A randomized trial comparing omega-3 fatty acid plasma levels after ingestion of emulsified and non-emulsified cod liver oil formulations.

Objectives: Emulsified formulations of omega-3 fatty acids may increase plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) compared with non-emulsified formulations. The current study evaluated plasma concentrations of DHA + EPA as well as DHA and EPA individually following administration of emulsified vs non-emulsified cod liver oil formulations.

Methods: In this randomized, 2-period, crossover study (ClinicalTrials.

Clinical and Vitamin Response to a Short-Term Multi-Micronutrient Intervention in Brazilian Children and Teens: From Population Data to Interindividual Responses.

Scope: Micronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals.

Methods And Results: A 6-week multivitamin/mineral intervention is conducted in 9-13 year olds.

B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline.

The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine β synthase (CβS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations.

Improved growth of toddlers fed a milk containing synbiotics.

Bifidobacterium longum (BL999), Lactobacillus rhamonosus (LPR), prebiotics (inulin and fructo-oligosaccharides), and long-chain polyunsaturated fatty acids (LCPUFA) are believed to have health benefits. In a randomized, double-blind, controlled trial we compared growth and development of toddlers fed milk containing synbiotics (BL999, LPR, and prebiotics) and LCPUFA or a control milk. Three hundred and ninety three healthy, 12 month-old toddlers were fed approximately 400 mL/day for 12 months.

Effect of a whey-predominant starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal comfort in infants.

Development of new infant formulas aims to replicate the benefits of breast milk. One benefit of breast milk over infant formulas is greater gastrointestinal comfort. We compared indicators of gastrointestinal comfort in infants fed a whey-predominant formula containing long-chain polyunsaturated fatty acids, galacto-oligo-saccharides and fructo-oligosaccharides, and infants fed a control casein-predominant formula without additional ingredients.

Preclinical evaluation of nilotinib efficacy in an imatinib-resistant KIT-driven tumor model.

The novel KIT inhibitor nilotinib is currently being evaluated for its clinical utility in the treatment of gastrointestinal stromal tumor. However, the effects of nilotinib in cells expressing commonly occurring KIT mutations remain to be fully defined. The aim of this study was therefore to investigate the efficacy of nilotinib against cells expressing imatinib-sensitive or imatinib-resistant KIT mutations and to evaluate [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging as a biomarker of nilotinib response in vivo.

Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer.

Background: Within estrogen receptor-positive breast cancer (ER+ BC), the expression levels of proliferation-related genes can define two clinically distinct molecular subtypes. When treated with adjuvant tamoxifen, those ER+ BCs that are lowly proliferative have a good prognosis (luminal-A subtype), however the clinical outcome of those that are highly proliferative is poor (luminal-B subtype).

Methods: To investigate the biological basis for these observations, gene set enrichment analysis (GSEA) was performed using microarray data from 246 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy.

Sustained clinical responses to tyrosine kinase inhibitor sunitinib in thyroid carcinoma.

The limited therapeutic options available for patients with metastatic papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC) necessitates the development of novel therapies. Identification of somatic rearrangements of the tyrosine kinase domain of the RET gene in PTC have improved our understanding of thyroid tumorigenesis. Sunitinib is active against the RET kinase and has both antineoplastic and antiangiogenic properties.

Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.

Purpose: This study was designed as "proof of concept" for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy.

Methods: Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [(18)F]fluorodeoxyglucose, [(18)F]fluoro-L: -thymidine, [(18)F]fluoro-azoazomycinarabinoside or [(18)F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia.

An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development.

In vivo models that recapitulate oncogene-dependent tumorigenesis will greatly facilitate development of molecularly targeted anticancer therapies. We have developed a model based on activating mutations in c-KIT in gastrointestinal stromal tumors (GISTs). This model comprises murine tumors of FDC-P1 cell lines expressing c-KIT mutations that render the tumors either responsive (V560G) or resistant (D816V) to the small-molecule c-KIT inhibitor, imatinib.

Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase.

Understanding the regulation of Akt has been of major interest for elucidating the control of normal cellular physiology as well as malignant transformation. The paradigm for activation of Akt involves phosphatidylinositol 3-kinase-dependent membrane localization followed by activating phosphorylation of Thr-308 and Ser-473. Many of the activating signals for Akt involve the stimulation of receptor and non-receptor tyrosine kinases, and the most potent activator known is the tyrosine phosphatase inhibitor pervanadate, highlighting a possible role for tyrosine phosphorylation in the regulation of the enzyme.