Purpose-Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models.Methods-Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous injection in the area of the nipple (OP), or surgically into the chest 2 nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays.Results-ODV produced less variable sized tumors and was a reliable method of implantation. ODV implantation into the chest 2 nd mammary pad rather than into the abdominal 4 th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression.
Conclusions-ODV
We report the results of thermodynamic measurements done on Ne films adsorbed on HiPCo™ singlewalled, closed-end, purified carbon nanotube bundles. The heat capacity was measured for 17 coverages between 0.015 and 1.14 single atomic layers for 1.8 K Ͻ T Ͻ 19 K. A few complementary adsorption isotherms were measured on the same cell over a similar range of coverages for 18.1 K Ͻ T Ͻ 29.5 K. Our results indicate that Ne deposits, in order, in high binding energy sites, the grooves on the outside of the bundles, the surface of the outer nanotubes, and after compressing the full monolayer, on a second layer. All of the films show solidlike behavior in the range studied. For the lowest coverage films, we compare our results to theoretical estimates and calculate the one-dimensional Debye temperature. For the higher coverage films, we calculate two-dimensional Debye temperatures and compare to results obtained on Ne adsorbed on flat graphite ͑Grafoil™͒. We estimate the two-dimensional ͑2D͒ compressibility of the films near monolayer completion from the vapor pressure isotherms. Agreement is found between the monolayer completion coverage inferred from heat-capacity isotherms and a minimum in the compressibility. In spite of the solidlike behavior and similarities to Ne/graphite, we do not observe any phase transition in the range of temperatures and coverages studied, which overlaps with the sublimation, melting, and vaporization transitions of 2D Ne.
Abstract. The importance of appropriate sample management in regulated bioanalysis is undeniable for clinical and non-clinical study support due to the fact that if the samples are compromised at any stage prior to analysis, the study results may be affected. Health authority regulations do not contain specific guidance on sample management; therefore, as part of the Global Bioanalysis Consortium (GBC), the A5 team was established to discuss sample management requirements and to put forward recommendations.The recommendations from the team concern the entire life span of the sample and include the following:1. Sampling procedures should be described in the protocol or within the laboratory manual. This information should include the volume of the sample to be collected, the required anticoagulant, light sensitivity, collection and storage containers, and labeling with a unique identifier. 2. The correct procedures for processing and then storing the samples after collection at the clinical/non-clinical testing site and during shipment are also very important to ensure the analyte(s) stability and should be documented. 3. Chain of custody for the samples must be maintained throughout the complete life span of each sample. This is typically maintained via paper and electronic data systems, including Laboratory Information Management Systems (LIMS) where available.4. Pre-and post-analysis storage location and conditions must also be clearly defined at the analytical laboratory. The storage temperature of the samples must be traceable and controlled by monitoring and warning alerts. The team suggests moving away from using temperatures and to adopt standard terminology of Broom temperature,^Brefrigerator,^Bfreezer,^and Bultrafreezer^that have defined and industry-wide accepted temperature ranges. 5. At the end of the study, documentation of the samples' disposal is required.
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