Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer.

Unlabelled: The emergence of resistance to targeted therapies restrains their efficacy. The development of rationally guided drug combinations could overcome this currently insurmountable clinical challenge. However, our limited understanding of the trajectories that drive the outgrowth of resistant clones in cancer cell populations precludes design of drug combinations to forestall resistance.

Pioneering Construction Materials through Prototypological Research.

The article at hand follows the understanding that future cities cannot be built the same way as existing ones, inducing a radical paradigm shift in how we produce and use materials for the construction of our habitat in the 21st century. In search of a methodology for an integrated, holistic, and interdisciplinary development of such new materials and construction technologies, the chair of Sustainable Construction at KIT Karlsruhe proposes the concept of "prototypological" research. Coined through joining the terms "prototype" and "typology", prototypology represents a full-scale application, that is an experiment and proof in itself to effectively and holistically discover all connected aspects and address unknowns of a specific question, yet at the same time is part of a bigger and systematic test series of such different typologies with similar characteristics, yet varying parameters.

Feasibility, sensitivity, and reliability of laser-induced fluorescence imaging of green fluorescent protein-expressing tumors in vivo.

Whole-body imaging of green fluorescent protein (GFP) can be used to test the efficiency of gene carriers for in vivo transduction. The aim of the current study was to determine the sensitivity and the accuracy of a GFP imaging procedure by in vivo investigation of GFP-expressing tumor cells. An improved method of whole-body GFP imaging made use of a laser excitation source and band-pass filters matched specifically to GFP and constitutive tissue fluorescence emission bands.

In vivo laser-induced fluorescence imaging of a rat pancreatic cancer with pheophorbide-a.

Laser-induced fluorescence (LIF) of pheophorbide-a (Ph-a) was used for imaging of a rat pancreatic tumor. Using a dimensionless function (the ratio of Ph-a fluorescence by bluish autofluorescence), the fluorescence contrasts between excised tumors and their paired pancreas were investigated up to 48 h after a 9 mg kg-1 Ph-a intravenous administration. Among five tested excitation wavelengths, 355 and 610 nm excitations gave the best distinctive contrasts, both 48 h after dye injection.

Photodynamic imaging of a rat pancreatic cancer with pheophorbide a.

Laser-induced fluorescence of pheophorbide a (Ph-a) was used for in vitro photodynamic imaging (PDI) of a rat pancreatic acinar tumor. A 400 nm excitation induced a 470 nm autofluorescence and a 678 nm dye fluorescence in tumors and their surrounding pancreas 24 h after a 9 mg kg-1 body weight Ph-a intravenous administration. With lower intensities in these blood-rich tumors than in pancreas, Ph-a fluorescence signals are unable to provide tumor images.