|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.
|Diagnostic Significance of microRNA Tumor Biomarkers in Fine Needle Aspirates (FNA) of Pancreatic Cancer|
Martina Doleshal 1, Anna E. Szafranska 1, Hayward S. Edmunds 2, Gregory J. Tsongalis 2, Murray Korc 2 and Emmanuel Labourier 1
Collection of pancreatic fine needle aspirates (FNAs) in RNARetain™ allows stabilization and protection of RNA in tissues containing high levels of nucleases; Differential miRNA expression in pancreatic FNAs accurately classifies benign and malignant tissue; Combinations of miRNA and mRNA expression signatures improve the separation between normal tissue and chronic pancreatitis; microRNAs are suitable analytes for molecular characterization of fine needle aspirates from pancreatic tissues.
|Apoptosis Inducing Novel microRNA for Breast cancer and Hepatocellular Carcinoma|
Arutselvan Natarajan, Sally J. DeNardo, Mark A. Zern, Senthil K. Venugopal
MicroRNA provides a mechanism to target cancer stem cells and restraint tumors cells permanently; this could lead to promising cancer therapeutics and imaging agents. Apoptosis inducing microRNA was identified to target HCC and breast cancer cells for imaging and therapy.
|SOME BIOLOGICAL PROPERTIES OF TRITERPENOID ACIDS|
S.N. Morozkina, O.I. Antimonova, E.M. Eremenko*, A.G. Shavva
Ursolic and betulinic acids acids induce the processes of apoptosis. We tested the risk of osteoporosis induction under influence of triterpenoids, since they can interact with glucocorticoid receptors. In experiments on oviriectomized rats we found that acids do not show any negative influence on percentage of mineral components in the femur and have cholesterol-lowering action under experimental conditions.
|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
|A genome-wide loss of function screen identifies new genes required for lung cancer cell proliferation|
PINNA G, ARAUJO N, MOROZOVA N, DETREZ MA & HAREL-BELLAN A
RNA interference (RNAi) provides an experimental tool for functional genomics analysis. We screened a genome-wide RNAi library to identify new genes involved in lung cancer cell proliferation. 72 % from the 257 genes identified were involved in general gene expression processes, 16 % were of unknown function or unrelated to proliferation, and 12% consisted of uncharacterized genes. These last sets of genes provide potential novel targets for lung cancer treatment.
|Computational analysis of high-throughputsmall RNA sequencing reveals microRNAs in a single-celled organism|
Schwach F, Studholme DJ, Molnar A, Thuenemann E, Burrell M, Perez-Martinez A, Moulton V and Baulcombe D
We present evidence that miRNA precursors are present in the single-celled green alga Chlamydomonas reinhardtii and that they give rise to mature miRNAs that regulate target genes by post-transcriptional RNA cleavage.