|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.
|Application of genetic programming in analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer|
Anirban P. Mitra, Arpit A. Almal, Ben George, David W. Fry, Peter F. Lenehan, Vincenzo Pagliarulo, Richard J. Cote, Ram H. Datar, William P. Worzel
Nodal involvement in bladder cancer is an independent indicator of prognosis. This study employed an iterative machine learning process called genetic programming on quantitative expression values of 70 genes to classify primary urothelial carcinoma samples into those associated with or without nodal metastasis. The generated rules showed a strong predilection for ICAM1, MAP2K6 and KDR resulting in gene expression motifs that cumulatively suggested a pattern ICAM1>MAP2K6>KDR for node positive ca
|Whole Body Endogenous Nitric Oxide Production in Patients with Decompensated Liver Disease|
Demoncheaux E., Elphick D.A., Dürner M.B., Higgins G.E., Crowther D., Williams E.J., Higenbottam T.W and Gleeson D
Increased nitric oxide (NO) production has been implicated in the pathogenesis of the hyperdynamic circulation found in patients with advanced liver disease. There were no differences between patients with liver disease and controls with regard whole body NO production. Our results, in a well characterised set of patients, argue against greater basal NOS-dependent whole body NO production in patients with decompensated liver disease.
|MS-Xelerator™: Advanced Algorithms for LC/MS Data Processing Applied to Biomarker Discovery, Differential Analysis and Quantitative Proteomics|
LC-MS based proteomic experiments are used to compare complex biological samples across multiple conditions. Fast, powerful computational tools are needed to explore and detect differences in the areas of Expression Proteomics and Biomarker Discovery. In general, specialized steps are necessary to solve these difficult problems (binning, alignment & normalization, peak picking, relative quantitation, etc.). MS-Xelerator is a collection of software tools dedicated to all of the above tasks.
|Caveolin-1 Expression as a Possible Biomarker in Pancreatic Cancer Diagnosis|
C. Tanase, E. Raducan, L. Albulescu, E. Codorean, M.I. Nicolescu, D.I. Popescu, M.L. Cruceru and A.C. Popa
Caveolin1 (Cav-1) function either as a tumor supressor or as a promoter of metastasis. Overexpresion of cav-1 was correlated with: tumoral grading, proliferration markers (Ki67, p53), serum tumor markers (CEA, CA19.9) and angiogenic markers (VEGF, bFGF).
|EM Algorithm for Gene Copy Number Estimation Using TaqMan® Assays|
Catalin Barbacioru, Kelly Li, Caifu Chen and Raymond Samaha
Recently, TaqMan® assays have been developed for detection of genetic variation at gene level using primers and probes designed for genomic DNA sequences. The R package TaqGCN contains classes and methods that can be used for data reading and plotting, and for predicting gene copy number.
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