Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Urban Physical Environments and the Duration of High Air Temperature: Focusing on Solar Radiation Trapping Effects

Urban heat island effects, which are the phenomenon wherein higher ambient air temperatures are measured in cities than in rural areas, have worsened urban thermal environments over the past decades. This study aims to analyze the effects of urban physical environments on the duration of high air temperature, using climate data collected from 217 Automatic Weather Stations in Seoul, Korea. In order to specify radiation trapping effects, interaction effects between sky view factors (SVF) and albedo values were analyzed using multiple regression analysis. The results indicate that increases in commercial and traffic areas lead to longer durations of high air temperature and that high urban porosity shortens the duration of high air temperature by improving urban ventilation. This study also indicates that the duration of high air temperature has a negative association with SVF; however, an analysis of interaction effects indicates that high-albedo materials diminish the positive effects of high SVF largely because of radiation trapping effects. These findings suggest that urban ventilation paths, high SVF, and materials with an appropriate albedo value play important roles in improving thermal comfort conditions, such as the duration of high air temperature

Analyzing Thermal Characteristics of Urban Streets Using a Thermal Imaging Camera: A Case Study on Commercial Streets in Seoul, Korea

Due to continuing city growth and global warming over the past decades, urban heat island (UHI) effects, referring to the phenomena wherein the ambient air temperatures in cities are higher than those in rural areas, have become a serious threat to urban populations. Impervious surfaces, buildings with low-albedo materials, and a lack of vegetated areas are the major causes of poor urban thermal environments, particularly during the summer. Previous research has focused primarily on the thermal characteristics of individual building units. Few studies consider the impact of the street-scale thermal environments on the surface temperature, which affects pedestrian thermal comfort. The purpose of this study is to analyze the thermal characteristics of various physical elements on urban streets using thermal imaging cameras, and present policy implications for improving pedestrian thermal comfort. This study examines street-scale thermal environments of three major commercial streets: Garosu road, Serosu road, and Narosu road, in Seoul, Korea. This study conducted field measurements both during the day and the night in June 2017 in order to investigate changes in the urban surface temperatures across time. The results show that street trees are the most effective mitigation element for reducing surface temperatures. With regard to building use types, the highest surface temperatures are typically measured near restaurant buildings. Building façades that are dark-colored or partially covered with a metal contribute to high surface temperatures. Similarly, the temperatures of artificial turf or wooden decks on urban streets are also significantly high during the daytime. The thermal characteristics of various urban street elements should be considered to reduce the surface temperature and mitigate the urban heat island effect

Diurnal and seasonal variations in the effect of urban environmental factors on air temperature: A consecutive regression analysis approach

This study investigates the diurnal and seasonal variations in the effect of environmental features on air temperature in Seoul, Korea. We expect that this study will lead to the identification of factors that can be applied for urban heat island mitigation strategies in summer without leading to an unintended result in winter. As our dependent variable, we employed the smoothed 31-day moving average of air temperatures, where we controlled the seasonal variation by normalizing the values observed from 247 automatic weather stations (AWS) from 2015 to 2016. Subsequently, we conducted consecutive log–log regression analyses of each day to examine patterns of change in regression coefficients and the significance of each independent variable. For independent variables, we applied built environment features including albedo, land-use, average building floors, the sky view factor, and green and water areas. This study provides analytical results regarding the relationship between environmental factors and air temperature. This study also addresses imperative issues for planners, especially regarding albedo, wind path, building geometry, and land use types. Finally, this study gives useful insights for managing the diurnal and seasonal variations of urban thermal environment in the mega-city.ISSN:1660-4601ISSN:1661-782

Application of Induced Pluripotent Stem Cells for Disease Modeling and 3D Model Construction: Focus on Osteoarthritis

Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have shown promising potential, specifically because of their accessibility and plasticity. Hence, the clinical applicability of iPSCs was investigated in various fields of research. However, only a few iPSC studies pertaining to osteoarthritis (OA) have been performed so far, despite the high prevalence rate of degenerative joint disease. In this review, we discuss some of the most recent applications of iPSCs in disease modeling and the construction of 3D models in various fields, specifically focusing on osteoarthritis and OA-related conditions. Notably, we comprehensively reviewed the successful results of iPSC-derived disease models in recapitulating OA phenotypes for both OA and early-onset OA to encompass their broad etiology. Moreover, the latest publications with protocols that have used iPSCs to construct 3D models in recapitulating various conditions, particularly the OA environment, were further discussed. With the overall optimistic results seen in both fields, iPSCs are expected to be more widely used for OA disease modeling and 3D model construction, which could further expand OA drug screening, risk assessment, and therapeutic capabilities

Psychological tactile sensor structure based on piezoelectric nanowire cell arrays

To produce artificial psychological feeling, especially 'pain', an electrical structure that mimics human skin has been studied. Touch by a sharp and a blunt object induces different deformations of the skin of human fingers. In order to imitate this phenomenon, a skin-mimicking device employing piezoelectric nanowire sensor arrays is used to generate an electrical 'pain' signal with signal processing when a pen cap presses the device. The electrical 'pain' signal is expected to enhance the protection mechanism of an android robot or mobile phone against harsh environments. © 2015 The Royal Society of Chemistry.1

Effect of germination environment on the biochemical compounds and anti-inflammatory properties of soybean cultivars.

In this study, we investigated changes in the isoflavone content, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activities (DPPH, ABTS), and anti-inflammatory activities of small-seeded and large-seeded soybean cultivars during germination (light/dark conditions). Total isoflavone content was higher at the seed stage in large-seeded soybeans, while it increased after 7 days of germination in small-seeded soybeans, particularly in response to light conditions, under which they had high TPC, TFC, and antioxidant activities. In large-seeded soybeans, the germination environment did not significantly affect TFC or DPPH inhibition, whereas TPC and ABTS inhibition were high under dark germination conditions. Extracts of sprouts exhibited superior anti-inflammatory activities. Nitric oxide production was slightly lower in small-seeded and large-seeded soybeans germinated under light and dark conditions, respectively. Our findings indicate that germinated soybeans improved nutritionally, and that enhancement of bioactivity under different germination environments could contribute to the selection of appropriate soybean cultivars

Recapitulation of methotrexate hepatotoxicity with induced pluripotent stem cell-derived hepatocytes from patients with rheumatoid arthritis

Abstract Background Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician’s attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient–derived induced pluripotent stem cells (RA-iPSCs) with MTX. Methods RA-iPSCs and healthy control iPSCs (HC-iPSCs) were established successfully. RA-iPSCs were differentiated into hepatocytes in two-dimensional (2D) monolayers and three-dimensional (3D) hepatocyte spheroid cultures; this process required growth factors such as BMP4, bFGF, HGF, and OSM. Immunofluorescence staining and flow cytometry were performed to confirm that the mature hepatocytes expressed cytokeratin 18, anti–alpha-1 antitrypsin, and albumin. MTX toxicity was evaluated via monitoring of cell viability, alanine aminotransferase, and mitochondrial status after MTX treatment in 2D and 3D cultures. Results RA-iPSCs generated from three RA patients suffering from MTX-induced hepatotoxicity differentiated into the endoderm lineage, hepatoblasts, and hepatocytes. In 2D culture, RA-iPSC-derived hepatocytes were more sensitive to MTX than healthy controls. A 3D culture system using hepatocyte spheroids also successfully recapitulated MTX-induced hepatotoxicity. The 3D culture system had several advantages, including longer culture periods under more complex conditions. Conclusions A patient-derived iPSC platform could recapitulate MTX toxicity. Simulation of drug toxicity in vitro may help clinicians choose safer drugs or less toxic doses