Engineered Models of Metastasis with Application to Study Cancer Biomechanics

Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types

Associations between daily ambient temperature and sedentary time among children 4-6 years old in Mexico City

Background Sedentary behavior is a worldwide public health concern. There is consistent and growing evidence linking sedentary behavior to mortality and morbidity. Early monitoring and assessment of environmental factors associated with sedentary behaviors at a young age are important initial steps for understanding children's sedentary time and identifying pertinent interventions. Objective This study examines the association between daily temperature (maximum, mean, minimum, and diurnal variation) and all-day sedentary time among 4-6 year old children in Mexico City (n = 559) from the year 2013 to 2015. Methods We developed a spatiotemporally resolved hybrid satellite-based land use regression temperature model and calculated percent daily sedentary time from aggregating 10-second epoch vertical counts captured by accelerometers that participants wore for one week. We modeled generalized additive models (GAMs), one for each temperature type as a covariate (maximum, mean, minimum, and diurnal variation). All GAMs included percent all-day sedentary time as the outcome and participant-level random intercepts to account for repeated measures of sedentary time. Our models were adjusted for demographic factors and environmental exposures. Results Daily maximum temperature, mean temperature, and diurnal variation have significant negative linear relationships with all-day sedentary time (p<0.01). There is no significant association between daily minimum temperature and all-day sedentary time. Children have on average 0.26% less daily sedentary time (approximately 2.2 minutes) for each 1 degrees C increase in ambient maximum temperature (range 7.1-30.2 degrees C), 0.27% less daily sedentary time (approximately 2.3 minutes) for each 1 degrees C increase in ambient mean temperature (range 4.3-22.2 degrees C), and 0.23% less daily sedentary time (approximately 2.0 minutes) for each 1 degrees C increase in diurnal variation (range 3.0-21.6 degrees C). Conclusions These results are contrary to our hypothesis in which we expected a curvilinear relationship between temperature (maximum, mean, minimum, and diurnal variation) and sedentary time. Our findings suggest that temperature is an important environmental factor that influences children's sedentary behavior

Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy.

Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo

Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy

Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up <i>via</i> endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo