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Abstract: Multiyear spaceflight will require innovative strategies to preserve vitamins in foods, in order to retain astronaut health and functionality long‐term. Furthermore, space foods must be low weight/volume to comply with cargo restrictions, and must retain sensory quality to ensure consumption. Low water activity products were developed, fortified with vitamins A, B1, B9, C, and E at twice their spaceflight requirements, stored for three years at 21 °C and one year at 38 °C, and analyzed annually for retained vitamin content and organoleptic quality. The vitamins were encapsulated in carbohydrate or lipid coatings and tested in relatively low and high fat versions of compressed bars and powdered drink mix formulations. Susceptibility to degradation at 21 °C followed the sequence B9 > A > B1 > C > E; degradation rates were fitted to first‐order kinetics. Vitamins A and C were more sensitive at the higher storage temperature. Vitamin retention was slightly higher in compressed bars verses powders. Effects of matrix lipid level on stability were vitamin dependent. Sensory characteristics for products stored three years at 21 °C remained mostly above 6.0 on a 9‐point hedonic scale, whereas those stored for one year at 38 °C remained mostly above 5.0. Compressed bars firmed significantly during storage. All vitamin levels after three years at 21 °C remained above the space flight requirements, demonstrating the suitability of the selected fortification schemes and food matrices for long‐term preservation. Practical Application: Vitamins A, B1, B9, C, and E were retained at 70% to 95% levels for three years at 21 °C in carefully formulated, fortified low water activity products. Product compression and vacuum packaging slightly helped to further preserve vitamins. The sensory quality of these products was retained throughout storage. [ABSTRACT FROM AUTHOR]

Electrostatically layered aluminosilicate nanocomposites have been prepared by the sequential deposition of poly(allylamine hydrochloride)/poly(acrylic acid)/poly(allylamine hydrochloride)/saponite(PAH/PAA/PAH/saponite)10 on poly(ethylene terephtalate)(PET) film. Exfoliated saponite nanoplatelets were obtained by extensive shaking, sonication, and centrifugation of a water suspension. To minimize permeability and improve the mechanical integrity, cross-linking of composite films was carried out at different temperatures. The formation of amide linkage induced through heating was observed by Fourier Transform Infrared(FT-IR) and x-ray photoelectron spectroscopy(XPS). The cross-linking of nanocomposites(PAH/PAA/PAH/saponite)10 showed 60% decrease in permeability of oxygen when compared with the pristine PET substrate film. In contrast, water permeability of the nanocomposite membrane was not affected by heating temperature and deposition cycles. [ABSTRACT FROM AUTHOR]

In the field of kinase inhibitors for applications in cancer research, tubulin is emerging as a targeted cellular protein that can significantly contribute to their activities. However, investigation of kinase inhibitors beyond the kinome is an area often neglected. Herein, we describe the results of pharmacological studies using drugs targeting kinases, tubulin or both. A key finding is that if cells are treated with a kinase inhibitor unintentionally targeting tubulin, their characteristic shape will diminish within a short timeframe. These changes in cell morphology are not seen when cells are treated with bona fide kinase inhibitors that do not directly target tubulin. Thus, early changes in cell morphology upon treatments are a strong indication that the inhibitor is directly targeting tubulin. Recognizing tubulin as a target of kinase inhibitors will build confidence in the future mechanistic studies using kinase inhibitors. [ABSTRACT FROM AUTHOR]

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo , resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501-15. ©2017 AACR ., (©2017 American Association for Cancer Research.)

The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer., (Copyright © 2017, American Association for the Advancement of Science.)