Clinical Use of Epidermal Growth Factor Receptor Testing in Patients With Advanced Lung Cancer by Physicians: Survey of US and International Patterns.

PURPOSE: Guidelines recommend testing for EGFR mutation at diagnosis of advanced non-small-cell lung cancer to guide treatment. Two surveys, 18 months apart, aimed to identify changes in EGFR mutation testing and treatment practices in non-small-cell lung cancer. METHODS: The first survey of 562 physicians from Canada, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, the United Kingdom, and the United States was conducted between December 2014 and January 2015. The second, between July and August 2016, surveyed 707 physicians in the same countries with the addition of China; China was excluded from year-on-year comparisons. RESULTS: Globally (excluding China), physicians requested EGFR mutation testing in 80% (excluding China; 2015: 81%) of patients before first-line therapy. In 2016, 18% of results were not received before initiating treatment, a significant improvement over 2015 (23%). Reasons for not testing included tumor histology, insufficient tissue, poor performance status, and long turnaround time, although this had significantly improved in 2016 from 2015. Prolonging of survival/extending life was deemed the most important therapy goal in first-line treatment of both cohorts. CONCLUSION: Improvements in availability of test results before first-line therapy were seen, but incomplete implementation of guidelines is still observed, resulting in a large proportion of patients not receiving tyrosine kinase inhibitor treatment on the basis of mutation status. The reasons for not testing remained the same, year-on-year: tumor histology, insufficient tissue, poor performance status, and long test turnaround time. Receiving timely results must be addressed, if treatment parity for eligible patients can be achieved. Physician education and closer guideline concordance are key steps to improve outcomes.

Nanoparticle colloidal stability in cell culture media and impact on cellular interactions.

Nanomaterials are finding increasing use for biomedical applications such as imaging, diagnostics, and drug delivery. While it is well understood that nanoparticle (NP) physico-chemical properties can dictate biological responses and interactions, it has been difficult to outline a unifying framework to directly link NP properties to expected in vitro and in vivo outcomes. When introduced to complex biological media containing electrolytes, proteins, lipids, etc., nanoparticles (NPs) are subjected to a range of forces which determine their behavior in this environment. One aspect of NP behavior in biological systems that is often understated or overlooked is aggregation. NP aggregation will significantly alter in vitro behavior (dosimetry, NP uptake, cytotoxicity), as well as in vivo fate (pharmacokinetics, toxicity, biodistribution). Thus, understanding the factors driving NP colloidal stability and aggregation is paramount. Furthermore, studying biological interactions with NPs at the nanoscale level requires an interdisciplinary effort with a robust understanding of multiple characterization techniques. This review examines the factors that determine NP colloidal stability, the various efforts to stabilize NP in biological media, the methods to characterize NP colloidal stability in situ, and provides a discussion regarding NP interactions with cells.

Surface charge of polymer coated SPIONs influences the serum protein adsorption, colloidal stability and subsequent cell interaction in vitro.

It is known that the nanoparticle-cell interaction strongly depends on the physicochemical properties of the investigated particles. In addition, medium density and viscosity influence the colloidal behaviour of nanoparticles. Here, we show how nanoparticle-protein interactions are related to the particular physicochemical characteristics of the particles, such as their colloidal stability, and how this significantly influences the subsequent nanoparticle-cell interaction in vitro. Therefore, different surface charged superparamagnetic iron oxide nanoparticles were synthesized and characterized. Similar adsorbed protein profiles were identified following incubation in supplemented cell culture media, although cellular uptake varied significantly between the different particles. However, positively charged nanoparticles displayed a significantly lower colloidal stability than neutral and negatively charged particles while showing higher non-sedimentation driven cell-internalization in vitro without any significant cytotoxic effects. The results of this study strongly indicate therefore that an understanding of the aggregation state of NPs in biological fluids is crucial in regards to their biological interaction(s).