Enhanced Imaging And Accelerated Photothermalysis Of A549 Human Lung Cancer Cells By Gold Nanospheres

Background & aims: Gold nanoparticles are excellent photon-thermal energy converters. The purpose of this work was to investigate the influence of gold nanoparticles on the photothermalysis of A549 lung tumor cells. Materials & methods: A549 lung tumor cells were exposed to goat antihuman immunoglobulin (lg)G-conjugated gold nanospheres (40 nm) and were then imaged under a dark-field microscope. The live cells were then subjected to photoirradiation-using a 633-nm laser at different power levels. The viability of tumor cells under laser irradiation was monitored by confocal microscopy using a viability-assay kit. Results & discussion: The death rates of A549 lung tumor cells after gold nanoparticle exposure increased significantly under laser irradiation. The maximum initial cell death rate was observed at a laser power level of 3.75 mW, with the initial deactivation rate accelerated by a factor of 6.6 and a total loss of 92% of cell viability. Conclusion: This work demonstrated potential applications of gold nanospheres as both imaging probes and enhancing agents for photothermal therapy of cancer. © 2008 Future Medicine Ltd

Long-term effects of BRAF inhibitors in melanoma treatment:friend or foe?

The clinical development of selective BRAF inhibitors for metastatic BRAF V600 mutant melanoma patients has been a major breakthrough in targeted therapeutics. Objective response rates of approximately 50% have been observed in the Phase III studies of the BRAF inhibitors vemurafenib and dabrafenib. The side effects can be relatively common, including proliferative skin toxicities. The latter range from hyperkeratosis and keratoacanthomas (KAs) to squamous cell carcinomas (SCCs) and new primary melanomas. In addition, case reports on the emergence of gastric/colonic polyps and RAS mutant malignancies have been described during BRAF inhibitor therapy. These events have been attributed to paradoxical activation of the MAPK pathway in BRAF wildtype cells exposed to selective BRAF inhibitors in addition to increased RAS activity. Combined BRAF and MEK inhibition appears to improve clinical outcomes and reduce cutaneous proliferation events as fewer KAs and SCCs have been observed with combination therapy. Next-generation pan-RAF inhibitors ('paradox breakers') and ERK inhibitors may further enhance clinical activity in metastatic BRAF-mutant melanoma patients and mitigate this paradoxical oncogenesis. Further investigation into the potential long-term effects of selective BRAF inhibitors is warranted as expanded use of these agents is expected in patients with BRAF-mutant melanoma and other malignancies