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https://www.readbyqxmd.com/read/27920407/biocomputing-drug-repurposing-toward-targeted-therapies
#1
Luca Cardone
No abstract text is available yet for this article.
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27918243/the-neuroimmune-transcriptome-and-alcohol-dependence-potential-for-targeted-therapies
#2
Anna Warden, Emma Erickson, Gizelle Robinson, R Adron Harris, R Dayne Mayfield
Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune system in regulating alcohol abuse and dependence, and has provided potential therapeutic targets. In this review, we discuss Toll-like-receptor pathways, hypothesized to be key players in many stages of the alcohol addiction cycle. The growing appreciation of the neuroimmune system's involvement in alcoholism has also led to consideration of crucial roles for glial cells, including astrocytes and microglia, in the brain's response to alcohol abuse...
December 5, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#3
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27899953/repurposing-drugs-in-oncology-redo-propranolol-as-an-anti-cancer-agent
#4
Pan Pantziarka, Gauthier Bouche, Vidula Sukhatme, Lydie Meheus, Ilse Rooman, Vikas P Sukhatme
Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#5
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27898018/combating-ebola-with-repurposed-therapeutics-using-the-cando-platform
#6
Gaurav Chopra, Sashank Kaushik, Peter L Elkin, Ram Samudrala
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27896969/reproducible-drug-repurposing-when-similarity-does-not-suffice
#7
Emre Guney
Repurposing existing drugs for new uses has attracted considerable attention over the past years. To identify potential candidates that could be repositioned for a new indication, many studies make use of chemical, target, and side effect similarity between drugs to train classifiers. Despite promising prediction accuracies of these supervised computational models, their use in practice, such as for rare diseases, is hindered by the assumption that there are already known and similar drugs for a given condition of interest...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27895313/repurposing-the-anti-malarial-drug-dihydroartemisinin-suppresses-metastasis-of-non-small-cell-lung-cancer-via-inhibiting-nf-%C3%AE%C2%BAb-glut1-axis
#8
Jie Jiang, Guojun Geng, Xiuyi Yu, Hongming Liu, Jing Gao, Hanxiang An, Chengfu Cai, Ning Li, Dongyan Shen, Xiaoqiang Wu, Lisheng Zheng, Yanjun Mi, Shuyu Yang
Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889480/therapeutic-manipulation-of-ageing-repurposing-old-dogs-and-discovering-new-tricks
#9
REVIEW
Venkatesh Mallikarjun, Joe Swift
Ageing is a leading risk factor for many debilitating diseases. While age-related diseases have been the subject of over a century of intense investigation, until recently, physiological ageing was considered unavoidable. Pharmacological and genetic studies have since shown that ageing is a malleable process and that its abrogation can prevent its associated diseases. This review summarises a sample of the most promising efforts to deliver the products of ageing research to the clinic. Current efforts include the use of clinically approved drugs that have since been repurposed, as well as the development of novel therapeutics, to target ageing...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27888804/niclosamide-and-its-analogs-are-potent-inhibitors-of-wnt-%C3%AE-catenin-mtor-and-stat3-signaling-in-ovarian-cancer
#10
Rebecca C Arend, Angelina I Londoño-Joshi, Abhishek Gangrade, Ashwini A Katre, Chandrika Kurpad, Yonghe Li, Rajeev S Samant, Pui-Kai Li, Charles N Landen, Eddy S Yang, Bertha Hidalgo, Ronald D Alvarez, J Michael Straughn, Andres Forero, Donald J Buchsbaum
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. Platinum-based therapy is the standard first line treatment and while most patients initially respond, resistance to chemotherapy usually arises. Major signaling pathways frequently upregulated in chemoresistant cells and important in the maintenance of cancer stem cells (CSCs) include Wnt/β-catenin, mTOR, and STAT3. The major objective of our study was to investigate the treatment of ovarian cancer with targeted agents that inhibit these three pathways...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888802/low-dose-triptolide-reverses-chemoresistance-in-adult-acute-lymphoblastic-leukemia-cells-via-reactive-oxygen-species-generation-and-dna-damage-response-disruption
#11
Haijun Zhao, Pengcheng Shi, Manman Deng, Zhiwu Jiang, Yin Li, Vinodh Kannappan, Weiguang Wang, Peng Li, Bing Xu
Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27886639/hyaluronan-derived-swelling-of-solid-tumors-the-contribution-of-collagen-and-cancer-cells-and-implications-for-cancer-therapy
#12
Chrysovalantis Voutouri, Christiana Polydorou, Panagiotis Papageorgis, Vasiliki Gkretsi, Triantafyllos Stylianopoulos
Despite the important role that mechanical forces play in tumor growth and therapy, the contribution of swelling to tumor mechanopathology remains unexplored. Tumors rich in hyaluronan exhibit a highly negative fixed charge density. Repulsive forces among these negative charges as well as swelling of cancer cells due to regulation of intracellular tonicity can cause tumor swelling and development of stress that might compress blood vessels, compromising tumor perfusion and drug delivery. Here, we designed an experimental strategy, using four orthotopic tumor models, to measure swelling stress and related swelling to extracellular matrix components, hyaluronan and collagen, as well as to tumor perfusion...
November 21, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27884742/antifungals
#13
REVIEW
Sonia Campoy, José L Adrio
The need for new antifungal agents is undeniable. Current therapeutics choices for the treatment of invasive fungal infections are limited to three classes of drugs. Most used antifungals agents are not completely effective due to the development of resistance, host toxicity and undesirable side effects that limit their use in medical practice. Invasive fungal infections have significantly increased over the last decades and the mortality rates remain unacceptably high. More threatening, new resistance patterns have been observed including simultaneous resistance to different antifungal classes...
November 21, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27878300/induction-of-dna-damage-and-apoptosis-in-human-leukemia-cells-by-efavirenz
#14
Ansgar Brüning, Julia Jückstock, Bernd Kost, Panagiotis Tsikouras, Tobias Weissenbacher, Sven Mahner, Ioannis Mylonas
As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27869790/the-genome-of-onchocerca-volvulus-agent-of-river-blindness
#15
James A Cotton, Sasisekhar Bennuru, Alexandra Grote, Bhavana Harsha, Alan Tracey, Robin Beech, Stephen R Doyle, Matthew Dunn, Julie C Dunning Hotopp, Nancy Holroyd, Taisei Kikuchi, Olivia Lambert, Amruta Mhashilkar, Prudence Mutowo, Nirvana Nursimulu, Jose M C Ribeiro, Matthew B Rogers, Eleanor Stanley, Lakshmipuram S Swapna, Isheng J Tsai, Thomas R Unnasch, Denis Voronin, John Parkinson, Thomas B Nutman, Elodie Ghedin, Matthew Berriman, Sara Lustigman
Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes...
November 21, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27869056/why-calpain-inhibitors-are-interesting-leading-compounds-to-search-for-new-therapeutic-options-to-treat-leishmaniasis
#16
Vitor Ennes-Vidal, Rubem Figueiredo Sadock Menna-Barreto, Marta Helena Branquinha, André Luis Souza Dos Santos, Claudia Masini D'Avila-Levy
Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials...
November 21, 2016: Parasitology
https://www.readbyqxmd.com/read/27865394/recent-developments-in-genomics-bioinformatics-and-drug-discovery-to-combat-emerging-drug-resistant-tuberculosis
#17
REVIEW
Soumya Swaminathan, Jagadish Chandrabose Sundaramurthi, Alangudi Natarajan Palaniappan, Sujatha Narayanan
Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27860440/integrating-clinical-phenotype-and-gene-expression-data-to-prioritize-novel-drug-uses
#18
H Paik, B Chen, M Sirota, D Hadley, A J Butte
Drug repositioning has been based largely on genomic signatures of drugs and diseases. One challenge in these efforts lies in connecting the molecular signatures of drugs into clinical responses, including therapeutic and side effects, to the repurpose of drugs. We addressed this challenge by evaluating drug-drug relationships using a phenotypic and molecular-based approach that integrates therapeutic indications, side effects, and gene expression profiles induced by each drug. Using cosine similarity, relationships between 445 drugs were evaluated based on high-dimensional spaces consisting of phenotypic terms of drugs and genomic signatures, respectively...
November 14, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27859674/an-integrative-drug-repurposing-pipeline-switching-viral-drugs-to-breast-cancer
#19
K Ramanathan, Kanika Verma, Velin Marita Sequeira, B Lokapriya Nandan, V Shanthi
The growing incidence rate of breast cancer, coupled with cellular chemotherapeutic resistance, has made this disease one of the most prevalent cancers among women worldwide. Despite the recent efforts to understand the underlying cause of the resistance due to mutation, there are no feasible tactics to overcome this bottleneck. This issue could be addressed by the concept of polypharmacology - disguising drugs present in the pharmacopeia for novel purposes (drug repurposing). Of note, we have proposed a multi-modal computational drug repositioning stratagem to predict drugs possessing anti-proliferative effect...
November 17, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27855602/targeting-stat1-in-both-cancer-and-insulin-resistance-diseases
#20
Chen Meng, Li-Bin Guo, Xiaolong Liu, Yih-Hsin Chang, Yao Lin
With the rapid development of targeted therapy and our understanding of the underlying molecular mechanisms, drug repurposing is becoming trendy in drug development field. Drugs that display promising therapeutic effects towards multiple diseases tend to target important signaling proteins. Insulin resistance and obesity are strongly associated and both are reported to be correlated with cancer, suggesting they may be linked via some critical pathways. Signal transducers and activator of transcription 1 (STAT1) is an important transcription factor involved in the regulation of multiple cellular processes such as proliferation, survival, inflammation, and angiogenesis...
November 17, 2016: Current Protein & Peptide Science
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