|A Novel Multiplexed Digital Gene Expression Technology|
Gary K. Geiss1,#, Roger Bumgarner2, Brian Birditt1, Timothy Dahl1, Naeem Dowidar1, Dwayne L. Dunaway1, H. Perry Fell1, Sean Ferree1, Renee D. George1, Tammy Grogan1, Jeffrey J. James1, Malini Maysuria1, Jeffrey D. Mitton1, Paola Oliveri4, Jennifer L. Osborn3, Tao Peng2, Amber L. Ratcliffe1, Philippa J. Webster1, Eric H. Davidson4, and Leroy Hood5
We describe a novel platform, the nCounter Analysis System, for sensitive, highly multiplexed, digital gene expression analysis based on NanoString’s novel molecular barcoding technology. Detection of individual mRNA molecules using an assigned sequence of six different fluorescent spots per probe are detected, and then the number of times that code sequence appears in a sample are counted.
|miRNAs in Treating Cardiomyopathy |
The study aims to design antigomirs against miRNAs involved in Cardiomyopathy. Potential miRNAs involved in the down regulation of certain important genes during this disorder have been identified. All reported miRNAs were scanned using an algorithm against these genes. At three step protocol was followed to take care of false positives and false negatives. Further, HL-1 cells (cardiomyocytes) are been transfected by anti-miRNAs for confirmation.
|Targeting Inflammatory Cytokines Using Adenoviruses: gene delivery of biological therapies in ovarian cancer|
Michael A. Salako, Hagen Kulbe, Iain A. McNeish, Frances R. Balkwill
Constitutive TNF-alpha expression is characteristic of the malignant ovarian surface epithelium. Adenoviral mutants hold great promise as gene therapy vectors but their efficacy is hindered by an inflammatory cascade orchestrated by TNF-alpha. We found that delivering TNF-alpha shRNA to ovarian cancer cells using oncolytic adenoviruses could reduce the inflammatory cascade generated by adenoviruses and also had direct anti-tumour activity on the cancer cells.
|Use of gamma scinitigraphy to understand inhaled device/formulation variables on delivery efficiency and|
Peter Scholes and Karen Jones
Systemic delivery of both small molecules and macromolecules via inhaled therapies is an area of significant ongoing research1. The pulmonary route offers the physiological benefits of a highly vascularised, large surface area for absorption which can promote high bioavailability and a rapid onset of action. For biomolecules such as peptides, proteins and nucleic acid derivatives, inhaled drug delivery can also provide a viable alterative to intravenous administration.
|Quantifying the Impact of a Drug on Gastric Emptying: Measuring the Pharmacodynamic Effect in Clinical Trials|
A Rankin, M Paterson, A Connor
Many drug classes are known to alter the rate of gastric emptying. Whilst there is no specific regulatory guidance requiring the impact of drugs on GE to be measured, it is important to fully understand the mode of action and the relationship between the pharmacokinetic profile and the pharmacodynamic response.
|Building Flexibility ino Phase I Protocols and Early Clinical Development Programs|
Lloyd Stevens and Gareth King
The transition of a drug candidate into Phase I and other early drug development programs is undergoing considerable examination and change. This has largely been brought about by commercial and scientific drivers to reduce attrition rates coupled with an evolving regulatory environment, all of which encourage the pharmaceutical industry to build both scientific focus and flexibility into the drug development program.
|Evaluation of Human Regional Bioavailability to Assess Whether Modified Release Development is Feasible|
A Connor, G King and K Jones
Many modified release (MR) oral formulations rely on bioavailability from the distal regions of the gastrointestinal (GI) tract (i.e. the ileum and colon). Therefore, by assessing the bioavailability of a drug following delivery to the distal intestines, it is possible to determine whether MR formulation development is achievable.
|THE OSTEOPROTECTIVE ACTION OF 6-OXA-8a-ANALOGUES OF STEROID ESTROGENS|
A.G. Shavva, V.N. Belov, A.Yu. Solovyev, S.N. Morozkina
We synthesized fourteen 6-oxa-8a-estrogens analogues and investigated osteoprotective and uterotropic actions. We demonstrated correlation: every modification in structure of 6-oxa-8-analogues leading to strong (>30%) reduction of uterotropic action induces slump of osteoprotective activity. This allows to make conclusion: main biotarget, responsible for appearance of osteoprotective action is a-estrogen receptor. We found steroid estrogen analogues with cholesterol-lowering properties without u
|Expression of stress response protein GRP78 is associated with the development of castration-resistant prostate cancer|
Llana Pootrakul, Anirban P. Mitra, Ram H. Datar, Shan-Rong Shi, Jie Cai, Debra Hawes, Susan G. Groshen, Amy S. Lee, Richard J. Cote
This study investigated the role of the GRP78 in prostate cancer progression and the development of castration-resistant prostate cancer, where cancer cells continue to survive despite the stress of an androgen-starved environment.
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