly valuable. In recent years, aggregation-induced emission luminogens (AIEgens) have emerged as advanced fluorescent materials for the design and preparation of organic nanoparticles (NPs); they also have unique advantages in biomedical applications, especially in cancer diagnosis and theranostics. In this review, we summarize the current status of the development of AIEgen-based NPs for in vivo cancer research, including in vivo tumor diagnosis, drug delivery, and photodynamic therapy...
April 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28433535/bioimaging-and-biodetection-assisted-with-tta-uc-materials
#5
REVIEW
Qingqing Dou, Lu Jiang, Dan Kai, Cally Owh, Xian Jun Loh
Upconversion of light has attracted intensive studies for biomedical research, because it enables deeper [SB1] tissue analysis owing to the longer wavelength of incident light, compared with conventional downconversion fluorescent materials. Triplet-triplet annihilation (TTA), as a typical mechanism of upconversion, does not necessitate high power excitation and exhibits a higher quantum yield than rare earth upconversion owing to more sensitizer options with higher absorption coefficients. A desirable wavelength range of excitation and emission can be realized by careful selection of the combination of sensitizer and activator...
April 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28428056/recent-development-of-synthetic-nonviral-systems-for-sustained-gene-delivery
#6
REVIEW
Yonggang Xiang, Nwe Nwe Linn Oo, Jin Ping Lee, Zibiao Li, Xian Jun Loh
Sustained gene delivery is of particular importance today because it circumvents the need for repeated therapeutic administration and provides spatial and temporal control of the release profile. Better understanding of the genetic basis of diseases and advances in gene therapy have propelled significant research on biocompatible gene carriers for therapeutic purposes. Varied biodegradable polymer-based architectures have been used to create new compositions with unique properties suitable for sustained gene delivery...
April 18, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28412474/kinetics-for-drug-discovery-an-industry-driven-effort-to-target-drug-residence-time
#7
REVIEW
Doris A Schuetz, Wilhelmus Egbertus Arnout de Witte, Yin Cheong Wong, Bernhard Knasmueller, Lars Richter, Daria B Kokh, S Kashif Sadiq, Reggie Bosma, Indira Nederpelt, Elena Segala, Marta Amaral, Dong Guo, Dorothee Andres, Victoria Georgi, Leigh A Stoddart, Steve Hill, Robert M Cooke, Chris De Graaf, Rob Leurs, Matthias Frech, Rebecca C Wade, Elizabeth Cunera Maria de Lange, Adriaan P IJzerman, Anke Müller-Fahrnow, Gerhard F Ecker
A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further...
April 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28400153/spatiotemporal-diversification-of-intrapatient-genomic-clones-and-early-drug-development-concepts-realize-the-roadmap-of-precision-cancer-medicine
#8
REVIEW
Dimitrios H Roukos
The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circulating tumor DNA-NGS for detecting circulating genomic subclones and their comparison to reveal intrapatient heterogeneity (IPH) could identify the dynamic emergence of resistant subclones in the neoadjuvant, adjuvant and metastatic setting...
April 8, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28390930/targeting-rabs-as-a-novel-therapeutic-strategy-for-cancer-therapy
#9
Xiaoyu Qin, Jiongyi Wang, Xinxin Wang, Feng Liu, Bin Jiang, Yanjie Zhang
Rab GTPases constitute the largest family of small GTPases. Rabs regulate not only membrane trafficking but also cell signaling, growth and survival, and development. Increasingly, Rabs and their effectors are shown to be overexpressed or subject to loss-of-function mutations in a variety of disease settings, including cancer progression. This review provides an overview of dysregulated Rab proteins in cancer, and highlights the signaling and secretory pathways in which they operate, with the aim of identifying potential avenues for therapeutic intervention...
April 5, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28390929/cancer-on-a-chip-systems-at-the-frontier-of-nanomedicine
#10
REVIEW
Yu Shrike Zhang, Yi-Nan Zhang, Weijia Zhang
Nanomedicine provides a unique opportunity for promoting drug efficacy through enhanced delivery mechanisms. However, its translation into the clinics has been relatively slow compared with the large amount of research occurring in laboratory settings. Given the limitations of conventional cell culture models and preclinical animal models, we discuss the potential utility of recently developed cancer-on-a-chip platforms, which maximally replicate the pathophysiology of the human tumor microenvironments, as alternatives for effective evaluation of nanomedicine...
April 5, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28390214/nanoparticles-for-immune-system-targeting
#11
REVIEW
Juan Du, Yu Shrike Zhang, Divia Hobson, Per Hydbring
Nanoparticles (NPs) are found in numerous applications used to modulate the immune system. They serve as drug delivery carriers or vaccine adjuvants and are utilized as therapeutics against a variety of diseases. NPs can be engineered to target distinct cellular components representing multiple pathways of immunity. The combination of NPs with immune system-targeting moieties has paved the way for improved targeted immune therapies. Here we provide an update of recent progress in this field.
April 5, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28388393/biomimetic-nanofibrous-scaffolds-for-neural-tissue-engineering-and-drug-development
#12
REVIEW
Jing Wu, Lili Xie, William Zhi Yuan Lin, Qiushui Chen
Neural tissue engineering aims to develop functional substitutes for damaged tissues, creating many promising opportunities in regeneration medicine and drug discovery. Biomaterial scaffolds routinely provide nerve cells with a physical support for cell growth and regeneration, yielding 3D extracellular matrix to mimic the in vivo cellular microenvironment. Among the various types of cellular scaffolds for reconstruction, biomimetic nanofibrous scaffolds are recognized as appropriate candidates by precisely controlling morphology and shape...
April 4, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28363518/laying-in-silico-pipelines-for-drug-repositioning-a-paradigm-in-ensemble-analysis-for-neurodegenerative-diseases
#13
REVIEW
Nikolas Dovrolis, George Kolios, George Spyrou, Ioanna Maroulakou
When faced with time- and money-consuming problems, new practices in pharmaceutical R&D arose when trying to alleviate them. Drug repositioning has great promise and when combined with today's computational power and intelligence it becomes more precise and potent. This work showcases current approaches of creating a computational pipeline for drug repositioning, along with an extensive example of how researchers can influence therapeutic approaches and further understanding, through either single or multiple disease studies...
March 29, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28363083/nanomaterial-scaffolds-to-regenerate-musculoskeletal-tissue-signals-from-within-for-neovessel-formation
#14
REVIEW
Zuyong Wang, Feng Wen, Poon Nian Lim, Qinyuan Zhang, Toshiisa Konishi, Dong Wang, Swee Hin Teoh, Eng San Thian
Current treatments for musculoskeletal disease and injury are restricted with the usage of autografts and allografts. Tissue engineering that applies the principles of biology and engineering to develop functional substitutes has potential promise of therapeutic regeneration for musculoskeletal tissues. However, engineering sizable tissues needs a vascular network to supply cells with nutrients, oxygen and signals after implantation. For this purpose, recent developments on therapeutic nanomaterials have been explored in delivering different vessel-inductive growth factors, small biomolecules and ions for scalable engineering into vascularizable scaffolds...
March 28, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28359841/harnessing-camp-signaling-in-musculoskeletal-regenerative-engineering
#15
REVIEW
Okechukwu Clinton Ifegwu, Guleid Awale, Komal Rajpura, Kevin W-H Lo, Cato T Laurencin
Several emerging small molecules have been established for the repair or regeneration of musculoskeletal tissues. Cyclic AMP (cAMP) and its analogs have been the purview of many researchers in that they have been implicated in the repair or regeneration of several musculoskeletal tissues, such as bone, muscle, ligament, cartilage, blood vessels, skin, and nerve. Owing to the varied signal transduction pathways associated with cAMP, it elicits several processes and is thought to either activate or enhance native growth factors, thereby circumventing the need for supraphysiological doses of therapeutic growth factors in musculoskeletal tissue regeneration...
March 27, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28341604/analysis-of-fda-approved-imaging-agents
#16
REVIEW
Michael S Kinch, Pamela Woodard
The development of imaging agents was initially driven following the discovery of X-ray technologies, but quickly evolved and expanded to include radiolabeling of cells and tissues to assist disease diagnosis and progression. The first imaging agents preceded the Great War but the field did not gain momentum until the 1950s. The approval rate for imaging NMEs continued at a high level for the remainder of the 20th century, but substantially decreased thereafter. This decline in approval rates corresponds with industry consolidation...
March 21, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28336175/the-academic-industrial-complex-navigating-the-translational-and-cultural-divide
#17
REVIEW
Stephen Freedman, Kevin Mullane
In general, the fruits of academic discoveries can only be realized through joint efforts with industry. However, the poor reproducibility of much academic research has damaged credibility and jeopardized translational efforts that could benefit patients. Meanwhile, journals are rife with articles bemoaning the limited productivity and increasing costs of the biopharmaceutical industry and its resultant predilection for mergers and reorganizations while decreasing internal research efforts. The ensuing disarray and uncertainty has created tremendous opportunities for academia and industry to form even closer ties, and to embrace new operational and financial models to their joint benefit...
March 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28288783/factors-related-to-drug-approvals-predictors-of-outcome
#18
REVIEW
Lawrence Liberti, Alasdair Breckenridge, Jarno Hoekman, Neil McAuslane, Pieter Stolk, Hubert Leufkens
There is growing interest in characterising factors associated with positive regulatory outcomes for drug marketing authorisations. We assessed empirical studies published over the past 15 years seeking to identify predictive factors. Factors were classified to one of four 'factor clusters': evidentiary support; product or indication characteristics; company experience or strategy; social and regulatory factors. We observed a heterogeneous mix of technical factors (e.g., study designs, clinical evidence of efficacy) and less studied social factors (e...
March 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28288782/exosomes-a-new-horizon-in-lung-cancer
#19
REVIEW
Irene Vanni, Angela Alama, Francesco Grossi, Maria Giovanna Dal Bello, Simona Coco
Circulating exosomes are the major mediators of cell-cell communication. They have been found in various body fluids of healthy individuals and patients with malignancies as cargos of several molecules including miRNAs. Several studies have underlined the role of exosome miRNAs in different tumor types, including lung cancer, suggesting their potential use as biomarkers and therapeutic agents. An overview of the biology and function of exosomes and exosome miRNAs as indicators of diagnosis and treatment response in lung cancer is presented...
March 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28284830/technological-advances-and-proteomic-applications-in-drug-discovery-and-target-deconvolution-identification-of-the-pleiotropic-effects-of-statins
#20
REVIEW
Cristina Banfi, Roberta Baetta, Erica Gianazza, Elena Tremoli
Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'...
March 8, 2017: Drug Discovery Today
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