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1.
PLoS One ; 12(1): e0169797, 2017.
Article in English | MEDLINE | ID: mdl-28085924

ABSTRACT

The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and eventually to choose the most effective drug and drug combination for individual patients in a cost effective and timely manner.


Subject(s)
Antibodies, Monoclonal/pharmacology , Doxorubicin/pharmacology , Microfluidic Analytical Techniques/instrumentation , Neoplasms/pathology , Staurosporine/pharmacology , Tumor Microenvironment/drug effects , Animals , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Biopsy , Cell Culture Techniques , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Female , Humans , Mice , Mice, Hairless , Mice, SCID , Neoplasms/drug therapy , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
2.
IEEE Geosci Remote Sens Lett ; 13(12): 1797-1801, 2016 Dec.
Article in English | MEDLINE | ID: mdl-33005110

ABSTRACT

Spaceborne spectrometers require spectral-temporal stability characterization to aid validation of derived data products. EO-1 began orbital precession in 2011 after exhausting onboard fuel resources. In the Libya-4 Pseudo Invariant Calibration Site (PICS) this resulted in a progressive shift from a mean local equatorial crossing time of ~10:00 AM in 2011 to ~8:30 AM in late 2015. Here, we studied precession impacts to Hyperion surface reflectance products using three atmospheric correction approaches from 2004 to 2015. Combined difference estimates of surface reflectance were < 5% in the visible near infrared (VNIR) and < 10% for most of the shortwave infrared (SWIR). Combined coefficient of variation (CV) estimates in the VNIR ranged from 0.025 - 0.095, and in the SWIR ranged from 0.025 - 0.06, excluding bands near atmospheric absorption features. Reflectances produced with different atmospheric models were correlated (R 2) in VNIR from 0.25 - 0.94 and SWIR from 0.12 - 0.88 (p < 0.01). The uncertainties in all models increased with terrain slope up to 15° and selecting dune flats could reduce errors. We conclude that these data remain a useful resource over this period.

3.
Astrobiology ; 12(9): 841-53, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22984872

ABSTRACT

We report the first science results from the Space Environment Viability of Organics (SEVO) payload aboard the Organism/Organic Exposure to Orbital Stresses (O/OREOS) free-flying nanosatellite, which completed its nominal spaceflight mission in May 2011 but continues to acquire data biweekly. The SEVO payload integrates a compact UV-visible-NIR spectrometer, utilizing the Sun as its light source, with a 24-cell sample carousel that houses four classes of vacuum-deposited organic thin films: polycyclic aromatic hydrocarbon (PAH), amino acid, metalloporphyrin, and quinone. The organic films are enclosed in hermetically sealed sample cells that contain one of four astrobiologically relevant microenvironments. Results are reported in this paper for the first 309 days of the mission, during which the samples were exposed for ∼2210 h to direct solar illumination (∼1080 kJ/cm(2) of solar energy over the 124-2600 nm range). Transmission spectra (200-1000 nm) were recorded for each film, at first daily and subsequently every 15 days, along with a solar spectrum and the dark response of the detector array. Results presented here include eight preflight and 16 in-flight spectra of eight SEVO sample cells. Spectra from the PAH thin film in a water-vapor-containing microenvironment indicate measurable change due to solar irradiation in orbit, while three other nominally water-free microenvironments show no appreciable change. The quinone anthrarufin showed high photostability and no significant spectroscopically measurable change in any of the four microenvironments during the same period. The SEVO experiment provides the first in situ real-time analysis of the photostability of organic compounds and biomarkers in orbit.


Subject(s)
Space Flight , Amino Acids/chemistry , Benzoquinones/chemistry , Extraterrestrial Environment , Metalloporphyrins/chemistry , Polycyclic Aromatic Hydrocarbons/analysis , Spectrum Analysis , Ultraviolet Rays
4.
Science ; 330(6003): 463-8, 2010 Oct 22.
Article in English | MEDLINE | ID: mdl-20966242

ABSTRACT

Several remote observations have indicated that water ice may be presented in permanently shadowed craters of the Moon. The Lunar Crater Observation and Sensing Satellite (LCROSS) mission was designed to provide direct evidence. On 9 October 2009, a spent Centaur rocket struck the persistently shadowed region within the lunar south pole crater Cabeus, ejecting debris, dust, and vapor. This material was observed by a second "shepherding" spacecraft, which carried nine instruments, including cameras, spectrometers, and a radiometer. Near-infrared absorbance attributed to water vapor and ice and ultraviolet emissions attributable to hydroxyl radicals support the presence of water in the debris. The maximum total water vapor and water ice within the instrument field of view was 155 ± 12 kilograms. Given the estimated total excavated mass of regolith that reached sunlight, and hence was observable, the concentration of water ice in the regolith at the LCROSS impact site is estimated to be 5.6 ± 2.9% by mass. In addition to water, spectral bands of a number of other volatile compounds were observed, including light hydrocarbons, sulfur-bearing species, and carbon dioxide.


Subject(s)
Moon , Water , Extraterrestrial Environment , Ice , Spectroscopy, Near-Infrared
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